Current Medical Diagnosis & Treatment 2015


Dermatologic Disorders

Timothy G. Berger, MD

Dermatologic diseases are diagnosed by the types of lesions they cause. To make a diagnosis: (1) identify the type of lesion(s) the patient exhibits by morphology establishing a differential diagnosis (Table 6–1); and (2) obtain the elements of the history, physical examination, and appropriate laboratory tests to confirm the diagnosis. Unique clinical situations, such as the ill ICU patient, lead to different diagnostic considerations.

Table 6–1. Morphologic categorization of skin lesions and diseases.


 Frequently Used Treatment Measures

  1. Bathing

Soap should be used only in the axillae and groin and on the feet by persons with dry or inflamed skin. Soaking in water for 10–15 minutes before applying topical corticosteroids enhances their efficacy (Soak and Smear). Bath oils can be used, but add little above the use of moisturizers, and may make the tub slippery, increasing the risk of falling.

  1. Topical Therapy

Nondermatologists should become familiar with a representative agent in each category for each indication (eg, topical corticosteroid, topical retinoid, etc).

  1. Corticosteroids—Topical corticosteroid creams, lotions, ointments, gels, foams, and sprays are presented inTable 6–2Topical corticosteroids are divided into classes based on potency. There is little (except price) to recommend one agent over another within the same class. For a given agent, an ointment is more potent than a cream. The potency of a topical corticosteroid may be dramatically increased by occlusion (covering with a water impermeable barrier) for at least 4 hours. Depending on the location of the skin condition, gloves, plastic wrap, moist pajamas covered by dry pajamas (wet wraps) or plastic occlusive suits for patients can be used. Caution should be used in applying topical corticosteroids to areas of thin skin (face, scrotum, vulva, skin folds). Topical corticosteroid use on the eyelids may result in glaucoma or cataracts. One may estimate the amount of topical corticosteroid needed by using the “rule of nines” (as in burn evaluation; see Figure 37–2). In general, it takes an average of 20–30 g to cover the body surface of an adult once. Systemic absorption does occur, but adrenal suppression, diabetes mellitus, hypertension, osteoporosis, and other complications of systemic corticosteroids are very rare with topical corticosteroid therapy.

Table 6–2. Useful topical dermatologic therapeutic agents.

  1. Emollients for dry skin (“moisturizers”)—Dry skin is not related to water intake but to abnormal function of the epidermis. Many types of emollients are available. Petrolatum, mineral oil, Aquaphor, Vanicream, and Eucerin cream are the heaviest and best. Emollients are most effective when applied to wet skin. If the skin is too greasy after application, pat dry with a damp towel. Vanicream is relatively allergen-free and can be used if allergic contact dermatitis to topical products is suspected.

The scaly appearance of dry skin may be improved by urea, lactic acid, or glycolic acid-containing products provided no inflammation (erythema or pruritus) is present.

  1. Drying agents for weepy dermatoses—If the skin is weepy from infection or inflammation, drying agents may be beneficial. The best drying agent is water, applied as repeated compresses for 15–30 minutes, alone or with aluminum salts (Burow solution, Domeboro tablets).
  2. Topical antipruritics—Lotions that contain 0.5% each of camphor and menthol (Sarna) or pramoxine hydrochloride 1% (with or without 0.5% menthol, eg, Prax, PrameGel, Aveeno Anti-Itch lotion) are effective antipruritic agents. Hydrocortisone, 1% or 2.5%, may be incorporated for its anti-inflammatory effect (Pramosone cream, lotion, or ointment). Doxepin cream 5% may reduce pruritus but may cause drowsiness. Pramoxine and doxepin are most effective when applied with topical corticosteroids. Topical capsaicin can be effective in some forms of neuropathic itch. Ice in a plastic bag covered by a thin cloth applied to itchy spots can be effective.
  3. Systemic Antipruritic Drugs
  4. Antihistamines—H1-blockers are the agents of choice for pruritus when due to histamine, such as in urticaria. Otherwise, they appear to benefit itchy patients only by their sedating effects. Hydroxyzine 25–50 mg nightly is atypical dose. Sedating and nonsedating antihistamines are of limited value for the treatment of pruritus associated with inflammatory skin disease. Agents that may treat pruritus better include antidepressants (such as doxepin, mirtazapine, and paroxetine) as well as agents that may act either centrally or peripherally directly on the neurons that perceive or modulate pruritus (such as gabapentin, pregabalin, and duloxetine). Aprepitant and opioid antagonists such as naltrexone and butorphenol can be very effective in select patients, but their exact role in the management of the pruritic patient is not yet defined.
  5. Systemic corticosteroids—(SeeChapter 26.)

American Academy of Dermatology. Medical student core curriculum.

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Elmariah SB et al. Topical therapies for pruritus. Semin Cutan Med Surg. 2011 Jun;30(2):118–26. [PMID: 21767774]

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Steinhoff M et al. Pruritus: management algorithms and experimental therapies. Semin Cutan Med Surg. 2011 Jun;30(2):127–37. [PMID: 21767775]


Protection from ultraviolet light should begin at birth and will reduce the incidence of actinic keratoses, melanoma, and some nonmelanoma skin cancers when initiated at any age. The best protection is shade, but protective clothing, avoidance of direct sun exposure during the peak hours of the day, and daily use of chemical sunscreens are important.

Fair-complexioned persons should use a sunscreen with an SPF (sun protective factor) of at least 15 and preferably 30–40 every day. Sunscreens with high SPF values (> 30) usually afford some protection against UVA as well as UVB and are helpful in managing photosensitivity disorders. The actual SPF achieved is about one-quarter or less than that listed on the product, since patients apply only one-quarter as much sunscreen per unit area when compared with the amount used in tests to determine the listed SPF. Repeated daily applications enhance sunscreen efficacy. Aggressive sunscreen use should be accompanied by vitamin D supplementation in persons at risk for osteopenia (eg, organ transplant recipients).

Bodekær M et al. Accumulation of sunscreen in human skin after daily applications: a study of sunscreens with different ultraviolet radiation filters. Photodermatol Photoimmunol Photomed. 2012 Jun;28(3):127–32. [PMID: 22548393]

Jou PC et al. UV protection and sunscreens: what to tell patients. Cleve Clin J Med. 2012 Jun;79(6):427–36. [PMID: 22660875]

Liu W et al. Sunburn protection as a function of sunscreen application thickness differs between high and low SPFs. Photodermatol Photoimmunol Photomed. 2012 Jun;28(3):120–6. [PMID: 22548392]

Mar V et al. Nodular melanoma: a distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia. J Am Acad Dermatol. 2013 Apr;68(4):568–75. [PMID: 23182058]

Ou-Yang H et al. High-SPF sunscreens (SPF≥70) may provide ultraviolet protection above minimal recommended levels by adequately compensating for lower sunscreen user application amounts. J Am Acad Dermatol. 2012 Dec;67(6):1220–7. [PMID: 22463921]

Petersen B et al. Sunscreen use and failures—on site observations on a sun-holiday. Photochem Photobiol Sci. 2012 Dec13;12(1):190–6. [PMID: 23023728]

Robinson JK et al. Prevention of melanoma with regular sunscreen use. JAMA. 2011 Jul20;306(3):302–3. [PMID: 21712528]

 Complications of Topical Dermatologic Therapy

Complications of topical therapy can be largely avoided. They fall into several categories: allergy, irritation, and overuse.

  1. Allergy

Of the topical antibiotics, neomycin and bacitracin have the greatest potential for sensitization. Diphenhydramine, benzocaine, vitamin E, aromatic essential oils, bee pollen, preservatives, fragrances, and even the topical corticosteroids themselves can cause allergic contact dermatitis.

  1. Irritation

Preparations of tretinoin, benzoyl peroxide, and other acne medications should be applied sparingly to the skin.

  1. Overuse

Topical corticosteroids may induce acne-like lesions on the face (steroid rosacea) and atrophic striae in body folds.




In general, a benign mole is a small (< 6 mm) lesion with a well-defined border and a single shade of pigment from beige or pink to dark brown. The physical examination must take precedence over the history.

Moles have a normal natural history. In the patient’s first decade of life, moles often appear as flat, small, brown lesions. They are called junctional nevi because the nevus cells are at the junction of the epidermis and dermis. Over the next two decades, these moles grow in size and often become raised, reflecting the appearance of a dermal component, giving rise to compound nevi (Figure 6–1). Moles may darken and grow during pregnancy. As white patients enter their seventh and eighth decades, most moles have lost their junctional component and dark pigmentation. At every stage of life, normal moles should be well-demarcated, symmetric, and uniform in contour and color.

 Figure 6–1. Benign, flat and macular compound nevus on the arm. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J.The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

Boulos S et al. Free skin cancer screening provides access to care. J Am Acad Dermatol. 2012 Oct;67(4):787–8. [PMID: 22980248]

McWhirter JE et al. Visual images for patient skin self-examination and melanoma detection: a systematic review of published studies. J Am Acad Dermatol. 2013 Jul;69(1):47–55. [PMID: 23474227]

U.S. Preventive Services Task Force. Screening for skin cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009 Feb3;150(3):188–93. [PMID: 19189908]

Walter FM et al. Effect of adding a diagnostic aid to best practice to manage suspicious pigmented lesions in primary care: randomised controlled trial. BMJ. 2012 Jul4; 345:e4110. [PMID: 22763392]


The term “atypical nevus” or “atypical mole” has supplanted “dysplastic nevus.” The diagnosis of atypical moles is made clinically and not histologically, and moles should be removed only if they are suspected to be melanomas. Clinically, these moles are large (≥ 6 mm in diameter), with an ill-defined, irregular border and irregularly distributed pigmentation (Figure 6–2). It is estimated that 5–10% of the white population in the United States has one or more atypical nevi, and recreational sun exposure is a primary risk for the development of atypical nevi in nonfamilial settings. Studies have defined an increased risk of melanoma in the following populations: patients with 50 or more nevi with one or more atypical moles and one mole at least 8 mm or larger, and patients with a few to many definitely atypical moles. These patients deserve education and regular (usually every 6–12 months) follow-up. Kindreds with familial melanoma (numerous atypical nevi and a family history of two first-degree relatives with melanoma) deserve even closer attention, as the risk of developing single or even multiple melanomas in these individuals approaches 50% by age 50.

 Figure 6–2. Atypical (dysplastic) nevus on the chest. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

Duffy K et al. The dysplastic nevus: from historical perspective to management in the modern era: part I. Historical, histologic, and clinical aspects. J Am Acad Dermatol. 2012 Jul;67(1): 1.e1–16. [PMID: 22703915]

Duffy K et al. The dysplastic nevus: from historical perspective to management in the modern era: part II. Molecular aspects and clinical management. J Am Acad Dermatol. 2012 Jul;67(1):19.e1–12. [PMID: 22703916]


Blue nevi are small, slightly elevated, blue-black lesions (Figure 6–3) that favor the dorsal hands. They are common in persons of Asian descent, and an individual patient may have several of them. If present without change for many years, they may be considered benign, since malignant blue nevi are rare. However, blue-black papules and nodules that are new or growing must be evaluated to rule out nodular melanoma.

 Figure 6–3. Blue nevus on the left cheek, with some resemblance to a melanoma. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

Barros JA et al. Comparative dermatology: blue nevus. An Bras Dermatol. 2012 Jul–Aug;87(4):661–2. [PMID: 22892793]

Longo C et al. Blue lesions. Dermatol Clin. 2013 Oct;31(4):637–47. [PMID: 24075551]

Phadke PA et al. Blue nevi and related tumors. Clin Lab Med. 2011 Jun;31(2):345–58. [PMID: 21549247]


Freckles (ephelides) and lentigines are flat brown spots. Freckles first appear in young children, darken with ultraviolet exposure, and fade with cessation of sun exposure. They are determined by genetic factors. In adults lentigines gradually appear in sun-exposed areas, particularly the dorsa of the hands, upper back, and upper chest, starting in the fourth to fifth decade of life, and are associated with photoaging and estrogen and progesterone use. They are macular, usually 3–5 mm in diameter. On the upper back, they may have a very irregular border (inkspot lentigines). They do not fade with cessation of sun exposure. They should be evaluated like all pigmented lesions: If the pigmentation is homogeneous and they are symmetric and flat, they are most likely benign. They can be treated with topical 0.1% tretinoin, 0.1% tazarotene, 2% 4-hydroxyanisole with 0.01% tretinoin, laser therapy, or cryotherapy.

Ezzedine K et al. Freckles and solar lentigines have different risk factors in Caucasian women. J Eur Acad Dermatol Venereol. 2013 Mar;27(3):e345–56. [PMID: 22924836]


Seborrheic keratoses are benign plaques, beige to brown or even black, 3–20 mm in diameter, with a velvety or warty surface (Figure 6–4). They appear to be stuck or pasted onto the skin. They are extremely common—especially in the elderly—and may be mistaken for melanomas or other types of cutaneous neoplasms. Although they may be frozen with liquid nitrogen or curetted if they itch or are inflamed, no treatment is needed.

 Figure 6–4. Seborrheic keratosis with “stuck on appearance” but irregular borders and color variation suspicious for possible melanoma. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

Choi JW et al. Differentiation of benign pigmented skin lesions with the aid of computer image analysis: a novel approach. Ann Dermatol. 2013 Aug;25(3):340–7. [PMID: 24003278]



 May be flat or raised.

 Should be suspected in any pigmented skin lesion with recent change in appearance.

 Examination with good light may show varying colors, including red, white, black, and bluish.

 Borders typically irregular.

 General Considerations

Malignant melanoma is the leading cause of death due to skin disease. In 2013, approximately 76,690 new melanomas were diagnosed in the United States, with 45,060 cases in men and 31,630 in women. Melanoma will cause an estimated 9480 deaths (two-thirds in men). One in four cases of melanoma occurs before the age of 40. Increased detection of early melanomas has led to increased survival, but melanoma fatalities continue to increase, especially in elderly men.

Tumor thickness is the single most important prognostic factor. Ten-year survival rates—related to thickness in millimeters—are as follows: < 1 mm, 95%; 1–2 mm, 80%; 2–4 mm, 55%; and > 4 mm, 30%. With lymph node involvement, the 5-year survival rate is 30%; with distant metastases, it is < 10%.

 Clinical Findings

Primary malignant melanomas may be classified into various clinicohistologic types, including lentigo maligna melanoma (arising on chronically sun-exposed skin of older individuals); superficial spreading malignant melanoma (two-thirds of all melanomas arising on intermittently sun-exposed skin); nodular malignant melanoma; acral-lentiginous melanomas (arising on palms, soles, and nail beds); ocular melanoma; and malignant melanomas on mucous membranes. These different clinical types of melanoma appear to have different oncogenic mutations, which may be important in the treatment of patients with advanced disease. Clinical features of pigmented lesions suspicious for melanoma are an irregular notched border where the pigment appears to be leaking into the normal surrounding skin; a topography that may be irregular, ie, partly raised and partly flat (Figure 6–5). Color variegation is present, and colors such as pink, blue, gray, white, and black are indications for referral. A useful mnemonic is the ABCD rule: “ABCD = Asymmetry, Border irregularity, Color variegation, and Diameter > 6 mm.” “E” for Evolution can be added. The history of a changing mole (evolution) is the single most important historical reason for close evaluation and possible referral. Bleeding and ulceration are ominous signs. A mole that stands out from the patient’s other moles deserves special scrutiny—the “ugly duckling sign.” A patient with a large number of moles is statistically at increased risk for melanoma and deserves careful and periodic examination, particularly if the lesions are atypical. Referral of suspicious pigmented lesions is always appropriate.

 Figure 6–5. Malignant melanoma, with multiple colors and classic “ABCDE” features. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

While superficial spreading melanoma is largely a disease of whites, persons of other races are still at risk for this and other types of melanoma, particularly acral lentiginous melanoma. These occur as dark, sometimes irregularly shaped lesions on the palms and soles and as new, often broad and solitary, darkly pigmented longitudinal streaks in the nails. Acral lentiginous melanoma may be a difficult diagnosis because benign pigmented lesions of the hands, feet, and nails occur commonly in more darkly pigmented persons and clinicians may hesitate to biopsy the palms, soles, and nail beds. As a result, the diagnosis is often delayed until the tumor has become clinically obvious and histologically thick. Clinicians should give special attention to new or changing lesions in these areas.


Treatment of melanoma consists of excision. After histologic diagnosis, the area is usually reexcised with margins dictated by the thickness of the tumor. Thin low-risk and intermediate-risk tumors require only conservative margins of 1–3 cm. Surgical margins of 0.5–1 cm for melanoma in situ and 1 cm for lesions < 1 mm in thickness are recommended.

Sentinel lymph node biopsy (selective lymphadenectomy) using preoperative lymphoscintigraphy and intraoperative lymphatic mapping is effective for staging melanoma patients with intermediate risk without clinical adenopathy and is recommended for all patients with lesions over 1 mm in thickness or with high-risk histologic features. Referral of intermediate-risk and high-risk patients to centers with expertise in melanoma is strongly recommended. Identifying the oncogenic mutations in patients with advanced melanoma may be important in their treatment. The long-term use of beta-blockers may reduce the risk of progression of high-risk melanoma.

Bichakjian CK et al; American Academy of Dermatology. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2011 Nov;65(5):1032–47. [PMID: 21868127]

Coit DG et al. Melanoma, versions 2.2013: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2013 Apr1;11(4):395–407. [PMID: 23584343]

Council ML. Common skin cancers in older adults: approach to diagnosis and management. Clin Geriatr Med. 2013 May;29(2):361–72. [PMID: 23571033]

De G iorgi V et al. Treatment with beta-blockers and reduced disease progression in patients with thick melanoma. Arch Intern Med. 2011 Apr25;171(8):779–81. [PMID: 21518948]

Fox MC et al. Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: PartI: management of stage III disease. J Am Acad Dermatol. 2013 Jan;68(1):1.e1–9. [PMID: 23244383]

Fox MC et al. Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: Part II: management of stage IV disease. J Am Acad Dermatol. 2013 Jan;68(1):13.e1–13. [PMID: 23244384]

Menzies AM et al. New combinations and immunotherapies for melanoma: latest evidence and clinical utility. Ther Adv Med Oncol. 2013 Sep;5(5):278–85. [PMID: 23997828]

Scolyer RA. Evolving concepts in melanoma classification and their relevance to multidisciplinary melanoma patient care. Mol Oncol. 2011 Apr;5(2):124–36. [PMID: 21482206]

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 Pruritic, exudative, or lichenified eruption on face, neck, upper trunk, wrists, and hands and in the antecubital and popliteal folds.

 Personal or family history of allergic manifestations (eg, asthma, allergic rhinitis, atopic dermatitis).

 Tendency to recur.

 Onset in childhood in most patients. Onset after age 30 is very uncommon.

 General Considerations

Atopic dermatitis looks different at different ages and in people of different races. Diagnostic criteria for atopic dermatitis must include pruritus, typical morphology and distribution (flexural lichenification, hand eczema, nipple eczema, and eyelid eczema in adults), onset in childhood, and chronicity. Also helpful are: (1) a personal or family history of atopic disease (asthma, allergic rhinitis, atopic dermatitis), (2) xerosis-ichthyosis, (3) facial pallor with infraorbital darkening, (4) elevated serum IgE, and (5) repeated skin infections.

 Clinical Findings

  1. Symptoms and Signs

Itching may be severe and prolonged. Rough, red plaques usually without the thick scale and discrete demarcation of psoriasis affect the face, neck, and upper trunk. The flexural surfaces of elbows and knees are often involved. In chronic cases, the skin is dry, leathery, and lichenified. In black patients with severe disease, pigmentation may be lost in lichenified areas. During acute flares, widespread redness with weeping, either diffusely or in discrete plaques, is common.

  1. Laboratory Findings

Food allergy is an uncommon cause of flares of atopic dermatitis in adults. Eosinophilia and increased serum IgE levels may be present.

 Differential Diagnosis

Atopic dermatitis must be distinguished from seborrheic dermatitis (less pruritic, frequent scalp and face involvement, greasy and scaly lesions, and quick response to therapy). Secondary staphylococcal infections may exacerbate atopic dermatitis, and should be considered during hyperacute, weepy flares of atopic dermatitis. Fissuring where the earlobe connects to the neck is a cardinal sign of secondary infection. Since virtually all patients with atopic dermatitis have skin disease before age 5, a new diagnosis of atopic dermatitis in an adult over age 30 should be made cautiously and only after consultation.


Patient education regarding gentle skin care and exactly how to use medications is critical in the successful management of atopic dermatitis.

  1. General Measures

Atopic patients have hyperirritable skin. Anything that dries or irritates the skin will potentially trigger dermatitis. Atopic individuals are sensitive to low humidity and often get worse in the winter. Adults with atopic disorders should not bathe more than once daily. Soap should be confined to the armpits, groin, scalp, and feet. Washcloths and brushes should not be used. After rinsing, the skin should be patted dry (not rubbed) and then immediately—within three minutes—covered with a thin film of an emollient such as Aquaphor, Eucerin, petrolatum, Vanicream, or a corticosteroid as needed. Vanicream can be used if contact dermatitis resulting from additives in medication is suspected. Atopic patients may be irritated by scratchy fabrics, including wools and acrylics. Cottons are preferable, but synthetic blends also are tolerated. Other triggers of eczema in some patients include sweating, ointments, hot baths, and animal danders.

  1. Local Treatment

Corticosteroids should be applied sparingly to the dermatitis once or twice daily and rubbed in well. Their potency should be appropriate to the severity of the dermatitis. In general, one should begin with triamcinolone 0.1% or a stronger corticosteroid then taper to hydrocortisone or another slightly stronger mild corticosteroid (alclometasone, desonide). It is vital that patients taper off corticosteroids and substitute emollients as the dermatitis clears to avoid the side effects of corticosteroids. Tapering is also important to avoid rebound flares of the dermatitis that may follow their abrupt cessation. Tacrolimus ointment (Protopic 0.03% or 0.1%) and pimecrolimus cream (Elidel 1%) can be effective in managing atopic dermatitis when applied twice daily. Burning on application occurs in about 50% of patients using Protopic and in 10–25% of Elidel users, but it may resolve with continued treatment. These medications do not cause skin atrophy or striae, avoiding the complications of long-term topical corticosteroid use. They are safe for application on the face and even the eyelids.

The US Food and Drug Administration (FDA) has issued a black box warning for both topical tacrolimus and pimecrolimus due to concerns about the development of T-cell lymphoma. The agents should be used sparingly and only in locations where less expensive corticosteroids cannot be used. Tacrolimus and pimecrolimus should be avoided in patients at high risk for lymphoma (ie, those with HIV, iatrogenic immunosuppression, prior lymphoma).

The treatment of atopic dermatitis is dictated by the pattern and stage of the dermatitis—acute/weepy, subacute/scaly, or chronic/lichenified.

  1. Acute weeping lesions—Use water or aluminum subacetate solution (Domeboro tablets, one in a pint of cool water) or colloidal oatmeal (Aveeno; dispense one box, and use as directed on box) as soothing or astringent soaks, baths, or wet dressings for 10–30 minutes two to four times daily. Lesions on extremities particularly may be bandaged for protection at night. Use high-potency corticosteroids after soaking but spare the face and body folds. Tacrolimus is usually not tolerated at this stage. Systemic corticosteroids may be required (see below).
  2. Subacute or scaly lesions—At this stage, the lesions are dry but still red and pruritic. Mid- to high-potency corticosteroids in ointment form should be continued until scaling and elevated skin lesions are cleared and itching is decreased substantially. At that point, patients should begin a 2- to 4-week taper from twice-daily to daily to alternate-day dosing with topical corticosteroids to reliance on emollients, with occasional use of corticosteroids on specific itchy areas. Instead of tapering the frequency of usage of a more potent corticosteroid, it may be preferable to switch to a low-potency corticosteroid. Tacrolimus and pimecrolimus are more expensive alternatives and may be added if corticosteroids cannot be stopped.
  3. Chronic, dry, lichenified lesions—Thickened and usually well-demarcated, they are best treated with high-potency to ultra-high-potency corticosteroid ointments. Nightly occlusion for 2–6 weeks may enhance the initial response. Occasionally, adding tar preparations such as LCD (liquor carbonis detergens) 10% in Aquaphor or 2% crude coal tar may be beneficial.
  4. Maintenance treatment—Once symptoms have improved, constant application of effective moisturizers is recommended to prevent flares. In patients with moderate disease, use of topical anti-inflammatories only on weekends or three times weekly can prevent flares.
  5. Systemic and Adjuvant Therapy

Systemic corticosteroids are indicated only for severe acute exacerbations. Oral prednisone dosages should be high enough to suppress the dermatitis quickly, usually starting with 40–60 mg daily for adults. The dosage is then tapered to nil over a period of 2–4 weeks. Owing to the chronic nature of atopic dermatitis and the side effects of chronic systemic corticosteroids, long-term use of these agents is not recommended for maintenance therapy. Bedtime doses of hydroxyzine, diphenhydramine, or doxepin may be helpful via their sedative properties in reducing perceived pruritus. Fissures, crusts, erosions, or pustules indicate staphylococcal infection clinically. Antistaphylococcal antibiotics given systemically—such as a first-generation cephalosporin or doxycycline if methicillin-resistant Staphylococcus aureus is suspected—may be helpful. Cultures to exclude methicillin-resistant S aureus are recommended. However, in this setting, continuing and augmenting the topical anti-inflammatory treatment often improves the dermatitis, despite the presence of infection. Phototherapy can be an important adjunct for severely affected patients, and the properly selected patient with recalcitrant disease may benefit greatly from therapy with UVB with or without coal tar or PUVA (psoralen plus ultraviolet A). Oral cyclosporine, mycophenolate mofetil, methotrexate, or azathioprine may be used for the most severe and recalcitrant cases.

 Complications of Treatment

The clinician should monitor for skin atrophy. Eczema herpeticum, a generalized herpes simplex infection manifested by monomorphic vesicles, crusts, or scalloped erosions superimposed on atopic dermatitis or other extensive eczematous processes, is treated successfully with oral acyclovir, 200 mg five times daily, or intravenous acyclovir in a dose of 10 mg/kg intravenously every 8 hours (500 mg/m2 every 8 hours). Smallpox vaccination is absolutely contraindicated in patients with atopic dermatitis or a history thereof because of the risk of eczema vaccinatum (widespread vaccinia infection, preferentially in areas of dermatitis).


Atopic dermatitis runs a chronic or intermittent course. Affected adults may have only hand dermatitis. Poor prognostic factors for persistence into adulthood in atopic dermatitis include onset early in childhood, early generalized disease, and asthma. Only 40–60% of these patients have lasting remissions.

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Eichenfield LF et al. Guidelines of care for the management of atopic dermatitis: section 2. Guidelines of care for the management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. In press.

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Ring J et al. Guidelines for treatment of atopic eczema (atopic dermatitis) part II. J Eur Acad Dermatol Venereol. 2012 Sep;26(9):1175–93. [PMID: 22813359]

Schmitt J et al. Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema: systematic review and meta-analysis of randomized controlled trials. Br J Dermatol. 2011 Feb;164(2):415–28. [PMID: 20819086]

Sidbury R et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. In press.

Sidbury R et al. Guidelines of care for the management of atopic dermatitis: section 4. Prevention of disease flares and use of adjunctive therapies and approaches. J Am Acad Dermatol. In press.

Torrelo A et al. Atopic dermatitis: impact on quality of life and patients’ attitudes toward its management. Eur J Dermatol. 2012 Jan–Feb;22(1):97–105. [PMID: 22237114]

Van Onselen J. Skin care in the older person: identifying and managing eczema. Br J Community Nurs. 2011 Dec;16(12): 576, 578–80, 582. [PMID: 22413402]

Van Velsen SG et al. Two-year assessment of effect of topical corticosteroids on bone mineral density in adults with moderate to severe atopic dermatitis. J Am Acad Dermatol. 2012 Apr;66(4):691–3. [PMID: 22421118]

LICHEN SIMPLEX CHRONICUS (Circumscribed Neurodermatitis)


 Chronic itching and scratching.

 Lichenified lesions with exaggerated skin lines overlying a thickened, well-circumscribed scaly plaque.

 Predilection for nape of neck, wrists, external surfaces of forearms, lower legs, scrotum, and vulva.

 General Considerations

Lichen simplex chronicus represents a self-perpetuating scratch-itch cycle—a learned behavior that is hard to disrupt.

 Clinical Findings

Intermittent itching incites the patient to scratch the lesions. Itching may be so intense as to interfere with sleep. Dry, leathery, hypertrophic, lichenified plaques appear on the neck, ankles, or perineum (Figure 6–6). The patches are rectangular, thickened, and hyperpigmented. The skin lines are exaggerated.

 Figure 6–6. Lichen simplex chronicus. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

 Differential Diagnosis

This disorder can be differentiated from plaque-like lesions such as psoriasis (redder lesions having whiter scales on the elbows, knees, and scalp and nail findings), lichen planus (violaceous, usually smaller polygonal papules), and nummular (coin-shaped) dermatitis. Lichen simplex chronicus may complicate chronic atopic dermatitis.


For lesions in extra-genital regions, superpotent topical corticosteroids are effective, with or without occlusion, when used twice daily for several weeks. In some patients, flurandrenolide (Cordran) tape may be effective, since it prevents scratching and rubbing of the lesion. The injection of triamcinolone acetonide suspension (5–10 mg/mL) into the lesions may occasionally be curative. Continuous occlusion with a flexible hydrocolloid dressing for 7 days at a time for 1–2 months may also be helpful. For genital lesions, see the section Pruritus Ani.


The disease tends to remit during treatment but may recur or develop at another site.

Szegedi K et al. Increased frequencies of IL-31-producing T cells are found in chronic atopic dermatitis skin. Exp Dermatol. 2012 Jun;21(6):431–6. [PMID: 22621183]



 Silvery scales on bright red, well-demarcated plaques, usually on the knees, elbows, and scalp.

 Nail findings including pitting and onycholysis (separation of the nail plate from the bed).

 Mild itching (usually).

 May be associated with psoriatic arthritis.

 Psoriasis patients are at increased risk for metabolic syndrome and lymphoma.

 Histopathology is not often useful and can be confusing.

 General Considerations

Psoriasis is a common benign, chronic inflammatory skin disease with both a genetic basis and known environmental triggers. Injury or irritation of normal skin tends to induce lesions of psoriasis at the site (Koebner phenomenon). Obesity worsens psoriasis, and significant weight loss in obese persons may lead to substantial improvement of their psoriasis. Psoriasis has several variants—the most common is the plaque type. Eruptive (guttate) psoriasis consisting of myriad lesions 3–10 mm in diameter occurs occasionally after streptococcal pharyngitis. Rarely, grave, occasionally life-threatening forms (generalized pustular and erythrodermic psoriasis) may occur. Plaque type or extensive erythrodermic psoriasis with abrupt onset may accompany HIV infection.

 Clinical Findings

There are often no symptoms, but itching may occur and be severe. Favored sites include the scalp, elbows, knees, palms and soles, and nails. The lesions are red, sharply defined plaques covered with silvery scales (Figure 6–7). The glans penis and vulva may be affected. Occasionally, only the flexures (axillae, inguinal areas) are involved. Fine stippling (“pitting”) in the nails is highly suggestive ofpsoriasis (Figure 6–8). Patients with psoriasis often have a pink or red intergluteal fold. Not all patients have findings in all locations, but the occurrence of a few may help make the diagnosis when other lesions are not typical. Some patients have mainly hand or foot dermatitis and only minimal findings elsewhere. There may be associated arthritis that is most commonly distal and oligoarticular, although the rheumatoid variety with a negative rheumatoid factor may occur. The psychosocial impact of psoriasis is a major factor in determining the treatment of the patient.

 Figure 6–7. Plaque psoriasis in the sacral region and intergluteal fold. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

 Figure 6–8. Nail pitting due to psoriasis. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

 Differential Diagnosis

The combination of red plaques with silvery scales on elbows and knees, with scaliness in the scalp or nail findings, is diagnostic. Psoriasis lesions are well demarcated and affect extensor surfaces—in contrast to atopic dermatitis, with poorly demarcated plaques in flexural distribution. In body folds, scraping and culture for Candida and examination of scalp and nails will distinguish psoriasis from intertrigo and candidiasis. Dystrophic changes in nails may simulate onychomycosis, but again, the general examination combined with a potassium hydroxide (KOH) preparation or fungal culture will be valuable in diagnosis. The cutaneous features of reactive arthritis (Reiter syndrome) mimic psoriasis.


There are many therapeutic options in psoriasis to be chosen according to the extent (body surface area [BSA] affected) and the presence of other findings (for example, arthritis). Certain drugs, such as beta-blockers, antimalarials, statins, and lithium, may flare or worsen psoriasis. Even tiny doses of systemic corticosteroids given to patients with psoriasis may lead to severe rebound flares of their disease when they are tapered. Never use systemic corticosteroids to treat flares of psoriasis. In general, patients with moderate to severe psoriasis should be managed by or in conjunction with a dermatologist.

  1. Limited Disease

For patients with numerous small plaques, phototherapy is the best therapy (see below). For patients with large plaques and < 10% of the BSA involved, the easiest regimen is to use a high-potency to ultra-high-potency topical corticosteroid cream or ointment. It is best to restrict the ultra-high-potency corticosteroids to 2–3 weeks of twice-daily use and then use them in a pulse fashion three or four times on weekends or switch to a midpotency corticosteroid. Topical corticosteroids rarely induce a lasting remission. Additional measures are therefore commonly added to topical corticosteroid therapy. Calcipotriene ointment 0.005% or calcitriol ointment 0.003%, both vitamin D analogs, are used twice daily for plaque psoriasis. Initially, patients are treated with twice-daily corticosteroids plus a vitamin D analog twice daily. This rapidly clears the lesions. The vitamin D analog is then used alone once daily and with the corticosteroid once daily for several weeks. Eventually, the topical corticosteroids are stopped, and once- or twice-daily application of the vitamin D analog is continued long-term. Calcipotriene usually cannot be applied to the groin or on the face because of irritation. Treatment of extensive psoriasis with vitamin D analogs may result in hypercalcemia, so that the maximum dose for calcipotriene is 100 g/week and for calcitriol is 200 g/week. Calcipotriene is incompatible with many topical corticosteroids (but not halobetasol), so if used concurrently it must be applied at a different time. Tar preparations such as Fototar cream, LCD (liquor carbonis detergens) 10% in Nutraderm lotion, alone or mixed directly with triamcinolone 0.1%, are useful adjuncts when applied twice daily. Occlusion alone has been shown to clear isolated plaques in 30–40% of patients. Thin, occlusive hydrocolloid dressings are placed on the lesions and left undisturbed for as long as possible (a minimum of 5 days, up to 7 days) and then replaced. Responses may be seen within several weeks.

For the scalp, start with a tar shampoo, used daily if possible. For thick scales, use 6% salicylic acid gel (eg, Keralyt), P & S solution (phenol, mineral oil, and glycerin), or fluocinolone acetonide 0.01% in oil (Derma-Smoothe/FS) under a shower cap at night, and shampoo in the morning. In order of increasing potency, triamcinolone 0.1%, or fluocinolone, betamethasone dipropionate, fluocinonide or amcinonide, and clobetasol are available in solution form for use on the scalp twice daily. For psoriasis in the body folds, treatment is difficult, since potent corticosteroids cannot be used and other agents are poorly tolerated. Tacrolimus ointment 0.1% or 0.03% or pimecrolimus cream 1% may be effective in penile, groin, and facial psoriasis.

  1. Moderate Disease

Psoriasis affecting 10–30% of the patient’s BSA is frequently treated with UV phototherapy, either in a medical office or via a home light unit. Systemic agents listed below may also be used.

  1. Generalized Disease

If psoriasis involves > 30% of the body surface, it is difficult to treat with topical agents. The treatment of choice is outpatient narrowband UVB (NB-UVB) three times weekly. Clearing occurs in an average of 7 weeks, but maintenance may be required. Severe psoriasis unresponsive to outpatient ultraviolet light may be treated in a psoriasis day care center with the Goeckerman regimen, which involves use of crude coal tar for many hours and exposure to UVB light. Such treatment may offer the best chance for prolonged remissions.

Psoralen plus UVA (PUVA) photochemotherapy may be effective even in patients who have not responded to standard NB-UVB treatment. Long-term use of PUVA is associated with an increased risk of skin cancer (especially squamous cell carcinoma and perhaps melanoma), particularly in persons with fair complexions. Thus, periodic examination of the skin is imperative. Atypical lentigines are a common complication. There can be rapid aging of the skin in fair individuals. Cataracts have not been reported with proper use of protective glasses. PUVA may be used in combination with other therapy, such as acitretin or methotrexate.

Methotrexate is very effective for severe psoriasis in doses up to 25 mg once weekly. It should be used according to published protocols. Long-term methotrexate use may be associated with cirrhosis. After receiving a 3.5–4 g cumulative dose, the patient should be referred to a hepatologist for consideration of a liver biopsy. Administration of folic acid, 1–2 mg daily, can eliminate nausea caused by methotrexate without compromising efficacy.

Acitretin, a synthetic retinoid, is most effective for pustular psoriasis in dosages of 0.5–0.75 mg/kg/d. Liver enzymes and serum lipids must be checked periodically. Because acitretin is a teratogen and persists for long periods in fat, women of childbearing age must wait at least 3 years after completing acitretin treatment before considering pregnancy. When used as single agents, retinoids will flatten psoriatic plaques, but will rarely result in complete clearing. Retinoids find their greatest use when combined with phototherapy—either UVB or PUVA, with which they are synergistic.

Cyclosporine dramatically improves psoriasis and may be used to control severe cases. Rapid relapse (rebound) is the rule after cessation of therapy, so another agent must be added if cyclosporine is stopped. The tumor necrosis factor (TNF) inhibitors etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira) are effective in pustular and chronic plaque psoriasis and are also effective for the associated arthritis. Infliximab provides the most rapid response and can be used for severe pustular or erythrodermic flares. Etanercept is used more frequently for long-term treatment at a dose of 50 mg twice weekly for 3 months, then 50 mg once weekly. All three TNF inhibitors can also induce or worsen psoriasis. IL-12/23 monoclonal antibodies (ustekinumab [Stelara]) are also effective and may be considered instead of using a TNF inhibitor. Given the large number of immunosuppressive and biologic agents available, consultation with a dermatologist is recommended when considering institution of treatment with a systemic agent for moderate to severe psoriasis.


The course tends to be chronic and unpredictable, and the disease may be refractory to treatment. Patients (especially those older than 40 years) should be monitored for metabolic syndrome, which correlates with the severity of their skin disease.

Arias-Santiago S et al. Atheroma plaque, metabolic syndrome and inflammation in patients with psoriasis. Eur J Dermatol. 2012 May– Jun;22(3):337–44. [PMID: 22503884]

Armstrong AW et al. Psoriasis and the risk of diabetes mellitus: a systematic review and meta-analysis. JAMA Dermatol. 2013 Jan;149(1):84–91. [PMID: 23407990]

Bailey EE et al. Combination treatments for psoriasis: a systematic review and meta-analysis. Arch Dermatol. 2012 Apr;148(4):511–22. [PMID: 22184718]

Gelfand JM et al. Comparative effectiveness of commonly used systemic treatments of phototherapy for moderate to severe plaque psoriasis in the clinical practice setting. Arch Dermatol. 2012 Apr;148(4):487–94. [PMID: 22508874]

Hendriks AG et al. Combinations of classical time-honoured topicals in plaque psoriasis: a systematic review. J Eur Acad Dermatol Venereol. 2013 Apr;27(4):399–410. [PMID: 22779910]

Hsu S et al. Consensus guidelines for the management of plaque psoriasis. Arch Dermatol. 2012 Jan;148(1):95–102. [PMID: 22250239]

Kim IH et al. Comparative efficacy of biologics in psoriasis: a review. Am J Clin Dermatol. 2012 Dec1;13(6):365–74. [PMID: 22967166]

Lebwohl MG et al. A randomized study to evaluate the efficacy and safety of adding topical therapy to etanercept in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2013 Sep;69(3):385–92. [PMID: 23643256]

Mason A et al. Topical treatments for chronic plaque psoriasis: an abridged Cochrane Systematic Review. J Am Acad Dermatol. 2013 Nov;69(5):799–807. [PMID: 24124809]

Reich K et al. Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials. Br J Dermatol. 2012 Jan;166(1):179–88. [PMID: 21910698]

Ryan C et al. Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials. JAMA. 2011 Aug24;306(8):864–71. [PMID: 21862748]

Samarasekere EJ et al. Topical therapies for the treatment of plaque psoriasis: systematic review and network meta-analyses. Br J Dermatol. 2013 May;168(5):954–67. [PMID: 23413913]



 Oval, fawn-colored, scaly eruption following cleavage lines of trunk.

 Herald patch precedes eruption by 1–2 weeks.

 Occasional pruritus.

 General Considerations

This is a common mild, acute inflammatory disease that is 50% more common in females. Young adults are principally affected, mostly in the spring or fall. Concurrent household cases have been reported.

 Clinical Findings

Itching is common but is usually mild. The diagnosis is made by finding one or more classic lesions. The lesions consist of oval, fawn-colored plaques up to 2 cm in diameter. The centers of the lesions have a crinkled or “cigarette paper” appearance and a collarette scale, ie, a thin bit of scale that is bound at the periphery and free in the center. Only a few lesions in the eruption may have this characteristic appearance, however. Lesions follow cleavage lines on the trunk (so-called Christmas tree pattern, Figure 6–9), and the proximal portions of the extremities are often involved. A variant that affects the flexures (axillae and groin), so called inverse pityriasis rosea, and a papular variant, especially in black patients, also occur. An initial lesion (“herald patch”) that is often larger than the later lesions often precedes the general eruption by 1–2 weeks. The eruption usually lasts 6–8 weeks and heals without scarring.

 Figure 6–9. Pityriasis rosea with scaling lesions following skin lines and resembling a Christmas tree. (Courtesy of EJ Mayeaux, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

 Differential Diagnosis

A serologic test for syphilis should be performed if at least a few perfectly typical lesions are not present and especially if there are palmar and plantar or mucous membrane lesions or adenopathy, features that are suggestive of secondary syphilis. For the nonexpert, an RPR (rapid plasma reagin) test in all cases is not unreasonable. Tinea corporis may present with red, slightly scaly plaques, but rarely are there more than a few lesions of tinea corporis compared to the many lesions of pityriasis rosea. Seborrheic dermatitis on occasion presents on the body with poorly demarcated patches over the sternum, in the pubic area, and in the axillae. Tinea versicolor lacks the typical collarette rimmed lesions. Certain drugs (eg, angiotensin-converting enzyme [ACE] inhibitors and metronidazole) and influenza immunization rarely may induce a skin eruption mimicking pityriasis rosea.


Pityriasis rosea often requires no treatment. In Asians, Hispanics, or blacks, in whom lesions may remain hyperpigmented for some time, more aggressive management may be indicated. Treatment is, otherwise, only indicated if the patient is symptomatic. While adequately controlled and reproduced trials have not demonstrated widely effective treatments, most dermatologists recommend UVB treatments, or prednisone as used for contact dermatitis for severe or severely symptomatic cases. For mild to moderate cases, topical corticosteroids of medium strength (triamcinolone 0.1%) and oral antihistamines may also be used if pruritus is bothersome.


Pityriasis rosea is usually an acute self-limiting illness that disappears in about 6 weeks.

Polate M et al. Palmar herald patch in pityriasis rosea. Australas J Dermatol. 2012 Aug;53(3):e64–5. [PMID: 22881477]

Sinha S et al. Coexistence of two atypical variants of pityriasis rosea: a case report and review of literature. Pediatr Dermatol. 2012 Jul–Aug;29(4):538–40. [PMID: 21906158]



 Dry scales and underlying erythema.

 Scalp, central face, presternal, interscapular areas, umbilicus, and body folds.

 General Considerations

Seborrheic dermatitis is an acute or chronic papulosquamous dermatitis that often coexists with psoriasis.

 Clinical Findings

Pruritus is an inconstant finding. The scalp, face, chest, back, umbilicus, eyelid margins, and body folds have dry scales or oily yellowish scurf (Figure 6–10). Patients with Parkinson disease, HIV infection, and patients who become acutely ill and are hospitalized often have seborrheic dermatitis.

 Figure 6–10. Seborrheic dermatitis. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

 Differential Diagnosis

There is a spectrum from seborrheic dermatitis to scalp psoriasis. Extensive seborrheic dermatitis may simulate intertrigo in flexural areas, but scalp, face, and sternal involvement suggests seborrheic dermatitis.


  1. Seborrhea of the Scalp

Shampoos that contain zinc pyrithione or selenium are used daily if possible. These may be alternated with ketoconazole shampoo (1% or 2%) used twice weekly. A combination of shampoos is used in refractory cases. Tar shampoos are also effective for milder cases and for scalp psoriasis. Topical corticosteroid solutions or lotions are then added if necessary and are used twice daily. (See treatment for scalp psoriasis, above.)

  1. Facial Seborrheic Dermatitis

The mainstay of therapy is a mild corticosteroid (hydrocortisone 1%, alclometasone, desonide) used intermittently and not near the eyes. If the disorder cannot be controlled with intermittent use of a mild topical corticosteroid alone, ketoconazole (Nizoral) 2% cream is added twice daily. Topical tacrolimus (Protopic) and pimecrolimus (Elidel) are steroid-sparing alternatives.

  1. Seborrheic Dermatitis of Nonhairy Areas

Low-potency corticosteroid creams—ie, 1% or 2.5% hydrocortisone, desonide, or alclometasone dipropionate—are highly effective.

  1. Seborrhea of Intertriginous Areas

Apply low-potency corticosteroid lotions or creams twice daily for 5–7 days and then once or twice weekly for maintenance as necessary. Ketoconazole or clotrimazole cream may be a useful adjunct. Tacrolimus or pimecrolimus topically may avoid corticosteroid atrophy in chronic cases.

  1. Involvement of Eyelid Margins

“Marginal blepharitis” usually responds to gentle cleaning of the lid margins nightly as needed, with undiluted Johnson & Johnson Baby Shampoo using a cotton swab.


The tendency is for lifelong recurrences. Individual outbreaks may last weeks, months, or years.

Hay RJ. Malassezia, dandruff and seborrhoeic dermatitis: an overview. Br J Dermatol. 2011 Oct;165(Suppl 2):2–8. [PMID: 21919896]


Mycotic infections are traditionally divided into two principal groups—superficial and deep. In this chapter, we will discuss only the superficial infections: tinea corporis and tinea cruris; dermatophytosis of the feet and dermatophytid of the hands; tinea unguium (onychomycosis); and tinea versicolor. See Chapter 36 for discussion of deep mycoses.

The diagnosis of fungal infections of the skin is usually based on the location and characteristics of the lesions and on the following laboratory examinations: (1) Direct demonstration of fungi in 10% KOH of scrapings from suspected lesions. “If it’s scaly, scrape it” is a time-honored maxim (Figure 6–11). (2) Cultures of organisms from skin scrapings. (3) Histologic sections of biopsies stained with periodic acid-Schiff (Hotchkiss-McManus) technique may be diagnostic if scrapings and cultures are falsely negative.

 Figure 6–11. KOH preparation of fungus demonstrating pseudohyphae and budding yeast forms. (Reproduced, with permission, from Nicoll D et al. Pocket Guide to Diagnostic Tests, 6th ed. McGraw-Hill, 2012.)

 Principles of Treatment

A diagnosis should always be confirmed by KOH preparation, culture, or biopsy. Many other diseases cause scaling, and use of an antifungal agent without a firm diagnosis makes subsequent diagnosis more difficult. In general, fungal infections are treated topically except for those involving the nails, those that are very extensive, or those that involve the hair follicles. In these situations, oral agents may be useful, with special attention to their side effects and complications, including hepatic toxicity.

 General Measures & Prevention

Since moist skin favors the growth of fungi, dry the skin carefully after bathing or after perspiring heavily. Talc or other drying powders may be useful. The use of topical corticosteroids for other diseases may be complicated by intercurrent tinea or candidal infection, and topical antifungals are often used in intertriginous areas with corticosteroids to prevent this.

  1. Tinea Corporis or Tinea Circinata (Body Ringworm)


 Ring-shaped lesions with an advancing scaly border and central clearing or scaly patches with a distinct border.

 On exposed skin surfaces or the trunk.

 Microscopic examination of scrapings or culture confirms the diagnosis.

 General Considerations

The lesions are often on exposed areas of the body such as the face and arms. A history of exposure to an infected cat may occasionally be obtained, usually indicating Microsporum infection. Trichophyton rubrum is the most common pathogen, usually representing extension onto the trunk or extremities of tinea cruris, pedis, or manuum.

 Clinical Findings

  1. Symptoms and Signs

Itching may be present. In classic lesions, rings of erythema have an advancing scaly border and central clearing (Figure 6–12).

 Figure 6–12. Tinea pedis and corporis. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

  1. Laboratory Findings

The diagnosis should be confirmed by KOH preparation or culture.

 Differential Diagnosis

Positive fungal studies distinguish tinea corporis from other skin lesions with annular configuration, such as the annular lesions of psoriasis, lupus erythematosus, syphilis, granuloma annulare, and pityriasis rosea. Psoriasis has typical lesions on elbows, knees, scalp, and nails. Secondary syphilis is often manifested by characteristic palmar, plantar, and mucous membrane lesions. Tinea corporis rarely has the large number of symmetric lesions seen in pityriasis rosea. Granuloma annulare lacks scales.


Complications include extension of the disease down the hair follicles (in which case it becomes much more difficult to cure) and pyoderma.


Treat infected household pets (Microsporum infections). To prevent recurrences, the use of foot powder and keeping feet dry by wearing sandals, or changing socks can be useful.


  1. Local Measures

Tinea corporis responds to most topical antifungals, including miconazole, clotrimazole, butenafine, and terbinafine, which are available over the counter (see Table 6–2). Terbinafine and butenafine require shorter courses and lead to the most rapid response. Treatment should be continued for 1–2 weeks after clinical clearing. Betamethasone dipropionate with clotrimazole (Lotrisone) is not recommended. Long-term improper use may result in side effects from the high-potency corticosteroid component, especially in body folds. Cases of tinea that are clinically resistant to this combination but respond to topical antifungals without the topical corticosteroid can occur.

  1. Systemic Measures

Griseofulvin (ultramicrosize), 250–500 mg twice daily, is used. Typically, 4–6 weeks of therapy are required. Itraconazole as a single week-long pulse of 200 mg daily is also effective in tinea corporis. Terbinafine, 250 mg daily for 1 month, is an alternative.


Body ringworm usually responds promptly to conservative topical therapy or to an oral agent within 4 weeks.

Rotta I et al. Efficacy of topical antifungals in the treatment of dermatophytosis: a mixed-treatment comparison meta-analysis involving 14 treatments. JAMA Dermatol. 2013 Mar;149(3):341–9. [PMID: 23553036]

  1. Tinea Cruris (Jock Itch)


 Marked itching in intertriginous areas, usually sparing the scrotum.

 Peripherally spreading, sharply demarcated, centrally clearing erythematous lesions.

 May have associated tinea infection of feet or toenails.

 Laboratory examination with microscope or culture confirms diagnosis.

 General Considerations

Tinea cruris lesions are confined to the groin and gluteal cleft. Intractable pruritus ani may occasionally be caused by a tinea infection.

 Clinical Findings

  1. Symptoms and Signs

Itching may be severe, or the rash may be asymptomatic. The lesions have sharp margins, cleared centers, and active, spreading scaly peripheries. Follicular pustules are sometimes encountered. The area may be hyperpigmented on resolution.

  1. Laboratory Findings

Hyphae can be demonstrated microscopically in KOH preparations. The organism may be cultured.

 Differential Diagnosis

Tinea cruris must be distinguished from other lesions involving the intertriginous areas, such as candidiasis, seborrheic dermatitis, intertrigo, psoriasis of body folds (“inverse psoriasis”), and erythrasma. Candidiasis is generally bright red and marked by satellite papules and pustules outside of the main border of the lesion. Candida typically involves the scrotum. Seborrheic dermatitis also often involves the face, sternum, and axillae. Intertrigo tends to be more red, less scaly, and present in obese individuals in moist body folds with less extension onto the thigh. Inverse psoriasis is characterized by distinct plaques. Other areas of typical psoriatic involvement should be checked, and the KOH examination will be negative. Erythrasma is best diagnosed with Wood (ultraviolet) light—a brilliant coral-red fluorescence is seen.


  1. General Measures

Drying powder (eg, miconazole nitrate [Zeasorb-AF]) can be dusted into the involved area in patients with excessive perspiration or occlusion of skin due to obesity.

  1. Local Measures

Any of the topical antifungal preparations listed in Table 6–2 may be used. Terbinafine cream is curative in over 80% of cases after once-daily use for 7 days.

  1. Systemic Measures

Griseofulvin ultramicrosize is reserved for severe cases. Give 250–500 mg orally twice daily for 1–2 weeks. One week of either itraconazole, 200 mg daily, or terbinafine, 250 mg daily, can be effective.


Tinea cruris usually responds promptly to topical or systemic treatment but often recurs.

  1. Tinea Manuum & Tinea Pedis (Dermatophytosis, Tinea of Palms & Soles, “Athlete’s Foot”)


 Most often presenting with asymptomatic scaling.

 May progress to fissuring or maceration in toe web spaces.

 Common cofactor in lower leg cellulitis.

 Itching, burning, and stinging of interdigital web; scaling palms, and soles; vesicles of soles in inflammatory cases.

 The fungus is shown in skin scrapings examined microscopically or by culture of scrapings.

 General Considerations

Tinea of the feet is an extremely common acute or chronic dermatosis. Most infections are caused by Trichophyton species.

 Clinical Findings

  1. Symptoms and Signs

The presenting symptom may be itching, burning, or stinging. Pain may indicate secondary infection with complicating cellulitis. Interdigital tinea pedis is the most common predisposing cause of lower leg cellulitis in healthy individuals. Regular examination of the feet of diabetic patients for evidence of scaling and fissuring and treatment of any identified tinea pedis may prevent complications. Tinea pedis has several presentations that vary with the location. On the sole and heel, tinea may appear as chronic noninflammatory scaling, occasionally with thickening and fissuring. This may extend over the sides of the feet in a “moccasin” distribution. The KOH preparation is usually positive. Tinea pedis often appears as a scaling or fissuring of the toe webs, perhaps with sodden maceration (Figure 6–13). As the web spaces become more macerated, the KOH preparation and fungal culture are less often positive because bacterial species begin to dominate. Finally, there may also be grouped vesicles distributed anywhere on the soles, generalized exfoliation of the skin of the soles, or nail involvement in the form of discoloration and thickening and crumbling of the nail plate.

 Figure 6–13. Tinea pedis in the interdigital space between fourth and fifth digits. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

  1. Laboratory Findings

KOH and culture does not always demonstrate pathogenic fungi from macerated areas.

 Differential Diagnosis

Differentiate from other skin conditions involving the same areas, such as interdigital erythrasma (use Wood light). Psoriasis may be a cause of chronic scaling on the palms or soles and may cause nail changes. Repeated fungal cultures should be negative, and the condition will not respond to antifungal therapy. Contact dermatitis will often involve the dorsal surfaces and will respond to topical or systemic corticosteroids. Vesicular lesions should be differentiated from pompholyx (dyshidrosis) and scabies by proper scraping of the roofs of individual vesicles. Rarely, gram-negative organisms may cause toe web infections, manifested as an acute erosive flare of interdigital disease. This entity is treated with aluminum salts (see below) and imidazole antifungal agents or ciclopirox.


The essential factor in prevention is personal hygiene. Wear open-toed sandals if possible. Use of sandals in community showers and bathing places is often recommended, though the effectiveness of this practice has not been studied. Careful drying between the toes after showering is essential. A hair dryer used on low setting may be used. Socks should be changed frequently, and absorbent nonsynthetic socks are preferred. Apply dusting and drying powders as necessary. The use of powders containing antifungal agents (eg, Zeasorb-AF) or chronic use of antifungal creams may prevent recurrences of tinea pedis.


  1. Local Measures
  2. Macerated stage—Treat with aluminum subacetate solution soaks for 20 minutes twice daily. Broad-spectrum antifungal creams and solutions (containing imidazoles or ciclopirox instead of tolnaftate and haloprogin) will help combat diphtheroids and other gram-positive organisms present at this stage and alone may be adequate therapy. If topical imidazoles fail, 1 week of once-daily topical allylamine treatment (terbinafine or butenafine) will often result in clearing.
  3. Dry and scaly stage—Use any of the antifungal agents listed inTable 6–2. The addition of urea 10–20% lotion or cream may increase the efficacy of topical treatments in thick (“moccasin”) tinea of the soles.
  4. Systemic Measures

Griseofulvin may be used for severe cases or those recalcitrant to topical therapy. If the infection is cleared by systemic therapy, the patient should be encouraged to begin maintenance with topical therapy, since recurrence is common. Itraconazole, 200 mg daily for 2 weeks or 400 mg daily for 1 week, or terbinafine, 250 mg daily for 2–4 weeks, may be used in refractory cases.


For many individuals, tinea pedis is a chronic affliction, temporarily cleared by therapy only to recur.

Bell-Syer SE et al. Oral treatments for fungal infections of the skin of the foot. Cochrane Database Syst Rev. 2012 Oct17;10: CD003584. [PMID: 23076898]

Matricciani L et al. Safety and efficacy of tinea pedis and onychomycosis treatment in people with diabetes: a systematic review. J Foot Ankle Res. 2011 Dec4;4:26. [PMID: 22136082]

Parish LC et al. A randomized, double-blind, vehicle-controlled efficacy and safety study of naftifine 2% cream in the treatment of tinea pedis. J Drugs Dermatol. 2011 Nov1;10(11):1282–8. [PMID: 22052309]

Vanhooteghem O et al. Chronic interdigital dermatophytic infection: a common lesion associated with potentially severe consequences. Diabetes Res Clin Pract. 2011 Jan;91(1):23–5. [PMID: 21035887]

  1. Tinea Versicolor (Pityriasis Versicolor)


 Velvety, tan, or pink macules or white macules that do not tan.

 Fine scales that are not visible but are seen by scraping the lesion.

 Central upper trunk the most frequent site.

 Yeast and short hyphae observed on microscopic examination of scales.

 General Considerations

Tinea versicolor is a mild, superficial Malassezia infection of the skin (usually of the upper trunk). This yeast is a colonizer of all humans, which accounts for the high recurrence rate after treatment. The eruption is often called to patients’ attention by the fact that the involved areas will not tan, and the resulting hypopigmentation may be mistaken for vitiligo. A hyperpigmented form is not uncommon.

 Clinical Findings

  1. Symptoms and Signs

Lesions are asymptomatic, but a few patients note itching. The lesions are velvety, tan, pink, or white macules that vary from 4–5 mm in diameter to large confluent areas. The lesions initially do not look scaly, but scales may be readily obtained by scraping the area. Lesions may appear on the trunk, upper arms, neck, and groin.

  1. Laboratory Findings

Large, blunt hyphae and thick-walled budding spores (“spaghetti and meatballs”) are seen on KOH. Fungal culture is not useful.

 Differential Diagnosis

Vitiligo usually presents with larger periorificial lesions. Vitiligo (and not tinea versicolor) is characterized by total depigmentation, not just a lessening of pigmentation. Vitiligo does not scale. Pink and red-brown lesions on the chest are differentiated from seborrheic dermatitis of the same areas by the KOH preparation.

 Treatment & Prognosis

Topical treatments include selenium sulfide lotion, which may be applied from neck to waist daily and left on for 5–15 minutes for 7 days; this treatment is repeated weekly for a month and then monthly for maintenance. Ketoconazole shampoo, 1% or 2%, lathered on the chest and back and left on for 5 minutes may also be used weekly for treatment and to prevent recurrence. Clinicians must stress to the patient that the raised and scaly aspects of the rash are being treated; the alterations in pigmentation may take months to fade or fill in.

Ketoconazole, 200 mg daily orally for 1 week or 400 mg as a single oral dose, with exercise to the point of sweating after ingestion, results in short-term cure of 90% of cases. Patients should be instructed not to shower for 8–12 hours after taking ketoconazole, because it is delivered in sweat to the skin. The single dose may not work in more hot and humid areas, and more protracted therapy carries a small risk of drug-induced hepatitis. Two doses of oral fluconazole, 300 mg, 14 days apart has similar efficacy. Without maintenance therapy, recurrences will occur in over 80% of “cured” cases over the subsequent 2 years. Imidazole creams, solutions, and lotions are quite effective for localized areas but are too expensive for use over large areas such as the chest and back.

Framil VM et al. New aspects in the clinical course of pityriasis versicolor. An Bras Dermatol. 2011 Nov–Dec;86(6):1135–40. [PMID: 22281901]

DISCOID & SUBACUTE LUPUS ERYTHEMATOSUS (Chronic Cutaneous Lupus Erythematosus)


 Localized red plaques, usually on the face.

 Scaling, follicular plugging, atrophy, dyspigmentation, and telangiectasia of involved areas.

 Histology distinctive.


 General Considerations

The two most common forms of chronic cutaneous lupus erythematosus (CCLE) are chronic scarring (discoid) lesions (DLE) and erythematous non-scarring red plaques (subacute cutaneous LE) (SCLE). Both occur most frequently in areas exposed to solar irradiation. Permanent hair loss and loss of pigmentation are common sequelae of discoid lesions. Systemic lupus erythematosus (SLE) is discussed inChapter 20. Patients with SLE may have DLE or SCLE lesions.

 Clinical Findings

  1. Symptoms and Signs

Symptoms are usually mild. The lesions consist of dusky red, well-localized, single or multiple plaques, 5–20 mm in diameter, usually on the head in DLE and the trunk in SCLE. In DLE, the scalp, face, and external ears may be involved. In discoid lesions, there is atrophy, telangiectasia, depigmentation, and follicular plugging. On the scalp, significant permanent hair loss may occur in lesions of DLE. In SCLE, the lesions are erythematous annular or psoriasiform plaques up to several centimeters in diameter and favor the upper chest and back.

  1. Laboratory Findings

In patients with DLE, the possibility of SLE should be considered if the following findings are present: positive antinuclear antibody (ANA), other positive serologic studies (eg, anti-double stranded DNA or anti-Smith antibody), high erythrocyte sedimentation rate, arthralgias/arthritis, presence of hypocomplementemia, widespread lesions (not localized to the head), or nail changes. Patients with marked photosensitivity and a picture otherwise suggestive of lupus may have negative ANA tests but are positive for antibodies against Ro/SSA or La/SSB (SCLE).

 Differential Diagnosis

The diagnosis is based on the clinical appearance confirmed by skin biopsy in all cases. In DLE, the scales are dry and “thumbtack-like” and can thus be distinguished from those of seborrheic dermatitis and psoriasis. Older lesions that have left depigmented scarring (classically in the concha of the ear) or areas of hair loss will also differentiate lupus from these diseases. Ten percent of patients with SLE have discoid skin lesions, and 5% of patients with discoid lesions have SLE. Medications (most commonly, hydrochlorothiazide, calcium channel blockers, H2-blockers and proton pump inhibitors, ACE inhibitors, TNF inhibitors, and terbinafine) may induce SCLE with a positive Ro/SSA.


  1. General Measures

Protect from sunlight. Use high-SPF (> 50) sunblock with UVB and UVA coverage daily. Caution: Do not use any form of radiation therapy. Avoid using drugs that are potentially photosensitizing when possible.

  1. Local Treatment

For limited lesions, the following should be tried before systemic therapy: high-potency corticosteroid creams applied each night and covered with airtight, thin, pliable plastic film (eg, Saran Wrap); or Cordran tape; or ultra-high-potency corticosteroid cream or ointment applied twice daily without occlusion.

  1. Local Infiltration

Triamcinolone acetonide suspension, 2.5–10 mg/mL, may be injected into the lesions of DLE once a month.

  1. Systemic Treatment
  2. Antimalarials—Caution:These drugs should be used only when the diagnosis is secure because they have been associated with flares of psoriasis, which may be in the differential diagnosis.
  3. HYDROXYCHLOROQUINE SULFATE0.2–0.4 g orally daily for several months may be effective and is often used prior to chloroquine. A minimum 3-month trial is recommended.
  4. CHLOROQUINE SULFATE250 mg daily may be effective in some cases where hydroxychloroquine is not.
  5. QUINACRINE (ATABRINE)100 mg daily may be the safest of the antimalarials, since eye damage has not been reported. It colors the skin yellow and is therefore not acceptable to some patients. It may be added to the other antimalarials for incomplete responses.
  6. Isotretinoin—Isotretinoin, 1 mg/kg/d, is effective in hypertrophic DLE lesions.
  7. Thalidomide—Thalidomide is effective in refractory cases in doses of up to 300 mg daily. Monitor for neuropathy.

Both isotretinoin and thalidomide are teratogens and should be used with appropriate contraception and monitoring in women of childbearing age.


The disease is persistent but not life-endangering unless systemic lupus is present. Treatment with one or more antimalarials is effective in more than half of cases. Although the only morbidity may be cosmetic, this can be of overwhelming significance in more darkly pigmented patients with widespread disease. Scarring alopecia can be prevented or lessened with close attention and aggressive therapy. Over years, DLE tends to become inactive. Drug-induced SCLE usually resolves over months when the inciting medication is stopped.

Cheeley J et al. Acitretin for the treatment of cutaneous T-cell lymphoma. J Am Acad Dermatol. 2013 Feb;68(2):247–54. [PMID: 22917895]

Chong BF et al. Determining risk factors for developing systemic lupus erythematosus in patients with discoid lupus erythematosus. Br J Dermatol. 2012 Jan;166(1):29–35. [PMID: 21910708]

Duarte-García A et al. Seasonal variation in the activity of systemic lupus erythematosus. J Rheumatol. 2012 Jul;39(7):1392–8. [PMID: 22660806]

Francès C et al. Low blood concentration of hydroxychloroquine in patients with refractory cutaneous lupus erythematosus: a French multicenter prospective study. Arch Dermatol. 2012 Apr;148(4):479–84. [PMID: 22508872]

Grönhagen CM et al. Subacute cutaneous lupus erythematosus and its association with drugs: a population-based matched case-control study of 234 patients in Sweden. Br J Dermatol. 2012 Aug;167(2):296–305. [PMID: 22458771]

Kuhn A et al. Photoprotective effects of a broad-spectrum sunscreen in ultraviolet-induced cutaneous lupus erythematosus: a randomized, vehicle-controlled, double-blind study. J Am Acad Dermatol. 2011 Jan;64(1):37–48. [PMID: 21167404]

Lowe G et al. A systematic review of drug-induced subacute cutaneous lupus erythematosus. Br J Dermatol. 2011 Mar;164(3):465–72. [PMID: 21039412]

Merola JF et al. Association of discoid lupus erythematosus with other clinical manifestations among patients with systemic lupus erythematosus. J Am Acad Dermatol. 2013 Jul;69(1):19–24. [PMID: 23541758]

Wahie S et al. Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus. Br J Dermatol. 2013 Sep;169(3):653–9. [PMID: 23581274]



 Localized or generalized erythematous scaling patches and plaques.



 Distinctive histology.

 General Considerations

Mycosis fungoides is a cutaneous T-cell lymphoma that begins on the skin and may involve only the skin for years or decades. Certain medications (including selective serotonin reuptake inhibitors) and photoallergy may produce eruptions clinically and histologically identical to those of mycosis fungoides.

 Clinical Findings

  1. Symptoms and Signs

Localized or generalized erythematous patches or plaques are present usually on the trunk. Plaques are almost always over 5 cm in diameter. Pruritus is a frequent complaint and can be severe. IL-31 may mediate the pruritus of Sézary syndrome. The lesions often begin as nondescript or nondiagnostic patches, and it is not unusual for the patient to have skin lesions for more than a decade before the diagnosis can be confirmed. Follicular involvement with hair loss is characteristic of mycosis fungoides, and its presence should raise the suspicion of mycosis fungoides for any pruritic eruption. In more advanced cases, tumors appear. Lymphadenopathy may occur locally or widely. Lymph node enlargement may be due to benign expansion of the node (dermatopathic lymphadenopathy) or by specific involvement with mycosis fungoides.

  1. Laboratory Findings

The skin biopsy remains the basis of diagnosis, though at times numerous biopsies are required before the diagnosis can be confirmed. In more advanced disease, circulating malignant T cells (Sézary cells) can be detected in the blood (T-cell gene rearrangement test). Eosinophilia may be present.

 Differential Diagnosis

Mycosis fungoides may be confused with psoriasis, a drug eruption, an eczematous dermatitis, or tinea corporis. Histologic examination can distinguish these conditions.


The treatment of mycosis fungoides is complex. Early and aggressive treatment has not proved to cure or prevent progression of the disease. Skin-directed therapies, including topical corticosteroids, topical mechlorethamine, bexarotene gel, and UV phototherapy, are used initially. If the disease progresses, PUVA plus retinoids, PUVA plus interferon, extracorporeal photophoresis, bexarotene, alpha-interferon with or without retinoids, interleukin 12, denileukin, and total skin electron beam treatment are used.


Mycosis fungoides is usually slowly progressive (over decades). Prognosis is better in patients with patch or plaque stage disease and worse in patients with erythroderma, tumors, and lymphadenopathy. Survival is not reduced in patients with limited patch disease. Elderly patients with limited patch and plaque stage disease commonly die of other causes. Overly aggressive treatment may lead to complications and premature demise.

Cheeley J et al. Acitretin for the treatment of cutaneous T-cell lymphoma. J Am Acad Dermatol. 2013 Feb;68(2):247–54. [PMID: 22917895]

Deonizio JM et al. The role of molecular analysis in cutaneous lymphomas. Semin Cutan Med Surg. 2012 Dec;31(4):234–40. [PMID: 23174493]

Ohmatsu H et al. Serum IL-31 levels are increased in patients with cutaneous T-cell lymphoma. Acta Derm Venereol. 2012 May;92(3):282–3. [PMID: 22456907]

Olsen EA et al. Clinical end points and response criteria in mycosis fungoides and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for the Research and Treatment of Cancer. J Clin Oncol. 2011 Jun20;29(18):2598–607. [PMID: 21576639]

Weberschock T et al. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2012 Sep12;9: CD008946. [PMID: 22972128]

EXFOLIATIVE DERMATITIS (Exfoliative Erythroderma)


 Scaling and erythema over most of the body.

 Itching, malaise, fever, chills, weight loss.

 General Considerations

Erythroderma describes generalized redness and scaling of the skin of > 30% BSA. A preexisting dermatosis is the cause of exfoliative dermatitis in two-thirds of cases, including psoriasis, atopic dermatitis, contact dermatitis, pityriasis rubra pilaris, and seborrheic dermatitis. Reactions to topical or systemic drugs account for about 15% of cases, cancer (underlying lymphoma, solid tumors and, most commonly, cutaneous T-cell lymphoma) for about 10%, and 10% are idiopathic. Causation of the remainder is indeterminable. At the time of acute presentation, without a clear-cut prior history of skin disease or drug exposure, it may be impossible to make a specific diagnosis of the underlying condition, and diagnosis may require continued observation.

 Clinical Findings

  1. Symptoms and Signs

Symptoms may include itching, weakness, malaise, fever, and weight loss. Chills are prominent. Redness and scaling is widespread. Loss of hair and nails can occur. Generalized lymphadenopathy may be due to lymphoma or leukemia or may be reactive. The mucosae are spared.

  1. Laboratory Findings

A skin biopsy is required and may show changes of a specific inflammatory dermatitis or cutaneous T-cell lymphoma. Peripheral leukocytes may show clonal rearrangements of the T-cell receptor in Sézary syndrome.

 Differential Diagnosis

It may be impossible to identify the cause of exfoliative erythroderma early in the course of the disease, so careful follow-up is necessary.


Debility (protein loss) and dehydration may develop in patients with generalized inflammatory exfoliative erythroderma; or sepsis may occur.


  1. Topical Therapy

Home treatment is with cool to tepid baths and application of mid-potency corticosteroids under wet dressings or with the use of an occlusive plastic suit. If the exfoliative erythroderma becomes chronic and is not manageable in an outpatient setting, the patient should be hospitalized. Keep the room at a constant warm temperature and provide the same topical treatment as for an outpatient.

  1. Specific Measures

Stop all medications, if possible. Systemic corticosteroids may provide spectacular improvement in severe or fulminant exfoliative dermatitis, but long-term therapy should be avoided (see Chapter 26). In addition, systemic corticosteroids must be used with caution because some patients with erythroderma have psoriasis and could develop pustular psoriasis. For cases of psoriatic erythroderma and pityriasis rubra pilaris, acitretin, methotrexate, cyclosporine, or a TNF inhibitor may be indicated. Erythroderma secondary to lymphoma or leukemia requires specific topical or systemic chemotherapy. Suitable antibiotic drugs with coverage for Staphylococcus should be given when there is evidence of bacterial infection.


Most patients recover completely or improve greatly over time but may require long-term therapy. Deaths are rare in the absence of cutaneous T-cell lymphoma. A minority of patients will suffer from undiminished erythroderma for indefinite periods.

Bhandarkar AP et al. Nevirapine induced exfoliative dermatitis in an HIV-infected patient. Indian J Pharmacol. 2011 Nov;43(6):738–9. [PMID: 22144790]

Li J et al. Erythroderma: a clinical and prognostic study. Dermatology. 2012;225(2):154–62. [PMID: 23037884]

Mumoli N et al. Severe exfoliative dermatitis caused by esomeprazole. J Am Geriatr Soc. 2011 Dec;59(12):2377–8. [PMID: 22188084]

Zattra E et al. Erythroderma in the era of biological therapies. Eur J Dermatol. 2012 Mar–Apr;22(2):167–71. [PMID: 22321651]


Isolated scaly patches may represent actinic (solar) keratoses, nonpigmented seborrheic keratoses, or Bowen or Paget disease.

  1. Actinic Keratoses

Actinic keratoses are small (0.2–0.6 cm) macules or papules—flesh-colored, pink, or slightly hyperpigmented—that feel like sandpaper and are tender when the finger is drawn over them. They occur on sun-exposed parts of the body in persons of fair complexion. Actinic keratoses are considered premalignant, but only 1:1000 lesions per year progress to become squamous cell carcinomas.

Application of liquid nitrogen is a rapid method of eradication. The lesions crust and disappear in 10–14 days. “Field treatment” with a topical agent to the anatomic area where the actinic keratoses are most prevalent (eg, forehead, dorsal hands, etc) can be considered in patients with multiple lesions in one region. The topical agents used for field treatment include fluorouracil, imiquimod, and ingenol mebutate. Photodynamic therapy can be effective in cases refractory to topical treatment. Any lesions that persist should be evaluated for possible biopsy.

Berman B et al. What is the role of field-directed therapy in the treatment of actinic keratosis? Part 2: commonly used field-directed and lesion-directed therapies. Cutis. 2012 Jun;89(6):294–301. [PMID: 22838095]

Gupta AK et al. Interventions for actinic keratoses. Cochrane Database Syst Rev. 2012 Dec12;12: CD004415. [PMID: 23235610]

Lebwohl M et al. Ingenol mebutate gel for actinic keratosis. N Engl J Med. 2012 Mar15;366(11):1010–9. [PMID: 22417254]

Morton CA et al. European guidelines for topical photodynamic therapy part 1: treatment delivery and current indications—actinic keratoses, Bowen’s disease, basal cell carcinoma. J Eur Acad Dermatol Venereol. 2013 May;27(5):536–44. [PMID: 23181594]

Werner RN et al. The natural history of actinic keratosis: a systematic review. Br J Dermatol. 2013 Sep;169(3):502–18. [PMID: 23647091]

  1. Bowen Disease & Paget Disease

Bowen disease (intraepidermal squamous cell carcinoma) can develop on both sun-exposed and non–sun-exposed skin. The lesion is usually a small (0.5–3 cm), well-demarcated, slightly raised, pink to red, scaly plaque and may resemble psoriasis or a large actinic keratosis. These lesions may progress to invasive squamous cell carcinoma. Excision or other definitive treatment is indicated.

Extramammary Paget disease, a manifestation of intraepidermal carcinoma or underlying genitourinary or gastrointestinal cancer, resembles chronic eczema and usually involves apocrine areas such as the genitalia. Mammary Paget disease of the nipple, a unilateral or rarely bilateral red scaling plaque that may ooze, is associated with an underlying intraductal mammary carcinoma (Figure 6–14). While these lesions appear as red patches and plaques in fair-skinned persons, in Asians, Hispanics, and other persons of color, hyperpigmentation may be prominent.

 Figure 6–14. Paget disease of the breast surrounding the nipple. (Courtesy of the University of Texas Health Sciences Center, Division of Dermatology; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

Bath-Hextall FJ et al. Interventions for cutaneous Bowen’s disease. Cochrane Database Syst Rev. 2013 Jun24;6: CD007281. [PMID: 23794286]

Hida T et al. Pigmented mammary Paget’s disease mimicking melanoma: report of three cases. Eur J Dermatol. 2012 Jan–Feb;22(1):121–4. [PMID: 22064040]

Sandoval-Leon AC et al. Paget’s disease of the nipple. Breast Cancer Res Treat. 2013 Aug;141(1):1–12. [PMID: 23929251]


Intertrigo is caused by the macerating effect of heat, moisture, and friction. It is especially likely to occur in obese persons and in humid climates. The symptoms are itching, stinging, and burning. The body folds develop fissures, erythema, and sodden epidermis, with superficial denudation. Candidiasis may complicate intertrigo. “Inverse psoriasis,” seborrheic dermatitis, tinea cruris, erythrasma, and candidiasis must be ruled out.

Maintain hygiene in the area, and keep it dry. Compresses may be useful acutely. Hydrocortisone 1% cream plus an imidazole or nystatin cream is effective. Recurrences are common.


HERPES SIMPLEX (Cold or Fever Sore; Genital Herpes)


 Recurrent small grouped vesicles on an erythematous base, especially in the orolabial and genital areas.

 May follow minor infections, trauma, stress, or sun exposure; regional lymph nodes may be swollen and tender.

 Viral cultures and direct fluorescent antibody tests are positive.

 General Considerations

Over 85% of adults have serologic evidence of herpes simplex type 1 (HSV-1) infections, most often acquired asymptomatically in childhood. Occasionally, primary infections may be manifested as severe gingivostomatitis. Thereafter, the patient may have recurrent self-limited attacks, provoked by sun exposure, orofacial surgery, fever, or a viral infection.

About 25% of the United States population has serologic evidence of infection with herpes simplex type 2 (HSV-2). HSV-2 causes lesions whose morphology and natural history are similar to those caused by HSV-1 but are typically located on the genitalia of both sexes. The infection is acquired by sexual contact. In monogamous heterosexual couples where one partner has HSV-2 infection, seroconversion of the noninfected partner occurs in 10% over a 1-year period. Up to 70% of such infections appeared to be transmitted during periods of asymptomatic shedding. Genital herpes may also be due to HSV-1.

 Clinical Findings

  1. Symptoms and Signs

The principal symptoms are burning and stinging. Neuralgia may precede or accompany attacks. The lesions consist of small, grouped vesicles that can occur anywhere but which most often occur on the vermilion border of the lips (Figure 6–15), the penile shaft, the labia, the perianal skin, and the buttocks. Any erosion in the anogenital region can be due to herpes simplex. Regional lymph nodes may be swollen and tender. The lesions usually crust and heal in 1 week.

 Figure 6–15. Herpes simplex type 1 vesicles at the vermillion border of the lip. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

  1. Laboratory Findings

Lesions of herpes simplex must be distinguished from chancroid, syphilis, pyoderma, or trauma. Direct fluorescent antibody slide tests offer rapid, sensitive diagnosis. Viral culture may also be helpful. Herpes serology is not used in the diagnosis of an acute genital ulcer. However, specific HSV-2 serology by Western blot assay or enzyme-linked immunosorbent assay (ELISA) can determine who is HSV-infected and potentially infectious. Such testing is very useful in couples in which only one partner reports a history of genital herpes.


Complications include pyoderma, eczema herpeticum, herpetic whitlow, herpes gladiatorum (epidemic herpes in wrestlers transmitted by contact), proctitis, esophagitis, neonatal infection, keratitis, and encephalitis.


The use of latex condoms and patient education have proved effective in reducing genital herpes transmission in some studies but have not proved beneficial in others. No single or combination intervention absolutely prevents transmission. Sunscreens are useful adjuncts in preventing sun-induced HSV-1 recurrences. Prophylactic use of oral acyclovir (200 mg four times daily) may prevent herpes recurrences. Comparable doses are 500 mg twice daily for valacyclovir and 250 mg twice daily for famciclovir. A preventive antiviral medication should be started beginning 24 hours prior to ultraviolet light exposure, dental surgery, or orolabial cosmetic surgery.


  1. Systemic Therapy

Three systemic agents are available for the treatment of herpes infections: acyclovir, its valine analog valacyclovir, and famciclovir. All three agents are very effective and, when used properly, virtually nontoxic. Only acyclovir is available for intravenous administration. In the immunocompetent, with the exception of severe orolabial herpes, only genital disease is treated. For first clinical episodes of herpes simplex, the dosage of acyclovir is 400 mg orally five times daily (or 800 mg three times daily); of valacyclovir, 1000 mg twice daily; and of famciclovir, 250 mg three times daily. The duration of treatment is from 7 to 10 days depending on the severity of the outbreak.

Most cases of recurrent herpes are mild and do not require therapy. In addition, pharmacotherapy of recurrent HSV is of limited benefit, with studies finding a reduction in the average outbreak by only 12–24 hours. To be effective, the treatment must be initiated by the patient at the first sign of recurrence. If treatment is desired, recurrent genital herpes outbreaks may be treated with 3 days of valacyclovir, 500 mg twice daily, 5 days of acyclovir, 200 mg five times a day, or 5 days of famciclovir, 125 mg twice daily. Valacyclovir, 2 g twice daily for 1 day, or famciclovir, 1 g once or twice in 1 day, are equally effective short-course alternatives, and can abort impending recurrences of both orolabial and genital herpes. The addition of a potent topical corticosteroid three times daily reduces the duration, size, and pain of orolabial herpes treated with an oral antiviral agent.

In patients with frequent or severe recurrences, suppressive therapy is most effective in controlling disease. Suppressive treatment will reduce outbreaks by 85% and reduces viral shedding by > 90%. This results in about a 50% reduced risk of transmission. The recommended suppressive doses, taken continuously, are acyclovir, 400 mg twice daily; valacyclovir, 500 mg once daily; or famciclovir, 125–250 mg twice daily. Long-term suppression appears very safe, and after 5–7 years a substantial proportion of patients can discontinue treatment.

  1. Local Measures

In general, topical therapy has only limited efficacy. It is strongly urged that 5% acyclovir ointment, if used at all, be limited to the restricted indications for which it has been approved, ie, initial herpes genitalis and mucocutaneous herpes simplex infections in immunocompromised patients. Penciclovir cream, to be applied at the first symptom every 2 hours while awake for 4 days for recurrent orolabial herpes, reduces the average attack duration from 5 days to 4.5 days.


Aside from the complications described above, recurrent attacks last several days, and patients recover without sequelae.

Antonelli G et al. Antiviral therapy: old and current issues. Int J Antimicrob Agents. 2012 Aug;40(2):95–102. [PMID: 22727532]

Kinchington PR et al. Herpes simplex virus and varicella zoster virus, the house guests who never leave. Herpesviridae. 2012 Jun12;3(1): 5. [PMID: 22691604]



 Pain along the course of a nerve followed by grouped vesicular lesions.

 Involvement is unilateral; some lesions (< 20) may occur outside the affected dermatome.

 Lesions are usually on face or trunk.

 Direct fluorescent antibody positive, especially in vesicular lesions.

 General Considerations

Herpes zoster is an acute vesicular eruption due to the varicella-zoster virus. It usually occurs in adults. With rare exceptions, patients suffer only one attack. Dermatomal herpes zoster does not imply the presence of a visceral malignancy. Generalized disease, however, raises the suspicion of an associated immunosuppressive disorder such as HIV infection. HIV-infected patients are 20 times more likely to develop zoster, often before other clinical findings of HIV disease are present. A history of HIV risk factors and HIV testing when appropriate should be considered, especially in patients with zoster who are younger than 55 years.

 Clinical Findings

Pain usually precedes the eruption by 48 hours or more and may persist and actually increase in intensity after the lesions have disappeared. The lesions consist of grouped, tense, deep-seated vesicles distributed unilaterally along a dermatome (Figure 6–16). The most common distributions are on the trunk or face. Up to 20 lesions may be found outside the affected dermatomes, even in immune-competent persons. Regional lymph glands may be tender and swollen.

 Figure 6–16. Herpes zoster. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

 Differential Diagnosis

Since poison oak and poison ivy dermatitis can occur unilaterally, they must be differentiated at times from herpes zoster. Allergic contact dermatitis is pruritic; zoster is painful. One must differentiate herpes zoster from lesions of herpes simplex, which occasionally occurs in a dermatomal distribution. Doses of antivirals appropriate for zoster should be used in the absence of a clear diagnosis. Facial zoster may simulate erysipelas initially, but zoster is unilateral and shows vesicles after 24–48 hours. Depending on the dermatome involved, the pain of preeruptive herpes zoster may lead the clinician to diagnose migraine, myocardial infarction, acute abdomen, herniated disk, etc.


Sacral zoster may be associated with bladder and bowel dysfunction. Persistent neuralgia, anesthesia or scarring of the affected area, facial or other nerve paralysis, and encephalitis may occur. Postherpetic neuralgia is most common after involvement of the trigeminal region, and in patients over the age of 55. Early (within 72 hours after onset) and aggressive antiviral treatment of herpes zoster reduces the severity and duration of postherpetic neuralgia. Zoster ophthalmicus (V1) can result in visual impairment.


An effective live herpes zoster vaccine (Zostavax) is available and recommended to prevent both herpes zoster and postherpetic neuralgia. It is approved for persons over the age of 50 and recommended in persons aged 60 and older, even in those who have had zoster.


  1. General Measures
  2. Immunocompetent host—Antiviral treatment within 72 hours of rash decreases the duration and severity of acute herpes zoster. Since such treatment also reduces postherpetic neuralgia, those with a risk of developing this complication should be treated (ie, those over age 50 and those with nontruncal eruption). In addition, younger patients with acute moderate to severe pain or rash may benefit from effective antiviral therapy. Treatment can be given with oral acyclovir, 800 mg five times daily; famciclovir, 500 mg three times daily; or valacyclovir, 1 g three times daily—all for 7 days (seeChapter 32). For reasons of increased bioavailability and ease of dosing schedule, the preferred agents are those given three times daily. Patients should maintain good hydration. The dose of antiviral should be adjusted for kidney function as recommended. Nerve blocks may be used in the management of initial severe pain. Ophthalmologic consultation is vital for involvement of the first branch of the trigeminal nerve, even if the patient has no ocular symptoms.

Systemic corticosteroids are effective in reducing acute pain, improving quality of life, and returning patients to normal activities much more quickly. They do not increase the risk of dissemination in immunocompetent hosts. If not contraindicated, a tapering 3-week course of prednisone, starting at 60 mg/d, should be considered for its adjunctive benefit in immunocompetent patients. Oral corticosteroids do not reduce the prevalence, severity, or duration of postherpetic neuralgia beyond that achieved by effective antiviral therapy. Adequate analgesia, including the use of opioids, tricyclic antidepressants, and gabapentin as necessary, should be given from the onset of zoster-associated pain.

  1. Immunocompromised host—Given the safety and efficacy of currently available antivirals, most immunocompromised patients with herpes zoster are candidates for antiviral therapy. The dosage schedule is as listed above, but treatment should be continued until the lesions have completely crusted and are healed or almost healed (up to 2 weeks). Because corticosteroids increase the risk of dissemination in immunosuppressed patients, they should not be used in these patients. Progression of disease may necessitate intravenous therapy with acyclovir, 10 mg/kg intravenously, three times daily. After 3–4 days, oral therapy may be substituted if there has been a good response to intravenous therapy. Adverse effects include decreased kidney function from crystallization, nausea and vomiting, and abdominal pain.

Foscarnet, administered in a dosage of 40 mg/kg two or three times daily intravenously, is indicated for treatment of acyclovir-resistant varicella-zoster virus infections.

  1. Local Measures

Calamine or starch shake lotions may be of some help.

  1. Postherpetic Neuralgia Therapy

The most effective treatment is prevention with vaccination of those at risk for developing zoster and early and aggressive antiviral therapy once zoster has occurred. Once established, postherpetic neuralgia may be treated with capsaicin ointment, 0.025–0.075%, or lidocaine (Lidoderm) topical patches. Chronic postherpetic neuralgia may be relieved by regional blocks (stellate ganglion, epidural, local infiltration, or peripheral nerve), with or without corticosteroids added to the injections. Tricyclic antidepressants, such as amitriptyline, 25–75 mg orally as a single nightly dose, are the first-line therapy beyond simple analgesics. Gabapentin, up to 3600 mg orally daily (starting at 300 mg orally three times daily), or duloxetine, up to 60–120 mg orally daily (starting at 30–60 mg orally daily) may be added for additional pain relief. Long-acting opioids may be appropriate. Referral to a pain management clinic should be considered in moderate to severe cases and in those failing the above treatments.


The eruption persists 2–3 weeks and usually does not recur. Motor involvement in 2–3% of patients may lead to temporary palsy.

Bruxelle J et al. Effectiveness of antiviral treatment on acute phase of herpes zoster and development of post herpetic neuralgia: review of international publications. Med Mal Infect. 2012 Feb;42(2):53–8. [PMID: 22169279]

Eilers R et al. Assessment of vaccine candidates for persons aged 50 and older: a review. BMC Geriatr. 2013 Apr15;13:32. [PMID: 23586926]

Gagliardi AM et al. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev. 2012 Oct17;10: CD008858. [PMID: 23076951]

O’Connor KM et al. Herpes zoster. Med Clin North Am. 2013 Jul;97(4):503–22. [PMID: 23809711]

Thyssen JP et al. Coin exposure may cause allergic nickel dermatitis: a review. Contact Dermatitis. 2013 Jan;68(1):3–14. [PMID: 22762130]

POMPHOLYX; VESICULOBULLOUS HAND ECZEMA (Formerly Known as Dyshidrosis, Dyshidrotic Eczema)


 Pruritic “tapioca” vesicles of 1–2 mm on the palms, soles, and sides of fingers.

 Vesicles may coalesce to form multiloculated blisters.

 Scaling and fissuring may follow drying of the blisters.

 Appearance in the third decade, with lifelong recurrences.

 General Considerations

This is an extremely common form of hand dermatitis, preferably called pompholyx (Gr “bubble”) or vesiculobullous dermatitis of the palms and soles. About half of patients have an atopic background and many patients report flares with stress. Patients with widespread dermatitis due to any cause may develop pompholyx-like eruptions as a part of an autoeczematization response. A bullous hand dermatitis that is followed by a widespread dermatitis may develop in patients taking intravenous immunoglobin (IVIG), particularly those being treated for neurologic conditions; the dermatitis resolves over weeks to months.

 Clinical Findings

Small clear vesicles stud the skin at the sides of the fingers and on the palms (Figure 6–17) or soles. They look like the grains in tapioca. They may be associated with intense itching. Later, the vesicles dry and the area becomes scaly and fissured.

 Figure 6–17. Pompholyx (acute vesiculobullous hand eczema). (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

 Differential Diagnosis

Unroofing the vesicles and examining the blister roof with a KOH preparation will reveal hyphae in cases of bullous tinea. Always examine the feet of a patient with a hand eruption because patients with inflammatory tinea pedis may have a vesicular dermatophytid of the palms. Nonsteroidal anti-inflammatory drugs (NSAIDs) may produce an eruption very similar to that of dyshidrosis on the hands.


There is no known way to prevent attacks if the condition is idiopathic. About one-third to one-half of patients with vesiculobullous hand dermatitis have a relevant contact allergen, especially nickel. Patch testing and avoidance of identified allergens can lead to improvement.


Topical and systemic corticosteroids help some patients dramatically. Since this is a chronic problem, systemic corticosteroids are generally not appropriate therapy. A high-potency topical corticosteroid used early in the attack may help abort the flare and ameliorate pruritus. Topical corticosteroids are also important in treating the scaling and fissuring that are seen after the vesicular phase. It is essential that patients avoid anything that irritates the skin; they should wear cotton gloves inside vinyl gloves when doing dishes or other wet chores, use long-handled brushes instead of sponges, and use a hand cream after washing the hands. Patients respond to PUVA therapy and injection of botulinum toxin into the palms as for hyperhidrosis.


For most patients, the disease is an inconvenience. For some, vesiculobullous hand eczema can be incapacitating.

Apfelbacher C et al. Characteristics and provision of care in patients with chronic hand eczema: updated data from the CARPE Registry. Acta Derm Venereol. 2014 Feb 26;94(2): 163–7. [PMID: 23995048]

Coenraads PJ. eczema. N Engl J Med. 2012 Nov8;367(19):1829–37. [PMID: 23134383]



 Noninflammatory blisters on sun-exposed sites, especially the dorsal surfaces of the hands.

 Hypertrichosis, skin fragility.

 Associated liver disease.

 Elevated urine porphyrins.

 General Considerations

Porphyria cutanea tarda is the most common type of porphyria. Cases are sporadic or hereditary. The disease is associated with ingestion of certain medications (eg, estrogens), and liver disease from alcoholism or hepatitis C. In patients with liver disease, hemosiderosis is often present.

 Clinical Findings

  1. Symptoms and Signs

Patients complain of painless blistering and fragility of the skin of the dorsal surfaces of the hands (Figure 6–18). Facial hypertrichosis and hyperpigmentation are common.

 Figure 6–18. Porphyria cutanea tarda. (Courtesy of Lewis Rose, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

  1. Laboratory Findings

Urinary uroporphyrins are elevated twofold to fivefold above coproporphyrins. Patients may also have abnormal liver function tests, evidence of hepatitis C infection, increased liver iron stores, and hemochromatosis gene mutations.

 Differential Diagnosis

Skin lesions identical to those of porphyria cutanea tarda may be seen in patients who receive maintenance dialysis and in those who take certain medications (tetracyclines and NSAIDs, especially naproxen, and voriconazole). In this so-called pseudoporphyria, the biopsy results are identical to those associated with porphyria cutanea tarda, but urine porphyrins are normal.


Barrier sun protection with clothing is required. Although the lesions are triggered by sun exposure, the wavelength of light triggering the lesions is beyond that absorbed by sunscreens.


Stopping all triggering medications and substantially reducing or stopping alcohol consumption may alone lead to improvement. Phlebotomy without oral iron supplementation at a rate of 1 unit every 2–4 weeks will gradually lead to improvement. Very low dose antimalarials (as low as 200 mg of hydroxychloroquine twice weekly), alone or in combination with phlebotomy, will increase the excretion of porphyrins, improving the skin disease. Deferasirox, an iron chelator can also improve porphyria cutanea tarda. Treatment is continued until the patient is asymptomatic. Urine porphyrins may be monitored.


Most patients improve with treatment. Sclerodermoid skin lesions may develop on the trunk, scalp, and face.

Balwani M et al. The porphyrias: advances in diagnosis and treatment. Hematology Am Soc Hematol Educ Program. 2012;2012:19–27. [PMID: 23233556]

Borghi A et al. Prolonged cyclosporine treatment of severe or recalcitrant psoriasis: descriptive study in a series of 20 patients. Int J Dermatol. 2012 Dec;51(12):1512–6. [PMID: 23171021]

Gerstenblith MR et al. Pompholyx and eczematous reactions associated with intravenous immunoglobulin therapy. J Am Acad Dermatol. 2012 Feb;66(2):312–6. [PMID: 21601310]

Pandya AG et al. Deferasirox for porphyria cutanea tarda: a pilot study. Arch Dermatol. 2012 Aug;148(8):898–901. [PMID: 22911183]

Poh-Fitzpatrick MB. Porphyria cutanea tarda: treatment options revisited. Clin Gastroenterol Hepatol. 2012 Dec;10(12):1410–1. [PMID: 22982098]

Singal AK et al. Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda. Clin Gastroenterol Hepatol. 2012 Dec;10(12):1402–9. [PMID: 22985607]

Van Meter JR et al. Iron, genes, and viruses: the porphyria cutanea tarda triple threat. Cutis. 2011 Aug;88(2):73–6. [PMID: 21916273]


Dermatitis herpetiformis is an uncommon disease manifested by pruritic papules, vesicles, and papulovesicles mainly on the elbows, knees, buttocks, posterior neck, and scalp. It appears to have its highest prevalence in Scandinavia and is associated with HLA antigens -B8, -DR3, and -DQ2. The diagnosis is made by light microscopy. Circulating antibodies to tissue transglutaminase are present in 90% of cases. NSAIDs may cause flares. Patients have gluten-sensitive enteropathy, but for the great majority it is subclinical. However, ingestion of gluten is the cause of the disease, and strict long-term avoidance of dietary gluten has been shown to decrease the dose of dapsone (usually 100–200 mg daily) required to control the disease and may even eliminate the need for treatment. Patients with dermatitis herpetiformis are at increased risk for development of gastrointestinal lymphoma, and this risk is reduced by a gluten-free diet.

Bolotin D et al. Dermatitis herpetiformis. Part I. Epidemiology, pathogenesis, and clinical presentation. J Am Acad Dermatol. 2011 Jun;64(6):1017–24. [PMID: 21571167]

Bolotin D et al. Dermatitis herpetiformis. Part II. Diagnosis, management, and prognosis. J Am Acad Dermatol. 2011 Jun;64(6):1027–33. [PMID: 21571168]

Cardones AR et al. Management of dermatitis herpetiformis. Immunol Allergy Clin North Am. 2012 May;32(2):275–81. [PMID: 22560140]

Kárpáti S et al. Dermatitis herpetiformis. Clin Dermatol. 2012 Jan–Feb;30(1):56–9. [PMID: 22137227]




 Superficial blisters filled with purulent material that rupture easily.

 Crusted superficial erosions.

 Positive Gram stain and bacterial culture.

 General Considerations

Impetigo is a contagious and autoinoculable infection of the skin caused by staphylococci or streptococci.

 Clinical Findings

  1. Symptoms and Signs

The lesions consist of macules, vesicles, bullae, pustules, and honey-colored gummy crusts that when removed leave denuded red areas (Figure 6–19). The face and other exposed parts are most often involved. Ecthyma is a deeper form of impetigo caused by staphylococci or streptococci, with ulceration and scarring. It occurs frequently on the extremities.

 Figure 6–19. Bullous impetigo. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

  1. Laboratory Findings

Gram stain and culture confirm the diagnosis. In temperate climates, most cases are associated with S aureus infection. Streptococcus species are more common in tropical infections.

 Differential Diagnosis

The main differential diagnoses are acute allergic contact dermatitis and herpes simplex. Contact dermatitis may be suggested by the history or by linear distribution of the lesions, and culture should be negative for staphylococci and streptococci. Herpes simplex infection usually presents with grouped vesicles or discrete erosions and may be associated with a history of recurrences. Viral cultures are positive.


Soaks and scrubbing can be beneficial, especially in unroofing lakes of pus under thick crusts. Topical agents such as bacitracin, mupirocin, or retapamulin can be attempted for infections limited to small areas. Mupirocin and retapamulin are more expensive than systemic treatments. In most cases, systemic antibiotics are indicated. Cephalexin, 250 mg four times daily, is usually effective. Doxycycline, 100 mg twice daily, is a reasonable alternative. Community-associated methicillin-resistant S aureus (CA-MRSA) may cause impetigo, and initial coverage for MRSA could include doxycycline, clindamycin, or trimethoprim-sulfamethoxazole (TMP-SMZ). About 50% of CA-MRSA cases are quinolone resistant. Recurrent impetigo is associated with nasal carriage of S aureus and is treated with rifampin, 600 mg daily for 5 days. Intranasal mupirocin ointment twice daily for 5 days clears the carriage of 40% of MRSA strains. Bleach baths (¼ to ½ cup per 20 liters of bathwater for 15 minutes 3–5 times weekly) for all family members, and the use of dilute household bleach to clean showers and other bath surfaces may help reduce the spread. Individuals should not share towels if there is a case of impetigo in the household.

Koning S et al. Interventions for impetigo. Cochrane Database Syst Rev. 2012 Jan18;1: CD003261. [PMID: 22258953]



 Erythema and edema, with pruritus, often followed by vesicles and bullae (in allergic contact dermatitis) in an area of contact with a suspected agent.

 Later, weeping, crusting, or secondary infection.

 A history of previous reaction to suspected contactant.

 Positive patch test (in allergic contact dermatitis).

 General Considerations

Contact dermatitis (irritant or allergic) is an acute or chronic dermatitis that results from direct skin contact with chemicals or allergens. Eighty percent of cases are due to excessive exposure to or additive effects of primary or universal irritants (eg, soaps, detergents, organic solvents) and are called irritant contact dermatitis. This appears red and scaly but not vesicular. The most common causes of allergic contact dermatitis are poison ivy or poison oak, topically applied antimicrobials (especially bacitracin and neomycin), anesthetics (benzocaine), hair-care products, preservatives, jewelry (nickel), rubber, essential oils, propolis (from bees), and adhesive tape. Occupational exposure is an important cause of allergic contact dermatitis. Weeping and crusting are typically due to allergic and not irritant dermatitis.

 Clinical Findings

  1. Symptoms and Signs

In allergic contact dermatitis, the acute phase is characterized by tiny vesicles and weepy and crusted lesions, whereas resolving or chronic contact dermatitis presents with scaling, erythema, and possibly thickened skin. Itching, burning, and stinging may be severe. The lesions, distributed on exposed parts or in bizarre asymmetric patterns, consist of erythematous macules, papules, and vesicles. The affected area is often hot and swollen, with exudation and crusting, simulating—and at times complicated by—infection. The pattern of the eruption may be diagnostic (eg, typical linear streaked vesicles on the extremities in poison oak or ivy dermatitis [Figure 6–20]) The location will often suggest the cause: Scalp involvement suggests hair dyes or shampoos; face involvement, creams, cosmetics, soaps, shaving materials, nail polish; and neck involvement, jewelry, hair dyes. Unilateral facial involvement suggests nickel contact dermatitis from cellphone cover (about 25% of which have free nickel on their surface).

 Figure 6–20. Contact dermatitis with linear pattern due to poison ivy. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

  1. Laboratory Findings

Gram stain and culture will rule out impetigo or secondary infection (impetiginization). If itching is generalized, then scabies should be considered. After the episode of allergic contact dermatitis has cleared, patch testing may be useful if the triggering allergen is not known.

 Differential Diagnosis

Asymmetric distribution, blotchy erythema around the face, linear lesions, and a history of exposure help distinguish acute contact dermatitis from other skin lesions. The most commonly mistaken diagnosis is impetigo. Chronic allergic contact dermatitis must be differentiated from scabies, atopic dermatitis, pompholyx, and other eczemas.


Prompt and thorough removal of the causative oil by washing with liquid dishwashing soap (eg, Dial Ultra) may be effective if done within 30 minutes after exposure to poison oak or ivy. Goop and Tecnu are also effective but much more costly without increased efficacy. The three most effective over-the-counter barrier creams that are applied prior to exposure and prevent/reduce the severity of the dermatitis are Stokogard, Hollister Moisture Barrier, and Hydropel.

The mainstay of prevention is identification of the agent causing the dermatitis and avoidance of exposure or use of protective clothing and gloves. In industry-related cases, prevention may be accomplished by moving or retraining the worker.


  1. Overview

While local measures are important, severe or widespread involvement is difficult to manage without systemic corticosteroids because even the highest-potency topical corticosteroids seem not to work well on vesicular and weepy lesions. Localized involvement (except on the face) can often be managed solely with topical agents. Irritant contact dermatitis is treated by protection from the irritant and use of topical corticosteroids as for atopic dermatitis (described above). The treatment of allergic contact dermatitis is detailed below.

  1. Local Measures
  2. Acute weeping dermatitis—Compresses are most often used. It is unwise to scrub lesions with soap and water. Calamine lotion may be used between wet dressings,especially for involvement of intertriginous areas or when oozing is not marked. Lesions on the extremities may be bandaged with wet dressings for 30–60 minutes several times a day. High potency topical corticosteroids in gel or cream form (eg, fluocinonide, clobetasol, or halobetasol) may help suppress acute contact dermatitis and relieve itching. This treatment should be followed by tapering of the number of applications per day or use of a mid-potency corticosteroid such as triamcinolone 0.1% cream to prevent rebound of the dermatitis. A soothing formulation is 2 oz of 0.1% triamcinolone acetonide cream in 7.5 oz Sarna lotion (0.5% camphor, 0.5% menthol, 0.5% phenol) mixed by the patient.
  3. Subacute dermatitis (subsiding)—Mid-potency (triamcinolone 0.1%) to high-potency corticosteroids (clobetasol, amcinonide, fluocinonide, desoximetasone) are the mainstays of therapy.
  4. Chronic dermatitis (dry and lichenified)—High-potency to superpotency corticosteroids are used in ointment form.
  5. Systemic Therapy

For acute severe cases, prednisone may be given orally for 12–21 days. Prednisone, 60 mg for 4–7 days, 40 mg for 4–7 days, and 20 mg for 4–7 days without a further taper is one useful regimen. Another is to dispense seventy-eight 5-mg pills to be taken 12 the first day, 11 the second day, and so on. The key is to use enough corticosteroid (and as early as possible) to achieve a clinical effect and to taper slowly enough to avoid rebound. A Medrol Dosepak (methylprednisolone) with 5 days of medication is inappropriate on both counts. (See Chapter 26.)


Allergic contact dermatitis is self-limited if reexposure is prevented but often takes 2–3 weeks for full resolution.

Jensen P et al. Excessive nickel release from mobile phones—a persistent cause of nickel allergy and dermatitis. Contact Dermatitis. 2011 Dec;65(6):354–8. [PMID: 22077435]

Thyssen JP et al. Coin exposure may cause allergic nickel dermatitis: a review. Contact Dermatitis. 2013 Jan;68(1):3–14. [PMID: 22762130]




 Occurs at puberty, though onset may be delayed into the third or fourth decade.

 Open and closed comedones are the hallmark of acne vulgaris.

 The most common of all skin conditions.

 Severity varies from purely comedonal to papular or pustular inflammatory acne to cysts or nodules.

 Face and upper trunk may be affected.

 Scarring may be a sequela of the disease or picking and manipulating by the patient.

 General Considerations

Acne vulgaris is polymorphic. Open and closed comedones, papules, pustules, and cysts are found. The disease is activated by androgens in those who are genetically predisposed.

In younger persons, acne vulgaris is more common and more severe in males. It does not always clear spontaneously when maturity is reached. Twelve percent of women and 3% of men over age 25 have acne vulgaris. This rate does not decrease until after age 44. The skin lesions parallel sebaceous activity. Pathogenic events include plugging of the infundibulum of the follicles, retention of sebum, overgrowth of the acne bacillus (Propionibacterium acnes) with resultant release of and irritation by accumulated fatty acids, and foreign body reaction to extrafollicular sebum. The mechanism of antibiotics in controlling acne is not clearly understood, but they may work because of their antibacterial or anti-inflammatory properties.

When a resistant case of acne is encountered in a woman, hyperandrogenism may be suspected. This may or may not be accompanied by hirsutism, irregular menses, or other signs of virilism. Polycystic ovary syndrome (PCOS) is the most common identifiable cause.

 Clinical Findings

There may be mild soreness, pain, or itching. The lesions occur mainly over the face, neck, upper chest, back, and shoulders. Comedones are the hallmark of acne vulgaris. Closed comedones are tiny, flesh-colored, noninflamed bumps that give the skin a rough texture or appearance. Open comedones typically are a bit larger and have black material in them. Inflammatory papules, pustules, ectatic pores, acne cysts, and scarring are also seen (Figure 6–21)

 Figure 6–21. Acne vulgaris, severe nodular cystic form with scarring. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

Acne may have different presentations at different ages. Preteens often present with comedones as their first lesions. Inflammatory lesions in young teenagers are often found in the middle of the face, extending outward as the patient becomes older. Women in their third and fourth decades (often with no prior history of acne) commonly present with papular lesions on the chin and around the mouth.

 Differential Diagnosis

In adults, acne rosacea presents with papules and pustules in the middle third of the face, but telangiectasia, flushing, and the absence of comedones distinguish this disease from acne vulgaris. A pustular eruption on the face in patients receiving antibiotics or with otitis externa should be investigated with culture to rule out an uncommon gram-negative folliculitis. Acne may develop in patients who use systemic corticosteroids or topical fluorinated corticosteroids on the face. Acne may be exacerbated or caused by irritating creams or oils. Pustules on the face can also be caused by tinea infections. Lesions on the back are more problematic. When they occur alone, staphylococcal folliculitis, miliaria (“heat rash”) or, uncommonly, Malassezia folliculitis should be suspected. Bacterial culture, trial of an antistaphylococcal antibiotic, and observing the response to therapy will help in the differential diagnosis. In patients with HIV infection, folliculitis is common and may be either staphylococcal folliculitis or eosinophilic folliculitis.


Cyst formation, pigmentary changes in pigmented patients, severe scarring, and psychological problems may result.


  1. General Measures
  2. Education of the patient—When scarring seems out of proportion to the severity of the lesions, clinicians must suspect that the patient is manipulating the lesions. It is essential that the patient be educated in a supportive way about this complication. Anxiety and depression are often the underlying cause of young women excoriating minor acne. It is wise to let the patient know that at least 4–6 weeks will be required to see improvement and that old lesions may take months to fade. Therefore, improvement will be judged according to the number of new lesions forming after 6–8 weeks of therapy. Additional time will be required to see improvement on the back and chest, as these areas are slowest to respond. If hair pomades are used, they should contain glycerin and not oil. Avoid topical exposure to oils, cocoa butter (theobroma oil), and greases.
  3. DIETA low glycemic diet that results in weight loss has been reported to improve acne in males aged 18–25. This improvement was associated with a reduction in insulin resistance. Hyperinsulinemia has also been associated with acne in eumenorrheic women. The metabolic syndrome with insulin resistance can also be a feature of PCOS in women. This finding suggests a possible common pathogenic mechanism for acne in both adult women and men.
  4. Comedonal Acne

Treatment of acne is based on the type and severity of lesions. Comedones require treatment different from that of pustules and cystic lesions. In assessing severity, take the sequelae of the lesions into account. An individual who gets only a few new lesions per month that scar or leave postinflammatory hyperpigmentation must be treated much more aggressively than a comparable patient whose lesions clear without sequelae. Soaps play little role in acne treatment, and unless the patient’s skin is exceptionally oily, a mild soap should be used to avoid irritation that will limit the usefulness of other topicals, all of which are themselves somewhat irritating. The agents effective in comedonal acne are listed below in the order in which they should be tried.

  1. Topical retinoids—Tretinoin is very effective for comedonal acne or for treatment of the comedonal component of more severe acne, but its usefulness is limited by irritation. Start with 0.025% cream (not gel) and have the patient use it at first twice weekly at night, then build up to as often as nightly. A few patients cannot use even this low-strength preparation more than three times weekly but even that may cause improvement. A lentil-sized amount is sufficient to cover the entire face. To avoid irritation, have the patient wait 20 minutes after washing to apply. Adapalene gel 0.1% and reformulated tretinoin (Renova, Retin A Micro, Avita) are other options for patients irritated by standard tretinoin preparations. Some patients—especially teenagers—do best on 0.01% gel. Although the absorption of tretinoin is minimal, its use during pregnancy is contraindicated. Patients should be warned that their acne may flare in the first 4 weeks of treatment. Tazarotene gel (0.05% or 0.1%) (Tazorac) is another topical retinoid approved for treatment of psoriasis and acne, and may be used in patients intolerant of the other retinoids.
  2. Benzoyl peroxide—Benzoyl peroxide products are available in concentrations of 2.5%, 4%, 5%, 8%, and 10%, but it appears that 2.5% is as effective as 10% and less irritating. In general, water-based and not alcohol-based gels should be used to decrease irritation. Benzoyl peroxide in combination with adapalene is available as a single formulation.
  3. Antibiotics—Use of topical antibiotics (see below) has been demonstrated to decrease pustular and comedonal lesions.
  4. Papular or Cystic Inflammatory Acne

Topical or oral antibiotics are the mainstay for treatment of inflammatory acne. The oral antibiotics of choice are tetracycline and doxycycline. Minocycline is often effective in acne unresponsive or resistant to treatment with these antibiotics but it is more expensive. Rarely, other antibiotics such as TMP-SMZ (one double-strength tablet twice daily), clindamycin (150 mg twice daily), or a cephalosporin (cefadroxil or cephalexin) may be used. Topical clindamycin phosphate and erythromycin are also used (see below). Topicals are probably the equivalent of about 500 mg/d of tetracycline given orally, which is half the usual starting dose. Topical antibiotics are used in three situations: for mild papular acne that can be controlled by topicals alone, for patients who refuse or cannot tolerate oral antibiotics, or to wean patients under good control from oral to topical preparations. To decrease resistance, benzoyl peroxide should be used in combination with the topical antibiotic.

  1. Mild acne—The first choice of topical antibiotics in terms of efficacy and relative lack of induction of resistantP acnesis the combination of erythromycin or clindamycin with benzoyl peroxide topical gel. Clindamycin (Cleocin T) lotion (least irritating), gel, or solution, or one of the many brands of topical erythromycin gel or solution, may be used twice daily and the benzoyl peroxide in the morning. (A combination of erythromycin or clindamycin with benzoyl peroxide is available.) The addition of tretinoin 0.025% cream or 0.01% gel at night may increase improvement, since it works via a different mechanism. Combination preparations of an antibiotic and benzoyl peroxide and antibiotic plus tretinoin are available, but there is no evidence that they are superior to the individual agents used separately.
  2. Moderate acne—Tetracycline, 500 mg twice daily, doxycycline, 100 mg twice daily, and minocycline, 50–100 mg twice daily, are all effective. When initiating minocycline therapy, start at 100 mg in the evening for 4–7 days, then 100 mg twice daily, to decrease the incidence of vertigo. Plan a return visit in 6 weeks and at 3–4 months after that. If the patient’s skin is quite clear, instructions should be given for tapering the dose by 250 mg for tetracycline, by 100 mg for doxycycline, or by 50 mg for minocycline every 6–8 weeks—while treating with topicals—to arrive at the lowest systemic dose needed to maintain clearing. In general, immediately lowering the dose to zero without other therapy results in prompt recurrence.

Tetracycline, minocycline, and doxycycline are contraindicated in pregnancy, but oral erythromycin may be used. It is important to discuss the issue of contraceptive failure when prescribing antibiotics for women taking oral contraceptives. Women may need to consider using barrier methods as well, and should report breakthrough bleeding.

Oral contraceptives or spironolactone (50–200 mg daily) may be added as an antiandrogen in women with antibiotic-resistant acne or in women in whom relapse occurs after isotretinoin therapy.

  1. Severe acne—
  2. ISOTRETINOINA vitamin A analog, isotretinoin is used for the treatment of severe cystic acne that has not responded to conventional therapy. A dosage of 0.5–1 mg/kg/d for 20 weeks for a cumulative dose of at least 120 mg/kg is usually adequate for severe cystic acne. Patients should be offered isotretinoin therapy before they experience significant scarring if they are not promptly and adequately controlled by antibiotics. The drug isabsolutely contraindicated during pregnancybecause of its teratogenicity; two serum pregnancy tests should be obtained before starting the drug in women and every month thereafter. Sufficient medication for only 1 month should be dispensed. Two forms of effective contraception must be used. Informed consent must be obtained before its use and patients must be enrolled in a monitoring program (iPledge). Side effects occur in most patients, usually related to dry skin and mucous membranes (dry lips, nosebleed, and dry eyes). If headache occurs, pseudotumor cerebri must be considered. Depression has been reported. Hypertriglyceridemia will develop in about 25% of patients, hypercholesterolemia in 15%, and a lowering of high-density lipoproteins in 5%. Minor elevations in liver function tests may develop in some patients. Fasting blood sugar may be elevated. Miscellaneous adverse reactions include decreased night vision, musculoskeletal symptoms, dry skin, thinning of hair, exuberant granulation tissue in lesions, and bony hyperostoses (seen only with very high doses or with long duration of therapy). Moderate to severe myalgias rarely necessitate decreasing the dosage or stopping the drug. Inflammatory bowel disease has first appeared after acne treatment with both tetracyclines and isotretinoin at a rate of 1:1000 cases treated or less. Causality of this association has not been established. Young adults with severe acne who are potential candidates for isotretinoin should be asked about any bowel symptoms prior to starting isotretinoin. Laboratory tests to be performed in all patients before treatment and after 4 weeks on therapy include complete blood cell count (CBC), cholesterol, triglycerides, and liver function studies.

Elevations of liver enzymes and triglycerides return to normal upon conclusion of therapy. The drug may induce long-term remissions in 40–60%, or acne may recur that is more easily controlled with conventional therapy. Occasionally, acne does not respond or promptly recurs after therapy, but it may clear after a second course.

  1. INTRALESIONAL INJECTION—In otherwise moderate acne, intralesional injection of dilute suspensions of triamcinolone acetonide (2.5 mg/mL, 0.05 mL per lesion) will often hasten the resolution of deeper papules and occasional cysts.
  2. LASER DERMABRASION—Cosmetic improvement may be achieved by excision and punch-grafting of deep scars and by abrasion of inactive acne lesions, particularly flat,superficial scars. The technique is not without untoward effects, since hyperpigmentation, hypopigmentation, grooving, and scarring have been known to occur. Dark-skinned individuals do poorly. Corrective surgery within 12 months after isotretinoin therapy may not be advisable. Active acne of all types can be treated with certain laser and photodynamic therapies. This can be considered when standard treatments are contraindicated or fail.


Acne vulgaris eventually remits spontaneously, but when this will occur cannot be predicted. The condition may persist throughout adulthood and may lead to severe scarring if left untreated. Patients treated with antibiotics continue to improve for the first 3–6 months of therapy. Relapse during treatment may suggest the emergence of resistant P acnes. The disease is chronic and tends to flare intermittently in spite of treatment. Remissions following systemic treatment with isotretinoin may be lasting in up to 60% of cases. Relapses after isotretinoin usually occur within 3 years and require a second course in up to 20% of patients.

Arowojolu AO et al. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012 Jul11;7: CD004425. [PMID: 22786490]

Garner SE et al. Minocycline for acne vulgaris: efficacy and safety. Cochrane Database Syst Rev. 2012 Aug15;8: CD002086. [PMID: 22895927]

Purdy S et al. Acne vulgaris. Clin Evid (Online). 2011 Jan5; 2011. [PMID: 21477388]

Rademaker M. Isotretinoin: dose, duration and relapse. What does 30 years of usage tell us? Australas J Dermatol. 2013 Aug;54(3):157–62. [PMID: 23013115]

Torrelo A et al. Atopic dermatitis: impact on quality of life and patients’ attitudes toward its management. Eur J Dermatol. 2012 Jan–Feb;22(1):97–105. [PMID: 22237114]

Williams HC et al. Acne vulgaris. Lancet. 2012 Jan 28;379(9813):361–72. [PMID: 21880356]



 A chronic facial disorder.

 A neurovascular component (erythema and telangiectasis and a tendency to flush easily).

 An acneiform component (papules and pustules) may also be present.

 A glandular component accompanied by hyperplasia of the soft tissue of the nose (rhinophyma).

 General Considerations

The pathogenesis of this disorder is not known. Topical corticosteroids applied to the face can induce rosacea-like conditions.

 Clinical Findings

Patients frequently report flushing or exacerbation of their rosacea due to heat, hot drinks, spicy food, sunlight, exercise, alcohol, emotions, or menopausal flushing. The cheeks, nose, and chin—at times the entire face—may have a rosy hue. No comedones are seen. In its mildest form, erythema and dilated vessels are seen on the cheeks. Inflammatory papules may be superimposed on this background and may evolve to pustules (Figure 6–22). Associated seborrhea may be found. The patient often complains of burning or stinging with episodes of flushing. Patients may have associated ophthalmic disease, including blepharitis and keratitis, that often requires systemic antibiotic therapy.

 Figure 6–22. Rosacea. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

 Differential Diagnosis

Rosacea is distinguished from acne by the presence of the neurovascular component and the absence of comedones. The rosy hue of rosacea and telangiectasis will pinpoint the diagnosis. Lupus is often misdiagnosed, but the presence of pustules excludes that diagnosis.


Educating patients to avoid the factors they know to produce exacerbations is important. Patients should wear a broad-spectrum sunscreen with UVA coverage; however, exquisite sensitivity to topical preparations may limit patient options. Zinc- or titanium-based sunscreens are better tolerated, and barrier protective silicones in the sunblock may enhance tolerance. Medical management is most effective for the inflammatory papules and pustules and the erythema that surrounds them. Rosacea is usually a lifelong condition, so maintenance therapy is required.

  1. Local Therapy

Avoidance of triggers (especially alcohol) and sucking on an ice cube may be effective in reducing facial erythema and flushing. Metronidazole (available as creams, gels, or lotions), 0.75% applied twice daily or 1% applied once daily, is the topical treatment of choice. If metronidazole is not tolerated, topical clindamycin (solution, gel, or lotion) 1% applied twice daily is effective. Response is noted in 4–8 weeks. Sulfur-sodium sulfacetamide-containing topicals are helpful in patients only partially responsive to topical antibiotics. Benzoyl peroxide, as in acne vulgaris, may be helpful in reducing the pustular component. Topical retinoids can be carefully added for maintenance. Topical brimonidine tartrate gel 0.5% can temporarily reduce the flush/redness of rosacea patients. Prolonged use did not lead to tachyphylaxis in short trials.

  1. Systemic Therapy

Tetracycline, 250 or 500 mg orally twice daily on an empty stomach, should be used when topical therapy is inadequate. Minocycline or doxycycline, 50–100 mg orally daily to twice daily, is also effective. Metronidazole or amoxicillin, 250–500 mg orally twice daily, or rifaximin, 550 mg orally twice daily, may be used in refractory cases. Side effects are few, although metronidazole may produce a disulfiram-like effect when the patient ingests alcohol and it may cause neuropathy with long-term use. Isotretinoin may succeed where other measures fail. A dosage of 0.5 mg/kg/d orally for 12–28 weeks is recommended. See precautions above. Telangiectases are benefitted by laser therapy, and phymatous overgrowth of the nose can be treated by surgical reduction.


Rosacea tends to be a persistent process. With the regimens described above, it can usually be controlled adequately.

Baldwin HE. Diagnosis and treatment of rosacea: state of the art. J Drugs Dermatol. 2012 Jun;11(6):725–30. [PMID: 22648219]

Moore A et al. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study. J Drugs Dermatol. 2014 Jan1;13(1):56–61. [PMID: 24385120]

Rice SA et al. Repeatedly red faced. Lancet. 2012 Apr21;379(9825): 1560. [PMID: 22521073]

Torpy JM et al. JAMA patient page. Rosacea. JAMA. 2012 Jun6;307(21): 2333. [PMID: 22706840]

van Zuuren EJ et al. Effective and evidence-based management strategies for rosacea: summary of a Cochrane systematic review. Br J Dermatol. 2011 Oct;165(4):760–81. [PMID: 21692773]

van Zuuren EJ et al. Interventions for rosacea. Cochrane Database Syst Rev. 2011 Mar16;(3): CD003262. [PMID: 21412882]

FOLLICULITIS (Including Sycosis)


 Itching and burning in hairy areas.

 Pustules in the hair follicles.

 General Considerations

Folliculitis has multiple causes. It is frequently caused by staphylococcal infection and may be more common in the diabetic patient. When the lesion is deep-seated, chronic, and recalcitrant on the head and neck, it is called sycosis.

Gram-negative folliculitis, which may develop during antibiotic treatment of acne, may present as a flare of acne pustules or nodules. Klebsiella, Enterobacter, Escherichia coli, and Proteus have been isolated from these lesions.

“Hot tub folliculitis,” caused by Pseudomonas aeruginosa, is characterized by pruritic or tender follicular, pustular lesions occurring within 1–4 days after bathing in a contaminated hot tub, whirlpool, or swimming pool. Rarely, systemic infections may result. Neutropenic patients should avoid these exposures.

Nonbacterial folliculitis may also be caused by friction and oils. Occlusion, perspiration, and rubbing, such as that resulting from tight jeans and other heavy fabrics on the upper legs can worsen this type of folliculitis.

Steroid acne may be seen during topical or systemic corticosteroid therapy.

A form of sterile folliculitis called eosinophilic folliculitis consisting of urticarial papules with prominent eosinophilic infiltration is common in patients with AIDS. It may appear first with institution of highly active antiretroviral therapy (HAART) and be mistaken for a drug eruption.

Pseudofolliculitis is caused by ingrowing hairs in the beard area. It occurs in men and women with tightly curled beard hair. In this entity, the papules and pustules are located at the side of and not in follicles. It may be treated by growing a beard, by using chemical depilatories, or by shaving with a foil-guard razor. Laser hair removal is dramatically beneficial in patients with pseudofolliculitis, requires limited maintenance, and can be done on patients of any skin color. Pseudofolliculitis is a true medical indication for such a procedure and should not be considered cosmetic.

 Clinical Findings

The symptoms range from slight burning and tenderness to intense itching. The lesions consist of pustules of hair follicles (Figure 6–23).

 Figure 6–23. Bacterial folliculitis. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

 Differential Diagnosis

It is important to differentiate bacterial from nonbacterial folliculitis. The history is important for pinpointing the causes of nonbacterial folliculitis, and a Gram stain and culture are indispensable. One must differentiate folliculitis from acne vulgaris or pustular miliaria (heat rash) and from infections of the skin such as impetigo or fungal infections. Pseudomonas folliculitis is often suggested by the history of hot tub use. Eosinophilic folliculitis in AIDS often requires biopsy for diagnosis.


Abscess formation is the major complication of bacterial folliculitis.


Correct any predisposing local causes such as oils or friction. Be sure that the water in hot tubs and spas is treated properly. If staphylococcal folliculitis is persistent, treatment of nasal or perineal carriage with rifampin, 600 mg daily for 5 days, or with topical mupirocin ointment 2% twice daily for 5 days, may help. Prolonged oral clindamycin, 150–300 mg/d for 4–6 weeks, or oral TMP-SMZ given 1 week per month for 6 months can be effective in preventing recurrent staphylococcal folliculitis and furunculosis. Bleach baths (¼ to ½ cup per 20 liters of bathwater for 15 minutes 3–5 times weekly) may reduce cutaneous staphylococcal carriage and not contribute to antibiotic resistance. Control of blood glucose in diabetes may reduce the number of these infections.


  1. Local Measures

Anhydrous ethyl alcohol containing 6.25% aluminum chloride (Xerac AC), applied three to seven times weekly to lesions and environs, may be helpful, especially for chronic frictional folliculitis of the buttocks. Topical antibiotics are generally ineffective if bacteria have invaded the hair follicle, but may be prophylactic if used as an aftershave in patients with recurrent folliculitis after shaving.

  1. Specific Measures

Pseudomonas folliculitis will clear spontaneously in non-neutropenic patients if the lesions are superficial. It may be treated with ciprofloxacin, 500 mg twice daily for 5 days.

Systemic antibiotics are recommended for bacterial folliculitis due to other organisms. Extended periods of treatment (4–8 weeks or more) with antistaphylococcal antibiotics are required if infection has involved the scalp or densely hairy areas such as the axilla, beard, or groin.

Gram-negative folliculitis in acne patients may be treated with isotretinoin in compliance with all precautions discussed above (see Acne Vulgaris).

Eosinophilic folliculitis may be treated initially by the combination of potent topical corticosteroids and oral antihistamines. In more severe cases, treatment is with one of the following: topical permethrin (application for 12 hours every other night for 6 weeks); itraconazole, 200–400 mg daily; UVB or PUVA phototherapy; or isotretinoin, 0.5 mg/kg/d for up to 5 months. A remission may be induced by some of these therapies, but long-term treatment may be required.


Bacterial folliculitis is occasionally stubborn and persistent, requiring prolonged or intermittent courses of antibiotics.

Lutz JK et al. Prevalence and antimicrobial-resistance of Pseudomonas aeruginosa in swimming pools and hot tubs. Int J Environ Res Public Health. 2011 Feb;8(2):554–64. [PMID: 21556203]

Weingartner JS et al. What is your diagnosis? Demodex folliculitis. Cutis. 2012 Aug;90(2): 62, 65–6, 69. [PMID: 22988646]

MILIARIA (Heat Rash)


 Burning, itching, superficial aggregated small vesicles, papules, or pustules on covered areas of the skin, usually the trunk.

 More common in hot, moist climates.

 Rare forms associated with fever and even heat prostration.

 General Considerations

Miliaria occurs most commonly on the trunk and intertriginous areas. A hot, moist environment is the most frequent cause. Occlusive clothing required for certain occupations may increase the risk. Bedridden febrile patients are susceptible. Plugging of the ostia of sweat ducts occurs, with ultimate rupture of the sweat duct, producing an irritating, stinging reaction. Increase in numbers of resident aerobes, notably cocci, plays a role. Medications that enhance sweat gland function (eg, clonidine, beta-blockers, opioids) may contribute.

 Clinical Findings

The usual symptoms are burning and itching. The lesions consist of small, superficial, red, thin-walled, discrete vesicles (miliaria crystallina), papules (miliaria rubra), or vesicopustules or pustules (miliaria pustulosa). The reaction virtually always affects the back in a hospitalized patient.

 Differential Diagnosis

Miliaria is to be distinguished from drug eruption and folliculitis.


Use of an antibacterial preparation such as chlorhexidine prior to exposure to heat and humidity may help prevent the condition. Frequent turning or sitting of the hospitalized patient may reduce miliaria on the back.


The patient should keep cool and wear light clothing. Triamcinolone acetonide, 0.1% in Sarna lotion, or a mid-potency corticosteroid in a lotion or cream should be applied two to four times daily. Secondary infections (superficial pyoderma) are treated with appropriate antistaphylococcal antibiotics. Anticholinergic drugs given by mouth may be helpful in severe cases, eg, glycopyrrolate, 1 mg twice daily.


Miliaria is usually a mild disorder, but severe forms (tropical anhidrosis and asthenia) result from interference with the heat-regulating mechanism.

Carter R 3rd et al. Patients presenting with miliaria while wearing flame resistant clothing in high ambient temperatures: a case series. J Med Case Rep. 2011 Sep22;5:474. [PMID: 21939537]

Carvalho R et al. sQUIZ your knowledge! “Water-drop” lesions in a febrile patient. Miliaria crystalline (MC). Eur J Dermatol. 2012 Jan–Feb;22(1):160–1. [PMID: 22370171]



 Severe pruritus of vulva, anus, or body folds.

 Superficial denuded, beefy-red areas with or without satellite vesicopustules.

 Whitish curd-like concretions on the oral and vaginal mucous membranes.

 Yeast and pseudohyphae on microscopic examination of scales or curd.

 General Considerations

Mucocutaneous candidiasis is a superficial fungal infection that may involve almost any cutaneous or mucous surface of the body. It is particularly likely to occur in diabetics, during pregnancy, and in obese persons. Systemic antibiotics, oral corticosteroids, and oral contraceptive agents may be contributory. Oral candidiasis may be the first sign of HIV infection (see Chapter 31).

 Clinical Findings

  1. Symptoms and Signs

Itching may be intense. Burning is reported, particularly around the vulva and anus. The lesions consist of superficially denuded, beefy-red areas in the depths of the body folds such as in the groin and the intergluteal cleft, beneath the breasts, at the angles of the mouth, and in the umbilicus. The peripheries of these denuded lesions are superficially undermined, and there may be satellite vesicopustules. Whitish, curd-like concretions may be present on mucosal lesions (Figure 6–24). Paronychia may occur (Figure 6–25).

 Figure 6–24. Oral mucosal candidiasis. (Courtesy of Sol Silverman, Jr., DDS, Public Health Image Library, CDC.)

 Figure 6–25. Acute paronychia. (Courtesy of EJ Mayeaux, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

  1. Laboratory Findings

Clusters of budding yeast and pseudohyphae can be seen under high power (400×) when skin scales or curd-like lesions have been cleared in 10% KOH. Culture can confirm the diagnosis.

 Differential Diagnosis

Intertrigo, seborrheic dermatitis, tinea cruris, “inverse psoriasis,” and erythrasma involving the same areas may mimic mucocutaneous candidiasis.


Systemic invasive candidiasis with candidemia may be seen with immunosuppression and in patients receiving broad-spectrum antibiotic and hypertonic glucose solutions, as in hyperalimentation. There may or may not be clinically evident mucocutaneous candidiasis.


  1. General Measures

Affected parts should be kept dry and exposed to air as much as possible. If possible, discontinue systemic antibiotics. For treatment of systemic invasive candidiasis, see Chapter 36.

  1. Local Measures
  2. Nails and paronychia—Apply clotrimazole solution 1% twice daily. Thymol 4% in ethanol applied once daily is an alternative.
  3. Skin—Apply nystatin ointment or clotrimazole cream 1%, either with hydrocortisone cream 1%, twice daily. Gentian violet 0.5% solution is economical and highly effective in treating cutaneous candidiasis (and also mucosal disease), but the purple discoloration represents a cosmetic issue for some patients.
  4. Vulvar and anal mucous membranes—For vaginal candidiasis, single-dose fluconazole (150 mg orally) is effective. Intravaginal clotrimazole, miconazole, terconazole, or nystatin may also be used. Long-term suppressive therapy may be required for recurrent or “intractable” cases. Non-albicanscandidal species may be identified by culture in some refractory cases and may respond to oral itraconazole, 200 mg twice daily for 2–4 weeks.
  5. Balanitis—This is most frequent in uncircumcised men, andCandidausually plays a role. Topical nystatin ointment is the initial treatment if the lesions are mildly erythematous or superficially erosive. Soaking with dilute aluminum acetate for 15 minutes twice daily may quickly relieve burning or itching. Chronicity and relapses, especially after sexual contact, suggest reinfection from a sexual partner who should be treated. Severe purulent balanitis is usually due to bacteria. If it is so severe that phimosis occurs, oral antibiotics—some with activity against anaerobes—are required; if rapid improvement does not occur, urologic consultation is indicated.
  6. Mastitis—Lancinating breast pain and nipple dermatitis in breast-feeding women may be a manifestation ofCandidacolonization/infection of the breast ducts. Treatment with oral fluconazole, 200 mg daily can be dramatically effective. Topical gentian violet 0.5% is also useful in these cases.


Cases of cutaneous candidiasis range from the easily cured to the intractable and prolonged.

Amir LH et al. The role of micro-organisms (Staphylococcus aureus and Candida albicans) in the pathogenesis of breast pain and infection in lactating women: study protocol. BMC Pregnancy Childbirth. 2011 Jul22;11:54. [PMID: 21777483]

Pienaar ED et al. Interventions for the prevention and management of oropharyngeal candidiasis associated with HIV infection in adults and children. Cochrane Database Syst Rev. 2010 Nov10;(11): CD003940. [PMID: 21069679]

Ray A et al. Interventions for prevention and treatment of vulvovaginal candidiasis in women with HIV infection. Cochrane Database Syst Rev. 2011 Aug10;(8): CD008739. [PMID: 21833970]



  1. Urticaria & Angioedema


 Eruptions of evanescent wheals or hives.

 Itching is usually intense but may on rare occasions be absent.

 Special forms of urticaria have special features (dermatographism, cholinergic urticaria, solar urticaria, or cold urticaria).

 Most incidents are acute and self-limited over a period of 1–2 weeks.

 Chronic urticaria (episodes lasting > 6 weeks) may have an autoimmune basis.

 General Considerations

Urticaria can result from many different stimuli on an immunologic or nonimmunologic basis. The most common immunologic mechanism is mediated by IgE, as seen in the majority of patients with acute urticaria; another involves activation of the complement cascade. Some patients with chronic urticaria demonstrate autoantibodies directed against mast cell IgE receptors. ACE inhibitor and angiotensin receptor blocker therapy may be complicated by urticaria or angioedema. In general, extensive costly workups are not indicated in patients who have urticaria. A careful history and physical examination are more helpful.

 Clinical Findings

  1. Symptoms and Signs

Lesions are itchy red swellings of a few millimeters to many centimeters (Figure 6–26). The morphology of the lesions may vary over a period of minutes to hours, resulting in geographic or bizarre patterns. Individual lesions in true urticaria last < 24 hours, and often only 2–4 hours. Angioedema is involvement of deeper subcutaneous tissue with swelling of the lips, eyelids, palms, soles, and genitalia.Angioedema is no more likely than urticaria to be associated with systemic complications such as laryngeal edema or hypotension. In cholinergic urticaria, triggered by a rise in core body temperature (hot showers, exercise), wheals are 2–3 mm in diameter with a large surrounding red flare. Cold urticaria is acquired or inherited and triggered by exposure to cold and wind (see Chapter 37).

 Figure 6–26. Urticaria. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

  1. Laboratory Findings

Laboratory studies are not likely to be helpful in the evaluation of acute or chronic urticaria. The most common causes of acute urticaria are foods, infections, and medications. The cause of chronic urticaria is often not found. In patients with individual lesions that persist past 24 hours, skin biopsy may confirm neutrophilic urticaria or urticarial vasculitis. A functional ELISA test can detect patients with an autoimmune basis for their chronic urticaria.

 Differential Diagnosis

Papular urticaria resulting from insect bites persists for days. A central punctum can usually be seen. Streaked urticarial lesions may be seen in the 24–48 hours before blisters appear in acute allergic plant dermatitis, eg, poison ivy, oak, or sumac. Urticarial response to heat, sun, water, and pressure are quite rare. Urticarial vasculitis may be seen as part of serum sickness, associated with fever and arthralgia. In this setting, a low serum complement level may be associated with severe systemic disease.

In hereditary angioedema, there is generally a positive family history and gastrointestinal or respiratory symptoms. Urticaria is not part of the syndrome, and lesions are not pruritic.


  1. General Measures

A detailed search by history for a cause of acute urticaria should be undertaken, and treatment may then be tailored to include the provocative condition. The chief causes are medications—eg, aspirin, NSAIDs, morphine, and codeine; arthropod bites—eg, insect bites and bee stings (though the latter may cause anaphylaxis as well as angioedema); physical factors such as heat, cold, sunlight, and pressure; and, presumably, neurogenic factors, as in cholinergic urticaria induced by exercise, excitement, hot showers, etc. Other causes may include penicillins and other medications; inhalants such as feathers and animal danders; ingestion of shellfish, tomatoes, or strawberries; infections such as viral hepatitis (causing urticarial vasculitis); and in selected patients salicylates and tartrazine dyes.

  1. Systemic Treatment

The mainstay of treatment initially includes H1-antihistamines (see above). Initial therapy is hydroxyzine, 10 mg twice daily to 25 mg three times daily, or as a single nightly dose of 50–75 mg to reduce daytime sedation. Cyproheptadine, 4 mg four times daily, may be especially useful for cold urticaria. “Nonsedating” or less sedating antihistamines are added if the generic sedating antihistamines are not effective. Options include fexofenadine, 60 mg twice daily (or 180 mg once daily); or cetirizine or loratadine, 10 mg daily. Higher doses of these second-generation antihistamines may be required to suppress urticaria (up to four times the standard recommended dose) than are required for allergic rhinitis. These high doses are safe and can be used in refractory cases.

Doxepin (a tricyclic antidepressant), 10–75 mg at bedtime, can be very effective in chronic urticaria. It has anticholinergic side effects.

H2-antihistamines in combination with H1-blockers may be helpful in patients with symptomatic dermatographism and to a lesser degree in chronic urticaria. UVB phototherapy can suppress some cases of chronic urticaria. If neutrophils are a significant component of the inflammatory infiltrate in chronic urticaria, dapsone or colchicine (or both) may be useful.

A few patients with chronic urticaria may respond to elimination of salicylates and tartrazine (coloring agent). Asymptomatic foci of infection—sinusitis, vaginal candidiasis, cholecystitis, and intestinal parasites—may rarely cause chronic urticaria. Systemic corticosteroids in a dose of about 40 mg daily will usually suppress acute and chronic urticaria. However, the use of corticosteroids is rarely indicated, since properly selected combinations of antihistamines with less toxicity are usually effective. Once corticosteroids are withdrawn, the urticaria virtually always returns if it had been chronic. Instead of instituting systemic corticosteroids, consultation should be sought from a dermatologist or allergist with experience in managing severe urticaria. Cyclosporine (3–5 mg/kg/d) and other immunosuppressives may be effective in severe cases of chronic urticaria. Omalizumab can be highly effective in patients with refractory chronic urticaria and should be considered when severe chronic urticaria fails to respond to high-dose antihistamines.

  1. Local Treatment

Local treatment is rarely rewarding.


Acute urticaria usually lasts only a few days to weeks. Half of patients whose urticaria persists for > 6 weeks will have it for years. Patients in whom angioedema develops with an ACE inhibitor may be switched to an angiotensin receptor blocker with caution (estimated cross reaction about 10%).

Ben-Shoshan M et al. Psychosocial factors and chronic spontaneous urticaria: a systematic review. Allergy. 2013 Feb;68(2):131–41. [PMID: 23157275]

Carr TF et al. Chapter 21: Urticaria and angioedema. Allergy Asthma Proc. 2012 May–Jun;33(Suppl 1):S70–2. [PMID: 22794694]

Church MK et al. H(1)-antihistamines and urticaria: how can we predict the best drug for our patient? Clin Exp Allergy. 2012 Oct;42(10):1423–9. [PMID: 22994340]

Maurer M et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013 Mar7;368(10):924–35. Erratum in: N Engl J Med. 2013 Jun13;368(24):2340–1. [PMID: 23432142]

  1. Erythema Multiforme


 Sudden onset of symmetric erythematous skin lesions with history of recurrence.

 May be macular, papular, urticarial, bullous, or purpuric.

 “Target” lesions with clear centers and concentric erythematous rings or “iris” lesions may be noted in erythema multiforme minor. These are rare in drug-associated erythema multiforme major.

 Erythema multiforme minor on extensor surfaces, palms, soles, or mucous membranes. Erythema multiforme major favors the trunk.

 Herpes simplex is the most common cause of erythema multiforme minor.

 Drugs are the most common cause of erythema multiforme major in adults.

 General Considerations

Erythema multiforme is an acute inflammatory skin disease that is divided clinically into minor and major types based on the clinical findings. Approximately 90% of cases of erythema multiforme minor follow outbreaks of herpes simplex, and so is now preferably termed “herpes-associated erythema multiforme.” The term “erythema multiforme major” has been replaced by three terms: Stevens-Johnson syndrome (SJS), with < 10% BSA skin loss; toxic epidermal necrolysis (TEN) when there is > 30% BSA skin loss; and SJS/TEN overlap for cases with between 10% and 30% BSA denudation. The abbreviation SJS/TEN is often used to refer to these three variants of what is considered one syndrome. All these clinical scenarios are characterized by toxicity and involvement of two or more mucosal surfaces (often oral and conjunctival). They are most often caused by medications, especially sulfonamides, NSAIDs, allopurinol, and anticonvulsants. Mycoplasma pneumoniae may trigger a skin eruption closely resembling SJS and may be the cause of SJS in up to 50% of children in some series. Erythema multiforme may also present as chronic or recurring ulceration localized to the oral mucosa, with skin lesions present in only half of the cases. The exposure to drugs associated with SJS/TEN may be systemic or topical (eg, eyedrops).

 Clinical Findings

  1. Symptoms and Signs

A classic target lesion, found most commonly in herpes-associated erythema multiforme, consists of three concentric zones of color change, most often found acrally on the hands and feet. Not all lesions will have this appearance (Figure 6–27). Drug-associated bullous eruptions in the SJS/TEN spectrum present with raised purpuric target-like lesions, with only two zones of color change and a central blister, or nondescript reddish or purpuric macules. Pain on eating, swallowing, and urination can occur if the appropriate mucosae are involved.

 Figure 6–27. Erythema multiforme. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

  1. Laboratory Findings

Blood tests are not useful for diagnosis. Skin biopsy is diagnostic. Direct immunofluorescence studies are negative.

 Differential Diagnosis

Urticaria and drug eruptions are the chief entities that must be differentiated from erythema multiforme minor. Individual lesions of true urticaria should come and go within 24 hours and are usually responsive to antihistamines. In erythema multiforme major, the differential diagnosis includes autoimmune bullous diseases (including pemphigus and pemphigoid), acute generalized exanthematous pustulosis, and, rarely, pustular psoriasis. The presence of a blistering eruption requires biopsy and consultation for appropriate diagnosis and treatment.


The tracheobronchial mucosa and conjunctiva may be involved in severe cases with resultant scarring. Ophthalmologic consultation is required if ocular involvement is present because vision loss is the major consequence of SJS/TEN.


  1. General Measures

TEN is best treated in a burn unit, or hospital setting with similar support. Otherwise, patients need not be admitted unless mucosal involvement interferes with hydration and nutrition. Patients who begin to blister should be seen daily. Open lesions should be managed like second-degree burns. Immediate discontinuation of the inciting medication (before blistering occurs) is a significant predictor of outcome. Delay in establishing the diagnosis and inadvertently continuing the offending medication results in higher morbidity and mortality.

  1. Specific Measures

The most important aspect of treatment is to stop the offending medication and to move patients with > 25–30% BSA involvement to an appropriate acute care environment. Nutritional and fluid support and high vigilance for infection are the most important aspects of care. Recent reviews of systemic treatments for SJS and TEN have been conflicting, but the largest series have failed to show statistically significant benefit with treatment. Some data support the use of high-dose corticosteroids. If corticosteroids are to be tried in more severe cases, they should be used early, before blistering occurs, and in moderate to high doses (prednisone, 100–250 mg) and stopped within days if there is no dramatic response. IVIG (1 g/kg/d for 4 days) has become standard of care at some centers for TEN cases. It has not been proven to reduce mortality. Oral and topical corticosteroids are useful in the oral variant of erythema multiforme. Oral acyclovir prophylaxis of herpes simplex infections may be effective in preventing recurrent herpes-associated erythema multiforme minor.

  1. Local Measures

Topical therapy is not very effective in this disease. For oral lesions, 1% diphenhydramine elixir mixed with Kaopectate or with 1% dyclonine may be used as a mouth rinse several times daily.


Erythema multiforme minor usually lasts 2–6 weeks and may recur. SJS/TEN may be serious with a mortality of about 30% in cases with > 30% BSA involvement.

Huang YC et al. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. Br J Dermatol. 2012 Aug;167(2):424–32. [PMID: 22458671]

Sokumbi O et al. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Int J Dermatol. 2012 Aug;51(8):889–902. [PMID: 22788803]

Vern-Gross TZ et al. Erythema multiforme, Stevens Johnson syndrome, and toxic epidermal necrolysis syndrome in patients undergoing radiation therapy: a literature review. Am J Clin Oncol. 2012 Aug13. [Epub ahead of print] [PMID: 22892429]

Zhu QY et al. Toxic epidermal necrolysis: performance of SCORTEN and the score-based comparison of the efficacy of corticosteroid therapy and intravenous immunoglobulin combined therapy in China. J Burn Care Res. 2012 Nov;33 (6):e295–308. [PMID: 22955159]

Ziemer M et al. Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with lupus erythematosus: a descriptive study of 17 cases from a national registry and review of the literature. Br J Dermatol. 2012 Mar;166(3):575–600. [PMID: 22014091]

  1. Erythema Migrans (See also Chapter 34)

Erythema migrans is a unique cutaneous eruption that characterizes the localized or generalized early stage of Lyme disease (borreliosis) (Figure 6–28).

 Figure 6–28. Erythema migrans due to Borrelia burgdorferi (Lyme disease). (Courtesy of James Gathany, Public Health Image Library, CDC.)


  1. Erysipelas


 Edematous, spreading, circumscribed, hot, erythematous area, with or without vesicles or bullae.

 Central face frequently involved.

 Pain, chills, fever, and systemic toxicity may be striking.

 General Considerations

Erysipelas is a superficial form of cellulitis that occurs classically on the cheek, caused by beta-hemolytic streptococci.

 Clinical Findings

  1. Symptoms and Signs

The symptoms are pain, malaise, chills, and moderate fever. A bright red spot appears first, very often near a fissure at the angle of the nose. This spreads to form a tense, sharply demarcated, glistening, smooth, hot plaque. The margin characteristically makes noticeable advances in days or even hours. The lesion is somewhat edematous and may pit slightly with the finger. Vesicles or bullae occasionally develop on the surface. The lesion does not usually become pustular or gangrenous and heals without scar formation. The disease may complicate any break in the skin that provides a portal of entry for the organism.

  1. Laboratory Findings

Leukocytosis is almost invariably present; blood cultures may be positive.

 Differential Diagnosis

Erysipeloid is a benign bacillary infection producing cellulitis of the skin of the fingers or the backs of the hands in fishermen and meat handlers.


Unless erysipelas is promptly treated, death may result from extension of the process and systemic toxicity, particularly in the elderly.


Place the patient at bed rest with the head of the bed elevated. Intravenous antibiotics effective against group A beta-hemolytic streptococci and staphylococci should be considered, but outpatient treatment with oral antibiotics have demonstrated equal efficacy. A 7-day course with penicillin VK, 250 mg, dicloxacillin, 250 mg, or a first-generation cephalosporin, 250 mg, orally four times a day. Alternatives in penicillin-allergic patients are clindamycin (250 mg twice daily orally for 7–14 days) or erythromycin (250 mg four times daily orally for 7–14 days), the latter only if the infection is known to be due to streptococci.


With appropriate treatment, rapid improvement is expected. Recurrence is uncommon.

Mortazavi M et al. Incidence of deep vein thrombosis in erysipelas or cellulitis of the lower extremities. Int J Dermatol. 2013 Mar;52(3):279–85. [PMID: 22913433]

Perelló-Alzamora MR et al. Clinical and epidemiological characteristics of adult patients hospitalized for erysipelas and cellulitis. Eur J Clin Microbiol Infect Dis. 2012 Sep;31(9):2147–52. [PMID: 22298240]

Picard D et al. Risk factors for abscess formation in patients with superficial cellulitis (erysipelas) of the leg. Br J Dermatol. 2013 Apr;168(4):859–63. [PMID: 23210619]

  1. Cellulitis


 Edematous, expanding, erythematous, warm plaque with or without vesicles or bullae.

 Lower leg is frequently involved.

 Pain, chills, and fever are commonly present.

 Septicemia may develop.

 General Considerations

Cellulitis, a diffuse spreading infection of the dermis and subcutaneous tissue, is usually on the lower leg (Figure 6–29) and most commonly due to gram-positive cocci, especially group A beta-hemolytic streptococci and S aureus. Rarely, gram-negative rods or even fungi can produce a similar picture. In otherwise healthy persons, the most common portal of entry for lower leg cellulitis is toe web intertrigo with fissuring, usually a complication of interdigital tinea pedis. Venous insufficiency can also predispose to lower leg cellulitis. Injection drug use and open ulcerations may also be complicated by cellulitis. Cellulitis in the diabetic foot may be a major problem and is often associated with neuropathy and hyperkeratotic nodules from ill-fitting shoes and abnormal weight bearing.

 Figure 6–29. Cellulitis. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

 Clinical Findings

  1. Symptoms and Signs

Cellulitis begins as a small patch, which from its onset is tender. Swelling, erythema, and pain are often present. The lesion expands over hours, so that from onset to presentation is usually 6 to 36 hours. As the lesion grows, the patient becomes more ill with progressive chills, fever, and malaise. If septicemia develops, hypotension may develop, followed by shock.

  1. Laboratory Findings

Leukocytosis or at least a neutrophilia (left shift) is present from early in the course. Blood cultures may be positive. If a central ulceration, pustule, or abscess is present, culture may be of value. Aspiration of the advancing edge has a low yield (20%) and is usually not performed. Instead, if an unusual organism is suspected and there is no loculated site to culture, a full thickness skin biopsy taken before antibiotics are given can be useful. Part is cultured and part processed for histologic evaluation with Gram stain. This technique is particularly useful in the immunocompromised patient. If a primary source for the infection is identified (wound, leg ulcer, toe web intertrigo), cultures from these sites isolate the causative pathogen in half of cases and can be used to guide antibiotic therapy.

 Differential Diagnosis

Two potentially life-threatening entities that can mimic cellulitis (ie, present with a painful, red, swollen lower extremity) include deep venous thrombosis and necrotizing fasciitis. The diagnosis of necrotizing fasciitis should be suspected in a patient who has a very toxic appearance, bullae, crepitus or anesthesia of the involved skin, overlying skin necrosis, and laboratory evidence of rhabdomyolysis (elevated creatine kinase [CK]) or disseminated intravascular coagulation. While these findings may be present with severe cellulitis and bacteremia, it is essential to rule out necrotizing fasciitis because rapid surgical debridement is essential. Other skin lesions that may resemble cellulitis include sclerosing panniculitis, an acute, exquisitely tender red plaque on the medial lower legs above the malleolus in patients with venous stasis or varicosities, and acute severe contact dermatitis on a limb, which produces erythema, vesiculation, and edema as seen in cellulitis, but with itching instead of pain. Bilateral lower leg cellulitis is rare and other diagnoses, especially severe stasis dermatitis, should be considered in this setting. Severe lower extremity stasis dermatitis usually develops over days to weeks rather than the hours of cellulitis. It is also not as tender to palpation as cellulitis.


Intravenous or parenteral antibiotics may be required for the first 2–5 days, with adequate coverage for Streptococcus and Staphylococcus. Hospitalization is required in cases with severe local symptoms and signs, hypotension, elevated serum creatinine, low serum bicarbonate, elevated creatine kinase, elevated white blood cell count with marked left shift, or elevated C-reactive protein. If CA-MRSA is suspected, therapy is vancomycin, clindamycin, or TMP-SMZ plus a beta-lactam. In mild cases or following the initial parenteral therapy, dicloxacillin or cephalexin, 250–500 mg four times daily for 5–10 days, is usually adequate. If MRSA is suspected, use of TMP-SMZ, clindamycin, or the combination of doxycycline plus rifampin should be considered. In patients in whom intravenous treatment is not instituted, the first dose of oral antibiotic can be doubled to achieve rapid high blood levels. In patients with recurrent lower leg cellulitis, oral penicillin 250 mg twice daily can delay the appearance of the next episode.

Hirschmann JV et al. Lower limb cellulitis and its mimics: part I. Lower limb cellulitis. J Am Acad Dermatol. 2012 Aug;67(2):163.e1–12. [PMID: 22794815]

Hirschmann JV et al. Lower limb cellulitis and its mimics: part II. Conditions that simulate lower limb cellulitis. J Am Acad Dermatol. 2012 Aug;67(2):177.e1–9. [PMID: 227948156]

Lazzarini L et al. Erysipelas-cellulitis of the leg: impact of the application of a guideline in an infectious diseases unit. J Chemother. 2011 Dec;23(6): 378. [PMID: 22233827]

Picard D et al. Risk factors for abscess formation in patients with superficial cellulitis (erysipelas) of the leg. Br J Dermatol. 2013 Apr;168(4):859–63. [PMID: 23210619]




 Relapsing crops of bullae.

 Often preceded by mucous membrane bullae, erosions, and ulcerations.

 Superficial detachment of the skin after pressure or trauma variably present (Nikolsky sign).

 Acantholysis on biopsy.

 Immunofluorescence studies and serum ELISA for pathogenic antibodies are confirmatory.

 General Considerations

Pemphigus is an uncommon intraepidermal blistering disease occurring on skin and mucous membranes. It is caused by autoantibodies to adhesion molecules expressed in the skin and mucous membranes. The cause is unknown, and in the preantibiotic, presteroid era, the condition was usually fatal within 5 years. The bullae appear spontaneously and are tender and painful when they rupture. Drug-induced pemphigus from penicillamine, captopril, and others has been reported. There are several forms of pemphigus: pemphigus vulgaris and its variant, pemphigus vegetans; and the more superficially blistering pemphigus foliaceus and its variant, pemphigus erythematosus. All forms may occur at any age but most commonly in middle age. The vulgaris form begins in the mouth in over 50% of cases. The foliaceus form is especially apt to be associated with other autoimmune diseases, or it may be drug-induced. Paraneoplastic pemphigus, a unique form of the disorder, is associated with numerous types of benign and malignant neoplasms but most frequently non-Hodgkin lymphoma.

 Clinical Findings

  1. Symptoms and Signs

Pemphigus is characterized by an insidious onset of flaccid bullae, crusts, and erosions in crops or waves (Figure 6–30). In pemphigus vulgaris, lesions often appear first on the oral mucous membranes. These rapidly become erosive. The scalp is another site of early involvement. Rubbing a cotton swab or finger laterally on the surface of uninvolved skin may cause easy separation of the epidermis (Nikolsky sign).

 Figure 6–30. Pemphigus. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

  1. Laboratory Findings

The diagnosis is made by light microscopy and by direct and indirect immunofluorescence (IIF) microscopy. Auto-antibodies to intercellular adhesion molecules can be detected with ELISA assays and have replaced the use of IIF in some centers.

 Differential Diagnosis

Blistering diseases include erythema multiforme, drug eruptions, bullous impetigo, contact dermatitis, dermatitis herpetiformis, and bullous pemphigoid, but flaccid blisters are not typical of these diseases, and acantholysis is not seen on biopsy. All of these diseases have clinical characteristics and different immunofluorescence test results that distinguish them from pemphigus.

Paraneoplastic pemphigus is clinically, histologically, and immunologically distinct from other forms of the disease. Oral erosions and erythematous plaques resembling erythema multiforme are seen. Survival rates are low because of the underlying malignancy.


Secondary infection commonly occurs; this is a major cause of morbidity and mortality. Disturbances of fluid, electrolyte, and nutritional intake can occur as a result of painful oral ulcers.


  1. General Measures

When the disease is severe, hospitalize the patient at bed rest and provide antibiotics and intravenous feedings as indicated. Anesthetic troches used before eating ease painful oral lesions.

  1. Systemic Measures

Pemphigus requires systemic therapy as early in its course as possible. However, the main morbidity in this disease is due to the side effects of such therapy. Initial therapy is with systemic corticosteroids: prednisone, 60–80 mg daily. In all but the most mild cases, a steroid-sparing agent is added from the beginning, since the course of the disease is long and the steroid-sparing agents take several weeks to exert their activity. Azathioprine (100–200 mg daily) or mycophenolate mofetil (1–1.5 g twice daily) are used most frequently. Rituximab treatment, especially early in the course, appears to be associated with therapeutic induction of a complete remission. Monthly IVIG at 2 g/kg intravenously over 3–4 days frequently is beneficial. In refractory cases, cyclophosphamide, pulse intravenous corticosteroids, and plasmapheresis can be used. Increased risk of thromboembolism is associated with IVIG therapy in these doses.

  1. Local Measures

In patients with limited disease, skin and mucous membrane lesions should be treated with topical corticosteroids. Complicating infection requires appropriate systemic and local antibiotic therapy.


The course tends to be chronic in most patients, though about one-third appear to experience remission. Infection is the most frequent cause of death, usually from S aureus septicemia.

Cianchini G et al. Therapy with rituximab for autoimmune pemphigus: results from a single-center observational study on 42 cases with long-term follow-up. J Am Acad Dermatol. 2012 Oct;67(4):617–22. [PMID: 22243765]

Leshem YA et al. Successful treatment of pemphigus with biweekly 1-g infusions of rituximab: A retrospective study of 47 patients. J Am Acad Dermatol. 2013 Mar;68(3);404–11. [PMID: 23044076]

Martin LK et al. A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus. J Am Acad Dermatol. 2011 May;64(5):903–8. [PMID: 21353333]

Tsuruta D et al. Diagnosis and treatment of pemphigus. Immunotherapy. 2012 Jul;4(7):735–45. [PMID: 22853759]

Venugopal SS et al. Diagnosis and clinical features of pemphigus vulgaris. Immunol Allergy Clin North Am. 2012 May;32(2):233–43. [PMID: 22560136]


Many other autoimmune skin disorders are characterized by formation of bullae, or blisters. These include bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, and pemphigoid gestationis.

Bullous pemphigoid is a relatively benign pruritic disease characterized by tense blisters in flexural areas, usually remitting in 5 or 6 years, with a course characterized by exacerbations and remissions. Most affected persons are over the age of 60 (often in their 70s or 80s), and men are affected twice as frequently as women. The appearance of blisters may be preceded by urticarial or edematous lesions for months. Oral lesions are present in about one-third of affected persons. The disease may occur in various forms, including localized, vesicular, vegetating, erythematous, erythrodermic, and nodular.

The diagnosis is made by biopsy and direct immunofluorescence examination. Light microscopy shows a subepidermal blister. With direct immunofluorescence, IgG and C3 are found at the dermal-epidermal junction. If the patient has mild disease, ultrapotent corticosteroids may be adequate. Prednisone at a dosage of 0.75 mg/kg daily is often used to achieve rapid control of more widespread disease. Although slower in onset of action, tetracycline or erythromycin, 500 mg three times daily, alone or combined with nicotinamide—not nicotinic acid or niacin—(up to 1.5 g/d), if tolerated, may control the disease in patients who cannot use corticosteroids or may allow decreasing or eliminating corticosteroids after control is achieved. Dapsone is particularly effective in mucous membrane pemphigoid. If these drugs are not effective, methotrexate, 5–25 mg weekly, or azathioprine, 50 mg one to three times daily, or mycophenolate mofetil (1 g twice daily) may be used as steroid-sparing agents.

Gaitanis G et al. High-dose intravenous immunoglobulin in the treatment of adult patients with bullous pemphigoid. Eur J Dermatol. 2012 May–Jun;22(3):363–9. [PMID: 22548754]

Schmidt E et al. Pemphigoid diseases. Lancet. 2013 Jan26;381(9863):320–32. [PMID: 23237497]

Tampoia M et al. Diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti-skin autoantibodies in autoimmune blistering skin diseases: A systematic review and meta-analysis. Autoimmun Rev. 2012 Dec;12(2):121–6. [PMID: 22781589]




 Verrucous papules anywhere on the skin or mucous membranes, usually no larger than 1 cm in diameter.

 Prolonged incubation period (average 2–18 months).

 Spontaneous “cures” are frequent in common warts (50% at 2 years).

 “Recurrences” (new lesions) are frequent.

 General Considerations

Warts (common, plantar, and genital) are caused by human papillomaviruses (HPVs). Typing of HPV lesions is NOT a part of standard medical evaluation except in the case of genital dysplasia.

 Clinical Findings

There are usually no symptoms. Tenderness on pressure occurs with plantar warts; itching occurs with anogenital warts (Figure 6–31). Flat warts are most evident under oblique illumination. Periungual warts may be dry, fissured, and hyperkeratotic and may resemble hangnails or other nonspecific changes. Plantar warts resemble plantar corns or calluses.

 Figure 6–31. Condylomata acuminata, or genital warts, of the anal region due to human papillomavirus. (Public Health Image Library, CDC.)

 Differential Diagnosis

Some warty-looking lesions are actually hypertrophic actinic keratoses or squamous cell carcinomas. Some genital warty lesions may be due to secondary syphilis (condylomata lata). The lesions of molluscum contagiosum are pearly with a central dell. In AIDS, wart-like lesions may be caused by varicella zoster virus.


Administration of a vaccine against certain genital HPV types can prevent infection with these wart types and reduce cervical dysplasia. It is recommended for teenagers and young adults (see Chapters 1and 18).


Treatment is aimed at inducing “wart-free” intervals for as long as possible without scarring, since no treatment can guarantee a remission or prevent recurrences. In immunocompromised patients, the goal is even more modest, ie, to control the size and number of lesions present.

  1. Removal

For common warts of the hands, patients are usually offered liquid nitrogen or keratolytic agents. The former may work in fewer treatments but requires office visits and is painful.

  1. Liquid nitrogen—Liquid nitrogen is applied to achieve a thaw time of 30–45 seconds. Two freeze-thaw cycles are given every 2–4 weeks for several visits. Scarring will occur if it is used incorrectly. Liquid nitrogen may cause permanent depigmentation in pigmented individuals. Cryotherapy is first-line physician applied surgical treatment for genital warts (condyloma acuminata).
  2. Keratolytic agents and occlusion—Salicylic acid products may be used against common warts or plantar warts. They are applied then occluded. Plantar warts may be treated by applying a 40% salicylic acid plaster after paring. The plaster may be left on for 5–6 days, then removed, the lesion pared down, and another plaster applied. Although it may take weeks or months to eradicate the wart, the method is safe and effective with almost no side effects. Chronic occlusion alone with water-impermeable tape (duct tape, adhesive tape) is less effective than cryotherapy.
  3. Podophyllum resin—For genital warts, the purified active component of the podophyllum resin, podofilox, is applied by the patient twice daily 3 consecutive days a week for cycles of 4–6 weeks. It is less irritating and more effective than “physician-applied” podophyllum resin. After a single 4-week cycle, 45% of patients were wart-free; but of these, 60% relapsed at 6 weeks. Thus, multiple cycles of treatment are often necessary. Patients unable to obtain the take home podofilox may be treated in the clinician’s office by painting each wart carefully (protecting normal skin) every 2–3 weeks with 25% podophyllum resin (podophyllin) in compound tincture of benzoin. Pregnant patientsshould not be so treated. Podophyllin is ineffective for common warts and plantar warts.
  4. Imiquimod—A 5% cream of this local interferon inducer has moderate activity in clearing external genital warts (EGWs). Treatment is once daily on 3 alternate days per week. Response may be slow, with patients who eventually cleared having responses at 8 weeks (44%) or 12 weeks (69%). There is a marked gender difference with respect to response, with 77% of women and 40% of men having complete clearing of their lesions. Once cleared, about 13% have recurrences in the short term.

In accidental exposure during pregnancy, there is less risk with imiquimod than with podophyllum resin (category B versus category X). Imiquimod is considerably more expensive than podophyllotoxin, but given the high rate of response in women and its safety, it appears to be the “patient-administered” treatment of choice for EGWs in women. In men, the more rapid response, lower cost, and similar efficacy make podophyllotoxin the initial treatment of choice, with imiquimod used for recurrences or refractory cases. Imiquimod has no demonstrated efficacy for—and should not be used to treat—plantar or common warts.

  1. Operative removal—Plantar warts may be removed by blunt dissection. For genital warts, snip biopsy (scissors) removal followed by light electrocautery is more effective than cryotherapy, especially for patients with pedunculated or large lesions.
  2. Laser therapy—The CO2laser can be effective for treating recurrent warts, periungual warts, plantar warts, and condylomata acuminata. It leaves open wounds that must fill in with granulation tissue over 4–6 weeks and is best reserved for warts resistant to all other modalities. Lasers with emissions of 585, 595, or 532 nm may also be used every 3–4 weeks to gradually ablate common or plantar warts. This is no more effective than cryotherapy in controlled trials. For genital warts, it has not been shown that laser therapy is more effective than electrosurgical removal. Photodynamic therapy can be considered in refractory widespread flat and genital warts.
  3. Other agents—Bleomycin diluted to 1 unit/mL may be injected into common and plantar warts. It has been shown to have a high cure rate. It should be used with caution on digital warts because of the potential complications of Raynaud phenomenon, nail loss, and terminal digital necrosis.
  4. Immunotherapy

Squaric acid dibutylester may be effective. It is applied in a concentration of 0.2–2% directly to the warts from once weekly to five times weekly to induce a mild contact dermatitis. Between 60% and 80% of warts clear over 10–20 weeks. Injection of Candida antigen starting at 1:50 dilution and repeated every 3–4 weeks may be similarly effective in stimulating immunologic regression of common and plantar warts.

  1. Physical Modalities

Soaking warts in hot (42.2°C) water for 10–30 minutes daily for 6 weeks has resulted in involution in some cases.


There is a striking tendency to the development of new lesions. Warts may disappear spontaneously or may be unresponsive to treatment.

Chelimo C et al. Risk factors for and prevention of human papillomaviruses (HPV), genital warts and cervical cancer. J Infect. 2013 Mar;66(3):207–17. [PMID: 23103285]

Chesson HW et al. Estimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus in the United States. Vaccine. 2012 Sep14;30(42):6016–9. [PMID: 22867718]

Giuliano AR et al. Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males. N Engl J Med. 2011 Feb3;364(5):401–11. [PMID: 21288094]

Hathaway JK. HPV: diagnosis, prevention, and treatment. Clin Obstet Gynecol. 2012 Sep;55(3):671–80. [PMID: 22828099]

Jemal A et al. Annual Report to the Nation on the Status of Cancer, 1975–2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst. 2013 Feb6;105(3):175–201. [PMID: 23297039]

Komericki P et al. Efficacy and safety of imiquimod versus podophyllotoxin in the treatment of anogenital warts. Sex Transm Dis. 2011 Mar;38(3):216–8. [PMID: 20938374]

Kwok CS et al. Topical treatments for cutaneous warts. Cochrane Database Syst Rev. 2012 Sep12;9: CD001781. [PMID: 22972052]

Patel H et al. Systematic review of the incidence and prevalence of genital warts. BMC Infect Dis. 2013 Jan25;13:39. [PMID: 23347441]


Molluscum contagiosum, caused by a poxvirus, presents as single or multiple dome-shaped, waxy papules 2–5 mm in diameter that are umbilicated (Figure 6–32). Lesions at first are firm, solid, and flesh-colored but upon reaching maturity become soft, whitish, or pearly gray and may suppurate. The principal sites of involvement are the face, lower abdomen, and genitals.

 Figure 6–32. Molluscum contagiosum lesion on the back. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

The lesions are autoinoculable and spread by wet skin-to-skin contact. In sexually active individuals, they may be confined to the penis, pubis, and inner thighs and are considered a sexually transmitted infection.

Molluscum contagiosum is common in patients with AIDS, usually with a helper T-cell count < 100/mcL. Extensive lesions tend to develop over the face and neck as well as in the genital area.

The diagnosis is easily established in most instances because of the distinctive central umbilication of the dome-shaped lesion. The best treatment is by curettage or applications of liquid nitrogen as for warts—but more briefly. When lesions are frozen, the central umbilication often becomes more apparent. Light electrosurgery with a fine needle is also effective. It has been estimated that individual lesions persist for about 2 months. They are difficult to eradicate in patients with AIDS unless immunity improves. However, in AIDS, with highly effective anti-retroviral treatment, molluscum do not need to be treated because they usually spontaneously clear.

Chen X et al. Molluscum contagiosum virus infection. Lancet Infect Dis. 2013 Oct;13(10):877–88. [PMID: 23972567]



 Pearly papule, erythematous patch > 6 mm, or nonhealing ulcer, in sun exposed areas (face, trunk, lower legs).

 History of bleeding.

 Fair-skinned person with a history of sun exposure (often intense, intermittent).

 General Considerations

Basal cell carcinomas are the most common form of cancer. They occur on sun-exposed skin in otherwise normal, fair-skinned individuals; ultraviolet light is the cause. The most common presentation is a papule or nodule that may have a central scab or erosion (Figure 6–33). Occasionally the nodules have stippled pigment (pigmented basal cell carcinoma). Intradermal nevi without pigment on the face of older white individuals may resemble basal cell carcinomas. Basal cell carcinomas grow slowly, attaining a size of 1–2 cm or more in diameter, usually only after years of growth. There is a waxy, “pearly” appearance, with telangiectatic vessels easily visible. It is the pearly or translucent quality of these lesions that is most diagnostic, a feature best appreciated if the skin is stretched. On the back and chest, basal cell carcinomas appear as reddish, somewhat shiny, scaly patches.

 Figure 6–33. Nodular basal cell carcinoma of the nose. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

Clinicians should examine the whole skin routinely, looking for bumps, patches, and scabbed lesions. When examining the face, look at the eyelid margins and medial canthi, the nose and alar folds, the lips, and then around and behind the ears.


Lesions suspected to be basal cell carcinomas should be biopsied, by shave or punch biopsy. Therapy is then aimed at eradication with minimal cosmetic deformity, often by excision and suturing with recurrence rates of 5% or less. The technique of three cycles of curettage and electrodesiccation depends on the skill of the operator and is not recommended for head and neck lesions. After 4–6 weeks of healing, it leaves a broad, hypopigmented, at times hypertrophic scar. Radiotherapy is effective and sometimes appropriate for older individuals (over age 65), but recurrent tumors after radiation therapy are more difficult to treat and may be more aggressive. Radiation therapy is the most expensive method to treat basal cell carcinoma and should only be used if other treatment options are not appropriate. Mohs surgery—removal of the tumor followed by immediate frozen section histopathologic examination of margins with subsequent reexcision of tumor-positive areas and final closure of the defect—gives the highest cure rates (98%) and results in least tissue loss. It is appropriate therapy for tumors of the eyelids, nasolabial folds, canthi, external ear, and temple; for recurrent lesions; or where tissue sparing is needed for cosmesis. Since up to half of patients with a basal cell carcinoma will develop a second lesion, patients with basal cell carcinomas must be monitored at least yearly to detect new or recurrent lesions.

Ad Hoc Task Force; Connolly SM et al. AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol. 2012 Oct;67(4):531–50. [PMID: 22959232]

Flohil SC et al. Trends in basal cell carcinoma incidence rates: a 37-Year Dutch observational study. J Invest Dermatol. 2013 Apr;133(4):913–8. [PMID: 23190883]



 Nonhealing ulcer or warty nodule.

 Skin damage due to long-term sun exposure.

 Common in fair-skinned organ transplant recipients.

Squamous cell carcinoma usually occurs subsequent to prolonged sun exposure on exposed parts in fair-skinned individuals who sunburn easily and tan poorly. It may arise from an actinic keratosis. The lesions appear as small red, conical, hard nodules that occasionally ulcerate (Figure 6–34). In actinically induced squamous cell cancers, rates of metastasis are estimated from retrospective studies to be 3–7%. Squamous cell carcinomas of the ear, temple, lip, oral cavity, tongue, and genitalia have much higher rates of recurrence or metastasis and require special management.

 Figure 6–34. Squamous cell carcinoma. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

Examination of the skin and therapy are essentially the same as for basal cell carcinoma. The preferred treatment of squamous cell carcinoma is excision. Electrodesiccation and curettage and x-ray radiation may be used for some lesions, and fresh tissue microscopically controlled excision (Mohs) is recommended for high-risk lesions (lips, temples, ears, nose) and for recurrent tumors. Follow-up for squamous cell carcinoma must be more frequent and thorough than for basal cell carcinoma, starting at every 3 months, with careful examination of lymph nodes for 1 year, then twice yearly thereafter. In addition, palpation of the lips is essential to detect hard or indurated areas that represent early squamous cell carcinoma. All such cases must be biopsied. Multiple squamous cell carcinomas are very common on the sun-exposed skin of organ transplant patients. The intensity of immunosuppression, not the use of any particular immunosuppressive agent, is the primary risk factor in determining the development of skin cancer after transplant. The tumors begin to appear after 5 years of immunosuppression. Voriconazole treatment appears to increase the risk of development of squamous cell carcinoma, especially in lung transplant patients. Regular dermatologic evaluation in at-risk organ transplant recipients is recommended. Biologic behavior of skin cancer in organ transplant recipients may be aggressive, and careful management is required. Other forms of immunosuppression such as chronic lymphocytic leukemia, HIV/AIDS, and chronic iatrogenic immunosuppression may also increase skin cancer risk and be associated with more aggressive skin cancer behavior.

Behshad R et al. Systemic treatment of locally advanced nonmetastatic cutaneous squamous cell carcinoma: a review of the literature. Br J Dermatol. 2011 Dec;165(6):1169–77. [PMID: 21777215]

Carroll RP et al. Conversion to sirolimus in kidney transplant recipients with squamous cell cancer and changes in immune phenotype. Nephrol Dial Transplant. 2013 Feb; 28(2):462–5. [PMID: 23223314]

Roozeboom MH et al. Clinical and histological prognostic factors for local recurrence and metastasis of cutaneous squamous cell carcinoma: analysis of a defined population. Acta Derm Venereol. 2013 Jul6;93(4):417–21. [PMID: 23138613]

Schmults CD et al. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. JAMA Dermatol. 2013 May;149(5):541–7. [PMID: 23677079]

Zwald FO et al. Skin cancer in solid organ transplant recipients: advances in therapy and management: part I. Epidemiology of skin cancer in solid organ transplant recipients. J Am Acad Dermatol. 2011 Aug;65(2):253–61. [PMID: 21763561]




 Pruritic, violaceous, flat-topped papules with fine white streaks and symmetric distribution.

 Lacy or erosive lesions of the buccal and vaginal mucosa; nail dystrophy.

 Commonly seen along linear scratch marks (Koebner phenomenon) on anterior wrists, penis, legs.

 Histopathologic examination is diagnostic.

 General Considerations

Lichen planus is an inflammatory pruritic disease of the skin and mucous membranes characterized by distinctive papules with a predilection for the flexor surfaces and trunk. The three cardinal findings are typical skin lesions, mucosal lesions, and histopathologic features of band-like infiltration of lymphocytes in the upper dermis. The most common drugs causing lichen planus-like reactions include sulfonamides, tetracyclines, quinidine, NSAIDs, beta-blockers, and hydrochlorothiazide. Lichenoid drug eruptions can resemble lichen planus clinically and histologically. Hepatitis C infection is found with greater frequency in lichen planus patients than in controls. Allergy to mercury and other metal containing amalgams can trigger oral lesions identical to lichen planus. Lichenoid drug eruptions can resemble lichen planus clinically and histologically.

 Clinical Findings

Itching is mild to severe. The lesions are violaceous, flat-topped, angulated papules, up to 1 cm in diameter, discrete or in clusters, with very fine white streaks (Wickham striae) on the flexor surfaces of the wrists and on the penis, lips, tongue as well as buccal, vaginal, esophageal, and anorectal mucous membranes. The papules may become bullous or eroded. The disease may be generalized (Figure 6–35). Mucous membrane lesions have a lacy white network overlying them that may be confused with leukoplakia. The presence of oral and vaginal lichen planus in the same patient is common. Patients with both these mucous membranes involved are at much higher risk for esophageal lichen planus. The Koebner phenomenon (appearance of lesions in areas of trauma) may be seen.

 Figure 6–35. Lichen planus. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

A special form of lichen planus is the erosive or ulcerative variety, a major problem in the mouth or genitalia. Squamous cell carcinoma develops in 5% of patients with erosive oral or genital lichen planus and may occur in esophageal lichen planus.

 Differential Diagnosis

Lichen planus must be distinguished from similar lesions produced by medications (see above) and other papular lesions such as psoriasis, lichen simplex chronicus, graft-versus-host disease, and syphilis. Lichen planus on the mucous membranes must be differentiated from leukoplakia. Erosive oral lesions require biopsy and often direct immunofluorescence for diagnosis since lichen planus may simulate other erosive diseases.


  1. Topical Therapy

Superpotent topical corticosteroids applied twice daily are most helpful for localized disease in nonflexural areas. Alternatively, high-potency corticosteroid cream or ointment may be used nightly under thin pliable plastic film.

Topical tacrolimus appears effective in oral and vaginal erosive lichen planus, but long-term therapy is required to prevent relapse. If tacrolimus is used, lesions must be observed carefully for development of cancer. Since absorption can occur through mucous membranes, serum tacrolimus levels should be checked at least once if widespread mucosal application (> 5–10 cm2) is used. If the erosive oral lichen planus lesions are adjacent to a metal containing amalgam, removal of the amalgam may result in clearing of the erosions.

  1. Systemic Therapy

Corticosteroids (see Chapter 26) may be required in severe cases or in circumstances where the most rapid response to treatment is desired. Unfortunately, relapse almost always occurs as the corticosteroids are tapered, making systemic corticosteroid therapy an impractical option for the management of chronic lichen planus. NB-UVB, bath PUVA, oral PUVA, and the combination of an oral retinoid plus PUVA (re-PUVA) are all forms of phototherapy that can improve lichen planus. Hydroxychloroquine, 200 mg orally twice daily, can also be effective in mucosal and cutaneous lichen planus.


Lichen planus is a benign disease, but it may persist for months or years and may be recurrent. Hypertrophic lichen planus and oral lesions tend to be especially persistent, and neoplastic degeneration has been described in chronically eroded lesions.

Cheng S et al. Interventions for erosive lichen planus affecting mucosal sites. Cochrane Database Syst Rev. 2012 Feb15;2: CD008092. [PMID: 22336835]

García-García V et al. New perspectives on the dynamic behaviour of oral lichen planus. Eur J Dermatol. 2012 Mar–Apr;22(2):172–7. [PMID: 22381396]

Le Cleach L et al. Clinical practice. Lichen planus. N Engl J Med. 2012 Feb23;366(8):723–32. [PMID: 22356325]

Sharma A et al. Lichen planus: an update and review. Cutis. 2012 Jul;90(1):17–23. [PMID: 22908728]

Throngprasom K et al. Interventions for treating oral lichen planus. Cochrane Database Syst Rev. 2011 Jul6;(7): CD001168. [PMID: 21735381]


 General Considerations

Before 1980 in the United States, this rare malignant skin lesion was seen mostly in elderly men, had a chronic clinical course, and was rarely fatal. Kaposi sarcoma occurs endemically in an often aggressive form in young black men of equatorial Africa, but it is rare in American blacks. Kaposi sarcoma continues to occur largely in homosexual men with HIV infection as an AIDS-defining illness. Kaposi sarcoma may complicate immunosuppressive therapy, and stopping the immunosuppression may result in improvement. Human herpes virus 8 (HHV-8), or Kaposi sarcoma-associated herpes virus (KSHV), is universally present in all forms of Kaposi sarcoma.

Red or purple plaques or nodules on cutaneous or mucosal surfaces are characteristic. Marked edema may occur with few or no skin lesions. Kaposi sarcoma commonly involves the gastrointestinal tract and can be screened for by fecal occult blood testing. In asymptomatic patients, these lesions are not sought or treated. Pulmonary Kaposi sarcoma can present with shortness of breath, cough, hemoptysis, or chest pain; it may be asymptomatic, appearing only on chest radiograph. Bronchoscopy may be indicated. The incidence of AIDS-associated Kaposi sarcoma is diminishing; however, chronic Kaposi sarcoma can develop in patients with HIV infection, high CD4 counts, and low viral loads. In this setting, the Kaposi sarcoma usually resembles the endemic form, being indolent and localized. At times, however, it can be clinically aggressive.


For Kaposi sarcoma in the elderly, palliative local therapy with intralesional chemotherapy or radiation is usually all that is required. In the setting of iatrogenic immunosuppression, the treatment of Kaposi sarcoma is primarily reduction of doses of immunosuppressive medications. In AIDS-associated Kaposi sarcoma, the patient should first be given effective anti-HIV antiretrovirals because in most cases this treatment alone is associated with improvement. Other therapeutic options include cryotherapy or intralesional vinblastine (0.1–0.5 mg/mL) for cosmetically objectionable lesions; radiation therapy for accessible and space-occupying lesions; and laser surgery for certain intraoral and pharyngeal lesions. Systemic therapy is indicated in patients with rapidly progressive skin disease (more than ten new lesions per month), with edema or pain, and with symptomatic visceral disease or pulmonary disease. Liposomal doxorubicin is highly effective in controlling these cases and has considerably less toxicity—and greater efficacy—than anthracycline monotherapy or combination chemotherapeutic regimens. Alpha-interferon may also be used. Paclitaxel and other taxanes can be effective even in patients who do not respond to anthracycline treatment.

La Ferla L et al. Kaposi’s sarcoma in HIV-positive patients: the state of art in the HAART-era. Eur Rev Med Pharmacol Sci. 2013 Sep;17(17):2354–65. [PMID: 24065230]

Lu CL et al. Immune reconstitution inflammatory syndrome of Kaposi’s sarcoma in an HIV-infected patient. J Microbiol Immunol Infect. 2013 Aug;46(4):309–12. [PMID: 22503798]

Régnier-Rosencher E et al. Treatments for classic Kaposi sarcoma: a systematic review of the literature. J Am Acad Dermatol. 2013 Feb;68(2):313–31. [PMID: 22695100]


Pruritus is a disagreeable sensation that provokes a desire to scratch. It is modulated by multiple factors, including anxiety, depression, and amphetamine and cocaine use. Calcium channel blockers can cause pruritus with or without eczema, even years after they have been started, and it may take up to 1 year for the pruritus to resolve after the calcium channel blocker has been stopped. Pruritus as a medical complaint is 40% as common as low back pain. Elderly Asian men are most significantly affected with 20% of all healthcare visits in Asian men over the age of 65 involving the complaint of itch. The quality of life of a patient with chronic pruritus is the same as a patient on hemodialysis. Most cases of pruritus are not mediated by histamine, hence the poor response of many pruritic patients to antihistamines. Neuropathic disease, especially in diabetics, is associated with pruritus, making neurally acting agents attractive new approaches to the management of pruritus.

Dry skin is the first cause of itch that should be sought, since it is common and easily treated. Other causes include scabies, atopic dermatitis, insect bites, pediculosis, contact dermatitis, drug reactions, urticaria, psoriasis, lichen planus, lichen simplex chronicus, and fiberglass dermatitis.

Persistent pruritus not explained by cutaneous disease or association with a primary skin eruption should prompt a staged workup for systemic causes. Perhaps the most common cause of pruritus associated with systemic disease is uremia in conjunction with hemodialysis. This condition and to a lesser degree the pruritus of liver disease may be helped by phototherapy with ultraviolet B or PUVA. Naltrexone and nalmefene have been shown to relieve the pruritus of liver disease. Naltrexone is not effective in pruritus associated with advanced chronic kidney disease, but gabapentin may be effective. Endocrine disorders such as hypothyroidism, hyperthyroidism, or hyperparathyroidism, psychiatric disturbances, lymphoma, leukemia, and other internal malignant disorders, iron deficiency anemia, and certain neurologic disorders may also cause pruritus. The treatment of chronic pruritus can be frustrating. Combinations of antihistamines, sinequan, gabapentin, mirtazapine, and opioid antagonists can be attempted in refractory cases. In cancer-associated and other forms of pruritus, aprepitant (Emend) 80 mg daily for several days can be dramatically effective.


Elimination of external factors and irritating agents may give complete relief. Pruritus accompanying a specific skin disease will subside when the skin disease is controlled. Pruritus accompanying serious internal disease may not respond to any type of therapy.

Bergasa NV. The itch of liver disease. Semin Cutan Med Surg. 2011 Jun;30(2):93–8. [PMID: 21767769]

Berger TG et al. Pruritus and renal failure. Semin Cutan Med Surg. 2011 Jun;30(2):99–100. [PMID: 21767770]

Berger TG et al. Pruritus in the older patient: a clinical review. JAMA. 2013 Dec11;310(22):2443–50. [PMID: 24327039]

Chiang HC et al. Cancer and itch. Semin Cutan Med Surg. 2011 Jun;30(2):107–12. [PMID: 21767772]

Serling SL et al. Approach to pruritus in the adult HIV-positive patient. Semin Cutan Med Surg. 2011 Jun;30(2):101–6. [PMID: 21767771]

Shive M et al. Itch as a patient-reported symptom in ambulatory care visits in the United States. J Am Acad Dermatol. 2013 Oct;69(4):550–6. [PMID: 23870201]

Summers EM et al. Chronic eczematous eruptions in the aging: further support for an association with exposure to calcium channel blockers. JAMA Dermatol. 2013 Jul;149(7):814–8. [PMID: 23636109]



 Itching, chiefly nocturnal, of the anogenital area.

 Examination is highly variable, ranging from no skin findings to excoriations and inflammation of any degree, including lichenification.

 General Considerations

Anogenital pruritus may be due to intertrigo, psoriasis, lichen simplex chronicus, or seborrheic or contact dermatitis (from soaps, colognes, douches, and various topical treatments) or it may be due to irritating secretions, as in diarrhea, leukorrhea, or trichomoniasis, or to local disease (candidiasis, dermatophytosis, erythrasma), and at times oxyuriasis (pinworms). Lichen sclerosus may at times be the cause. Erythrasma at any anatomic location (Figure 6–36) is easily diagnosed by demonstration of coral-red fluorescence with Wood light; it is easily cured with erythromycin orally or topically.

 Figure 6–36. Erythrasma of the axilla. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

In pruritus ani, hemorrhoids are often found, and leakage of mucus and bacteria from the distal rectum onto the perianal skin may be important in cases in which no other skin abnormality is found.

Many women experience pruritus vulvae. Pruritus vulvae does not usually involve the anal area, though anal itching may spread to the vulva. In men, pruritus of the scrotum is most commonly seen in the absence of pruritus ani. Up to one-third of causes of anogenital pruritus may be due to nerve impingements of the lumbosacral spine, so referral for evaluation of lumbosacral spine disease is appropriate if no skin disorder is identified, and topical therapy is ineffective.

Squamous cell carcinoma of the anus and extramammary Paget disease are rare causes of genital pruritus.

 Clinical Findings

  1. Symptoms and Signs

The only symptom is itching. Physical findings are usually not present, but there may be erythema, fissuring, maceration, lichenification, excoriations, or changes suggestive of candidiasis or tinea.

  1. Laboratory Findings

Urinalysis and blood glucose testing may lead to a diagnosis of diabetes mellitus. Microscopic examination or culture of tissue scrapings may reveal yeasts or fungi. Stool examination may show pinworms. Radiologic studies may demonstrate spinal disease.

 Differential Diagnosis

The etiologic differential diagnosis consists of Candida infection, parasitosis, local irritation from contactants or irritants, nerve impingement and other primary skin disorders of the genital area such as psoriasis, seborrhea, intertrigo, or lichen sclerosus.


Instruct the patient in proper anogenital hygiene after treating systemic or local conditions. If appropriate, physical therapy and exercises to support the lower spine are recommended.


  1. General Measures

Treating constipation, preferably with high-fiber management (psyllium), may help. Instruct the patient to use very soft or moistened tissue or cotton after bowel movements and to clean the perianal area thoroughly with cool water if possible. Women should use similar precautions after urinating. Avoid “baby wipes” as they frequently contain preservatives that cause allergic contact dermatitis.

  1. Local Measures

Pramoxine cream or lotion or hydrocortisone-pramoxine (Pramosone), 1% or 2.5% cream, lotion, or ointment, is helpful in managing pruritus in the anogenital area. The ointment or cream should be applied after a bowel movement. Topical doxepin cream 5% is similarly effective, but it may be sedating. The use of strong corticosteroids on the scrotum may lead to persistent severe burning upon withdrawal of the drug. Underclothing should be changed daily, and in men, the seam of their “boxers” should not rub against or contact the scrotum. Balneol Perianal Cleansing Lotion or Tucks premoistened pads, ointment, or cream may be very useful for pruritus ani. About one-third of patients with scrotal or anal pruritus will respond to capsaicin cream 0.006%. Treatment for underlying spinal neurologic disease may be required.


Although benign, anogenital pruritus is often persistent and recurrent.

Serling SL et al. Approach to pruritus in the adult HIV-positive patient. Semin Cutan Med Surg. 2011 Jun;30(2):101–6. [PMID: 21767771]

Thorstensen KA et al. Recognition and management of vulvar dermatologic conditions: sclerosus, lichen planus, and lichen simplex chronicus. J Midwifery Womens Health. 2012 May–Jun;57(3):260–75. [PMID: 22594865]



 Generalized very severe itching.

 Burrows, vesicles and pustules, especially on finger webs and in wrist creases.

 Mites, ova, and brown dots of feces visible microscopically.

 Red papules or nodules on the scrotum and on the penile glans and shaft are pathognomonic.

 General Considerations

Scabies is caused by infestation with Sarcoptes scabiei. The infestation usually spares the head and neck (though even these areas may be involved in infants, in the elderly, and in patients with AIDS). Scabies is usually acquired by sleeping with or in the bedding of an infested individual or by other close contact. The entire household may be affected. Facility-associated scabies is increasingly common, primarily in long-term care facilities. Index patients are usually elderly and immunosuppressed. When these patients are hospitalized, hospital-based epidemics can occur. These epidemics are difficult to eradicate since many health care workers become infected and spread the infestation to other patients.

 Clinical Findings

  1. Symptoms and Signs

Itching is almost always present and can be quite severe. The lesions consist of more or less generalized excoriations with small pruritic vesicles, pustules, and “burrows” in the web spaces and on the heels of the palms, wrists (Figure 6–37), elbows, around the axillae, and on the breasts of women. The feet are a good place to identify burrows, since they may have been scratched off in other locations. The burrow appears as a short irregular mark, 2–3 mm long and the width of a hair. Characteristic nodular lesions may occur on the scrotum or penis and along the posterior axillary line.

 Figure 6–37. Scabies. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

  1. Laboratory Findings

The diagnosis should be confirmed by microscopic demonstration of the organism, ova, or feces in a mounted specimen, examined with tap water. Best results are obtained when multiple lesions are scraped, choosing the best unexcoriated lesions from interdigital webs, wrists, elbows, or feet. A No. 15 blade is used to scrape each lesion until it is flat. Pinpoint bleeding may result from the scraping. Patients with crusted/hyperkeratotic scabies must be evaluated for immunosuppression (especially HIV and HTLV-1 infections) if no iatrogenic cause of immunosuppression is present.

 Differential Diagnosis

Scabies must be distinguished from the various forms of pediculosis, from bedbug and flea bites, and from other causes of pruritus.

 Treatment & Prognosis

Treatment is aimed at killing scabies mites and controlling the dermatitis, which can persist for months after effective eradication of the mites. Bedding and clothing should be laundered or cleaned or set aside for 14 days in plastic bags. High heat (60°C) is required to kill the mites and ova. Unless treatment is aimed at all infected persons in a family or institutionalized group, reinfestations will probably occur.

Permethrin 5% cream is highly effective and safe in the management of scabies. Treatment consists of a single application for 8–12 hours, repeated in 1 week.

Pregnant patients should be treated only if they have documented scabies themselves. Permethrin 5% cream once for 12 hours—or 5% or 6% sulfur in petrolatum applied nightly for 3 nights from the collarbones down—may be used.

Patients will continue to itch for several weeks after treatment. Use of triamcinolone 0.1% cream will help resolve the dermatitis. Scabies in nursing home patients, institutionalized or mentally impaired (especially Down syndrome) patients, and AIDS patients may be much more difficult to treat.

Most failures in normal persons are related to incorrect use or incomplete treatment of the housing unit. In these cases, repeat treatment with permethrin once weekly for 2 weeks, with reeducation regarding the method and extent of application, is suggested. In immunocompetent individuals, ivermectin in a dose of 200 mcg/kg is effective in about 75% of cases with a single dose and 95% of cases with two doses 2 weeks apart. In immunosuppressed hosts and those with crusted (hyperkeratotic) scabies, multiple doses of ivermectin (every 2 weeks for two or three doses) plus topical therapy with permethrin once weekly may be effective when topical treatment and oral therapy alone fail. Oral ivermectin can be very beneficial in mass treatment to eradicate infections in institutions or villages.

If secondary pyoderma is present, it is treated with systemic antibiotics. In areas where nephritogenic streptococcal strains are prevalent, infestation with scabies or exposure to scabies-infested dogs may be followed by acute post-streptococcal glomerulonephritis.

Persistent pruritic postscabietic papules may be treated with mid- to high-potency corticosteroids or with intralesional triamcinolone acetonide (2.5–5 mg/mL).

Currier RW et al. Scabies in animals and humans: history, evolutionary perspectives, and modern clinical management. Ann N Y Acad Sci. 2011 Aug; 1230:E50–60. [PMID: 22417107]

Gunning K et al. Pediculosis and scabies: treatment update. Am Fam Physician. 2012 Sep15;86(6):535–41. [PMID: 23062045]

Monsel G et al. Management of scabies. Skin Therapy Lett. 2012 Mar;17(3):1–4. [PMID: 22446818]

Shimose L et al. Diagnosis, prevention, and treatment of scabies. Curr Infect Dis Rep. 2013 Oct;15(5):426–31. [PMID: 23904181]



 Pruritus with excoriation.

 Nits on hair shafts; lice on skin or clothes.

 Occasionally, sky-blue macules (maculae ceruleae) on the inner thighs or lower abdomen in pubic louse infestation.

 General Considerations

Pediculosis is a parasitic infestation of the skin of the scalp, trunk, or pubic areas. Body lice usually occur among people who live in overcrowded dwellings with inadequate hygiene facilities. Pubic lice may be sexually transmitted. Head lice may be transmitted by shared use of hats or combs. Adults contacting children with head lice frequently acquire the infestation.

There are three different varieties: (1) pediculosis pubis, caused by Phthirus pubis (pubic louse, “crabs”); (2) pediculosis corporis, caused by Pediculus humanus var corporis (body louse); and (3) pediculosis capitis, caused by Pediculus humanus var capitis (head louse).

Head and body lice are similar in appearance and are 3–4 mm long. The body louse can seldom be found on the body, because the insect comes onto the skin only to feed and must be looked for in the seams of the clothing. Trench fever, relapsing fever, and typhus are transmitted by the body louse in countries where those diseases are endemic.

 Clinical Findings

Itching may be very intense in body louse infestations, and scratching may result in deep excoriations, especially over the upper shoulders, posterior flanks, and neck. In some cases, only itching is present, with few excoriations seen. Pyoderma may be the presenting sign. Head lice can be found on the scalp or may be manifested as small nits resembling pussy willow buds on the scalp hairs close to the skin. They are easiest to see above the ears and at the nape of the neck. Pubic louse infestations are occasionally generalized, particularly in hairy individuals; the lice may even be found on the eyelashes and in the scalp.

 Differential Diagnosis

Head louse infestation must be distinguished from seborrheic dermatitis, body louse infestation from scabies and bedbug bites, and pubic louse infestation from anogenital pruritus and eczema.


Body lice are treated by disposing of the infested clothing and addressing the patient’s social situation. For pubic lice, permethrin rinse 1% for 10 minutes and permethrin cream 5% applied for 8 hours are effective. Sexual contacts should be treated. Clothes and bedclothes should be washed and dried at high temperature.

Permethrin 1% cream rinse (Nix) is a topical over-the-counter pediculicide and ovicide and is the treatment of choice for head lice. It is applied to the scalp and hair and left on for 8 hours before being rinsed off. Permethrin resistance of head lice is common. Malathion lotion 1% (Ovide) is very effective, but it is highly volatile and flammable, so application must be done in a well-ventilated room or out of doors. Topical ivermectin and spinosad 0.9% suspension are new agents that appear superior to previous treatments. For involvement of eyelashes, petrolatum is applied thickly twice daily for 8 days, and remaining nits are then plucked off.

Gunning K et al. Pediculosis and scabies: treatment update. Am Fam Physician. 2012 Sep15;86(6):535–41. [PMID: 23062045]

Ivermectin (Sklice) topical lotion for head lice. Med Lett Drugs Ther. 2012 Aug6;54(1396):61–3. [PMID: 22869290]



 Localized rash with pruritus.

 Furuncle-like lesions containing live arthropods.

 Tender erythematous patches that migrate (“larva migrans”).

 Generalized urticaria or erythema multiforme in some patients.

 General Considerations

Some arthropods (eg, mosquitoes and biting flies) are readily detected as they bite. Many others are not because they are too small, because there is no immediate reaction, or because they bite during sleep. Reactions are allergic and may be delayed for hours to days. Patients are most apt to consult a clinician when the lesions are multiple and pruritus is intense.

Many persons will react severely only to their earliest contacts with an arthropod, thus presenting pruritic lesions when traveling, moving into new quarters, etc. Body lice, fleas, bedbugs, and mosquitoes should be considered. Bedbug exposure typically occurs in hotels and in housing with inadequate hygiene but also may occur in stable domiciles. Spiders are often incorrectly believed to be the source of bites; they rarely attack humans, though the brown recluse spider (Loxosceles laeta, L reclusa) may cause severe necrotic reactions and death due to intravascular hemolysis, and the black widow spider(Latrodectus mactans) may cause severe systemic symptoms and death. (See also Chapter 38.) The majority of patient-diagnosed, physician-diagnosed, and even published cases of brown recluse spider bites (or loxoscelism) are incorrect, especially if made in areas where these spiders are not endemic. Many of these lesions are actually due to CA-MRSA.

In addition to arthropod bites, the most common lesions are venomous stings (wasps, hornets, bees, ants, scorpions) or bites (centipedes), furuncle-like lesions due to fly maggots or sand fleas in the skin, and a linear creeping eruption due to a migrating larva.

 Clinical Findings

The diagnosis may be difficult when the patient has not noticed the initial attack but suffers a delayed reaction. Individual bites are often in clusters and tend to occur either on exposed parts (eg, midges and gnats) or under clothing, especially around the waist or at flexures (eg, small mites or insects in bedding or clothing). The reaction is often delayed for 1–24 hours or more. Pruritus is almost always present and may be all but intolerable once the patient starts to scratch. Secondary infection may follow scratching. Urticarial wheals are common. Papules may become vesicular. The diagnosis is aided by searching for exposure to arthropods and by considering the patient’s occupation and recent activities.

The principal arthropods are as follows:

  1. Fleas:Fleas are bloodsucking ectoparasites that feed on dogs, cats, humans, and other species. Flea saliva produces papular urticaria in sensitized individuals. To break the life cycle of the flea, one must treat the home and pets, using quick-kill insecticides, residual insecticides, and a growth regulator.
  2. Bedbugs:In crevices of beds or furniture; bites tend to occur in lines or clusters. Papular urticaria is a characteristic lesion of bedbug (Cimex lectularius) bites. Bedbugs are not restricted to any socioeconomic group and are a major health problem in some major metropolitan areas, especially in commercial and residential hotels.
  3. Ticks:Usually picked up by brushing against low vegetation.
  4. Chiggers or red bugs:These are larvae of trombiculid mites. A few species confined to particular regions and locally recognized habitats (eg, berry patches, woodland edges, lawns, brush turkey mounds in Australia, poultry farms) attack humans, often around the waist, on the ankles, or in flexures, raising intensely itching erythematous papules after a delay of many hours. The red chiggers may sometimes be seen in the center of papules that have not yet been scratched.
  5. Bird and rodent mites:Larger than chiggers, bird mites infest birds and their nests. Bites are multiple anywhere on the body. Room air conditioning units may suck in bird mites and infest the inhabitants of the room. Rodent mites from mice or rats may cause similar effects. If the domicile has evidence of rodent activity, then rodent mite dermatitis should be suspected, as the mites are rarely found. Pet rodents or birds may be infested with mites, maintaining the infestation.
  6. Mites in stored products:These are white and almost invisible and infest products such as copra, vanilla pods, sugar, straw, cottonseeds, and cereals. Persons who handle these products may be attacked, especially on the hands and forearms and sometimes on the feet.
  7. Caterpillars of moths with urticating hairs:The hairs are blown from cocoons or carried by emergent moths, causing severe and often seasonally recurrent outbreaks after mass emergence. The gypsy moth is a cause in the eastern United States.
  8. Tungiasis:Tungiasis is due to the burrowing flea known as Tunga penetrans and is found in Africa, the West Indies, and South and Central America. The female burrows under the skin, sucks blood, swells to 0.5 cm, and then ejects her eggs onto the ground. Ulceration, lymphangitis, gangrene, and septicemia may result, in some cases with lethal effect. Simple surgical removal is usually performed.


Arthropod infestations are best prevented by avoidance of contaminated areas, personal cleanliness, and disinfection of clothing, bedclothes, and furniture as indicated. Chiggers and mites can be repelled by permethrin applied to the head and clothing. (It is not necessary to remove clothing.) Bedbugs are no longer repelled by permethrin. Aggressive cleaning, usually requiring removal of the affected occupant from the domicile, may be necessary to eradicate bedbug infestation in a residence.


Living arthropods should be removed carefully with tweezers after application of alcohol and preserved in alcohol for identification. In endemic Rocky Mountain spotted fever areas, ticks should not be removed with the bare fingers.

Corticosteroid lotions or creams are helpful. Topical antibiotics may be applied if secondary infection is suspected. Localized persistent lesions may be treated with intralesional corticosteroids.

Stings produced by many arthropods may be alleviated by applying papain powder (Adolph’s Meat Tenderizer) mixed with water, or aluminum chloride hexahydrate (Xerac AC).

Extracts from venom sacs of bees, wasps, yellow jackets, and hornets are available for immunotherapy of patients at risk for anaphylaxis.

Doggett SL et al. Bed bugs: clinical relevance and control options. Clin Microbiol Rev. 2012 Jan;25(1):164–92. [PMID: 22232375]

Haddad V Jr et al. Tropical dermatology: venomous arthropods and human skin: Part I. Insecta. J Am Acad Dermatol. 2012 Sep;67(3):331.e1–14. [PMID: 22890734]

Haddad V Jr et al. Tropical dermatology: venomous arthropods and human skin: Part II. Diplopoda, Chilopoda, and Arachnida. J Am Acad Dermatol. 2012 Sep;67(3):347.e1–9. [PMID: 22890735]




 Painful red nodules without ulceration on anterior aspects of legs.

 Slow regression over several weeks to resemble contusions.

 Women are predominantly affected by a ratio of 10:1 compared to men.

 Some cases associated with infection, inflammatory bowel disease, or drug exposure.

 General Considerations

Erythema nodosum is a symptom complex characterized by tender, erythematous nodules that appear most commonly on the extensor surfaces of the lower legs. It usually lasts about 6 weeks and may recur. The disease may be associated with various infections—streptococcosis, primary coccidioidomycosis, other deep fungal infections, tuberculosis, Yersinia pseudotuberculosis and Y enterocoliticainfection, diverticulitis, or syphilis. It may accompany sarcoidosis, Behçet disease, and inflammatory bowel disease. Erythema nodosum may be associated with pregnancy or with use of oral contraceptives.

 Clinical Findings

  1. Symptoms and Signs

The subcutaneous swellings are exquisitely tender and may be preceded by fever, malaise, and arthralgia. They are most often located on the anterior surfaces of the legs below the knees but may occur on the arms, trunk, and face. The lesions, 1–10 cm in diameter, are at first pink to red; with regression, all the various hues seen in a contusion can be observed (Figure 6–38).

 Figure 6–38. Erythema nodosum. (Used, with permission, from Berger TG, Dept Dermatology, UCSF.)

  1. Laboratory Findings

Evaluation of patients presenting with acute erythema nodosum should include a careful history (including drug exposures) and physical examination for prior upper respiratory infection or diarrheal illness, symptoms of any deep fungal infection endemic to the area, a chest radiograph, a PPD, and two consecutive ASO/DNAse B titers at 2- to 4-week intervals. If no underlying cause is found, only a small percentage of patients will go on to develop a significant underlying illness (usually sarcoidosis) over the next year.

 Differential Diagnosis

Erythema induratum from tuberculosis is seen on the posterior surfaces of the legs and may ulcerate. Lupus panniculitis presents as tender nodules on the buttocks and posterior arms that heal with depressed scars. In polyarteritis nodosa, the subcutaneous nodules are often associated with a fixed livedo. In the late stages, erythema nodosum must be distinguished from simple bruises and contusions.


First, the underlying cause should be identified and treated. Primary therapy is with NSAIDs in usual doses. Saturated solution of potassium iodide, 5–15 drops three times daily, results in prompt involution in many cases. Complete bed rest may be advisable if the lesions are painful. Systemic therapy directed against the lesions themselves may include corticosteroid therapy (see Chapter 26) unless contraindicated by associated infection.


The lesions usually disappear after about 6 weeks, but they may recur.

Chen S et al. Mycobacterium tuberculosis infection is associated with the development of erythema nodosum and nodular vasculitis. PLoS One. 2013 May1;8(5):e62653. [PMID: 23650522]

Chong TA et al. Diverticulitis: an inciting factor in erythema nodosum. J Am Acad Dermatol. 2012 Jul;67(1):e60–2. [PMID: 22703921]

Eimpunth S et al. Tender cutaneous nodules of the legs: diagnosis and clinical clues to diagnosis. Int J Dermatol. 2013 May;52(5):560–6. [PMID: 22928517]

Passarini B et al. Erythema nodosum. G Ital Dermatol Venereol. 2013 Aug;148(4):413–7. [PMID: 23900162]



 Extremely painful inflammatory swelling based on a hair follicle that forms an abscess.

 Predisposing condition (diabetes mellitus, HIV disease, injection drug use) sometimes present.

 Coagulase-positive S aureus is the causative organism.

 General Considerations

A furuncle (boil) is a deep-seated infection (abscess) caused by S aureus and involving the entire hair follicle and adjacent subcutaneous tissue. The most common sites of occurrence are the hairy parts exposed to irritation and friction, pressure, or moisture. Because the lesions are autoinoculable, they are often multiple. Diabetes mellitus (especially if using insulin injections), injection drug use, allergy injections, and HIV disease all increase the risk of staphylococcal infections by increasing the rate of carriage. Certain other exposures including hospitalization, athletic teams, prisons, military service, and homelessness may also increase the risk of infection.

A carbuncle consists of several furuncles developing in adjoining hair follicles and coalescing to form a conglomerate, deeply situated mass with multiple drainage points.

 Clinical Findings

  1. Symptoms and Signs

Pain and tenderness may be prominent. The abscess is either rounded or conical. It gradually enlarges, becomes fluctuant, and then softens and opens spontaneously after a few days to 1–2 weeks to discharge a core of necrotic tissue and pus. The inflammation occasionally subsides before necrosis occurs. Infection of the soft tissue around the nails (paronychia) may be due to staphylococci when it is acute or Candida when chronic.

  1. Laboratory Findings

There may be slight leukocytosis, but a white blood cell count is rarely required. Pus can be cultured to rule out MRSA or other bacteria. Culture of the anterior nares may identify chronic staphylococcal carriage in cases of recurrent cutaneous infection.

 Differential Diagnosis

The most common entity in the differential is an inflamed epidermal inclusion cyst that suddenly becomes red, tender, and expands greatly in size over one to a few days. The history of a prior cyst in the same location, the presence of a clearly visible cyst orifice, and the extrusion of malodorous cheesy rather than purulent material helps in the diagnosis. Tinea profunda (deep dermatophyte infection of the hair follicle) may simulate recurrent furunculosis. Furuncle is also to be distinguished from deep mycotic infections, such as sporotrichosis; from other bacterial infections, such as anthrax and tularemia (rare); from atypical mycobacterial infections; and from acne cysts. Hidradenitis suppurativa (acne inversa) presents with recurrent tender sterile abscesses in the axillae and groin, on the buttocks, or below the breasts. The presence of old scars or sinus tracts plus negative cultures suggests this diagnosis.


Serious and sometimes fatal complications of staphylococcal infection such as septicemia can occur.


Identifying and eliminating the source of infection is critical to prevent recurrences after treatment. The source individual may have chronic dermatitis or be an asymptomatic carrier. Local measures such as meticulous handwashing; no sharing of towels and clothing; aggressive scrubbing of showers, bathrooms and surfaces with bleach; bleach baths (¼–½ cup per 20 liters of bathwater for 15 minutes 3–5 times weekly) and isolation of infected patients who reside in institutions to prevent spread are all effective measures.


  1. Specific Measures

Incision and drainage is recommended for all loculated suppurations and is the mainstay of therapy. Systemic antibiotics are usually given, although they offer little beyond adequate incision and drainage. Sodium dicloxacillin or cephalexin, 1 g daily in divided doses by mouth for 10 days, is usually effective. Doxycycline 100 mg twice daily, trimethoprim-sulfamethoxazole double-strength one tablet twice daily, and clindamycin 150–300 mg twice daily are effective in treating MRSA. Recurrent furunculosis may be effectively treated with a combination of cephalexin (250–500 mg four times daily) ordoxycycline (100 mg twice daily) for 2–4 weeks plus either rifampin (300 mg twice daily for 5 days for 2–4 weeks) or long-term clindamycin (150–300 mg daily for 1–2 months). Shorter courses of antibiotics (7–14 days) plus longer-term daily chlorhexidine whole body washing and intranasal, axilla, and anogenital mupirocin may also cure recurrent furunculosis. Family members, pets, and intimate contacts may need evaluation for staphylococcal carrier state and perhaps concomitant treatment. Stopping high-risk behavior such as injection drug use can also prevent recurrence of furunculosis.

  1. Local Measures

Immobilize the part and avoid overmanipulation of inflamed areas. Use moist heat to help larger lesions “localize.” Use surgical incision and drainage after the lesions are “mature.” To incise and drain an acute staphylococcal paronychia, insert a flat metal spatula or sharpened hardwood stick into the nail fold where it adjoins the nail. This will release pus from a mature lesion.


Recurrent crops may harass the patient for months or years.

Daly JM et al. Management of skin and soft tissue infections in community practice before and after implementing a “best practice” approach: an Iowa Research Network (IRENE) intervention study. J Am Board Fam Med. 2011 Sep–Oct;24(5):524–33. [PMID: 21900435]

Davido B et al. Recurrent furunculosis: Efficacy of the CMC regimen—skin disinfection (chlorhexidine), local nasal antibiotic (mupirocin), and systemic antibiotic (clindamycin). Scand J Infect Dis. 2013 Nov;45(11):837–41. [PMID: 23848409]

Demos M et al. Recurrent furunculosis: a review of the literature. Br J Dermatol. 2012 Oct;167(4):725–32. [PMID: 22803835]

Parnes B et al. Improving the management of skin and soft tissue infections in primary care: a report from State Networks of Colorado Ambulatory Practices and Partners (SNOCAP-USA) and the Distributed Ambulatory Research in Therapeutics Network (DARTNet). J Am Board Fam Med. 2011 Sep–Oct;24(5):534–42. [PMID: 21900436]



 Firm dermal papule or nodule.

 Overlying black comedone or “punctum.”

 Expressible foul-smelling cheesy material.

 May become red and drain, mimicking an abscess.

 General Considerations

Epidermal inclusion cysts (EICs) are common, benign growths of the upper portion of the hair follicle. They are common in Gardner syndrome and may be the first stigmata of the condition.

EICs favor the face and trunk and may complicate nodulocystic acne vulgaris. Individual lesions range in size from 0.3 cm to several centimeters. An overlying pore or punctum is characteristic. Lateral pressure may lead to extrusion of a foul-smelling, cheesy material.

 Differential Diagnosis

EICs are distinguished from lipomas by being more superficial (in the dermis not the subcutaneous fat) and by their overlying punctum. Many other benign and malignant tumors may superficially resemble EICs, but all lack the punctum.


EICs may rupture, creating an acute inflammatory nodule very similar to an abscess. Cultures of the expressed material will be sterile.


Treatment is not required if asymptomatic. Inflamed lesions may be treated with incision and drainage or intralesional triamcinolone acetomide 5–10 mg/mL. For large or symptomatic cysts, surgical excision is curative.

Baek SO et al. Giant epidermal inclusion facial cyst. J Craniofac Surg. 2011 May;22(3):1149–51. [PMID: 21586975]



 Painful or pruritic erythema, edema, or vesiculation on sun-exposed surfaces: the face, neck, hands, and “V” of the chest.

 Inner upper eyelids spared, as is the area under the chin.

 General Considerations

In most cases, photosensitivity is an acute or chronic skin reaction due to hypersensitivity to ultraviolet radiation. It is caused by certain medications, by lupus erythematosus, and some inherited disorders including the porphyrias. Contact photosensitivity may occur with plants, perfumes, and sunscreens. Three percent of persons with atopic dermatitis, especially middle-aged women, are photosensitive.

Photodermatitis is manifested as phototoxicity—a tendency for the individual to sunburn more easily than expected—or, as photoallergy, a true immunologic reaction that often presents with dermatitis.

 Clinical Findings

  1. Symptoms and Signs

The acute inflammatory phase of phototoxicity, if severe enough, is accompanied by pain, fever, gastrointestinal symptoms, malaise, and even prostration. Signs include erythema, edema, and possibly vesiculation and oozing on exposed surfaces. Peeling of the epidermis and pigmentary changes often result. The key to diagnosis is localization of the rash to photoexposed areas, though these eruptions may become generalized with time to involve even photoprotected areas. The lower lip may be affected.

  1. Laboratory Findings

Blood and urine tests are generally not helpful unless porphyria cutanea tarda is suggested by the presence of blistering, scarring, milia (white cysts 1–2 mm in diameter) and skin fragility of the dorsal hands, and facial hypertrichosis. Eosinophilia may be present in chronic photoallergic responses.

 Differential Diagnosis

The differential diagnosis is long. If a clear history of the use of a topical or systemic photosensitizer is not available and if the eruption is persistent, then a workup including biopsy and light testing may be required. Photodermatitis must be differentiated from contact dermatitis that may develop from one of the many substances in suntan lotions and oils, as these may often have a similar distribution. Sensitivity to actinic rays may also be part of a more serious condition such as porphyria cutanea tarda or lupus erythematosus. These disorders are diagnosed by appropriate blood or urine tests. Phenothiazines, quinine or quinidine, griseofulvin, sulfonamides (especially hydrochlorothiazide), NSAIDs, and antibiotics (eg, some tetracyclines, quinolones, TMP-SMZ) may photosensitize the skin. Polymorphous light eruption (PMLE) is a very common idiopathic photodermatitis and often has its onset in the third to fourth decades except in Native Americans and Latinos, in whom it may present in childhood. PMLE is chronic in nature. Transitory periods of spontaneous remission do occur. The action spectrum of PMLE may also extend into the long ultraviolet wavelengths (UVA; 320–400 nm). Drug-induced photosensitivity is triggered by UVA.


Some individuals continue to be chronic light reactors even when they apparently are no longer exposed to photosensitizing drugs.


While sunscreens are useful agents in general and should be used by persons with photosensitivity, patients may react to such low amounts of energy that sunscreens alone may not be sufficient. Sunscreens with an SPF of 30–60 and broad UVA coverage, containing dicamphor sulfonic acid (Mexoryl SX), avobenzone (Parasol 1789), titanium dioxide, and micronized zinc oxide, are especially useful in patients with photoallergic dermatitis. Photosensitivity due to porphyria is not prevented by sunscreens and requires barrier protection (clothing) to prevent outbreaks.


  1. Specific Measures

Medications should be suspected in cases of photosensitivity even if the particular medication (such as hydrochlorothiazide) has been used for months.

  1. Local Measures

When the eruption is vesicular or weepy, treatment is similar to that of any acute dermatitis, using cooling and soothing wet dressing.

Sunscreens should be used as described above. Mid-potency to high-potency topical corticosteroids are of limited benefit in sunburn reactions but may help in PMLE and photoallergic reactions. Since the face is often involved, close monitoring for corticosteroid side effects is recommended.

  1. Systemic Measures

Aspirin may have some value for fever and pain of acute sunburn. Systemic corticosteroids in doses as described for acute contact dermatitis may be required for severe photosensitivity reactions. Otherwise, different photodermatoses are treated in specific ways.

Patients with severe photoallergy may require immunosuppressives, such as azathioprine, in the range of 50–300 mg/d, or cyclosporine, 3–5 mg/kg/d.


The most common phototoxic sunburn reactions are usually benign and self-limited. PMLE and some cases of photoallergy can persist for years.

Kiss F et al. A review of UVB-mediated photosensitivity disorders. Photochem Photobiol Sci. 2012 Dec13;12(1):37–46. [PMID: 23023766]

Sharma VK et al. Photodermatoses in pigmented skin. Photochem Photobiol Sci. 2013 Jan;12(1):65–77. [PMID: 23123922]




 Past history of varicosities, thrombophlebitis, or postphlebitic syndrome.

 Irregular ulceration, often on the medial aspect of the lower legs above the malleolus.

 Edema of the legs, varicosities, hyperpigmentation, and red and scaly areas (stasis dermatitis) and scars from old ulcers support the diagnosis.

 General Considerations

Patients at risk may have a history of venous insufficiency, either with obvious varicosities or with a past history of thrombophlebitis, or with immobility of the calf muscle group (paraplegics, etc). Red, pruritic patches of stasis dermatitis often precede ulceration. Because venous insufficiency plays a role in between 75% and 90% of lower leg ulcerations, testing of venous competence is a required part of a leg ulcer evaluation even when no changes of venous insufficiency are present. The left leg is usually more severely affected than the right.

 Clinical Findings

  1. Symptoms and Signs

Classically, chronic edema is followed by a dermatitis, which is often pruritic. These changes are followed by hyperpigmentation, skin breakdown, and eventually sclerosis of the skin of the lower leg (Figure 6–39). The ulcer base may be clean, but it often has a yellow fibrin eschar that may require surgical removal. Ulcers that appear on the feet, toes, or above the knees should be approached with other diagnoses in mind.

 Figure 6–39. Venous stasis ulcer near the medial malleolus. (Courtesy of Maureen Sheehan, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

  1. Laboratory Findings

Thorough evaluation of the patient’s vascular system (including measurement of the ankle/brachial index [ABI]) is essential. If the ABI is < 0.7, the patient should be referred to a vascular surgeon for surgical evaluation. Doppler and light rheography examinations as office procedures are usually sufficient (except in the diabetic) to elucidate the cause of most vascular cases of lower leg ulceration.

 Differential Diagnosis

The differential includes vasculitis, pyoderma gangrenosum, arterial ulcerations, infection, trauma, skin cancer, arachnid bites, and sickle cell anemia. When the diagnosis is in doubt, a punch biopsy from the border (not base) of the lesion may be helpful.


Compression stockings to reduce edema are the most important means of prevention. Compression should achieve a pressure of 30 mm Hg below the knee and 40 mm Hg at the ankle. The stockings should not be used in patients with arterial insufficiency with an ABI < 0.7. Pneumatic sequential compression devices may be of great benefit when edema is refractory to standard compression dressings.


  1. Local Measures

Clean the base of the ulcer with saline or cleansers such as Saf-Clens. A curette or small scissors can be used to remove the yellow fibrin eschar; local anesthesia may be used if the areas are very tender.

The ulcer is treated with metronidazole gel to reduce bacterial growth and odor. Any red dermatitic skin is treated with a medium- to high-potency corticosteroid ointment. The ulcer is then covered with an occlusive hydroactive dressing (DuoDerm, Hydrasorb or Cutinova) or a polyurethane foam (Allevyn) followed by an Unna zinc paste boot. This is changed weekly. The ulcer should begin to heal within weeks, and healing should be complete within 4–6 months. If the patient is diabetic, becaplermin (Regranex) may be applied to those ulcers that are not becoming smaller or developing a granulating base. Some ulcerations require grafting. Full- or split-thickness grafts often do not take, and pinch grafts (small shaves of skin laid onto the bed) may be effective. Cultured epidermal cell grafts may accelerate wound healing, but they are very expensive. They should be considered in refractory ulcers, especially those that have not healed after a year or more of conservative therapy. Manuka honey has been purported to accelerate wound healing, but comparative controlled trials of efficacy are lacking.

No topical intervention has evidence to suggest that it will improve healing of arterial leg ulcers.

  1. Systemic Therapy

Pentoxifylline, 400 mg three times daily administered with compression dressings, is beneficial in accelerating healing of venous insufficiency leg ulcers. Zinc supplementation is occasionally beneficial in patients with low serum zinc levels. The diagnosis of cellulitis in the setting of a venous insufficiency ulcer can be very difficult. Surface cultures are of limited value. The diagnosis of cellulitis should be considered in the following settings: 1) expanding warmth and erythema surrounding the ulceration with or without 2) increasing pain of the ulceration. The patient may also report increased exudate from the ulceration, but this without the other cardinal findings of cellulitis does not confirm the diagnosis of cellulitis. If cellulitis accompanies the ulcer, systemic antibiotics are recommended: dicloxacillin, 250 mg orally four times a day, or levofloxacin, 500 mg once daily for 1–2 weeks is usually adequate. Routine use of antibiotics and treating bacteria isolated from a chronic ulcer without clinical evidence of infection is discouraged. If the ulcer fails to heal or there is a persistent draining tract in the ulcer, an underlying osteomyelitis should be sought.


The combination of limited debridement, compression dressings or stockings, and newer moist dressings will heal the majority of venous stasis ulcers within months (average 18 months). These need to be applied at least 80% of the time to optimize ulcer healing. Topical growth factors, antibiotics, debriding agents, and xenografts and autografts can be considered in recalcitrant cases, but they are usually not required in most patients. The failure of venous insufficiency ulcerations to heal is most often related to not using the basic treatment methods consistently, rather than failure to use these specific modalities.Ongoing control of edema is essential to prevent recurrent ulceration. The use of compression stockings following ulcer healing is critical to prevent recurrence, with recurrence rates 2–20 times higher if patients do not comply with compression stocking use. If the ABI is < 0.5, the prognosis for healing is poor. Patients with an ABI below 0.5 or refractory ulcerations (or both) should be considered for surgical procedure (artery-opening procedures or ablation of the incompetent superficial vein).

Bryan LJ et al. Higher soluble P-selectin is associated with chronic venous insufficiency: the San Diego Population Study. Thromb Res. 2012 Nov;130(5):716–9. [PMID: 22892384]

Chaby G et al; Angio-Dermatology Group of the French Society of Dermatology. Prognostic factors associated with healing of venous leg ulcers: a multicentre, prospective, cohort study. Br J Dermatol. 2013 Nov;169(5):1106–13. [PMID: 23909381]

Mosti G et al. High compression pressure over the calf is more effective than graduated compression in enhancing venous pump function. Eur J Vasc Endovasc Surg. 2012 Sep;44(3):332–6. [PMID: 22819741]

Mowatt-Larssen E et al. Treatment of primary varicose veins has changed with the introduction of new techniques. Semin Vasc Surg. 2012 Mar;25(1):18–24. [PMID: 22595477]

Uhl JF et al. Anatomy of the foot venous pump: physiology and influence on chronic venous disease. Phlebology. 2012 Aug;27(5):219–30. [PMID: 22847928]



Although the color of skin may be altered by many diseases and agents, the vast majority of patients have either an increase or decrease in pigment secondary to some inflammatory disease such as acne or atopic dermatitis.

Other pigmentary disorders include those resulting from exposure to exogenous pigments such as carotenemia, argyria, and tattooing. Other endogenous pigmentary disorders are attributable to metabolic substances—including hemosiderin (iron)—in purpuric processes; or to homogentisic acid in ochronosis; and bile pigments.


First, determine whether the disorder is hyperpigmentation or hypopigmentation, ie, an increase or decrease in normal skin colors. Each may be considered to be primary or to be secondary to other disorders.

  1. Primary Pigmentary Disorders
  2. Hyperpigmentation—The disorders in this category are nevoid, congenital or acquired, and include pigmented nevi, ephelides (juvenile freckles), and lentigines (senile freckles). Hyperpigmentation occurs also in arsenical melanosis or in association with Addison disease.Melasma (chloasma)occurs as patterned hyperpigmentation of the face, usually as a direct effect of estrogens. It occurs not only during pregnancy but also in 30–50% of women taking oral contraceptives, and rarely in men. One report suggests that such men have low testosterone and elevated luteinizing hormone levels.
  3. Hypopigmentation and depigmentation—The disorders in this category are vitiligo, albinism, and piebaldism. In vitiligo, pigment cells (melanocytes) are destroyed (Figure 6–40). Vitiligo, present in approximately 1% of the population, may be associated with other autoimmune disorders such as autoimmune thyroid disease, pernicious anemia, diabetes mellitus, and Addison disease.

 Figure 6–40. Vitiligo of the hands. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

  1. Secondary Pigmentary Disorders

Any damage to the skin (irritation, allergy, infection, excoriation, burns, or dermatologic therapy such as chemical peels and freezing with liquid nitrogen) may result in hyperpigmentation or hypopigmentation. Several disorders of clinical importance are described below.

  1. Hyperpigmentation—The most common type of secondary hyperpigmentation occurs after another dermatologic condition, such as acne, and is most commonly seen in moderately complexioned persons (Asians, Hispanics, and light-skinned African Americans). It is called post-inflammatory hyperpigmentation.

Pigmentation may be produced by certain drugs, eg, chloroquine, chlorpromazine, minocycline, and amiodarone. Fixed drug eruptions to phenolphthalein in laxatives, to TMP-SMZ, to NSAIDs, and to tetracyclines, for example, are further causes.

  1. Hypopigmentation—Leukodermamay complicate atopic dermatitis, lichen planus, psoriasis, DLE, and lichen simplex chronicus. Practitioners must exercise special care in using liquid nitrogen on any patient with olive or darker complexions, since doing so may result in hypopigmentation or depigmentation, at times permanent. Intralesional or intra-articular injections of high concentrations of corticosteroids may also cause localized temporary hypopigmentation.

 Differential Diagnosis

The evaluation of pigmentary disorders is helped by Wood’s light, which accentuates epidermal pigmentation and highlights hypopigmentation. Depigmentation, as seen in vitiligo, enhances with Wood’s light examination, whereas postinflammatory hypopigmentation does not.


Actinic keratoses and skin cancers are more likely to develop in persons with vitiligo. Severe emotional trauma may occur in extensive vitiligo and other types of hypopigmentation and hyperpigmentation, particularly in naturally dark-skinned persons.

 Treatment & Prognosis

  1. Hyperpigmentation

Therapeutic bleaching preparations generally contain hydroquinone. Hydroquinone has occasionally caused unexpected hypopigmentation, hyperpigmentation, or even secondary ochronosis and pigmented milia, particularly with prolonged use.

The role of exposure to ultraviolet light cannot be overstressed as a factor promoting or contributing to most disorders of hyperpigmentation, and such exposure should be minimized. Melasma, ephelides, and postinflammatory hyperpigmentation may be treated with varying success with 3–4% hydroquinone cream, gel, or solution and a sunscreen containing UVA photoprotectants (Avobenzone, Mexoryl, zinc oxide, titanium dioxide). Tretinoin cream, 0.025–0.05%, may be added. Superficial melasma responds well, but if there is predominantly dermal deposition of pigment (does not enhance with Wood’s light), the prognosis is poor. Response to therapy may take months and requires avoidance of sunlight. Hyperpigmentation often recurs after treatment if the skin is exposed to ultraviolet light. Solar lentigines respond to liquid nitrogen application. Tretinoin, 0.1% cream and tazarotene 0.1% used over 10 months, will fade solar lentigines (liver spots), hyperpigmented facial macules in Asians, and postinflammatory hyperpigmentation in blacks. New laser systems for the removal of epidermal and dermal pigments are available, and referral should be considered for patients whose responses to medical treatment are inadequate.

  1. Hypopigmentation

In secondary hypopigmentation, repigmentation may occur spontaneously. Cosmetics such as Covermark and Dermablend are highly effective for concealing disfiguring patches. Therapy of vitiligo is long and tedious, and the patient must be strongly motivated. If < 20% of the skin is involved (most cases), topical tacrolimus 0.1% twice daily is the first-line therapy. A superpotent corticosteroid may also be used, but local skin atrophy from prolonged use may ensue. With 20–25% involvement, narrowband UVB or oral PUVA is best. Severe phototoxic response (sunburn) may occur with PUVA. The face and upper chest respond best, and the fingertips and the genital areas do not respond as well to treatment. Years of treatment may be required.

Korobko IV. Review of current clinical studies of vitiligo treatments. Dermatol Ther. 2012 Nov;25(Suppl 1):S17–27. [PMID: 23237034]

Passeron T. Melasma pathogenesis and influencing factors—an overview of the latest research. J Eur Acad Dermatol Venereol. 2013 Jan;27(Suppl 1):5–6. [PMID: 23205539]

Rivas S et al. Treatment of melasma with topical agents, peels and lasers: an evidence-based review. Am J Clin Dermatol. 2013 Oct;14(5):359–76. [PMID: 23881551]

Sheth VM et al. Comorbidities associated with vitiligo: a ten-year retrospective study. Dermatology. 2013;227(4):311–5. [PMID: 24107643]

Vrijman C et al. The prevalence of thyroid disease in patients with vitiligo: a systematic review. Br J Dermatol. 2012 Dec;167(6):1224–35. [PMID: 22860695]

BALDNESS (Alopecia)

 Baldness Due to Scarring (Cicatricial Alopecia)

Cicatricial baldness may occur following chemical or physical trauma, lichen planopilaris, bacterial or fungal infections, severe herpes zoster, chronic DLE, scleroderma, and excessive ionizing radiation. The specific cause is often suggested by the history, the distribution of hair loss, and the appearance of the skin, as in lupus erythematosus. Biopsy is useful in the diagnosis of scarring alopecia, but specimens must be taken from the active border and not from the scarred central zone.

Scarring alopecias are irreversible and permanent. It is important to diagnose and treat the scarring process as early in its course as possible.

 Baldness Not Associated with Scarring

Nonscarring alopecia may occur in association with various systemic diseases such as SLE, secondary syphilis, hyperthyroidism or hypothyroidism, iron deficiency anemia, and pituitary insufficiency. The only treatment necessary is prompt and adequate control of the underlying disorder and usually leads to regrowth of the hair.

Androgenetic (male pattern) baldness, the most common form of alopecia, is of genetic predetermination. The earliest changes occur at the anterior portions of the calvarium on either side of the “widow’s peak” and on the crown (vertex). The extent of hair loss is variable and unpredictable. Minoxidil 5% is available over the counter and can be specifically recommended for persons with recent onset (< 5 years) and smaller areas of alopecia. Approximately 40% of patients treated twice daily for a year will have moderate to dense growth. Finasteride (Propecia), 1 mg orally daily, has similar efficacy and may be additive to minoxidil. As opposed to minoxidil, finasteride is used only in males.

Hair loss or thinning of the hair in women results from the same cause as common baldness in men (androgenetic alopecia) and may be treated with topical minoxidil. A workup consisting of determination of serum testosterone, DHEAS, iron, total iron-binding capacity, thyroid function tests, and a complete blood count will identify most other causes of hair thinning in premenopausal women. Women who complain of thin hair but show little evidence of alopecia need follow-up, because > 50% of the scalp hair can be lost before the clinician can perceive it.

Telogen effluvium is transitory increase in the number of hairs in the telogen (resting) phase of the hair growth cycle. This may occur spontaneously, may appear at the termination of pregnancy, may be precipitated by “crash dieting,” high fever, stress from surgery or shock, malnutrition, or may be provoked by hormonal contraceptives. Whatever the cause, telogen effluvium usually has a latent period of 2–4 months. The prognosis is generally good. The condition is diagnosed by the presence of large numbers of hairs with white bulbs coming out upon gentle tugging of the hair. Counts of hairs lost by the patient on combing or shampooing often exceed 150 per day, compared to an average of 70–100. In one study, a major cause of telogen effluvium was found to be iron deficiency, and the hair counts bore a clear relationship to serum iron levels. If iron deficiency is suspected, a serum ferritin should be obtained, and the value followed with supplementation.

Alopecia areata is of unknown cause but is believed to be an immunologic process. Typically, there are patches that are perfectly smooth and without scarring. Tiny hairs 2–3 mm in length, called “exclamation hairs,” may be seen. Telogen hairs are easily dislodged from the periphery of active lesions. The beard, brows, and lashes may be involved. Involvement may extend to all of the scalp hair (alopecia totalis) or to all scalp and body hair (alopecia universalis). Severe forms may be treated by systemic corticosteroid therapy, although recurrences follow discontinuation of therapy. Alopecia areata is occasionally associated with Hashimoto thyroiditis, pernicious anemia, Addison disease, and vitiligo.

Intralesional corticosteroids are frequently effective for alopecia areata. Triamcinolone acetonide in a concentration of 2.5–10 mg/mL is injected in aliquots of 0.1 mL at approximately 1- to 2-cm intervals, not exceeding a total dose of 30 mg per month for adults. Alopecia areata is usually self-limiting, with complete regrowth of hair in 80% of patients with focal disease. Some mild cases are resistant to treatment, as are the extensive totalis and universalis types. Support groups for patients with extensive alopecia areata are very beneficial.

In trichotillomania (the pulling out of one’s own hair), the patches of hair loss are irregular and short growing hairs are always present, since they cannot be pulled out until they are long enough. The patches are often unilateral, occurring on the same side as the patient’s dominant hand. The patient may be unaware of the habit.

Alkhalifah A. Alopecia areata update. Dermatol Clin. 2013 Jan;31(1):93–108. [PMID: 23159179]

Mirmirani P. Managing hair loss in midlife women. Maturitas. 2013 Feb;74(2):119–22. [PMID: 23182767]

Ucak H et al. Prognostic factors that affect the response to topical treatment in patchy alopecia areata. J Eur Acad Dermatol Venereol. 2014 Jan;28(1):34–40. [PMID: 23181708]


  1. Morphologic Abnormalities of the Nails


Acquired nail disorders may be classified as local or those associated with systemic or generalized skin diseases.

  1. Local Nail Disorders

Onycholysis (distal separation of the nail plate from the nail bed, usually of the fingers) is caused by excessive exposure to water, soaps, detergents, alkalies, and industrial cleaning agents. Candidal infection of the nail folds and subungual area, nail hardeners, and drug-induced photosensitivity may cause onycholysis, as may hyperthyroidism, hypothyroidism, and psoriasis.

  1. Distortion of the nail occurs as a result of chronic inflammation of the nail matrix underlying the eponychial fold. Such changes may also be caused by warts, tumors, or cysts, impinging on the nail matrix.
  2. Discoloration and crumbly thickened nails are noted in dermatophyte infection and psoriasis.
  3. Allergic reactions (to resins in undercoats and polishes or to nail glues) are characterized by onycholysis or by grossly distorted, hypertrophic, and misshapen nails.
  4. Nail Changes Associated with Systemic or Generalized Skin Diseases

Beau lines (transverse furrows) may follow any serious systemic illness.

  1. Atrophy of the nails may be related to trauma or to vascular or neurologic disease.
  2. Clubbed fingers may be due to the prolonged hypoxemia associated with cardiopulmonary disorders (Figure 6–41) (SeeChapter 9).

 Figure 6–41. Clubbing of the fingers in congenital heart disease. (Courtesy of Richard P. Usatine, MD; used, with permission, from Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J.The Color Atlas of Family Medicine. McGraw-Hill, 2009.)

  1. Spoon nails may be seen in anemic patients.
  2. Stippling or pitting of the nails is seen in psoriasis, alopecia areata, and hand eczema.
  3. Nail hyperpigmentation may be caused by many chemotherapeutic agents, but especially the taxanes.

 Differential Diagnosis

Onychomycosis may cause nail changes identical to those seen in psoriasis. Careful examination for more characteristic lesions elsewhere on the body is essential to the diagnosis of the nail disorders. Cancer should be suspected (eg, Bowen disease or squamous cell carcinoma) as the cause of any persistent solitary subungual or periungual lesion.


Toenail changes may lead to an ingrown nail—in turn often complicated by bacterial infection and occasionally by exuberant granulation tissue. Poor manicuring and poorly fitting shoes may contribute to this complication. Cellulitis may result.

 Treatment & Prognosis

Treatment consists usually of careful debridement and manicuring and, above all, reduction of exposure to irritants (soaps, detergents, alkali, bleaches, solvents, etc). Longitudinal grooving due to temporary lesions of the matrix, such as warts, synovial cysts, and other impingements, may be cured by removal of the offending lesion.

  1. Tinea Unguium (Onychomycosis)

Tinea unguium is a trichophyton infection of one or more (but rarely all) fingernails or toenails. The species most commonly found is T rubrum. “Saprophytic” fungi may rarely (< 5%) cause onychomycosis.

The nails are lusterless, brittle, and hypertrophic, and the substance of the nail is friable. Laboratory diagnosis is mandatory since only 50% of dystrophic nails are due to dermatophytosis. Portions of the nail should be cleared with 10% KOH and examined under the microscope for hyphae. Fungi may also be cultured. Periodic acid-Schiff stain of a histologic section of the nail plate will also demonstrate the fungus readily. Each technique is positive in only 50% of cases so several different tests may need to be performed.

Onychomycosis is difficult to treat because of the long duration of therapy required and the frequency of recurrences. Fingernails respond more readily than toenails. For toenails, treatment is limited to patients with discomfort, inability to exercise, and immune compromise.

In general, systemic therapy is required to effectively treat nail onychomycosis. Topical therapy has limited value and the adjunctive value of surgical procedures is unproven. Efficacy of laser treatments is lacking, especially with regard to long-term cures. Fingernails can virtually always be cured and toenails are cured 35–50% of the time and are clinically improved about 75% of the time. In all cases, before treatment, the diagnosis should be confirmed. The costs of the various treatment options should be known and the most cost-effective treatment chosen. Drug interactions must be avoided. Ketoconazole, due to its higher risk for hepatotoxicity, is not recommended to treat any form of onychomycosis. For fingernails, ultramicronized griseofulvin 250 mg orally three times daily for 6 months can be effective. Alternative treatments are (in order of preference) oral terbinafine 250 mg daily for 6 weeks, oral itraconazole 400 mg daily for 7 days each month for 2 months, and oral itraconazole 200 mg daily for 2 months. Off-label use of fluconazole, 400 mg once weekly for 6 months, can also be effective, but there is limited evidence for this option. Once clear, fingernails usually remain free of disease for some years.

Onychomycosis of the toenails does not respond to griseofulvin therapy or topical treatments. The best treatment, which is also FDA approved, is oral terbinafine 250 mg daily for 12 weeks. Liver function tests and a complete blood count with platelets are performed monthly during treatment. Pulse oral itraconazole 200 mg twice daily for 1 week per month for 3 months is inferior to standard terbinafine treatments, but it is an acceptable alternative for those unable to take terbinafine. The courses of terbinafine or itraconazole may need to be repeated 6 months after the first treatment cycle if fungal cultures of the nail are still positive.

Bergstrom KG. Onychomycosis: is there a role for lasers? J Drugs Dermatol. 2011 Sep1;10(9):1074–75. [PMID: 22052283]

Dehesa L et al. Treatment of inflammatory nail disorders. Dermatol Ther. 2012 Nov–Dec;25(6):525–34. [PMID: 23210751]

Gupta AK et al. New therapeutic options for onychomycosis. Expert Opin Pharmacother. 2012 Jun;13(8):1131–42. Erratum in: Expert Opin Pharmacother.2013 Jan;14(1):149. [PMID: 22533461]

Shemer A. Update: medical treatment of onychomycosis. Dermatol Ther. 2012 Nov;25(6):582–93. [PMID: 23210757]



 Usually, abrupt onset of widespread, symmetric erythematous eruption.

 May mimic any inflammatory skin condition.

 Constitutional symptoms (malaise, arthralgia, headache, and fever) may be present.

 General Considerations

As is well recognized, only a minority of cutaneous drug reactions result from allergy. True allergic drug reactions involve prior exposure, an “incubation” period, reactions to doses far below the therapeutic range, manifestations different from the usual pharmacologic effects of the drug, involvement of only a small portion of the population at risk, restriction to a limited number of syndromes (anaphylactic and anaphylactoid, urticarial, vasculitic, etc), and reproducibility.

Rashes are among the most common adverse reactions to drugs and occur in 2–3% of hospitalized patients. Amoxicillin, TMP-SMZ, and ampicillin or penicillin are the most common causes of urticarial and maculopapular reactions. Toxic epidermal necrolysis and Stevens-Johnson syndrome are most commonly produced by sulfonamides and anticonvulsants. Phenolphthalein, pyrazolone derivatives, tetracyclines, NSAIDs, TMP-SMZ, and barbiturates are the major causes of fixed drug eruptions. Calcium channel blockers are a common cause of pruritus and eczemas in the elderly.

 Clinical Findings

  1. Symptoms and Signs

Drug eruptions are generally classified as “simple” or “complex.” Simple drug eruptions involve an exanthem, usually appear in the second week of drug therapy, and have no associated constitutional or laboratory findings. Antibiotics, including the penicillins and quinolones are the most common causes. Complex drug eruptions (also called drug-induced hypersensitivity syndromes [DIHS]) occur during the third week of treatment on average and have constitutional and laboratory findings. These may include fevers, chills, hematologic abnormalities (especially eosinophilia), and abnormal liver or kidney function. A mnemonic for complex eruptions is “DRESS” (DRug Eruption with Eosinophilia and Systemic Symptoms). The most common causes are the long-acting sulfonamides, allopurinol, and anticonvulsants. The use of anticonvulsants to treat bipolar disorder and chronic pain has led to an apparent increase in these reactions. In patients of certain races, polymorphisms of antigen presenting major histocompatibility (MHC) loci increases risk for the development of severe drug eruptions. In Han Chinese, HLA typing is indicated before institution of carbamazepine treatment, for example. Coexistent reactivation of Epstein-Barr virus, HHV-6, or cytomegalovirus is often present and may be important in the pathogenesis of these complex drug eruptions. Table 6–3 summarizes the types of skin reactions, their appearance and distribution, and the common offenders in each case.

Table 6–3. Skin reactions due to systemic drugs.

  1. Laboratory Findings

Routinely ordered blood work is of no value in the diagnosis of simple drug eruptions. In complex drug eruptions, the CBC, liver biochemical tests, and renal function tests should be monitored. Skin biopsies may be helpful in making the diagnosis.

 Differential Diagnosis

Observation after discontinuation, which may be a slow process, helps establish the diagnosis. Rechallenge, though of theoretical value, may pose a danger to the patient and is best avoided.


Some cutaneous drug reactions may be associated with visceral involvement. The organ systems involved depend on the individual medication or drug class. Most common is an infectious mononucleosis-like illness and hepatitis associated with administration of anticonvulsants. Myocarditis may be a serious complication of drug-induced hypersensitivity syndrome. Months after recovering from DRESS, patients may suffer hypothyroidism.


  1. General Measures

Systemic manifestations are treated as they arise (eg, anemia, icterus, purpura). Antihistamines may be of value in urticarial and angioneurotic reactions. Epinephrine 1:1000, 0.5–1 mL intravenously or subcutaneously, should be used as an emergency measure. In DIHS, systemic corticosteroids may be required, starting at about 1 mg/kg/d and tapering very slowly.

  1. Local Measures

SJS/TEN with extensive blistering eruptions resulting in erosions and superficial ulcerations, which demand hospitalization and nursing care as for burn patients, develops in some DIHS patients.


Drug rash usually disappears upon withdrawal of the drug and proper treatment. DIHS may be associated with autoimmune phenomena, including abnormal thyroid function. This can occur months after the hypersensitivity syndrome has resolved.

Bourgeois GP et al. A review of DRESS-associated myocarditis. J Am Acad Dermatol. 2012 Jun;66(6):e229–36. [PMID: 21658796]

Hausmann O et al. Etiology and pathogenesis of adverse drug reactions. Chem Immunol Allergy. 2012;97:32–46. [PMID: 22613852]

Summers EM et al. Chronic eczematous eruptions in the aging: further support for an association with exposure to calcium channel blockers. JAMA Dermatol. 2013 Jul;149(7):814–8. [PMID: 23636109]

Walsh S et al. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): is cutaneous phenotype a prognostic marker for outcome? A review of clinicopathological features of 27 cases. Br J Dermatol. 2013 Feb;168(2):391–401. [PMID: 23034060]

Wei CY et al. A recent update of pharmacogenomics in drug-induced severe skin reactions. Drug Metab Pharmacokinet. 2012;27(1):132–41. [PMID: 22041139]

Winnicki M et al. A systematic approach to systemic contact dermatitis and symmetric drug-related intertriginous and flexural exanthema (SDRIFE): a closer look at these conditions and an approach to intertriginous eruptions. Am J Clin Dermatol. 2011 Jun1;12(3):171–80. [PMID: 21469762]

Yin ZQ et al. Meta-analysis on the comparison between two topical calcineurin inhibitors in atopic dermatitis. J Dermatol. 2012 Jun;39(6):520–6. [PMID: 22409418]

1Hirsutism is discussed in Chapter 26.