ACP medicine, 3rd Edition
Elizabeth A. Abel MD1
Clinical Professor of Dermatology
Stanford University School of Medicine
The author has served as advisor or consultant to Abbott Laboratories, Amgen, Inc., Biogen Idec, Inc., and Genentech, Inc.
Papulosquamous disorders comprise a group of dermatoses that have distinct morphologic features.1 The characteristic primary lesion of these disorders is a papule, usually erythematous, that has a variable amount of scaling on the surface. Plaques or patches form through coalescence of the primary lesions. Some common papulosquamous dermatoses are pityriasis rosea, lichen planus, seborrheic dermatitis, tinea corporis, pityriasis rubra pilaris, psoriasis [see 2:III Psoriasis], and parapsoriasis. Drug eruptions, tinea corporis, and secondary syphilis may also have a papulosquamous morphology. Some papulosquamous disorders may be a cutaneous manifestation of AIDS.2
Pityriasis rosea is a relatively common, self-limited, exanthematous disease characterized by oval papulosquamous lesions on the trunk and proximal areas of the extremities. Pityriasis rosea typically appears during the spring and fall in temperate climates3; its incidence is highest in persons between 10 and 35 years of age.4
A population-based 10-year epidemiologic survey identified 939 patients with pityriasis rosea, about one third of whom had antecedent acute infection or atopy.5 It also showed that peak incidence occurred at 20 to 24 years of age, that the incidence was higher in colder months, and that recurrences were rare. Occurrences among household contacts are uncommon. This study also noted that the incidence of disease had appeared to decline.
A viral etiology has been suggested for pityriasis rosea on the basis of immunologic and histologic data. The superficial dermis contains aggregates of CD4+ helper T cells in perivascular locations and increased numbers of Langerhans cells. It has been postulated that IgM antibodies to keratinocytes cause the secondary form of the eruption. An association between human herpesvirus type 7 (HHV-7) and pityriasis rosea was initially reported in 1997.6 Studies using polymerase chain reaction and immunohistochemical analyses of tissue samples to detect HHV-7 DNA sequences and antigens have provided inconclusive evidence of a causal relationship between HHV-7 and pityriasis rosea. In a retrospective study of 13 patients and 14 control subjects, the prevalence of HHV-7 was lower in lesional skin of patients with pityriasis rosea than in control subjects.7 A subsequent seroepidemiologic study of HHV-6 and HHV-7 was conducted in 44 patients with pityriasis rosea and in 25 patients with other skin eruptions. Although in this study several patients with pityriasis rosea had antibody titers consistent with active infection, the overall prevalence of HHV-6 and HHV-7 was no greater in patients with pityriasis rosea than in control subjects.8 A meta-analysis reviewed the data from 13 studies and found insufficient evidence to support a causal relationship between HHV-7 infection and pityriasis rosea.9 A viral etiology of pityriasis rosea thus remains elusive. Certain drugs that cause a pityriasis rosea-like eruption have been implicated in the etiology of this disorder. These drugs include the antihypertensive agent captopril, metronidazole, isotretinoin (13-cis-retinoic acid), penicillamine, arsenic, gold, bismuth, barbiturates, and clonidine.4
The primary lesion, called a herald patch, appears first as a slightly raised, salmon-colored oval patch with a fine, wrinkled scale resembling cigarette paper. Typically, 7 to 10 days after the appearance of the herald patch, there occurs a bilaterally symmetrical eruption of smaller lesions; this secondary eruption occurs mainly on the trunk and upper extremities [see Figure 1]. Secondary lesions tend to follow cleavage lines (Langer lines) in a so-called fir tree distribution. A V-shaped formation on the upper chest and upper back, a circumferential pattern around the shoulders and hips, and a transverse pattern on the lower anterior trunk and lower back are seen in most patients.10 The lesions are occasionally pruritic. The secondary rash is frequently more helpful in making a diagnosis than the initial herald patch, which is often misdiagnosed.10 Atypical manifestations occur in 20% of persons affected. Such manifestations include a purpuric form of pityriasis rosea that resembles vasculitis, as well as papular, vesicular, pustular, and urticarial forms. An inverse variant of pityriasis rosea, more common in children than in adults, is characterized by lesions on the face and extremities, with relatively few lesions appearing on the trunk.4
Figure 1. Pityriasis Rosea
Pityriasis rosea commonly presents with a single large salmon-colored plaque called a herald patch (arrow). Appearance of the isolated lesion is followed in a week to 10 days by a bilaterally symmetric papulosquamous eruption, mainly on the trunk and upper extremities.
Because lesions of pityriasis rosea may closely resemble those of secondary syphilis, a serologic test for syphilis may be indicated. Lesions may also resemble tinea corporis or tinea versicolor and should be examined by fungal scrapings and potassium hydroxide (KOH) wet mounts. A careful drug history must be obtained to exclude the possibility of a drug eruption.
Pityriasis rosea lesions resolve spontaneously after 6 to 8 weeks. The patient should be reassured that the disorder is benign and self-limited; such reassurance, together with educating the patient about the disease, is the most important aspect of treatment. Lesions are variably pruritic. Symptoms should be treated with bland emollients or systemic antipruritics. Sun exposure may accelerate clearing. Irradiation with ultraviolet B (UVB) sunlamps is beneficial in decreasing the severity of disease, especially when treatment is initiated within the first week of the eruption. One study found that 10 erythemogenic exposures of UVB substantially decreased the extent of pityriasis rosea, although it neither altered the duration of the disorder nor improved the itching.11 Other evidence suggests that UVB therapy may hasten resolution of the rash but may cause hyperpigmentation.12
In a double-blind, placebo-controlled study in India, oral erythromycin administered in divided doses for 14 days was effective in treating patients with pityriasis rosea.13 In this cohort, upper respiratory tract infections preceded the skin eruption in 68.8% of the 90 patients. A complete response, with complete resolution of skin lesions occurring within 2 weeks, was reported in 33% of the treatment group, as compared with 0% in the placebo group. The duration of disease was comparable for the two groups of patients. Although not all patients with pityriasis rosea benefit from erythromycin therapy, a trial of erythromycin is a safe treatment approach.
Lichen planus is a localized or generalized eruption with violaceous, flat-topped, polygonal papules and little or no observable scaling [seeFigure 2]. It is often localized to the oral mucosa; 25% of patients with oral lichen planus have skin involvement as well.14 The incidence is highest in young to middle-aged persons. Lichen planus usually appears in the fifth or sixth decade and affects women more often than men.
Figure 2. Lichen Planus
Violaceous, flat-topped, polygonal papules are typical of lichen planus. A common location is the flexor aspect of the wrists and forearms.
The etiology of lichen planus is unknown. An alteration in basal keratinocytes that induces humoral and cell-mediated immune responses has been postulated as a mechanism. Skin and mucous membrane lesions resembling lichen planus have been observed in patients with graft versus host disease (GVHD) [see 2:VI Cutaneous Adverse Drug Reactions]. Lichen planus has also been associated with other immune-mediated diseases, including ulcerative colitis, bullous pemphigoid, myasthenia gravis with thymoma, primary biliary cirrhosis, and chronic active hepatitis.15
There is an increased prevalence of viral hepatitis, especially hepatitis C, in patients with lichen planus. In a multicenter study of 303 sequential patients with lichen planus, the prevalence of hepatitis C virus (HCV) was 19.1%, compared with 3.2% in control subjects.16 The role of HCV in the pathogenesis of lichen planus is not clearly understood; some investigators suggest that the cause of lichen planus may be related to the pattern of immune dysregulation induced by HCV.17 There are a number of reports of lichen planus occurring after administration of different types of hepatitis B vaccine.18 This is a rare occurrence, considering the widespread use of this vaccine; several cases have been reported from France and Italy, and one case has been reported from the Middle East. An immunologic mechanism has been postulated as the cause. The latency period ranges from several days to 3 months after any one of the three usual injections of vaccine.
A variety of drugs have been reported to cause lichenoid reactions in the skin, usually sparing the mucous membranes. Such drugs include beta blockers, methyldopa, penicillamine, quinidine, and quinine. Other drugs that have been implicated but for which causal evidence is insufficient include angiotensin-converting enzyme inhibitors, sulfonylurea agents, carbamazepine, gold, and lithium.19 In one study, the administration of penicillamine for primary biliary cirrhosis was followed by the development of lichen planus in 17 of 24 patients20; in addition, after treatment with penicillamine, the skin eruption became worse in three of seven patients with biliary cirrhosis and preexisting lichen planus. Nonsteroidal anti-inflammatory drugs have been documented to cause a lichenoid drug eruption; these drugs include naproxen, indomethacin, diflunisal, ibuprofen, acetylsalicylic acid, and salsalate.21 Although the latency period is highly variable, symptoms usually develop within a few months after drug initiation and resolve within weeks to months after discontinuance of the offending agent.
Lichen planus appears as flat-topped, shiny, violaceous papules, often with a fine, reticulated scale on the surface. Common sites of involvement include the skin, nails, mucous membranes, vulva, and penis. Wickham striae—white, lacy patterns on the papule surface—are apparent on magnification with a hand lens.22 The occurrence of papules along a scratch line, as in linear lichen planus, is referred to as the Koebner phenomenon [see Figure 3]. In the hypertrophic form of the disease, papules coalesce to form thick plaques or nodules that are often found on the lower extremities. Pruritus may be severe, particularly in the generalized or hypertrophic forms of the disease. Common sites of involvement are the flexor surfaces of the wrists, the sacrum, the mucous membranes of the mouth, the medial thighs, and the genitalia. Mucous membrane lesions show a white, reticulated mosaic pattern [see Figure 4]. A severe erosive form of lichen planus can involve the oral mucous membranes. In rare cases, lesions occur in the esophagus, causing esophageal stricture and dysphagia.23
Figure 3. Kobner Phenomenon
Koebner's phenomenon, the appearance of lesions along a scratch line, may be seen in patients with lichen planus.
Figure 4. Lichen Planus of Mucous Membranes
Lichen planus of the mucous membrane assumes a white, reticulated mosaic pattern, as seen above on the buccal mucosa.
A follicular form known as lichen planopilaris may result in scarring alopecia. Variants of lichen planus with distinct morphologic features include actinic, annular, bullous, hypertrophic, linear, ulcerative, and zosteriform forms. The nails may also be involved [see 2:XIV Diseases of the Nail]. The clinical features of some forms of lichen planus may resemble those of lupus erythematosus.22
Skin biopsy confirms the clinical diagnosis of lichen planus. Typically, the epidermis shows hyperkeratosis, a prominent granular layer, liquefaction degeneration of the basal cell layer, and an intense upper dermal inflammatory infiltrate. Immuno peroxidase studies using monoclonal antibodies to cell surface antigens have shown that most cells in the infiltrate are of the helper-inducer T cell subset. Colloid bodies (Civatte bodies) coated with immunoglobulin are frequently seen in the dermal papillae. On ultrastructural examination, numerous Langerhans cells can be observed at the dermoepidermal junction.
Limited data exist for making evidence-based recommendations regarding treatment of lichen planus.24,25 Definitive clinical trials have not been performed, and information on the efficacy of treatments is derived from small trials and anecdotal evidence.
Emollients, topical glucocorticoids, a short course of systemic corticosteroids, and systemic antipruritics have been used to treat cutaneous lichen planus. Most experts recommend medium- to high-potency topical corticosteroids as first-line treatment for localized cutaneous lichen planus. Oral corticosteroids may be used for generalized cutaneous lichen planus. As an alternative to systemic corticosteroids, systemic retinoids, such as acitretin, are beneficial in some patients with cutaneous forms of lichen planus.26 Azathioprine has been used for its steroid-sparing effect in erosive and generalized lichen planus.27
Other therapies that have been reported to have efficacy in the treatment of cutaneous lichen planus include phototherapy (psoralen plus ultraviolet A [PUVA]), cyclosporine, and hydroxychloroquine.24 In a trial of oral psoralen photochemotherapy for widespread recalcitrant lichen planus, clinical remission occurred in six of seven patients and correlated with the disappearance of the upper dermal infiltrate.28 Oral cyclosporine has also been effective, but potential renal toxicity and hypertension limit its long-term use.22 Recombinant interferon alfa-2b, administered subcutaneously every other day, was successful in the treatment of generalized lichen planus in three patients with no evidence of hepatitis, further supporting the cell-mediated immunologic etiology of this disease.29
For lichen planus that is localized to the oral mucosa, a high-potency corticosteroid such as clobetasol in a vehicle that is adherent to the mucosal surface (Orabase) is helpful.24,29 Intralesional injections of corticosteroids may be used to treat localized, recalcitrant lesions. Use of miconazole gel in combination with chlorhexidine mouth rinses is effective for prophylaxis against oral candidiasis.30 Topical isotretinoin gel is an effective alternative to corticosteroids, although relapses often occur after discontinuance of this medication.31 In a double-blind, placebo-controlled study of 22 patients with biopsy-proven oral lichen planus, an 8-week course of 0.1% isotretinoin gel was found to be effective.31 Cyclosporine mouth rinses have been helpful for some patients. A 6-month course of hydroxychloroquine, 200 to 400 mg daily, was successful in nine of 10 patients with oral lichen planus; ulcers healed and pain decreased after 1 to 2 months.32 Topical tacrolimus, a macrolide that suppresses T cell activation, was used to treat erosive mucosal lichen planus in 19 patients whose conditions were resistant to conventional treatment. Therapeutic levels of tacrolimus were demonstrated in eight patients, and areas of ulceration showed a mean decrease of 73.3% over the 8-week study period; however, 13 of 17 patients suffered a relapse after cessation of therapy.33 Topical pimecrolimus cream is being evaluated as a treatment for oral erosive lichen planus.34 The role of these agents in the treatment of lichen planus must be further investigated, particularly in view of the alert by the Food and Drug Administration issued in 2005 regarding a possible link between use of topical tacrolimus and pimecrolimus and cases of lymphoma and skin cancer.
Genital and Perianal Lesions
Mild, nonerosive disease can be controlled with topical corticosteroids; erosive disease, although more difficult to treat, may be treated with topical corticosteroids in combination with other topical or systemic medications.35 Topical tacrolimus36,37 and topical pimecrolimus38 may be useful in the treatment of recalcitrant cases that have failed to respond to other therapies.
Patients who experience an acute outbreak of lichen planus have a good prognosis; in most cases, the papules clear within several months to a year. The chronic form, however, may last for 10 years or longer. In a study following the long-term course of lichen planus in 214 patients for 8 to 12 years, lichen planus cleared in two thirds of the patients within 1 year. The recurrence rate was 49%, which was higher than recurrence rates reported in previous studies; the authors attributed the high rate of recurrence to treatment with potent topical corticosteroids.39
Seborrheic dermatitis is a papulosquamous condition that is often associated with excessive oiliness or seborrhea, dandruff, and well-defined red, scaly patches on the face, trunk, and intertriginous areas.40 Some cases may progress to a severe exfoliative erythroderma. Seborrheic dermatitis is a common skin disorder that occurs in otherwise healthy adults. It is increasingly prevalent in middle-aged and elderly persons. Seborrheic dermatitis does not occur before puberty except during infancy (usually between 2 and 12 weeks of age), at which time transplacentally derived maternal hormones are present. The prognosis in adults is one of lifelong recurrence, with each episode lasting weeks to months.
The cause of seborrheic dermatitis is unknown. An occasional association with neurologic abnormalities, especially parkinsonism, has been observed. Genetic predisposition, emotional stress, diet, hormones, and climatic factors may also influence this disorder. It is thought that an association exists between the yeastlike organism Pityrosporum and seborrheic dermatitis. Seborrheic dermatitis may, in part, be the result of an abnormal or inflammatory immune response to this yeast, or it may be caused by an epidermal hyperproliferation of this organism.41
Patients with classic seborrheic dermatitis may have normal or reduced rates of sebum excretion; therefore, seborrhea is not essential for the development of this disorder.42 However, seborrhea may play a role in the seborrheic dermatitis present in certain patients, such as those with parkinsonism. Reduction of seborrhea with improvement of the dermatitis has been observed after a favorable neurologic response to levodopa treatment for parkinsonism.
The scale associated with seborrheic dermatitis may be yellowish and either dry or greasy. Sites of predilection are the areas of sebaceous gland activity [see Figure 5], such as the scalp, eyebrows, eyelids, forehead, nasolabial folds, and presternal or interscapular regions. Blepharitis involves granular inflammation of the lid margin, with scaling and shedding of debris into the eye, which may cause conjunctivitis. Seborrheic dermatitis is the most common cause of otitis externa. When the scalp is involved, lesions often extend along the frontal hairline, forming a band of erythema. The postauricular area is a common site of involvement. Lesions of the trunk may consist of erythematous follicular papules covered by greasy scales, which may coalesce to form large plaques or circinate patches. Seborrheic dermatitis can be seen in areas of male pattern baldness, but it is not a cause of hair loss unless there has been a severe intervening secondary infection resulting in a scarring alopecia.
Figure 5. Seborrheic Dermatitis
Seborrheic dermatitis seen on the face of this patient involves sites of sebaceous gland activity.
Seborrheic dermatitis should be considered in the differential diagnosis of chronic eczematous dermatitis and in that of papulosquamous disorders, particularly psoriasis. The clinical features of seborrheic dermatitis limited to the scalp and face may resemble those associated with psoriasis, giving rise to the term sebopsoriasis. Histologic features range from psoriasiform changes of acanthosis and parakeratosis to the spongiosis of eczema. Seborrheic dermatitis of the face may resemble the facial lesions found in lupus erythematosus or other photosensitivity dermatoses. Lesions on the trunk may be confused with tinea versicolor, but the latter is easily excluded by skin scraping and KOH preparation or Wood light examination. Atopic dermatitis and psoriasis, especially when partially treated, are also included in the differential diagnosis.
SEBORRHEIC DERMATITIS ASSOCIATED WITH AIDS
Severe seborrheic dermatitis can be one of the most common and earliest manifestations of AIDS. From 30% to 80% of patients with AIDS have seborrheic dermatitis, compared with 3% to 5% of HIV-negative young adults.43 Lesions may be explosive in onset and are often resistant to therapy. Clinical features include a predominantly inflammatory papular eruption on the face, with a tendency to spare the scalp, in contrast to the mild erythema and scaling of the scalp typical of seborrheic dermatitis in persons without AIDS. Truncal involvement in seborrheic areas is common in AIDS patients, and the lesions may resemble psoriasis. Although the cause of the association of seborrheic dermatitis with AIDS is unknown, immunologic dysfunction may lead to an overgrowth of the yeast P. orbiculare in seborrheic areas.
Skin biopsy specimens from AIDS patients with seborrheic dermatitis have distinct histologic features, including keratinocyte necrosis, leukoexocytosis, a superficial perivascular infiltrate of plasma cells, and, frequently, neutrophils.44
The condition on the scalp usually responds well to frequent—as often as daily—shampooing with a preparation containing 3% to 5% sulfur and 2% to 3% salicylic acid. Good response has also been reported with use of ciclopirox 1% shampoo once or twice weekly.45 For the face and nonhairy areas, a mild cream containing precipitated 3% sulfur and 3% salicylic acid is effective. Involved areas also respond well to low-potency topical glucocorticoids, such as 1% hydrocortisone cream or desonide cream. Caution, however, must be exercised in the use of high-potency fluorinated steroid preparations, especially on the face and in skin folds; prolonged application may lead to chronic skin changes, such as atrophy and telangiectasia. Wet dressings followed by a topical antibiotic preparation are helpful in treating intertriginous areas, in which maceration and superficial secondary infection may occur.
Topical antifungal agents have been used in the treatment of seborrheic dermatitis. In addition to their antifungal properties, certain azoles (e.g., bifonazole, itraconazole, and ketoconazole) have demonstrated anti-inflammatory activity, which may be beneficial in alleviating symptoms.46 In one study, 575 patients with seborrheic dermatitis underwent twice-weekly treatments with 2% ketoconazole shampoo; an excellent response was seen in 88% of the patients.47 Continued prophylactic treatment once weekly over 6 months was helpful in preventing relapse of the disorder in a significant number of patients.
In a trial of 38 patients with seborrheic dermatitis, 1% metroni dazole gel was found to be effective. Improvement was noted after 2 weeks, and marked improvement or complete clearing was noted at 8 weeks48; however, in a randomized, controlled trial, metronidazole 0.75% gel and placebo were found to have similar efficacy.49 In a small randomized, open-label clinical trial, pimecrolimus 1% cream and betamethasone 1% cream were both found to be effective in reducing symptoms of seborrheic dermatitis, but relapses were observed more frequently with betamethasone.50 A multicenter, randomized, controlled trial found oral terbinafine (an antimycotic allylamine compound) to be effective in patients with moderate to severe seborrheic dermatitis.51
Seborrheic blepharitis may be treated by applying baby shampoo with a cotton-tipped applicator to debride scales. If topical corticosteroids are required, the patient should be referred to an ophthalmologist to monitor potential side effects to the eye, such as increased intraocular pressure, glaucoma, cataracts, and activation of latent herpes infection.1
Treatment of HIV-associated seborrheic dermatitis is similar to that of seborrheic dermatitis in general, although HIV-associated seborrheic dermatitis is apt to be recalcitrant, requiring intensive, prolonged therapy. Treatment of the underlying HIV infection may lead to improvement of the associated seborrheic dermatitis.
Pityriasis Rubra Pilaris
Pityriasis rubra pilaris is a relatively uncommon chronic inflammatory dermatosis that is considered to be a disorder of keratinization. The age distribution is bimodal, occurring either in childhood or in the fifth decade; the clinical course is variable. An autosomal dominant inheritance has been postulated for the juvenile form of the disease.52 Patients with the classic adult form of the disease have the best prognosis; resolution usually occurs over a 3-year period.
Typically, pityriasis rubra pilaris initially manifests itself as a seborrheic dermatitis-like eruption that occurs on sun-exposed areas of the body; this eruption is followed by the development of follicular papules that coalesce into psoriasiform patches on the trunk and extremities, with progression to erythroderma. Generalized involvement is characterized by yellow-orange erythema with desquamation. Diffuse areas of involvement generally show islands of spared skin [see Figure 6]. Additional features are palmoplantar hyperkeratosis [see Figure 7] and prominent follicular plugging over the dorsal aspects of the fingers. Pruritus is usually mild or absent. A pityriasis rubra pilaris-like eruption with follicular hyperkeratosis is a little known but distinctive cutaneous manifestation of dermatomyositis.53
Figure 6. Pityriasis Rubra Pilaris
Islands of spared skin within a background of diffuse erythema are present on the legs of this patient with pityriasis rubra pilaris.
Figure 7. Pityriasis Rubra Pilaris
Plantar hyperkeratosis and confluent erythematous follicular papules typical of pityriasis rubra pilaris are seen on the ankle and foot of this patient.
The response of patients with pityriasis rubra pilaris to conventional antipsoriatic therapies, such as topical corticosteroids, tars, and oral methotrexate, is often unsatisfactory; some patients, however, have shown a favorable response to topical calcipo triene (known outside the United States as calcipotriol).54 UVB phototherapy may exacerbate the disease.55 High-dose vitamin A in excess of 200,000 IU daily has been used but can cause liver or central nervous system toxicity. An oral retinoid such as acitretin or isotretinoin is indicated for the treatment of pityriasis rubra pilaris in men and postmenopausal women. In an early study involving 45 patients with pityriasis rubra pilaris, isotretinoin produced definite improvement in 50% of the patients after 4 weeks of therapy.56 Remission of up to 6 months was sustained in some patients after the drug was withdrawn. Long-term use of this drug in patients with keratinizing disorders has been associated with irreversible skeletal toxicity. Because teratogenicity is a concern, women of childbearing age must use effective birth control with either agent.
In a study of patients with pediatric pityriasis rubra pilaris, isotretinoin achieved the best response among a range of therapies including steroids, systemic retinoids, and methotrexate; five of six patients treated with isotretinoin showed 90% to 100% clearing of lesions within 6 months of initiation of treatment.57 Cyclosporine, 5 mg/kg/day, was effective in the treatment of three adult patients with pityriasis rubra pilaris, with a favorable response being noted within 2 to 4 weeks of initiation of therapy; however, relapse occurred when the dose was decreased to 1.2 mg/kg/day.58
Numerous reports have suggested that infliximab, a monoclonal antibody that binds to tumor necrosis factor-α, may be useful in the treatment of cutaneous inflammatory diseases, such as pityriasis rubra pilaris.59 The drug is currently approved by the FDA for the treatment of rheumatoid arthritis and Crohn disease; further investigation is required to determine its efficacy for cutaneous dermatoses.
Parapsoriasis encompasses a variety of relatively uncommon chronic inflammatory dermatoses of unknown etiology that are resistant to conventional treatment. Despite the designation parapsoriasis, the clinical appearance of the noninfiltrated scaly patches or plaques is distinct from that of psoriatic lesions. Classification of these disorders is controversial and is further complicated by the use of several terms to denote a single entity and by the use of various systems of nomenclature. A proposed standard nomenclature divides parapsoriasis into two distinct subgroups: pityriasis lichenoides, which may be acute or chronic, and small- and large-plaque parapsoriasis.60
The acute form of pityriasis lichenoides, also known as pityriasis lichenoides et varioliformis acuta (PLEVA) or Mucha-Habermann disease, is characterized by the abrupt onset of a generalized eruption of reddish-brown maculopapules that evolve during a period of weeks to months. Lesions are typically present at all stages of evolution and may be vesicular, hemorrhagic, crusted, or necrotic [see Figure 8]. Healing with varioliform scarring is common. Nonspecific histologic features include intraepidermal lymphocytes and erythrocytes, dermal hemorrhage, and a lymphocytic vasculitis.61 Skin lesions of PLEVA may resemble those of lymphomatoid papulosis, which has immunohistologic features of a CD30+ cutaneous T cell lymphoma.62 Lymphomatoid papulosis occurs as a chronic, recurrent, self-healing papulo nodular eruption; an association with mycosis fungoides has been observed in some patients. T cell clonality has been documented by PCR in 20 patients with PLEVA; similar findings have been made in patients with lymphomatoid papulosis.63 Investigators have suggested that PLEVA is a lymphoproliferative process rather than an inflammatory reaction to various trigger factors, such as infectious agents. One case report demonstrated that pityriasis lichenoides lesions evolved concomitantly with a known Epstein-Barr virus (EBV)-mediated disease (i.e., acute infectious mononucleosis), suggesting that pityriasis lichenoides may be caused by EBV infection.64
Figure 8. Acute Pityriasis Lichenoides
Hemorrhagic brown-crusted varioliform papules are present on the lower legs of this patient with the acute form of pityriasis lichenoides.
A chronic form of pityriasis lichenoides, pityriasis lichenoides chronica, shows milder skin changes without necrosis. Lesions evolve during a period of weeks and may recur over many years.
Treatment of both acute and chronic forms of pityriasis lichenoides is generally unsatisfactory. Topical corticosteroids, tars, and systemically administered methotrexate have all been tried, with variable success. Ultraviolet radiation from sunlamps65 and oral psoralen photochemotherapy66 may have a beneficial effect on the course of disease. High-dose tetracycline, 2 g/day for 1 month or more,67 and minocycline, 100 mg once or twice daily, have also been shown to be effective treatments. A rare type of Mucha-Habermann disease known as Degos disease (also called malignant atrophic papulosis), characterized by fever and hemorrhagic and papulonecrotic lesions, responds rapidly to the administration of methotrexate [see 15:VIII Systemic Vasculitis Syndromes].68
SMALL- AND LARGE-PLAQUE PARAPSORIASIS
Small-plaque parapsoriasis consists of slightly scaly, thin, oval erythematous plaques of less than 5 cm in diameter, commonly located on the trunk and proximal extremities. The variant—digitate dermatosis—shows elongated lesions falling along lines of skin cleavage. The two diseases follow similar chronic, benign courses [see Figure 9].
Figure 9. Small-Plaque Parapsoriasis
The digitate variant of small-plaque parapsoriasis is seen in this patient.
Clinically, large-plaque parapsoriasis consists of slightly thickened, red-brown, scaly plaques that are more than 10 cm in diameter and have ill-defined borders; such lesions are present mainly on the proximal extremities and the buttocks and on the breasts of women [see Figure 10]. Frequently, there is a component of poikiloderma, which includes mottled hyperpigmentation and hypopigmentation, atrophy, and telangiectasia. Early lesions may show a nonspecific histology; late lesions show atypical lymphocytes within the epidermis.
Figure 10. Large-Plaque Parapsoriasis
Large-plaque parapsoriasis as seen on the buttocks of this patient may eventuate in cutaneous T cell lymphoma.
It is important to differentiate large-plaque parapsoriasis from the small-plaque form because about 10% of cases of large-plaque parapsoriasis result in a cutaneous T cell lymphoma (mycosis fungoides).60 Large-plaque lesions may be present for many years before malignant transformation is recognized histologically. The malignant change is suggested clinically by increased pruritus and progressive induration of lesions. The retiform variant may show prominent poikiloderma with atrophy and has a greater potential for malignant transformation.69 Studies of T cell subsets using monoclonal antibodies to membrane markers have shown a variable predominance of helper T cells in the cutaneous infiltrates in atrophic parapsoriasis; such findings suggest a similarity to lesions of mycosis fungoides, although epidermotropism is absent.70 Patients with this form of the disease should be evaluated with repeated biopsies of untreated lesions. Once a definitive diagnosis of mycosis fungoides has been established, specific treatment of this disease may be instituted.
Treatment of large- and small-plaque parapsoriasis is similar to that of pityriasis lichenoides chronica [see Pityriasis Lichenoides, above].
Papulosquamous and psoriasiform eczematous dermatitis may progress to generalized skin involvement with erythema and scaling, known as exfoliative erythroderma. Other causes of erythroderma include drug eruption, contact dermatitis, and pityriasis rubra pilaris. Eyrthroderma is a rare skin disorder that occurs more often as an exacerbation of a preexisting skin disorder; less commonly, it is idiopathic. There are no accurate studies on the incidence of erythroderma. On the basis of a survey of all dermatologists in the Netherlands, however, the annual incidence was estimated to be one to two patients per 100,000 inhabitants.71
Most cases of exfoliative erythroderma are associated with exacerbation of an underlying dermatosis, such as psoriasis, pityriasis rubra pilaris, seborrheic dermatitis, drug eruptions, atopic dermatitis, or contact dermatitis.72 Some patients have idiopathic erythroderma, also called red man syndrome.69 Common associated skin findings include palmoplantar keratoderma, alopecia, and nail dystrophy. Skin biopsy usually shows nonspecific inflammation. Lymph node biopsy may reveal dermatopathic lymphadenopathy. In some patients, idiopathic erythroderma may progress to cutaneous T cell lymphoma (e.g., erythrodermic mycosis fungoides and Sézary syndrome) [see Figure 11] [see 2:X Malignant Cutaneous Tumors].
Figure 11. Erythroderma in Sezary Syndrome
Erythroderma, which appears as total skin erythema and scaling, can occur as a result of papulosquamous and eczematous disorders caused by a variety of diseases. Cutaneous T cell lymphoma, as seen in this patient with Szary syndrome, can result in erythroderma.
Systemic symptoms associated with erythroderma include fever and chills, dehydration from transepidermal water loss, and high-output cardiac failure.
Nonspecific treatment includes restoration of fluid and electrolyte balance and supportive measures such as administration of antipruritics, application of cool compresses and mild topical corticosteroids, and bed rest. Antibiotics may be required for treatment of secondary bacterial infection. Generally, more aggressive topical and systemic therapies are avoided until the inflammation subsides. More specific treatment depends on the underlying diagnosis and cause of the erythroderma. For example, in patients with erythroderma that is secondary to Sézary syndrome, treatment would be directed toward the underlying cutaneous T cell lymphoma [see 2:X Malignant Cutaneous Tumors]. For erythroderma caused by a drug eruption, the offending drug must be discontinued. Systemic agents such as acitretin and methotrexate may be used to treat psoriatic erythroderma [see 2:III Psoriasis]. Drug-induced erythroderma may have the best prognosis.72
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Editors: Dale, David C.; Federman, Daniel D.