ACP medicine, 3rd Edition


Approach to the Diagnosis of Skin Disease

Robert T. Brodell MD1

Professor of Internal Medicine and Clinical Professor of Dermatopathology in Pathology

Stephen E. Helms MD2

Associate Professor of Clinical Internal Medicine

1Northeastern Ohio Universities College of Medicine and Case Western Reserve University School of Medicine

2Northeastern Ohio Universities College of Medicine

The authors have no commercial relationships with manufacturers of products or providers of services discussed in this chapter.

July 2007

Patients frequently see their primary care physician for skin disease1; however, compared with dermatologists, primary care physicians treat substantially fewer patients with common skin conditions, and the types of cutaneous disease they treat tend to be few in number.2,3 One study reported that over a 1-year period, the number of patient visits to dermatology offices for the treatment of acne or contact dermatitis was 728 and 352, respectively; by contrast, internists averaged three and nine visits a year, respectively, and family physicians averaged eight and 27 visits a year.2 The relative inexperience with cutaneous presentations gives rise to possible error in the dermatologic care offered by nondermatologists. Some studies have reported that nondermatologists perform poorly in the diagnosis and treatment of skin disease.4 One area of concern is the apparent low proficiency among nondermatologists in the diagnosis of skin cancer.5,6 Most problems encountered by primary care physicians in the treatment of skin disease can be attributed to difficulties in establishing the accurate diagnosis of cutaneous presentations.

Diagnosis of a cutaneous disease is most reliably achieved by a stepwise approach to patient evaluation that begins with an examination of the morphologic features of the skin lesions and frequently culminates in diagnostic testing.7 This chapter reviews the primary skin lesions by which dermatologic diseases are categorized (e.g., papulosquamous diseases, blistering diseases, nonscaling erythematous and infiltrative diseases, and tumors) and presents a method by which the physician can narrow the possible causes of a specific presentation and arrive at a diagnosis in a cost-effective manner.

Approach to the Patient with a Dermatologic Lesion

Dermatology is a visual specialty, and physical examination is primarily oriented toward observing the skin. Dermatologists approach skin disease in a manner that has been tested over time and perpetuated in the training of medical students and residents. A simple diagnostic evaluation based on the approach preferred by dermatologists allows primary care physicians to narrow the possible causes of a cutaneous presentation and arrive at an accurate diagnosis.

Diagnostic Evaluation

Diagnostic evaluation of a cutaneous presentation begins with a brief patient history that is directed at the nature of the chief complaint and its onset; factors that aggravate and alleviate symptoms; and responses to over-the-counter or prescription medications. This is followed by careful inspection of the skin. In examining a patient with a rash, the first step is to try to identify primary lesions (i.e., lesions that appear early in the disease process) [see Morphologic Classification of Skin Disorders, Primary Lesions, below]); these lesions help to categorize the disease and provide the basis for diagnosis. Information derived from the identification of primary lesions is augmented by an examination of primary lesions that have undergone change. Secondary changes to primary lesions may occur naturally or after trauma, such as scratching [see Morphologic Classification of Skin Disorders, Secondary Changes, below]. The location, distribution, and configuration of primary lesions and their secondary changes are analyzed. Then the findings are categorized to promote the development of a differential diagnosis.

After an examination of the lesions, a more complete patient history is obtained, including the patient's family history, social history, and medical history. The expanded patient history is followed by a focused general medical examination. In the context of a detailed patient history, the general medical examination often provides diagnostic clues that further narrow the differential diagnosis.

The final step in a dermatologic examination comprises various forms of testing (e.g., dermatologic testing, skin biopsy, and laboratory tests) [see Arriving at a Diagnosis, below] to confirm the diagnosis or sufficiently narrow the differential diagnosis to permit selection of the most appropriate treatment. If the diagnosis remains uncertain after testing, consultation with a dermatologist may be useful in establishing the diagnosis. The patient is typically scheduled for a follow-up visit after initiation of treatment. The purpose of the follow-up visit is to assess the response to therapy and to confirm that the proper diagnosis was rendered.

Suboptimal Methods of Diagnosis and Management

Errors in dermatologic diagnosis can be classified into several categories. It is worth exploring these problems to avoid falling into predictable traps.

Treating Symptoms Rather than Diseases

Establishing the underlying cause of symptoms is a guiding principle in medicine; however, the treatment of dermatologic presentations frequently focuses on symptom management without addressing the underlying cause. This approach is seldom an efficient or effective form of management. For example, treatment of pruritus with antihistamines is a poor substitute for establishing a definitive diagnosis of the underlying condition that is causing this symptom. In the case of a patient with severe itching associated with dermatitis herpetiformis, treatment with a topical corticosteroid may give temporary relief from pruritus; however, a careful examination would most likely reveal grouped papulovesicles on the extensor surfaces of the extremities, and a biopsy would confirm the diagnosis of dermatitis herpetiformis. Treatment of dermatitis herpetiformis with a gluten-free diet and oral dapsone would lead to dramatic, long-lasting remission.

Snapshot Approach to Diagnosis

A snapshot diagnosis is rendered on the basis of the physical appearance of a rash or other form of lesion in the absence of any other data. This method of examination is quick; however, it can lead to inaccurate diagnosis and imprecise and inadequate treatment. For example, a patient with widespread scaling, erythema, lichenification, and excoriations may appear to have eczema. On careful examination, however, burrows are detected in the patient's finger webs. The patient reports that itching is more severe at night and that family members are also experiencing itching. A scabies preparation test discloses the presence of mites, confirming the diagnosis as scabies infestation. Thus, a snap diagnosis of eczema and treatment with topical steroids would have been inappropriate in this case.

Shotgun Management

A suboptimal approach to the management of a dermatologic presentation is touted by physicians who believe that all rashes look alike and are either inflammatory or infectious. This leads to the shotgun approach to management, which advocates increasing the potential for successful treatment of an unknown skin disease by treating all possible causes. For example, the use of a topical steroid/antifungal preparation for a papulosquamous process may seem a prudent treatment of two possible disorders—namely, eczema and superficial fungal infection; however, if the patient has a dermatophyte-induced fungal infection, the topical steroid may decrease local immunity and prevent the elimination of fungal organisms. This management strategy is expensive, increases the risk of iatrogenic disease, and delays appropriate diagnosis and treatment.

A shotgun approach may also be used in diagnostic evaluation; such an approach entails the ordering of a broad battery of tests in the hope of stumbling upon the correct diagnosis. This inefficient method can lead to false positive results that confuse rather than confirm the diagnosis.

All rashes present physical diagnostic clues that are useful in establishing a diagnosis. A careful evaluation of the lesions' morphologic characteristics, coupled with a thorough patient history and examination, will most likely provide an accurate diagnosis. If the diagnosis remains uncertain, the morphologic condition of the lesion will suggest which specific tests are appropriate for arriving at the diagnosis.

Morphologic Classification of Skin Disorders

Primary Lesions

The first step in the diagnosis of a rash is to identify primary lesions [see Table 1]. Primary lesions are those physical characteristics of skin disease that appear initially and are most useful in developing a differential diagnosis. The characterizing features of primary lesions include whether they are flat or raised, solid or fluid filled, dark or light in color, large or small, smooth or rough. Lesions may be few or numerous, localized or widespread. The newly erupted and undisturbed lesions are most often helpful in categorizing skin conditions in a manner that leads to a correct diagnosis.

Table 1 Primary Lesions: Consensus Definitions of Dermatologic Morphologic Terms7

Morphologic Term

DLP Proposed Definition


A fluid-filled blister greater than 0.5 cm in diameter; fluid can be clear, serous, hemorrhagic, or pus-filled


An enlarged hair follicular infundibulum primarily containing keratin and lipids and having a plugged, dilated follicular opening (blackhead) or a clinically unapparent follicular opening (whitehead)


A flat area of skin or mucous membranes having a color different from the surrounding tissue and a diameter generally less than 0.5 cm; macules may have nonpalpable, fine scales


A dermal or subcutaneous firm, well-defined lesion usually greater than 0.5 cm in diameter


A discrete, solid, elevated body usually less than 0.5 cm in diameter; papules are further classified by shape, size, color, and surface change


A flat area of skin or mucous membranes having a color different from the surrounding tissue and a diameter generally greater than 0.5 cm; patches may have nonpalpable, fine scales


A discrete, solid, elevated body usually broader than it is thick and measuring more than 0.5 cm in diameter; plaques may be further classified by shape, size, color, and surface change


A circumscribed elevation that contains pus; pustules are usually less than 0.5 cm in diameter


Fluid-filled cavity or elevation less than 0.5 cm in diameter; fluid may be clear, serous, hemorrhagic, or pus-filled


An edematous, transitory papule or plaque

DLP—Dermatology Lexicon Project

Primary skin lesions can be defined simply. Flat lesions are referred to as macules when they are smaller than 0.5 cm and as patches when they are greater than 0.5 cm in diameter [see Figures 1a, 1b, and 1c]. Small raised bumps are referred to as papules [see Figures 2a and2b], and large lesions of this type are referred to as nodules; nodules typically have a deeper dermal component [see Figure 2c]. Discrete, broad, raised eruptions are referred to as plaques [see Figure 2d]. Raised lesions containing fluid (commonly known as blisters) are referred to as vesicles when smaller than 0.5 cm [see Figures 3a and 3b] and as bullae when larger than 0.5 cm in diameter [see Figure 3c]. Vesicles and bullae are usually clear but may be turbid. White or yellow fluid-filled lesions are called pustules. Atrophic lesions exhibit a thinned epidermis that is often depressed; they have a scaly, shiny surface that has the texture of cigarette paper. An edematous transitory papule or plaque is called a wheal [see Figure 4].


Figure 1. (a) Schematic drawing of macules (lesions < 0.5 cm) or patches (lesions > 0.5 cm). Macules and patches are flat areas of skin for which the color and texture differ from that of the surrounding tissue. (b) Nonblanching erythematous macules and patches are present in a patient with a drug eruption. (c) Depigmented macules are noted on the face of a patient with vitiligo.


Figure 2. (a) Schematic drawing of papules (lesions < 0.5 cm) or nodules (lesions > 0.5 cm). Papules and nodules are discrete, solid, elevated lesions. (b) A raised, dome-shaped, erythematous papule is seen in a case of dermatofibroma. (c) A raised, flat-topped, erythematous, and hyperkeratotic nodule with scalloped edges is present in a patient with squamous cell carcinoma. (d) Large, erythematous plaques of psoriasis have an annular appearance, owing to their elevated margins.


Figure 3. (a) Drawing of a vesicle (lesions < 0.5 cm) or bulla (lesions > 0.5 cm). Vesicles, bullae, and pustules are fluid-filled elevations or cavities in the skin. Vesicles and bullae are clear; pustules are turbid and pus filled. (b) Small, clear, fluid-filled vesicles on an erythematous base are present in a patient who has herpes zoster. (c) Large, clear, fluid-filled bullae are present in a patient with bullous pemphigoid. The bullae are associated with erythematous patches.


Figure 4. Multiple linear, erythematous wheals secondary to scratching are noted on the back of a patient with chronic urticaria and dermatographism.

The shape of primary lesions often provides diagnostic clues. Primary lesions may be round, oval, angular, or irregular; flat-topped or domed; or umbilicated or verrucous. The borders of primary lesions may be well circumscribed or poorly defined; the presence or absence of an elevated border may be a useful finding.

Secondary Changes

Secondary changes to lesions provide valuable diagnostic information; however, they are not as useful as primary lesions in arriving at a specific diagnosis [see Table 2]. Secondary changes may represent a late stage in the natural history of primary lesions, or they may be the result of trauma such as from scratching or rubbing of the skin. Secondary changes to lesions include the following:

Table 2 Selected Secondary Lesions: Consensus Definitions of Dermatologic Morphologic Terms7

Morphologic Term

DLP Proposed Definition


Abnormally keratinized cutaneous projection taller than it is broad


A localized loss of the epidermal or mucosal epithelium


A linear crack or cleavage within the skin usually found with thickened skin


A circumscribed loss of the epidermis and at least the upper dermis; ulcers are further classified by their depth, border/shape, edge, and tissue at their base

  • Scales: small flakes of superficial skin.
  • Scale crusts: scales combined with serous exudate.
  • Excoriations: abrasions resulting from the scratching of elevated lesions.
  • Erosions: localized loss of epithelium.
  • Ulcers: denuded areas of epidermis and some portion of dermis. Ulcers may be open or covered with a black eschar [see Figures 5a and5b].
  • Scars: raised or depressed fibrous lesions caused by trauma or disease.
  • Cutaneous horns: keratotic projections extending from a skin lesion.
  • Fissures: cracks that extend through the epidermis into the dermis.

Figure 5. (a) Drawing of a Skin Ulceration. A skin ulceration is a circumscribed lesion denuded of epidermis and at least some dermis. (b) A well-defined 3.5 by 4.0 cm ulceration with an erythematous granulating base is present in a patient who has early evolving pyoderma gangrenosum.

Numerous additional terms are helpful in characterizing the morphologic presentation of skin lesions [see Table 3]. It is critical that exacting definitions of descriptive terms be used by all clinicians if a reproducible method of diagnosis is to be promulgated. The Dermatology Lexicon Project (DLP) has provided an expert consensus of definitions for dermatologic terms [see Tables 1, 2,3].8

Table 3 Other Important Morphologic Terms: Consensus Definitions of Dermatologic Morphologic Terms7

Morphologic Term

DLP Proposed Definition


A localized accumulation of pus in the dermis or subcutaneous tissue; frequently red, warm, and tender


A thinning of tissue defined by the location (e.g., epidermal atrophy, dermal atrophy, or subcutaneous atrophy)


A threadlike linear or serpiginous tunnel in the skin typically made by a parasite


An inflammatory nodule composed of coalescing furuncles


A discoloration of the skin or mucous membranes resulting from extravasation of blood that exhibits color change over time; the characteristic transition is from blue-black to brown-yellow to green


Localized, blanchable redness of the skin or mucous membranes


Desquamation of the superficial epidermis appearing as a fine scaling or as peeling sheets


A follicle-centered nodule caused by a suppurative infection characterized by pain, redness, and perhaps visible pus; usually greater than 1 cm in diameter


Hardening of the skin beneath the epidermis, usually caused by edema, dermal sclerosis, inflammation, or infiltration


Purpuric nonblanchable macules resulting from tiny hemorrhages, initially measuring 1 to 2 mm


An area of variegated pigmentation, atrophy, and telangiectasia


Hemorrhaging into skin or mucous membranes that varies in size, color, and duration; types of purpura include palpable purpura, ecchymosis, and petechiae


Visible, persistent dilation of small, superficial cutaneous blood vessels

Morphologic Patterns of Presentation

Once the patient has been examined for primary and secondary lesions, the diagnostician must consider the overall presentation of the rash and determine its location, distribution, and configuration—three factors essential in determining a diagnosis.


The location refers to the particular site where the lesion or lesions are found. The location should be carefully defined because some skin diseases target specific anatomic areas. Notation of involved anatomic sites should be as specific as possible, listing not only the involved sites but the affected aspects of those sites. For example, facial lesions may occur in the periorbital or perioral areas; hand lesions may occur on the fingers or palm; and foot lesions may occur on the toes or sole. Lesions might also be found on the upper arm or the forearm, the lower leg or the thigh, and the trunk. It is important to further describe the affected areas as being on the right or left side and on the proximal or distal, medial or lateral, dorsal or ventral, and flexural or extensor surfaces of the involved anatomic sites.


The distribution of lesions describes the overall pattern of an eruption in relation to the entire cutaneous surface. The rash may be localized to one area of the body, may involve several areas, or may extend over much of the body surface. Rashes may be symmetrical or asymmetrical, and they may be present primarily on the trunk or on the extremities. Rashes may be present on exposed skin (i.e., skin that is not covered by clothing) or unexposed skin. These characteristics should be carefully noted because a particular distribution will narrow the differential diagnosis.


The configuration of lesions refers to the pattern exhibited by multiple lesions within a defined area. Because the configuration of lesions may vary according to the disorder, any detectable pattern may be helpful in arriving at a definitive diagnosis. Some of the more common configurations include the following:

  • Grouped or herpetiform configuration: multiple small lesions appearing within a small, defined area [see Figure 6].
  • Zosteriform configuration: lesions occurring within a dermatone.
  • Linear configuration: lesions oriented along a line [see Figure 7].
  • Annular configuration: lesions appearing in a ringlike pattern.
  • Target (iris) configuration: lesions appearing in concentric rings.
  • Arcuate configuration: lesions appearing in a semicircular pattern.
  • Polycyclic configuration: lesions appearing as interlocking rings.
  • Serpiginous configuration: lesions appearing in snakelike whorls.
  • Digitate configuration: lesions resembling the size and shape of a fingertip.

Figure 6. Close-up view of a herpetiform pattern of vesicles on an erythematous base within a dermatome in a patient with herpes zoster.


Figure 7. Linear arrangement of papules in a patient with contact dermatitis caused by poison ivy.

When lesions coalesce over large areas, they are termed confluent. Erythroderma describes a widespread confluence of rash covering nearly the entire cutaneous surface.


The color of cutaneous lesions also provides important diagnostic clues. Lesions may be flesh-colored, hyperpigmented or hypopigmented, erythematous, or virtually any color of the rainbow. Purpuric rashes caused by the extravasation of red blood cells show no blanching on diascopy (i.e., a test in which a glass slide or lens is pressed against the skin).

Categories of Skin Diseases

The appearance of individual lesions on the skin (e.g., primary lesions and their secondary changes) determines the major category of skin disease in which a rash or growth should be classified. The most common skin diseases and many important rare conditions can be classified into one of five disease categories on the basis of their characteristic lesions. Once the category is determined, the diseases within that category are considered in the differential diagnosis of the presenting disorder [see Table 4].

Table 4 Categories of Skin Disease

Papulosquamous diseases (discrete papules or plaques with scaling)

Psoriasis vulgaris

Chronic atopic dermatitis

Lichen planus

Pityriasis rosea

Fungal infections

Secondary syphilis

Mycosis fungoides

Blistering diseases (vesicles, bullae, pustules)

Acute allergic contact dermatitis

Bullous pemphigoid

Pemphigus vulgaris

Dermatitis herpetiformis

Herpesvirus infections

Bacterial folliculitis

Nonscaling erythematous (macules, patches, wheals) and infiltrative diseases (plaques)


Morbilliform drug eruptions

Viral exanthems


Leukemia and lymphoma cutis


Diseases of pigmentation (macules or patches of various colors)


Tinea versicolor

Pityriasis alba

Café au lait macules


Benign and premalignant tumors (macules, papules, nodules, tumors)

Actinic keratosis

Basal cell carcinoma

Squamous cell carcinoma





Melanocytic nevi

Adnexal tumors

As a clinician's dermatologic knowledge becomes more sophisticated, additional categories can be considered, including (but not limited to) diseases of the hair, nails, or mucous membranes; photosensitivity diseases; diseases of vascular reactivity; ulcerative skin conditions; and conditions typical of specific distributions, such as diseases of the genitalia, feet and hands, and eyelids. Manuals of differential diagnosis based on the morphology of lesions and other physical features are plentiful and can be quite helpful in determining a diagnosis.

Arriving at a Diagnosis

It is important to begin the assessment of a skin condition with a broad differential diagnosis, noting the presentation as characteristic of one of the categories of skin disease [see Table 4]. Using physical findings, patient history, and diagnostic testing, the differential diagnosis is gradually narrowed until a diagnosis is determined. A review of illustrations of specific primary and secondary skin lesions in various dermatology atlases may also aid in arriving at a diagnosis [see Online Atlases of Dermatology]. For example, scaling conditions, including rashes composed of both papules and plaques, are characterized as papulosquamous skin diseases; each papulosquamous condition [seeTable 4 and Online Atlases of Dermatology] should be considered in the differential diagnosis of a scaling rash. The specific features of each of the papulosquamous conditions are compared with the patient's lesions to systematically identify the disorder. It is critical that the initial differential diagnosis be broadly defined. Jumping to an early conclusion and not systematically considering all of the possible papulosquamous disorders can result in an incorrect diagnosis. In fact, if the actual diagnosis is not among the diseases that are considered initially, it is much more difficult to determine the correct diagnosis.

Diagnosis is almost always more difficult than treatment. Consultation with a dermatologist is recommended when the diagnosis is uncertain, particularly in cases in which treatment may fail or may lead to iatrogenic disease. The dermatologist may help define the primary lesions that permit the accurate categorization of the disease process and, in turn, suggest the diagnosis.

If a diagnosis remains in doubt, a follow-up visit with the patient should be scheduled because, as the disease progresses, the development of primary lesions and lesion distribution may make the diagnosis more apparent. In addition, single, confirmatory tests often prove helpful in the diagnosis of cutaneous presentations; tests used to confirm a diagnosis include a Wood light examination, potassium hydroxide (KOH) preparation, sampling for fungal culture, scabies preparation, Tzanck preparation, patch testing, skin biopsy, dark-field microscopic examination, microscopic hair-shaft analysis, Gram stain, and viral or bacterial cultures.

A Wood light examination is performed by shining a black light on the skin in a dimly lit room. Epidermal pigmentation (e.g., lentigines) is highlighted by this examination, whereas dermal pigmentation (e.g., Mongolian spot) disappears. The Wood lamp can also aid the search for depigmented spots such as ash-leaf macules in babies with tuberous sclerosis.

A KOH test for fungal infections involves applying KOH to scales of skin or hair shafts to clear the keratin so that fungal hyphae and spores can be identified. For example, scales can be lightly scraped onto a glass slide after placing the slide on the advancing margin of an annular plaque with central clearing. After a coverslip is applied, 2.5% KOH preparation is applied to the slide next to the coverslip. The KOH preparation spreads under the coverslip by capillary action. After gentle heating, excess KOH is blotted away, and the specimen is examined under a microscope. Fungal infections can also be confirmed by obtaining scales by lightly scraping papulosquamous lesions and sprinkling the scales onto Sabouraud dextrose agar. This agar preparation is then incubated at room temperature for several weeks, after which it is analyzed for colony growth, color, and morphology.

A scabies preparation test involves applying oil to excoriated lesions—frequently found on wrists and finger webs—and lightly scraping the burrows to obtain their contents. The scrapings are placed on a slide with coverslip; the test is positive if scabies mites, eggs, or feces are visible on microscopic examination.

Tzanck preparations are smears obtained from the base of intact vesicles and stained with one of a variety of nuclear stains. A finding of multinucleated giant cells suggests a diagnosis of herpes simplex or herpes zoster infection.

Patch testing is performed to objectively elucidate the specific cause of an allergic contact dermatitis. Standard allergens are applied under patches for 24 hours, and the reactions are read 48 hours and 1 week later.

Skin biopsies are helpful in confirming the diagnosis of a variety of inflammatory and neoplastic diseases. Dark-field microscopic examination of serous fluid from genital ulcers identifies spirochetes in lesions of primary syphilis. Hair-shaft analysis is helpful when alopecia is caused by hair-shaft abnormalities. Finally, viral and bacterial cultures using specific swabs can provide laboratory confirmation of a variety of viral and bacterial diseases.

Online Atlases of Dermatology

A cooperation between the Department of Clinical Social Medicine, University of Heidelberg, and the Department of Dermatology, University of Erlangen


Interactive Dermatology Atlas

University of North Carolina School of Medicine Dermatology Slide Atlas

Dermatologic Image Database

Department of Dermatology, University of Iowa College of Medicine

Loyola University Dermatology Medical Education Website


Figures 1a, 2a, 3a, and 5a Dragonfly Media Group.


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Editors: Dale, David C.; Federman, Daniel D.