1 How many skin diseases exist? What are the two main categories of skin lesions?

There are more than 1400 skin diseases. Yet, only 30 are important, common, and worth knowing. The first step toward their recognition is the separation of primary from secondary lesions (Table 3-1).

Table 3-1 Dermatologic Lesions

2 What are the major primary lesions?

3 What are the major secondary lesions?

4 Are there other ways to classify skin lesions?

Many ways. One divides lesions into four groups based on the relationship with the surrounding skin:

5 What is the pattern of distribution?

Beside the distribution in the body (i.e., generalized versus localized), this descriptor refers to the relationship of lesions to one another:

6 What is the configuration of a skin lesion?

It is the outline of the lesion as observed from above. The most common configurations are:

7 How should an initial cutaneous exam be done?

From head to toe. Patients should fully disrobe, so that the entire body can be inspected—including palms, soles, scalp, and mouth. If a total skin exam is not feasible, a targeted exam of lesions, as guided by history, is also appropriate. Either way, always attempt to complete at least an upper body exam, since the trunk represents a large but easily examinable surface area.

8 How should a specific lesion be examined in order to better classify it?

Not only by looking at it, but also by touching it, which is key for determining its characteristics and relationship to the surrounding skin: papular, sclerotic, soft, mobile, rough, or smooth. Note that, in contrast to other fields of medicine, a thorough physical examination is key for dermatologic diagnoses. In fact, it is much more key than history.

9 And so, what are the required components of a dermatologic diagnosis?

Based on the aforementioned criteria, a dermatologic diagnosis requires first of all the recognition of both the primary and the secondary lesions. Once that is done, lesions must be assessed based on:

10 What are the tools necessary for a dermatologic diagnosis?

Primarily three:

11 How does one prepare a potassium hydroxide (KOH) stain for fungi?

Scrape a few scales off the skin, and place them onto a glass slide. Then, pour potassium hydroxide (10%) onto the slide, and apply a coverslip. After gently warming up the slide (usually over a match), examine the preparation under a microscope for hyphae and spores.

12 What is a Tzanck test?

A test commonly used for herpes virus infection. Pioneered by the Russian dermatologist Arnault Tzanck (1886–1954), it is carried out by unroofing a vesicle with a scalpel, scraping its base, applying the material to a microscope slide, fixing it with 95% alcohol, and preparing it with a standard Wright or Giemsa stain. If positive, the test reveals multinucleated giants cells, confirming that the cause of the lesion is either herpes simplex or varicella zoster.

13 What skin appendages should be part of a thorough dermatologic exam?

Definitely hair (including eyebrows, eyelashes, and scalp), but also fingernails and toenails. As opposed to hair, these are rarely of concern to the patient, yet they may narrow the differential diagnosis, guide work-up, and provide important clues for the identification of systemic illnesses. Hence, it is the physician’s responsibility to examine them thoroughly.

14 How should fingernails and toenails be assessed?

If covered by polish, clean them first with a solvent like acetone. Then pay attention to color and shape but also to anatomic details (Fig. 3-25):

Figure 3-25 Anatomy of the fingernail.

Although fingernails tend to be more informative than toenails (since they grow more rapidly and suffer fewer traumas), always examine them both. Inspect them first without applying any pressure. Then, blanch the fingertip to see if a pigmented lesion changes color (which would argue for discoloration of the vascular bed rather than the nail plate). Finally, place a penlight against the finger pulp and shine it through the nail. If upon illumination a discoloration disappears, it is also more likely to be in the vascular bed than in the soft tissue or matrix. When indicated, scrape the nail plate surface, and do a potassium hydroxide preparation to rule out fungal disease. Note that nail changes due to systemic disease (as opposed to trauma) often occur in the matrix, so that the leading edge of the abnormality (for example, a pigmentation change) is usually shaped like the distal portion of the matrix. To estimate the time of initial insult, measure the distance from the proximal nail fold (cuticle) to the leading edge of the pigmentation change, remembering that nails grow 0.1–0.15   mm/day.

15 What systemic conditions are associated with changes in nail shape or growth?

Figure 3-26 Characteristic lesions of the nails.

16 What systemic conditions are associated with changes in nail color?

17 How are nail findings classified?

Growth Disturbances

19 What is clubbing?

A condition that can be (1) idiopathic; (2) congenital (dominant trait); or (3) a clue to serious underlying pathology, including cardiovascular, hepatobiliary, mediastinal, endocrine, gastrointestinal, neoplastic, infectious, and, especially, pulmonary (see Chapter 13, questions 101–116).

20 What is onycholysis?

“Loosening of the nail” in Greek, it consists of separation of the nail plate from the nail bed. This begins at the free edge and progresses proximally, causing a traumatic uplifting of the distal plate. Usually incomplete, it results in white discoloration of the affected area, often complicated by secondary microbial colonization. Typically traumatic, it may also result from any local problem that separates the plate from the nail bed, such as periungual warts or onychomycosis. It also may originate from eczematous or drug disorders, reactions to acrylic nails or nail-hardeners, and psoriasis. The latter may at times occur with complete separation of the nail, which is either mechanically lifted off the bed or separated by traumatic bleeding. Absent local explanations, thyrotoxicosis must be ruled out (“Plummer’s nails”). This may also cause brown nail discoloration.

21 What is nail pitting?

An early but nonspecific sign of psoriasis that can also occur in alopecia areata and chronic dermatitis. Nails are pocked by multiple tiny depressions, which may eventually cause the nail to crumble. Pitting is due to loss of parakeratotic cells from the surface of the plate, starting in the proximal nail matrix and migrating distally.

22 What are the nail findings of psoriasis?

Many, affecting 10–55% of patients and <5% of those with no other cutaneous manifestation. If untreated, they can lead to functional and social impairment. They are especially common in psoriatic arthritis (53–86% of patients), even though only 10–20% of all psoriatic patients have the arthritis.

23 What is koilonychia (spooning)?

A “spoon-shaped” deformity of the nail, usually large enough to hold a drop of liquid. Normal in infants (but resolving after the first few years of life), it also may result from trauma, recurrent exposure to petroleum-based solvents, or nail-patella syndrome. It is also seen in Raynaud’s disease or lupus erythematosus, but rarely in isolation. Finally, it can occur with iron deficiency (with or without anemia) or, paradoxically, hemochromatosis (check iron, hemoglobin).

24 What is yellow nail syndrome?

An autosomal-dominant disease characterized by absent/hypoplastic and easily dislocated patellae, skeletal abnormalities, nephropathy, glaucoma, and fingernail dysplasia. This consists of slow nail growth, with a “heaped-up” or thickened appearance, excessive transverse curvature, loss of the lunula, and a yellowish/greenish discoloration. Eventually, the nail thickens and may even detach. Yellow/green nails may result from any condition that slows nail growth (such as infection, like Pseudomonas) or impedes lymphatic circulation. Hence, they have been associated with lymphedema of the extremities or face. They also have been linked to respiratory involvement (including chronic bronchiectasis or sinusitis), pleural effusions, internal malignancies, immunodeficiency syndromes, and rheumatoid arthritis (usually as a result of thiol drugs, such as bucillamine and gold sodium thiomalate). Microvascular hyperpermeability with protein leakage would explain the link of yellow nail syndrome with infection, hypoalbuminemia, pleural effusion, and lymphedema.

25 What are brittle nails (onychorrhexis)?

Nails whose distal plate splits into layers, with irregular, frayed, and torn borders—almost resembling the scaling of dry skin. Present in 20% of adults (and even more in older subjects), brittle nails may be hereditary or simply aging-related. They also may be due to strong solvents or repeated immersion in water (e.g., dishwashers). Dysmetabolic states (such as hyperthyroidism, malnutrition, and iron or calcium deficiency) must always be ruled out.

26 What is longitudinal ridging (Reedy nails)?

A normal variant of patients older than 50, but one that also can occur in younger subjects. It may even represent a brittle nail variation. Ridges typically extend from the proximal nail fold to the distal plate, with some being very prominent, especially in older women. They are usually multiple, but at times may be single—like in patients with lichen planus (see questions 38 and 210–216).

27 What is nail beading?

A condition due to faster matrix turnover. It is quite common in rheumatoid arthritis (RA). In a study of 119 RA patients and an equal number of controls, “global” beading (i.e., involving >50% of the nail) on at least six fingernails (or four toenails) was highly suggestive of underlying disease, with a positive predictive value of 95%. Beading, however, is uncommon in early RA, thus limiting its diagnostic value. Beading can occur with itraconazole too, since this also increases nail growth.

28 What is onychogryphosis?

A thickened nail plate, often due to trauma plus mycotic infection. Eventually, the nail curves inward, resembling a claw (gryphon is dragon in Greek) and “pinching” the nail bed (pincer nail).

Transverse Linear Lesions

30 What is leukonychia?

A condition characterized by white spots, patches, or streaks between the nail and nail bed. It is due to tiny bubbles of subungual air trapped in the plate layers after trauma. Leukonychia (white nail in Greek) may involve the entire nail (total), or present instead as lines (striate) or dots (punctate). Total leukonychia is a congenital dominant disorder, whereas striate or punctate forms are instead traumatic. The latter resolve with time, since spots eventually grow out with the nail plate

31 What are Beau’s lines?

Transverse grooves on the fingernails of patients recovering from a serious illness (like a myocardial infarction). This produces a transient intermittent inflammation of the matrix, resulting in arrested growth. Grooves will progress distally with the nail, eventually coming into view and finally moving out as the nail elongates. First described by the French Joseph H.S. Beau (1806–1865).

32 What are bitten nails lesions?

Lesions that may resemble Beau’s lines, insofar as they, too, are transversal indentations (no pun intended), although, more commonly, they present as absence of the free nail edge, produced by nervous biting and chewing. They are an important clue to underlying psychosocial pathology.

33 What are Muehrcke’s lines (ML)?

Two arcuate, narrow, and transverse white lines—parallel to the lunula and separated by an otherwise normal nail. Named after the American nephrologist who first described them in 1956, ML usually involve the second, third, and fourth fingers. They reflect a vascular abnormality in the nail bed (typically, subungual edema), and not in the nail plate. Hence, they do not progress distally with nail growth. Common in hypoalbuminemia (<2.2   gm/100   mL), they disappear with its resolution. In his original study, Muehrcke found paired, transverse, white bands in 23/31 (74%) patients with nephrotic syndrome and 8/9 with hypoalbuminemia (<2.3   gm/100   mL) from other causes. Lines were instead absent in all healthy subjects, and in those with albumin >2.2   gm/100   mL. Bands were more prominent after albumin had been <1.8   gm/100   mL for at least 4 months. In another study by Conn and Smith, Muehrcke lines were seen in 10/44 (23%) patients with hypoalbuminemia from various debilitating illnesses, but absent in those with normal serum levels. Hence, ML occurs in hypoalbuminemia from many reasons, including nephrotic syndrome, but also liver disease and malnutrition. Additionally, they can occur in pellagra, Hodgkin’s disease, sickle cell anemia, or nail damage from paraquat and chemotherapeutic agents. Although transverse white bands in the nail plate are often due to trauma to the matrix at the proximal nail fold (leukonychia), Muehrcke’s (and Mees’) lines are instead associated with a systemic disease. They typically span the entire breadth of the nail bed/plate, tend to be more homogenous, have a contour similar to the distal lunula (with a rounded distal edge and smoother borders), occur on several nails at once, and typically follow a generalized insult. Trauma-induced transverse white bands tend to be more linear, do not spread across the entire breadth of the nail plate, resemble the contour of the proximal nail fold (where trauma occurred), and have a history of localized trauma to the cuticle.

34 What are Mees’ lines?

They are transverse white lines distal to the cuticle, and typically laid down during a generalized illness or after a poisoning. In contrast to Muehrcke’s lines, Mees’ lines (also called Reynolds’ or Aldrich’s) are in the nail plate. Hence, they move distally with it. Differential diagnosis includes arsenic or thallium (2–3 weeks after an acute poisoning, or following chronic exposure), cancer chemotherapy, Hodgkin’s lymphoma, and other systemic disorders, such as severe cardiac or renal disease. They were first described by the Dutch physician R.A. Mees.

35 What are the traumatic changes of the nail?

Subungual hematomas are posttraumatic hematogenous extravasation in the nail bed. When partially digested and oxidized, a subungual hematoma may turn into a brownish and transversal dark band, often associated with indentation or damage of the nail plate.

Longitudinal Linear Lesions

37 What is longitudinal melanonychia?

A condition characterized by brownish/blackish longitudinal streaks or bands. Very common in dark-skinned individuals, it reflects melanin deposition from a normal increase of melanocytes in the nail bed. Yet, it also may indicate a much more ominous subungual melanoma. Hence, it presents a clinical challenge. When in doubt, always biopsy the nail matrix and bed.

38 What is lichen planus of the nail?

A condition present in 10% of patients with lichen planus. The most common finding is thinning of the nail plate, leading to longitudinal grooving and ridging (see also question 26). Hyperpigmentation, subungual hyperkeratosis, onycholysis, and longitudinal melanonychia can also be present.

Vascular and Nail Bed Changes

40 What are splinter hemorrhages?

Tiny and linear red hemorrhages, extending from the free margin of the nail bed toward the proximal end. Traditionally linked to subacute bacterial endocarditis or trichinosis, they are more commonly due to trauma. According to conventional teaching, traumatic “splinters” extend all the way into the edge of the nail, whereas embolic splinters (like those of endocarditis) are fully contained within the nail bed. There is, however, little evidence to support this differentiation.

41 What are azure half-moons in nail beds?

The nails of Wilson’s disease (hepatolenticular degeneration). Lunulae are not white, but bluish.

42 What are Lindsay’s nails?

Half-and-half nails, with a white proximal half, and a dark distal half (usually brownish, but also reddish or pink). Named after the American physician who first described them in 1967, Lindsay’s nails have a sharp linear demarcation between the two halves, parallel to the nail edge. Of the 25 patients first described by Dr. Lindsay, 21 had chronic renal failure and two had minor nephropathy.

43 What are Terry’s nails?

Nails characterized by whitening of the proximal 80% of the nail, leaving a small rim of peripheral reddening, usually as sharply demarcated as in Lindsay’ nails. Named after the British physician who described them in 1954, Terry’s nails are seen in older subjects and patients with heart failure, cirrhosis, or non–insulin-dependent diabetes. They probably are due to subungual edema.

44 What are red half-moons in nail beds?

A variety of Terry’s nails, also described by him in the same 1954 Lancet paper. They are characterized by a lunula that is not white, but red. They also are called the nails of cardiac failure. In fact, all these half-and-half nails (Lindsay’s, Terry’s, and the red half-moons in nail beds) reflect conditions causing subungual edema, such as cardiac, hepatic, and renal disease.

45 How does vasculitis of the nail present?

With typical nail fold changes, like cuticular hypertrophy (with small, hemorrhagic infarcts) and periungual telangiectasias. These are common in scleroderma or dermatomyositis.

Infections

47 What is tinea unguium?

A dermatophytic infection of the nail, characterized by onychauxis (hypertrophy of the nail plate caused by keratin pileup); onycholysis (nail plate separation from the nail bed); and dystrophic, thickened, broken, and discolored nails (white, yellow, brown, black). Browning of the plate (with peeling and splitting of the edge) also occurs, together with ridging and white spots. Note that, although dystrophic nails are often onychomycotic, half of them are not (and instead due to trauma, psoriasis, or lichen planus). Hence, always do scraping and KOH staining to rule out fungal infection.

48 What is paronychia?

An acute or chronic inflammation of the perionychium, with redness, swelling, and tenderness.

49 How does pseudomonal infection of the nail present?

With a greenish nail, due to iron compounds produced by pseudomonas organisms invading the nail between the nail plate and nail bed. The darker the discoloration, the deeper the bacterial progression into the plate layers. This eventually causes it to lift altogether from the nail bed.

50 What are blue lines?

The result of minocycline therapy.

51 How is the hair assessed?

Region by region, first the scalp and then the body—including axillae, extremities, and pubic region. Evaluate quantity and distribution of hair, plus thickness and texture. Since alopecia is often caused by inflammation of the scalp, look for scaling, redness, crusts, and papules. Note that of the three scaling scalp lesions (seborrheic dermatitis, psoriasis, and tinea capitis), only tinea is associated with alopecia.

52 What is folliculitis?

An infection of hair follicles, most commonly due to staphylococci, but also gram-negative organisms and even fungi. In fact, Pityrosporum, the organism responsible for tinea versicolor, can overgrow in the follicles of patients with HIV and cause folliculitis.

53 What is eosinophilic folliculitis?

A disorder of unknown etiology, characterized by recurrent crops of sterile pustules and papules, often intensely pruritic, and presenting in multiple cycles of remissions and exacerbations. Although labeled as a folliculitis, it is actually a “sterile eosinophilic pustulosis” since lesions are not restricted to the hair follicle. It is probably an autoimmune response against sebocytes or some other components of sebum that usually occurs in the third to fifth decade of life. It can affect all races, but predominates in Asians. It presents as an area of erythematous papules and pustules, facial in 85% of patients, but also on the back and extensor surface of upper extremities. Papules eventually become confluent, creating indurate plaques with a healing center and a spreading periphery. These ultimately fade away, leaving residual hyperpigmentation and scaling. In HIV-infected patients, eosinophilic folliculitis (EF) presents with widespread urticarial lesions or large erythematous plaques with excoriations, often severe and persistent. Also seen in lymphoma, leukemia, myelodysplastic syndrome, atopy, and bone marrow transplantation.

Acne

55 Who develops acne?

Usually puberal teens, although girls may develop it one or more years before menarche. Men tend to have more severe acne, but this usually resolves by the second decade. In women, it often lingers well into the 40s and 50s, often with perimenstrual flares.

56 What are the other clinical presentations of acne?

The two most common are steroid acne and acne rosacea, although the latter is more than a variant of acne, and probably a completely different process of middle-aged and older people.

57 What is acne rosacea?

An acne-like rash that affects the central and flush/blush areas of the face (forehead, nose, cheeks, chin). Vascular lability is so typical that many patients have a history of facial flushing in childhood or early teens, often triggered by dietary and environmental factors (like hot drinks, alcohol, spicy foods, but also temperature changes and even emotions). Ocular rosacea may be accompanied by conjunctival injection, and rarely, chalazion and episcleritis. Although rare, there may be extrafacial involvement of the neck and upper part of the chest. Overall, symptoms of rosacea are intermittent, but can progressively lead to permanent flushing of the skin, with telangiectasias of cheeks and nose, lymphedema, and, ultimately, skin coarseness with acne-like papulopustular eruption. Yet, unlike acne, there is neither seborrhea (i.e., greasiness of the skin) nor comedones. In fact, rosacea may present with drying and peeling. Hyperplasia of sebaceous glands may eventually lead to a thickened and disfigured nose (rhinophyma). Still, this can be an isolated finding, and in fact, some authors even consider it a separate entity. Note that although rosacea is much more frequent in subjects of Celtic ancestry, it has also been described in dark-skinned individuals, such as African-Americans.

58 What is steroid acne?

An acne-like rash that may begin as early as 2 weeks after administration of systemic corticosteroids. In contrast to plain acne, lesions are monomorphous (generally pustules and dome-shaped papules) and covering the trunk, shoulders, and upper arms. A rosacea-like syndrome (including perioral dermatitis) also can result from the indiscriminate use of potent corticosteroids on the face.

59 How is acne diagnosed?

Clinically, based on a mixture of lesion types in the appropriate location.

Herpes Simplex

61 Who develops herpes simplex?

Any age group, even though certain involvements are age-specific, such as stomatitis in children, labialis in adults, genitalis in sexually active subjects, and lumbosacral in patients older than 40.

62 What is the typical clinical course of herpes simplex?

63 What are the other clinical presentations of herpes simplex?

64 How is herpes simplex diagnosed?

Usually by clinical appearance (grouped umbilicated vesicles on an erythematous base). Still, a Tzanck preparation is diagnostic. Direct immunofluorescent antibody staining of infected cells is also an effective and rapid method of diagnosis. Viral cultures grow herpes simplex virus in several days. Biopsy of lesions demonstrates reticular and ballooning degeneration of the epidermis, multinucleated giant cells, and intranuclear inclusions.

Varicella

66 Who develops varicella?

Mostly children younger than 10 years. Only 5% of cases occur in subjects older than 15.

67 What is the typical clinical course of varicella?

Incubation is 2 weeks, with patients being highly contagious for 2–4 weeks (from 1–2 days before exanthema until crusting of all lesions).

68 How are the other clinical presentations of varicella?

More severe in adults than in children, with higher fever, constitutional symptoms, and pneumonia (4% of cases). During pregnancy, varicella can be transmitted to the fetus, producing serious developmental abnormalities. In immunocompromised patients, it causes a more extensive and persistent rash, with higher morbidity and mortality, and even hemorrhagic complications.

69 How is varicella diagnosed?

By the classic appearance of the rash, often supported by a history of recent exposure. Conversely, to distinguish disseminated herpes simplex from varicella, a culture is often needed.

Herpes Zoster

71 Who develops herpes zoster?

Older subjects, with more than two thirds of cases occurring in patients older than 50 and less than 10% of cases in those younger than 20. It is also more common in immunosuppressed patients. Zoster in infants is usually associated with a history of maternal varicella infection during gestation.

72 What is the typical clinical course?

The rash erupts and progresses to complete crusting over 1 week, then resolves over several weeks. Postherpetic neuralgia (pain persisting after all crusts have fallen off) occurs in 15% of patients and is more common in the older population.

73 What are the other presentations of herpes zoster?

Scabies (see questions 255–257)

75 What are the skin lesions of DH?

They are clusters of flesh-colored to erythematous herpetiform papules and vesicles. These are inflammatory, pruritic, and mostly located on the extensor surfaces (elbows, knees, buttocks, shoulders, and the posterior/nuchal scalp). Lesions may often present not as vesicles, but as erosions and crusts. Palms and soles usually are spared, and so is the buccal mucosa.

76 What is the course of DH?

A lifelong one, with remissions and exacerbations. Symptoms can be controlled with dapsone in 24–48 hours. A gluten-free diet can also provide control without medications.

Pemphigus and Pemphigoid

78 What are the clinical features of pemphigus vulgaris (PV)?

It can affect all races, although more commonly Jewish and other Mediterranean groups. Its peak of onset is during the fifth and sixth decades. The primary lesion is a flaccid blister filled with clear fluid, and originating from a normal or erythematous skin base. Since blisters are fragile, they rupture easily, producing large, shallow, and painful erosions that heal slowly. Hence, erosions are the most common skin manifestation of the disease. Still, mucosal lesions (usually oral) are the most common presenting manifestation, affecting 50–70% of patients and often preceding cutaneous involvement by several months. Since intact bullae are rare in the mouth, most patients have irregularly shaped erosions of gingival, buccal, or palatine mucosa. These are painful, slow to heal, and interfere with eating, drinking, or swallowing. Other involved mucosae include conjunctiva, esophagus, larynx, labia, vagina, cervix, penis, urethra, and anus.

79 Are there any other causes of PV?

A form of PV (but also BP, see question 80) can be drug induced, resulting from penicillamine, captopril, thiol-containing compounds, and rifampin. Emotional stress can also trigger it. Finally, PV may occur in other autoimmune diseases, including myasthenia gravis and thymoma.

80 What is bullous pemphigoid (BP)?

Another autoimmune and blistering skin disease, except that in contrast to PV it rarely involves mucous membranes, it rarely erodes (lesions are subepidermal and thus the bullae have thicker roofs), and it is typically pruritic. Caused by the binding of circulating IgG autoantibodies to the skin basement membrane, BP is more common than PV, affects older patients (average age 65), and runs a chronic course marked by remissions and exacerbations. Onset may be subacute or acute, with widespread, tense, and often pruritic blisters. These may at times arise from persistent urticarial lesions, but also from chronic nonbullous inflammatory diseases, such as lichen planus and psoriasis. Rupture of the blisters leaves painful and disabling erosions, especially when involving palms and soles. Still, the primary lesion of BP is the bulla: tense, arising from normal-appearing as well as erythematous skin, and affecting any part of the body (even though flexural areas are usually a preferential site). Involvement of ocular and oral mucosae is rare (only 10–25% of patients), but when it occurs, oral intake may be limited because of dysphagia.

81 What is Nikolsky’s sign? What is its significance?

It is a sign described in 1896 by Pyotr W. Nikolsky, a Russian dermatologist who taught at Warsaw and Rostov. It consists in the superficial separation of normal-appearing epidermis into an erosion, as a result of the shearing stress produced by sliding a finger on it. It is due to poor adhesion of the epidermal cells (acantholysis). Hence, it occurs in bullous diseases like pemphigus, but not pemphigoid, where the epidermal split is much deeper. Still, it is not entirely specific for PV, since it can occur in other active blistering diseases, such as scalded skin syndrome.

82 What is Asboe-Hansen sign?

Another sign of PV; lateral pressure on the edge of a blister may spread it into unaffected skin.

Drug Reactions

84 What is erythema multiforme (EM)?

A relatively benign process characterized by target or targetoid lesions, with or without blisters, in a symmetric and acral distribution. In fact, the rash favors palms and soles, dorsum of hands, face, and extensor surfaces of extremities (Fig. 3-27). It is often associated with oral lesions, but rarely involves more than one mucosal surface. Although it can be caused by drugs, it is most commonly a sequela of herpes virus infection. It has low morbidity, no mortality, but frequent recurrences. It may be associated with epidermal detachment, yet denudation always involves <10% of BSA.

Figure 3-27 Erythema multiforme. The eruption consists of annular and papular erythema over the acral areas.

(From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

85 What is Stevens-Johnson syndrome (SJS)?

A potential dermatologic emergency. First described in 1922 by the American pediatricians Albert Stevens and Frank Johnson, SJS is characterized by widespread purpuric macules and targetoid lesions, usually more common on face and torso, and with concomitant mucosal involvement of more than one site (usually the eyes, mouth, and genitalia; Fig. 3-28). Lesions may undergo full-thickness epidermal necrosis, although this is limited by definition to <10% of cutaneous surface. Hence, mortality is much less than in TEN (only 5%).

Figure 3-28 Stevens-Johnson syndrome. Typical mucosal inflammation of the mouth, lips, andf conjunctiva.

(From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

86 What is toxic epidermal necrolysis (TEN)?

Also known as Lyell’s syndrome, this is a true dermatologic emergency characterized by widespread skin and mucosal denudation. Skin lesions are erythematous and target-like macules associated with full-thickness epidermal necrosis and detachment of >30% BSA (Fig. 3-29). It is fatal in 50% of the cases, usually because of sepsis and respiratory distress. Mortality is related to BSA involvement: 11% for BSA (which is actually more of a SJS-TEN transitional form), and 35% for BSA >30%.

Figure 3-29 Toxic epidermal necrolysis. The patient demonstrates the typical “telangiectatic” blanching erythema and blistering that progress to denuding of the epidermis.

(From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

87 Describe the presentation of SJS/TEN

Constitutional symptoms (fever, cough, or sore throat) precede the cutaneous lesions by 1–3 days. Then photophobia appears, followed by a diffuse “cayenne pepper” eruption that is extremely tender to touch and symmetrically distributed on the face and upper torso. This consists of poorly defined erythematous macules with darker purpuric centers (targetoid lesions) that coalesce, blister, and ulcerate. Sheets of skin may then lift off as in a severe thermal burn, especially in TEN.

88 What is the difference between “targetoid” lesions of SJS/TEN and “targets” of EM?

The SJS/TEN lesions have only two zones of color: a central dusky purpura (or central bulla), surrounded by a macular erythema. Conversely, a classic target lesion of EM has three zones of color: a central dusky purpura (or central bulla), a surrounding edematous pale zone, and a surrounding macular erythema. Except for the central bulla, the initial lesion of SJS/TEN is also typically flat. Conversely, lesions of EM are more likely palpable.

89 What are the skin manifestations of SJS/TEN?

Lesions begin symmetrically on face and upper torso, and then extend rapidly. Maximal extension occurs in 2–3 days, but occasionally takes only a few hours. Individual macules are usually present around large areas of confluence. Lesions may predominate in sun-exposed areas, but may also affect the entire epidermis, including nail beds. The hairy scalp, however, usually remains intact. Palms and soles develop a painful edematous erythema. Flaccid blisters are typically present, together with full-thickness epidermal necrosis. Nondenuded areas have a wrinkled paper appearance. A Nikolsky sign is easily demonstrated by applying lateral pressure to the bullae. Full skin detachment usually occurs in areas subjected to pressure, such as shoulders, sacrum, or buttocks. Areas of denuded epidermis are dark red with oozing surfaces.

90 Is there any mucosal involvement in SJS/TEN?

Yes. Mucosae are involved in almost all patients with SJS/TEN—not only those with extensive cutaneous manifestations. In fact, mucosal lesions may precede skin lesions. Preferential sites include the oropharynx and esophagus, tracheobronchial tree, GI tract, genitalia, and anus. Painful oral erosions cause severe crusting of the lips, increased salivation, and impaired alimentation. Intact expectorated cylindrical casts of bronchial epithelium may also occur, and involvement of genitalia can lead to painful micturition. Patients with GI manifestations often develop a profuse protein-rich diarrhea. Of all mucosal lesions, the most problematic are the ocular ones, since they often leave sequelae. Initially, the conjunctivae are erythematous and painful, with lids often stuck together. Efforts to loosen them may result in tearing of the epidermis. Eventually, pseudomembranous conjunctival erosions form synechiae between the eyelids and conjunctivae, with inverted eyelashes, keratitis, corneal erosions, and corneal/conjunctival neovascularization.

91 What are the sequelae of SJS/TEN?

Variable. Some patients rapidly lose large areas of the skin in just a few days, whereas others begin re-epithelialization almost as quickly. Predicting the course at initial presentation is not possible. Overall, re-epithelialization is usually complete within 3 weeks, but pressure and mucosal areas may remain eroded and crusted for 2 weeks or longer. Long-term sequelae of SJS/TEN vary based on site:

92 What is the cause of SJS/TEN?

Almost exclusively a drug reaction, 1–3 weeks from administration. The most frequent offenders are antibiotics (especially trimethoprim-sulfamethoxazole and other sulfonamides, but also aminopenicillins, quinolones, and cephalosporins); anticonvulsants (including phenobarbital, phenytoin, valproic acid, and carbamazepine), and finally nonsteroidal anti-inflammatory drugs, allopurinol, and even corticosteroids. HIV patients have greater risk of TEN, and often tend to be younger. This may be related to their increased use of sulfonamides. Finally, TEN has been reported in systemic lupus erythematosus or acute graft versus host disease. Infections with herpesvirus, Mycoplasma pneumoniae, or Yersinia may also occur in SJS, but even more in EM.

93 What is the mechanism of TEN?

Unclear. Early histology shows full-thickness epidermal necrosis, with little or no lymphocytic infiltrate, suggesting that TEN is not induced by inflammation but by a cellular toxin, which is why steroids and immunosuppressive therapy are not effective and, in fact, possibly detrimental.

94 How do you separate staphylococcal scalded skin syndrome (SSSS) from TEN?

TEN is characterized by a deeper split in the epidermis (i.e., at the dermoepidermal junction). The split in SSSS is instead higher, and just inferior to the stratum corneum (the uppermost layer of the epidermis). Hence, SSSS lesions are more superficial and heal more quickly, while TEN is usually treated in burn units (which is crucial for survival: referral in less than 7 days after onset has a mortality rate of 4%, whereas referral beyond 7 days has a mortality rate of 83%). SSSS, on the other hand, is commonly treated with antibiotics, since it is induced by a staphylococcal toxin. Note that TEN also is called toxic epidermal necrolysis of the Lyell type (from the British dermatologist who first described it) to distinguish it from toxic epidermal necrolysis of the Ritter type (from the Austrian dermatologist who described it in 1878)—another name for SSSS.

95 What are the other major cutaneous manifestations of drug reactions?

96 What is a drug-induced photosensitivity reaction?

A cutaneous disease resulting from the combined effects of light and a chemical substance—administered either systemically (medication) or topically (cream). A drug-induced photosensitivity is more likely to be triggered by UV-A (320–400   nm) than UV-B wavelengths (290–320   nm). Conversely, UV-B wavelengths are more likely to cause sunburn and nonmelanoma skin cancer.

97 What are the most common photosensitizing medications?

The usual suspects:

These are mostly responsible for phototoxic reactions. Topical substances are instead photosensitizing through a photoallergic reaction. Among these are fragrances (musk ambrette) and sunscreens (especially if containing salicylates, cinnamates, benzophenones, and para-aminobenzoic acid). Some drugs are photoallergic, too, including dapsone, hydrochlorothiazide, quinidine, and hypoglycemic agents (sulfonylureas, such as glipizide and glyburide). As for all drug reactions, consider timing, rates of reactions, response to withdrawal, and re-challenge.

Urticaria

99 What are the skin manifestations of urticaria?

The primary lesion is the wheal, a whitish-to-reddish, well-demarcated, edematous papule or plaque with a pale center. This is usually surrounded by a halo and quite pruritic. Wheals may be linear, round, oval, annular, arcuate, serpiginous, or generalized. They vary from several millimeters to 10   cm, affecting mostly the trunk, buttocks, and chest, although they also can occur anywhere. They last from minutes to hours, always resolving with no postinflammatory pigmentary changes or scaling. If individual lesions last longer than a day (and are associated with pigmentary changes or symptoms other than pruritus—such as pain or burning), consider performing a biopsy to exclude urticarial vasculitis, a forme fruste of leukocytoclastic vasculitis that may be associated with internal organ involvement.

100 What is angioedema?

An urticarial variant characterized by subcutaneous swelling in the distensible tissues of eyelids, lips, and oral mucosal membranes (including tongue). May result in respiratory distress.

101 What is the clinical course of urticaria?

102 What are the other clinical presentations of urticaria?

1. Hereditary angioedema: Autosomal dominant, it presents in the second to fourth decade of life with sudden attacks of angioedema that often last for days and can be life threatening. Due to low or nonfunctional C1 inhibitor, with diagnosis being suggested by a low C4 level.

2. Physical urticarias: appear in response to a stimulus, such as cold, sunlight, trauma, water:

Dermatographism (wheals at site of skin-stroking)

Pressure urticaria (severe swelling with deep pain several hours after localized pressure is applied, most commonly on feet and buttocks)

Aquagenic urticaria (elicited by water, as in a cold or hot shower)

Cold urticaria (from rewarming of skin exposed to cold; most common on hands and feet)

Solar urticaria (urticaria on unshielded skin after exposure to sunlight)

Cholinergic urticaria (on face and trunk, pruritic, induced by exercise and emotional stress)

103 How is urticaria diagnosed?

By its classic and fleeting lesions. Always inquire about association with medicine intake, food exposure, recent illness, and physical stimuli, but delay work-up for underlying causes until the problem becomes chronic. Then, do a thorough physical exam, a complete blood count and differential, biochemistry screening, urinalysis, hepatitis B surface antigen, sinus films, oral examination, stool specimens for ova and parasites, and an elimination diet.

Miscellaneous

Warts

106 How are warts transmitted?

By direct or indirect contact, especially when the normal epithelial barrier has been disrupted.

107 What are the major types of warts?

Figure 3-30 Common wart of the hand.

(From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

Figure 3-31 Flat warts of the face.

(From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

Actinic Keratosis

Squamous Cell Carcinoma (SCC)

109 How does SCC present?

In a myriad of morphologic variants, although typically as a scaly, erythematous, and hyperkeratotic plaque, often with superficial ulceration and no defined translucent border (Fig. 3-32).

Figure 3-32 A, Squamous cell carcinoma of the ear, demonstrating a nodule with central scale and crust. B, Large verrucous carcinoma of the sole of the foot. Verrucous carcinomas often reach large sizes before diagnosis because they are often treated as warts.

(From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

110 Where in the skin does SCC originate?

From keratinocytes located in the epidermis, just above the basal layer.

111 Describe the evolution of SCC. Why is it important?

SCC starts as a group of atypical cells in sun-exposed areas, such as head and neck in 70% of the cases (mostly the lower lip, external ear, and periauricular region, but also forehead and scalp), and arms and hands in the remainder. At this early stage, the lesion presents as actinic keratosis (i.e., a flat, scaly, and pink macule). This is precancerous but may not evolve into SCC. As the atypical cells fill the entire epidermis but do not breach the basal layer, the lesion becomes SCC in situ (Bowen’s disease). The next and final step is progression to invasive SCC, wherein the atypical cells penetrate below the basement membrane and into the dermis.

112 What is the course of SCC?

When it arises in actinically damaged skin, SCC rarely metastasizes. Risk factors for spread include depth of invasion, degree of cellular differentiation, and origin in a mucous membrane. Therefore, SCC of the lips has a much greater potential for systemic metastases.

Bowen’s Disease

Basal Cell Carcinoma (BCC)

115 What is the usual clinical course of BCC?

Usually so benign that it used to be called basal cell epithelium. If untouched, it grows locally, with the potential of becoming highly destructive, but rarely metastatic.

Acrochordons (Skin Tags)

117 What are the causes of skin tags?

Unknown. Proposed etiologies include:

118 What is the evidence behind the association between skin tags and type 2 diabetes?

Suggestive. In a study of 118 subjects with acrochordons, 41% had either impaired glucose tolerance or overt type 2 diabetes. There was, however, no correlation between glucose intolerance and location, size, color, or number of acrochordons.

Vitiligo

120 How does vitiligo present?

As milky white, nonscaly, and sharply demarcated macules and patches of variable size (Fig. 3-33). These are often symmetric, and commonly involving areas of repeated trauma, such as elbows, ventral wrists, knees, axillae, dorsal hands, and feet. Other targets include mucous membranes and periorificial sites (eyes, nose, ears, lips, gums, genitals, areolas, and nipples). Lesions eventually increase in number and become confluent, taking on bizarre shapes. They may also appear at sites of injury (koebnerization). Localized vitiligo (i.e., restricted to one area) is less common.

Figure 3-33 Extensive vitiligo in a African-American woman.

(From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

121 What are the other associated cutaneous findings?

Prematurely gray hair, piebaldism (see question 122), halo nevi, alopecia areata, and ocular abnormalities, such as chorioretinitis, retinal pigmentary abnormalities, and iritis. The scalp is the hair most frequently involved, followed by eyebrows, pubis, and axillae. Vitiligo of the scalp usually presents as a localized patch of white or gray hair, but total scalp depigmentation (leukotrichia) may also occur, usually indicating low likelihood of repigmentation.

122 What is piebaldism?

A rare autosomal dominant disease of melanocyte development, characterized by a focal lack of melanocytes resulting in a congenital white forelock and multiple symmetric hypopigmented or depigmented macules. From the old English piebald, spotted, this phenomenon was first described by Roman, Greek, and Egyptian writers. In time, the presence of a stable white forelock in families even led to the creation of telltale surnames, such as Whitlock, Horlick, and Blaylock.

123 What are the characteristics of piebaldism?

Eighty to ninety percent of individuals have a white forelock, typically from birth. The central frontal scalp can also be permanently white, as may be eyebrow and eyelash hair. Finally, white spots may occur on the face, trunk, and extremities. Piebaldism is one of the cutaneous signs of Waardenburg’s syndrome, along with heterochromia of irides, lateral displacement of inner canthi, and deafness (see Chapter 4, questions 106 and 107).

124 When does vitiligo appear?

At any age, although most frequently in the first two decades of life. It affects 1–2% of the U.S. population and is considered autoimmune, a mechanism corroborated by its association with other autoimmune disorders. People of color are affected more frequently, but are also more apt to seek treatment because of the greater cosmetic impact. Male-to-female ratio is equal. One third of patients report another affected family member, suggesting a genetic component.

125 What is the typical course of vitiligo?

Unpredictable, but generally characterized by slow progression, which may be interrupted by periods of stability. Spontaneous repigmentation also may occur, but generally is incomplete.

126 What are the other clinical presentations of vitiligo?

127 How is vitiligo diagnosed?

Clinically. In patients with fair skin, the lack of contrast between normal and diseased areas may make the identification of lesions more difficult, so that a Wood’s lamp becomes necessary. A biopsy will demonstrate no melanocytes, but their presence does not exclude the diagnosis.

128 What systemic diseases are associated with vitiligo?

At least 10% of patients have serologic or clinical evidence of autoimmune disorders, the most common being thyroid diseases, especially hypothyroidism of the Hashimoto variety. Diabetes, Addison’s, pernicious anemia, alopecia areata, and uveitis (Vogt-Koyanagi syndrome) are also frequent. A careful history and appropriate screening are therefore necessary. Still, treatment of concomitant diseases does not influence the course of vitiligo.

Tinea Versicolor

130 How does TV look?

As the name implies (versicolor means multicolor), the condition is characterized by numerous, well-marginated, finely scaly, oval-to-round macules over the trunk and/or chest. These range in color from white to red to brown, and can be pruritic. They eventually coalesce, forming irregular patches of discoloration. The diagnosis is usually confirmed by potassium hydroxide (KOH) examination of scales. This demonstrates both the cigar-butt mycelial hyphae and the round thick-walled spores, in a pattern often referred to as “spaghetti and meatballs,” or “bacon and eggs.” Note that TV is more noticeable during the summer, since lesions cannot tan, thus making the discrepancy with surrounding skin even more apparent.

131 How does TV present in immunocompromised hosts?

As an inverse form, affecting not the trunk, but the face, extremities, and flexural regions. Cell-mediated immunity plays a pathogenetic role, since lymphocyte function is impaired in TV.

Tinea Versicolor (previously discussed)

133 What are the causes of AN?

The most common are factors that stimulate epidermal keratinocyte and dermal fibroblast proliferation. In benign AN, these may be either insulin or an insulin-like growth substance; in the malignant form, they are instead neoplastic products. Overall, AN can occur with:

134 How common is acanthosis nigricans associated with malignancy? How does it present?

It comprises one fifth of all cases, usually due to an aggressive underlying neoplasm—a GI adenocarcinoma in 90% of cases and a gastric in 60%. AN often develops concurrently with the tumor, although it may predate the tumor (by up to 15 years) or follow it. In 25–50% of patients, AN presents as oral lesions (mostly tongue and lips), which are seldom pigmented. Indistinguishable from the benign form, malignant AN is usually not associated with obesity. Instead, its skin lesions are more extensive, more rapidly spreading, atypical in location (palms, soles, and mucosae), and often symptomatic. Regression and progression follow the course of the underlying tumor.

Melanocytic Nevi (Common, Atypical, Dysplastic)

136 What about congenital nevi?

They are nevi that are present at birth or soon thereafter. They are probably hamartomas, since they contain many skin elements, but a predominance of melanocytes. Large congenital nevi have a low (5%) but real risk for malignant transformation into melanoma. Hence, the need for prophylactic excision. In a rare autosomal dominant condition, family members acquire with time many large nevi, sometimes more than 100 (see FAMMM, discussed in question 141).

137 List and describe the different types of common nevi (moles).

Melanocytic nevi are classified according to histology:

138 What are the features of a melanocytic nevus?

The most important is stability—in size, height, color, and outline. Also, lack of symptoms (i.e., not itchy, painful, irritated, or bleeding), even color (usually tan to brown), and small size (<1   cm).

139 What are atypical or dysplastic nevi (Clark nevi)?

They are acquired variants typical of families of northern European descent, with fair skin, light-colored hair, freckles, and other Celtic features. The United Kingdom, Netherlands, Germany, and occasionally Poland and Russia are the most affected countries. Patients present with hundreds of relatively broad lesions that are flat or thinly papular. The more numerous the nevi, the greater the likelihood of melanoma (see discussion on familial atypical multiple mole and melanoma in question 141). Still, dysplastic nevi are just a marker for risk, and not necessarily a precursor. Hence, removal of all dysplastic nevi may not really alter the risk.

140 Describe the characteristics of dysplastic nevi.

They are larger than common moles (5–15   mm in diameter) and often variegated (tan to dark brown to pink). They occur in both sun-exposed and sun-protected areas, more commonly the back, chest, buttocks, breasts, and scalp. Since they grow through lateral extension, they often assume the configuration of a fried egg, with a central papule and a surrounding macular area of differing pigmentation. Due to their lateral extension, they have notched and poorly defined rims.

141 What is FAMMM?

It is the familial atypical multiple mole and melanoma (FAMMM) syndrome (also known as dysplastic nevus syndrome), in which family members develop >100 melanocytic nevi, which is far more than the average number of common nevi (15–20). Lifetime risk for melanoma is high. In fact, close to 100% for individuals with >100 lesions and more than two family members with melanoma history.

Seborrheic Keratoses

143 Describe the morphology of seborrheic keratoses (SK).

Lesions are round to oval, pigmented, initially flat, but subsequently raised and with a velvety to finely verrucous surface. Margins are sharp (as if stuck on normal skin) and have a soft and greasy look. Usually <1   cm at onset, they grow thicker and larger with time, while new lesions continue to appear. Often aligned in the direction of skin folds, they can have keratotic plugging on the surface. Although more common in sun-exposed areas (and often arising from solar lentigines), they may occur anywhere, except for the palms, soles, and mucous membranes.

144 What is dermatosis papulosa nigra?

An SK variant, with earlier onset than the ordinary form. It affects the upper cheeks and lateral orbits of dark-skinned individuals, with small, multiple, pedunculated, and heavily pigmented lesions.

Signs of Leser-Trélat

Melanoma

147 Who gets melanomas?

Light-skinned individuals with (1) excessive childhood sun exposure and blistering sunburns, (2) numerous or atypical nevi, and/or (3) a family history of the disease. Hence, do regular and thorough skin exams, since these may detect lesions at an earlier and thinner stage. Median age of onset for superficial spreading melanoma (by far the most common type) is 44, but melanomas are also the most common reported cancers in whites during the second and third decades.

148 What are the morphologic warning signs of melanoma?

As always, start with history. Since half of all melanomas are initially discovered by the patient, inquire about new moles or preexisting ones that have recently changed size, color, shape, or sensation. Note that melanomas often develop in melanocytic nevi, but half arise de novo. Tenderness, pain, itching, and bleeding suggest instead more invasive lesions. Ask about personal or family history of melanoma, tendency to burn, and prior sunburns. On physical exam, rely on (1) the ABCD(E) checklist, and (2) the revised Glasgow 7-point checklist.

149 What is the ABCD(E) checklist?

A commonly used acronym for identifying the warning signs of malignant melanoma. Developed in 1985, it considers a lesion suspicious when it has more than one of the five following features (see Fig. 3-34):

Figure 3-34 Cutaneous melanomas. Top panels show images of cutaneous melanomas emphasizing the ABCD features of asymmetry, border irregularity, color variegation, and diameter greater than 6   mm. Scale bars represent approximately 5   mm. Bottom panels show the back of a male patient with numerous moles, demonstrating evolution of one mole into melanoma over an 11-month period. Note the increased diameter and darkening of the lesion in the right panel compared with the left panel.

(From Abbasi NR, Shaw HM, Rigel DS, et al: Early diagnosis of cutaneous melanoma: Revisiting the ABCD criteria. JAMA 292:2771–2776, 2004, with permission.).

150 How good is the ABCD(E) checklist?

Two studies have assessed its accuracy. The first found a 92% sensitivity for lesions with >1/5 diagnostic features. The second evaluated instead the accuracy of only the BCD items, and found 100% sensitivity and 98% specificity for lesions with all three features. Still, the major problem is D, since some melanomas are <6   mm. Because D considerably lowers the checklist’s sensitivity, some authors have suggested dropping it altogether. Yet, available data argue against this approach and propose instead changing the “E” from “Elevation” and “Enlargement” to “Evolving” because significant elevation is not apparent in most early melanomas, and thus not a good warning sign of early disease; enlargement can be inaccurate, too, since it focuses primarily on change in size and not, for example, in color, which can be very important in the progress of the disease. Evolving, on the other hand, would include not only evolution (i.e., change of any kind, color included), but also elevation and enlargement. It also supports the observation that 89–95% of 100 consecutively accrued melanomas demonstrate changes in these features, and 100% show changes in at least one feature. Hence, beware of evolving nevi that change size, shape, surface (especially bleeding), symptoms (itching, tenderness), or shades of color. Also, beware of new pigmented lesions.

151 How capable are physicians of recognizing melanomas?

It depends. Overall, ability to detect melanomas has a 50–97% sensitivity and 96–99% specificity. Dermatologists’ examinations are more sensitive, both in real patients and images of lesions. Nondermatologists provide the correct diagnosis significantly less frequently than dermatologists (60% versus 74% of the time). Early detection through history and physical exam is crucial, since thickness of the tumor at excision is the primary prognostic determinant.

152 What is the Revised Glasgow 7-Point Checklist?

A British-developed diagnostic aid that relies on four major and three minor criteria. It also relies heavily on the concept of evolution (i.e., change). In fact, the three major criteria are historical (change in size, shape, and color), while the four minor are instead physical and often late-appearing: (1) inflammation, (2) crusting or bleeding, (3) sensory change, and (4) diameter >7   mm. A scoring system assigns two points for each major criterion and one for each minor. Patients with >1 major criterion should be referred to a dermatologist. Patients with scores >3 should be referred, too.

153 How good is the 7-point checklist?

Several studies have found sensitivity of 79–100% and specificity of 30–37%.

154 How should the physical exam be conducted?

As thoroughly as possible: head to toe in a well-lit room. Always include scalp, oral mucosa, genital area, nails, and interdigital skin of hands and feet. Complete cutaneous examinations are 6.4 times more likely to detect a melanoma than only partial examinations. In cases of multiple nevi, pay special attention to those with unusual features. Remember that melanomas may also arise from the skin, eyes, ears, GI tract, leptomeninges, and orogenital mucosae.

155 What are the major clinical-histopathologic types of melanoma?

They are five, and all first growing radially (often for months and years) before eventually going deep. Only nodular melanoma grows vertically right away. Hence, it lacks the typical ABCDE warning signs and presents instead with elevation and/or ulceration/bleeding.

156 What is the major prognostic indicator of stage I melanoma?

The histologic level of the lesion. The thinner and higher in the skin, the better. Patients with lesions <0.75   mm in thickness have 98% 5-year survival, whereas those with lesions >4   mm have survival rates <50%. Overall, lesions >1.0   mm have a more ominous outcome. Other factors associated with a worse prognosis are vertical growth phase, high mitotic rate, involvement of blood vessels, presence of microscopic satellites, and ulceration with decreased lymphoid infiltrates. The best outcome is in young women with lesions on the extremity rather than the trunk or head.

Signs of Sun Damage

158 What are the most common yellow lesions of the skin?

Cutaneous xanthomas and necrobiosis lipoidica (see also questions 258 and 259).

159 What are xanthomas?

Lesions caused by accumulation of lipid-laden macrophages, usually because of primary (familial, congenital) or secondary dyslipidemia. Secondary hypercholesterolemia, for example, can occur in pregnancy, hypothyroidism, cholestasis, and acute intermittent porphyria. Secondary hypertriglyceridemia is instead associated with diabetes, alcoholism, pancreatitis, gout, and oral contraceptives. Combined disorders occur in nephrosis, chronic renal failure, and steroid therapy.

160 What is the significance of cutaeous xanthomas?

Other than being a cosmetic nuisance, they suggest dysmetabolism. They also may precede a diagnosis of hyperlipidemia, although this is often known through atherosclerosis or pancreatitis.

161 How do xanthomas present?

The hyperlipidemic xanthomas present as xanthelasmas or true xanthomas (tuberous, tendinous, eruptive, plane, and generalized plane). The normolipemic xanthomas are instead more disseminated or verruciform.

162 What is xanthelasma palpebrarum?

The most common cutaneous xanthoma, often presenting in the absence of xanthomas anywhere else, even though histologically identical. In contrast to true xanthomas (that can occur at any age), xanthelasmas usually affect older subjects (>40) and women twice as often as men. From the Greek xanthos (yellow) and elasma (beaten metal plate), they present as soft, yellow, velvety, and sharply marginated plaques that eventually grow into papules and may even coalesce into larger lesions. Typical of the inner canthus of the eyelids (upper more than lower), they are often bilateral and symmetric, flat-topped, and totally asymptomatic. They are associated with hyperlipidemia in 50% of cases, usually one of the primary types (II or IV mostly), but occasionally a secondary, too.

163 What are tuberous xanthomas?

They are firm, painless, and red-yellow nodules that classically develop in pressure areas, such as the buttocks and the extensor surfaces of knees and elbows. They also may occur in the eyelids and yet not be xanthelasmas since nodular in type. Lesions come in many sizes but often coalesce to form large and multilobated tumors. Tuberous xanthomas are associated with hypercholesterolemia and increased low-density lipoprotein (LDL) levels, either primary or secondary.

164 What are tendinous xanthomas?

Slowly enlarging subcutaneous nodules that are typically present over tendons (Achilles) and other extensor surfaces of feet and hands. Often related to trauma, they occur in patients with severe hypercholesterolemia and high LDL, either primary or secondary.

165 What are eruptive xanthomas?

Small and red-yellow papules on an erythematous base, typically erupting in crops over the buttocks, shoulders, and extensor surfaces of extremities (more rarely over the face or oral mucosa) (Fig. 3-35). Often pruritic and tender, they usually resolve spontaneously in a few weeks. Eruptive xanthomas are associated with hypertriglyceridemia, particularly types I, IV, and V (high very low-density lipoprotein [VLDL] level and chylomicrons), yet they also may occur in secondary hyperlipidemias, especially if related to diabetes.

Figure 3-35 Eruptive xanthomas. Typical yellowish-brown papules. White material was applied by the patient to remove these “warts.”

(From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

166 What are plane xanthomas?

Macular lesions, only rarely raised, and occurring anywhere in the skin, including the face, neck, thorax, and flexures. Generalized plane xanthomas can cover very large areas. They may occur in secondary hyperlipidemias (especially cholestasis), whereas in type III dysbetalipoproteinemia, they typically involve the palmar creases. They also can coexist with monoclonal gammopathy.

167 What is xanthoma disseminatum and verruciform?

Two forms of xanthomas that can occur in normolipemic adults, usually as a reaction to local stimuli. The course is benign, often with spontaneous resolution—especially the disseminatum form, which presents as red-yellow papules and nodules over flexures. The verruciform form instead involves the oral cavity, presenting as a single papillomatous yellow lesion, often requiring excision.

Scaling Diseases Without Epithelial Disruption

169 What is the cause of psoriasis? Who gets it?

There is a strong but still undefined genetic influence, particularly in cases with earlier onset. Gender ratios are equal, and overall prevalence is 1–2% in the United States. Although it may appear at any time, the peak of onset is the third decade, with a much smaller group developing it in their 60s.

170 What are the clinical features of psoriasis?

Classic psoriasis vulgaris (from the Greek psoriasis, itchy—which indeed these lesions are) presents as sharply demarcated, circular to oval erythematous papules and plaques of varying size. These are often covered by a white scale due to epidermal hyperproliferation and dermal inflammation. Scales may be thick and “mica-like” (micaceous) because of a silvery white look. Their removal typically causes tiny bleeding droplets (Auspitz sign). Associated pitting and dystrophy of the nails are also quite common. Sites of predilection include the scalp, elbows, knees, genitalia, lumbosacral region, and extensor surfaces of the extremities. Degree of involvement is variable.

171 What are other characteristics of psoriatic lesions?

Newly developed lesions tend to be small (1–3   mm) but easily coalescing, resulting in large plaques with often a gyrate pattern. Note that psoriasis, lichen planus, vitiligo, and warts are the only skin diseases characterized by the Koebner’s phenomenon, in which lesions appear 7–14 days after skin trauma (scratching, for example). Koebner’s occurs in 40–80% of plaque psoriasis cases.

172 Who was Koebner?

Heinrich Koebner (1838–1904) was a German dermatologist with a penchant for melodrama. This included self-inoculation with various kinds of skin infections so that he could demonstrate typical lesions during lectures—all because PowerPoint had not been invented yet.

173 What is the typical clinical course of psoriasis?

One of variable extent and duration, even though usually as a lifelong disease. Spontaneous remissions occur with unpredictable frequency, and patients may move from one clinical form to another. Acute flares may evolve into more severe disease, such as pustular or erythrodermic (see question 174).

174 What are the other clinical presentations of psoriasis?

Psoriasis is a heterogeneous disorder with a spectrum of clinical variants:

175 How is psoriasis diagnosed?

Appearance usually suffices. Distribution of lesions (scalp, elbows, knees, and gluteal folds), Koebner’s phenomenon, and nail pitting are also classic clues. A skin biopsy may help in more perplexing cases and typically shows acanthosis, parakeratosis, neutrophils in the stratum corneum, and a lymphohistiocytic infiltrate in the papillary dermis.

176 What other disease is often associated with psoriasis?

Psoriatic arthritis, in one tenth of cases. When this precedes skin involvement, you must do a complete exam, especially of scalp, genitalia (looking for hidden plaques), and nails.

Dermatophytes

178 What is tinea?

Tinea (from medieval Latin, a gnawing worm) originally indicated larvae of insects that fed on clothes and books. Subsequently, it came to indicate parasitic infestation of the skin. By the mid-16th century, the term was used to describe diseases of the hairy scalp, with the term ringworm indicating instead those skin diseases that assumed a ring form, including tinea per se. Only in 1880, through the work of Sabouraud, was the agent of tinea capitis infection demonstrated, and it became clear that the disease was due to a class of fungi, the dermatophytes.

179 How are dermatophytoses classified?

By the body region involved (Table 3-5). Note that fungal involvement can affect multiple sites. Hence, if you see lesions on the buttocks, always ask, “Can I see your feet?” Almost invariably there will be typical fungal lesions in the fourth web space.

Table 3-5 Classification of Dermatophytoses by Body Region

180 What are the clinical features of dermatophyte infections?

The main symptom is pruritus. On exam, areas affected tend to be those with humid or moist skin, which provides a favorable environment for fungal growth. Different types of tinea may present with different findings, especially based on area involved. Still, the primary lesions remain the same: pruritic, erythematous, and scaly plaques, with active border and central clearing. Papules, vesicles, and bullae may occur too.

181 What is the frequency of dermatophytoses?

It depends. Tinea corporis occurs in any age group. Tinea cruris and pedis predominantly affect the adult population, particularly individuals using communal showers or pools. Tinea pedis is the most common dermatophytosis worldwide (10% of the U.S. population). Onychomycosis is quite common, too, with prevalence in adult American males of approximately 3% and incidence that increases steadily with age. Conversely, tinea capitis is usually a disease of children.

182 How are dermatophytoses diagnosed?

By microscopic examination. This relies on the presence of septate hyphae on potassium hydroxide (KOH) preparation of lesion scrapings or nail clippings (conversely, examination of hairs from scalp infection typically demonstrates spores involving the hair shaft). As a general rule, “if it scales, you should scrape it” (and then do a KOH on it). This rule applies to all scales, independent of location. If the KOH exam is negative, a culture should be obtained on Sabouraud’s dextrose agar with antibiotics.

Lupus Erythematosus (see later)

184 Who gets it?

Any age group, although usually 10- to 35-year-olds—women twice more frequently than men.

185 What are the clinical features of pityriasis rosea?

From the Greek pityron (bran, dandruff) and rosea (pink), PR presents half of the time with a solitary 2–3   cm macule that heralds the eruption (the herald patch). This is a round or oval lesion, salmon colored (rosea), and usually located on the trunk. Over a few days it enlarges into a larger patch (up to 10   cm), with a collarette of fine scale (pityron) just inside a well-demarcated border. Because of its annular shape, the lesion may be mistaken for tinea corporis, hence, the frequent need for a KOH preparation. The herald patch is followed in 1–2 weeks by a diffuse eruption on the trunk, neck, and inner aspects of the proximal extremities. During this phase (which also lasts 2 weeks), 50–100 isolated, small (0.5–1.5   cm), bilateral, and symmetric macules may appear. Lesions are nonconfluent and similar in morphology to the herald patch (i.e., oval or football shaped), although with much less (if any) scaling. They typically have their long axis along the lines of cleavage of the skin, parallel to the rib lines, thus forming a Christmas tree pattern. Mild to moderate pruritus occurs in 75% of patients, and photosensitivity also may be present. Oral involvement is uncommon (<10% of cases), as it is lymphadenopathy. Hence, its difference with syphilis. The eruption eventually resolves completely over 6 weeks, but may range 2–10 weeks.

186 What is the typical clinical course of pityriasis rosea?

Benign. The rash generally resolves without sequelae or recurrence. Yet, in dark-skinned individuals there may be a residual postinflammatory hyperpigmentation.

187 What are the causes of pityriasis rosea?

Although no agent has been isolated, some data suggest it might be a viral exanthema, possibly due to an upper respiratory infection:

188 How is pityriasis rosea diagnosed?

By clinical observation of the rash characteristics:

Note that biopsy is nondiagnostic, while serology may become necessary to rule out secondary syphilis.

Secondary Syphilis (see later)

190 What are the clinical features of atopic dermatitis?

The hallmark is uncontrolled scratching in response to itching, causing an itch-scratch cycle that eventually leads to the classic lesions. The “primary” lesion of atopic dermatitis (AD) has actually been debated, and indeed multiple skin findings may coexist:

Other supporting features of AD include involvement of skin creases (such as fronts of ankles or neck, folds of elbows, and areas behind the knees); history of generally dry skin (xerosis); and history of atopic diseases. Visible flexural dermatitis (or dermatitis involving the cheeks, forehead, or outer limbs of children younger than 4 years) is also quite supportive.

191 Describe the distribution of atopic dermatitis lesions.

Age-related:

Generalized involvement may develop at any age (see Fig. 3-36).

Figure 3-36 Phases of atopic dermatitis. A, Infantile phase. Typical erythematous, oozing, and crusted plaques seen on the cheek of an infant with atopic dermatitis. B, Childhood phase. Close-up view of a lichenified, excoriated, crusted, and secondarily infected plaque on the right knee of a 5-year-old girl. C, Adolescent or young adult phase. Classic lichenified flexural plaque in a young man.

From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

192 Who develops atopic dermatitis?

Usually children, with 85% of cases in the first year of life and 95% before age 5. Prevalence is high and rising, with 10–12% of American children and 0.9% of adults being affected. Patients often have a personal or family history of other atopic diseases, such as allergic rhinitis, asthma, hay fever, or urticaria. Associated findings include dry, lackluster skin, Hertoghe sign (lateral thinning of eyebrows), and Dennie-Morgan fold (an extra infraorbital eyelid fold).

193 Describe the course of atopic dermatitis.

More severe and persistent in childhood, but eventually improving with age. Still, in 50% of patients the disease persists well into adulthood. Risk factors for persistence include a family history of atopy, early disease in childhood, and severe cutaneous lesions.

194 What are the other clinical presentations of atopic dermatitis?

The most severe forms progress to erythroderma, which consists of generalized scaling and redness associated with fever, high-output cardiac failure, systemic infection, and heat loss. This represents a severe complication and may require hospitalization. Note that erythroderma can occur in other skin diseases, such as psoriasis, seborrheic dermatitis, and drug reactions.

195 How is atopic dermatitis diagnosed?

Clinically. Major criteria include typical morphology and distribution, chronic or relapsing course, and personal or family history of atopy and pruritus. Elevated serum IgE levels and specific IgE-mediated sensitization (as measured by skin test or radioallergosorbent test [RAST]) also support the diagnosis. Biopsy is nondiagnostic, with varying degrees of acanthosis, spongiosis, and mixed dermal infiltrate. Note that pruritus unaccompanied by rash can occur not only in atopic dermatitis, but also in scabies, dermatitis herpetiform, pre-bullous pemphigoid, drug eruption, liver disease, renal disease, polycythemia fever, and malignancies (especially lymphoma).

196 What other skin diseases can be associated with atopic dermatitis?

Definitely superinfections, especially with S. aureus (hallmark being oozing and crusting), but also warts, molluscum contagiosum, dermatophytosis, and herpes simplex. The latter may progress to Kaposi’s varicelliform eruption, a disseminated form of the disease.

Eczematous Diseases: Stasis Dermatitis

198 How does it present?

With erythematous, scaly, and eczematous plaques of the lower extremities, brown hyperpigmentation, and edema. An aching discomfort is often present (at times pruritic), but severe pain is rare. Diffuse red-brown discolorations representing intradermal deposits of hemosiderin (from degraded, extravasated erythrocytes) are also quite common. Lesions typically involve the medial ankle, but with time may progress to the foot and/or medial lower leg. In severe cases, an ulceration may develop. Superinfection with bacteria leads to honey-colored crusting, whereas superimposed cutaneous candidiasis causes monomorphous pustules.

199 Who develops stasis dermatitis and ulceration?

Adults older than 50 (with prevalence reaching 20% by age 70); women are more frequently affected than men. It is often preceded by a history of dependent leg edema, due to venous insufficiency or phlebitis.

200 What is the clinical course?

Chronic, with large and recalcitrant ulcers that heal with elevation and compression bandages. Dermatitis usually responds to mid-potency steroids and compression stockings.

201 How are stasis dermatitis and ulceration diagnosed?

Clinically. Still, a vascular evaluation is necessary to rule out arterial disease. Pulses are normal.

Eczematous Diseases: Seborrheic Dermatitis

203 What causes it?

Nobody knows. It has been linked to Malassezia furfur, immunologic abnormalities, and complement activation, with exacerbations related to stress, scratching, and changes in humidity or seasons. Very common in Parkinson’s and in people with AIDS, among whom it is widespread and refractory.

204 What are the primary lesions of seborrheic dermatitis?

Erythematous papules and plaques, with greasy-appearing yellow scales and crusts (inflammatory dandruff). The yellow color is usually the result of serum exuding on the surface of the scale. Although lesions may occur in both hairy and nonhairy skin, the word seborrhea is Greek for overflow of sebum. Hence, oily and hairy areas of the head and neck are the most hit. These include the scalp, forehead, eyebrows, glabella, lash line, nasolabial folds, beard, and retroauricular skin, but also the ear canal and submentum. More severe disease may involve the central chest (midsternum), back, and intertriginous regions (umbilicus, axillae, inframammary and inguinal folds, perineum, or anogenital crease). Involvement of intertrigines is usually nonscaling. The scalp may be varyingly affected: from small and patchy scaling versus diffuse and adherent crusts. Blepharitis also may occur, and pruritus is common.

205 Who develops seborrheic dermatitis?

Mostly subjects with oily skin, males slightly more than females. Onset is after puberty, with peak in the fourth and seventh decades. Yet SD is also common in infants younger than 6 months old.

206 How does SD present in babies?

As erythematous plaques covered with greasy-appearing scales and crusts, typically involving the scalp (cradle cap) and intertriginous regions. Spontaneous resolution is the rule, usually by 6 months.

207 What is the typical course of seborrheic dermatitis in adults?

Chronic, with periods of exacerbation (winter/early spring) and remission (summer). Activity is heralded by burning, scaling, and itching, followed by lesions that present as greasy and brownish scalings over an inflamed skin. Superinfection with oozing and crusting is common.

208 How is seborrheic dermatitis diagnosed?

By the typical clinical appearance. Biopsy is nondiagnostic.

Nonscaling Lesions—Table 3-6

Lichen Planus

211 Who gets lichen planus?

Men and women in their 40s; 10% have positive family history, suggesting genetic predisposition.

212 What is the primary lesion of lichen planus?

The papule. This is characterized by five Ps: planar, purple, polygonal, pruritic, and papular. LP lesions are shiny, 1–4   mm in size, flat-topped, violaceous, occasionally scaling, and invariably pruritic. Morphologically, however, they can be quite variable, and even bullous and verrucoid. LP papules typically affect the trunk (especially sacral areas) and extremities (tibial areas and flexor surfaces of the wrists). They can be discrete, but more often occur in clusters of lines or circles, usually coalescing into small 1–2   cm plaques. Wickham striae (white or gray streaks forming a reticular pattern on a violaceous background) are often present, especially on oral lesions. Indeed, lesions are called lichen planus because they are flat (planus in Latin) and often aggregate like lichens on a rock. LP is one of the few skin diseases with Koebner’s phenomenon.

213 What other sites beside the skin may be involved?

LP can occur on mucous membranes, genitalia, nails (see question 38), and the scalp. The latter can progress to atrophic cicatricial alopecia.

214 How common are mucosal lesions?

Common. They can occur without skin involvement and may be asymptomatic or slightly burning. Usually localized on the tongue and buccal mucosa, they are often associated with Wickham striae. Ulcerated lesions tend to be painful, and in men may undergo malignant transformation. LP lesions also can occur on other mucosae, such as the tonsils, larynx, GI tract, and conjunctivae.

215 How about the genital lesions of LP?

In men they present as papules on the glans, with a typical annular configuration and associated cutaneous manifestations. Vulvar involvement ranges instead from reticulate papules to severe erosions, causing pruritus, dyspareunia, and even vulvar and urethral stenosis.

216 What is the course of lichen planus?

Characterized by an initial and localized eruption followed in a week or so by a generalized rash. This reaches maximal spread at 2–16 weeks. Lesions resolve within 6 months in 50% of patients and within 18 months in 85%. Oral LP lasts longer (5 years on average). Recurrences are rare.

Purpura

218 What are the two major types of purpura?

Noninflammatory and inflammatory (vasculitis).

219 What is noninflammatory purpura?

It is blood extravasation into the skin or mucous membranes, nonindurated and nonpalpable.The most common is a traumatic bruise. Yet, noninflammatory purpuras usually reflect a hemostatic problem, such as (1) thrombocytopenia (most common cause of purpura) and platelet dysfunction, (2) thrombocythemia, and (3) vascular disorders (e.g., structural vessel malformation, disorders of connective tissue, small vessel vasculitis).

220 How are noninflammatory purpuras classified?

By size, shape, and depth. In this regard, blood extravasations can be divided into four groups:

221 What about the “inflammatory” purpura?

It is a lesion due to extravasation not only of red cells, but also leukocytes. Hence, inflammatory purpura is by definition indurated and palpable. It indicates small vessel vasculitis.

222 What is leukocytoclastic vasculitis (LCV)?

A histopathologic term for small-vessel vasculitis. LCV may be acute or chronic and usually carries a good prognosis unless internal involvement is present.

223 How do LCV lesions present?

They may be either localized to the skin or extended to internal organs, most commonly the GI tract, kidneys, and joints—but also the lungs, heart, and central nervous system.

224 What are the characteristics of LCV lesions?

225 What is livedo reticularis?

A rare manifestation of cutaneous vasculitis, since it reflects involvement of medium-sized rather than small-sized vessels. It is characterized by a purplish, streak-like net.

226 What are the causes of cutaneous vasculitis?

It depends on the patient’s age:

1. In children the most common cause is Henoch-Schönlein purpura, followed at a great distance by leukocytoclastic hypersensitivity (i.e., drug reaction).

2. In adults, cutaneous vasculitis is often due to immune complexes, although other autoantibodies can do it, too. Yet, 30–50% of all cases are idiopathic. The rest are caused by:

Drugs, especially antibiotics (particularly beta-lactams), diuretics, nonsteroidal anti-inflammatory drugs, but also foods or food additives.

Infections, including upper respiratory tract infections (particularly beta-hemolytic streptococcal), viral hepatitis (especially C, probably through the presence of cryoglobulins), HIV, and endocarditis. Vasculitis usually postdates the infection.

Collagen vascular diseases, especially rheumatoid arthritis, Sjögren syndrome, and lupus erythematosus. Vasculitis often denotes active disease and possibly poorer prognosis. Note that cutaneous vasculitis is rarely seen in patients with involvement of larger vessels, such as polyarteritis nodosa, Churg-Strauss syndrome, or Wegener’s syndrome.

Inflammatory bowel disease (such as ulcerative colitis or Crohn’s disease).

Malignancy (especially lymphoproliferative diseases, particularly hairy cell leukemia). Still, cancer is a rare cause, accounting for <1% of all cases of cutaneous vasculitis.

Kaposi’s Sarcoma

227 What are the major types of Kaposi’s sarcoma? Describe each.

Classic (traditional): Now relatively rare, this is the KS of shins or feet of older men of either Mediterranean or Eastern European descent (Ashkenazi Jews). It begins as purplish papules slowly progressing to plaques. Rarely fatal. In fact, most patients die with KS rather than of KS.

Epidemic (AIDS-associated): Present in more than one third of AIDS patients. Lesions are more varied and widespread than in the classic form, ranging from macules to papules, to plaques or ulcers, all red-purple in color (Fig. 3-37). Mean survival is 15–24 months, although antiretroviral therapy has extended it. Visceral involvement is common, including genital, oral, GI, and pulmonary sites.

Endemic (African): Cutaneous and/or lymphatic. Common (10% of all cancers), aggressive, 15:1 male-to-female ratio, and possible in children. Endemic in Uganda, Congo, and Zambia.

Iatrogenic: From immunosuppression, may regress with its termination. Often with GI bleeding.

Figure 3-37 Kaposi’s sarcoma. Multiple violaceous plaques following the lines of skin cleavage in a pityriasis rosea-like pattern are seen on the turnk of an HIV-positive patient.

(From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

228 What is the presentation of KS?

229 What is the cause of KS?

There is definitely a KS-associated herpes virus (human herpesvirus [HHV] type 8), first identified in 1994, and subsequently linked to all four types. Yet, HHV-8 is probably necessary but not sufficient. Also, it is unclear whether KS is a hyperplasia or tumor and whether it is multicentric or metastatic.

230 How is Kaposi’s sarcoma (KS) diagnosed?

It is suspected clinically and diagnosed histologically.

231 Who was Kaposi?

Moritz Kaposi (1837–1902) was a Viennese dermatologist. Born Moritz Kohn in Kaposvar, Hungary, he chose to rename himself after his native town when he converted to Catholicism. A conceited chap famous for never saying, “I don’t know,” Kaposi linked his name not only to KS, but also to one of the earliest descriptions of lupus erythematosus and dermatitis herpetiform.

Lupus Erythematosus

233 What are the cutaneous manifestations of LE?

Primarily three:

These are histopathologically similar but clinically very different.

234 What is the presentation of acute cutaneous lupus erythematosus?

The typical one is an acute and focal butterfly rash, involving the cheeks and bridge of the nose. This is often painful or pruritic and may even be photodistributed (forehead, periorbital area, chin, ears, and neck). In fact, a temporal association with sun exposure is very common. More rarely (and usually in older patients), ACLE presents with a generalized maculopapular rash that represents a photosensitive dermatitis. At times may even occur as a widespread blistering phototoxic reaction, resembling toxic epidermal necrolysis (TEN).

235 Is ACLE associated with SLE?

It is strongly associated with the systemic manifestations of LE (i.e., SLE) and its serology. In fact, malar rash occurs in 55–90% of all SLE patients; generalized maculopapular eruption in 35%.

236 What is the course of ACLE?

A waxing and waning, with sun-related exacerbations lasting for days to weeks. At times, it can become quite protracted, usually resolving with postinflammatory hyperpigmentation. It rarely scars, but at times ulcerates. Ulcerations of oral and nasal mucosae are also common, either painful or painless. ACLE may coexist with SCLE, but much more rarely with CCLE (i.e., discoid lupus).

237 What laboratory studies are positive in ACLE?

The same studies that are positive in SLE:

238 What are the lesions of SCLE?

Although at times generalized, these are primarily subacute lesions of sun-exposed areas in white subjects, predominantly women. They begin as erythematous papules or plaques, eventually evolving into annular lesions (mimicking erythema annulare) or papulosquamous and scaling ones resembling psoriasis or lichen planus. Usually asymptomatic (at times mildly pruritic), they wax and wane, always healing with neither scarring nor atrophy. They may, however, leave residual dyspigmentation. Sunscreens, topical steroids, and antimalarials can be effective.

239 Is SCLE associated with SLE?

Only with very few manifestations of SLE, except for musculoskeletal symptoms, which are present in one half of all SCLE patients (arthralgia, often symmetric, of the hands and wrists). Yet full-blown arthritis is less common (<2%). Laboratory abnormalities, like ANA and, especially, anti-Ro (SS-A) autoantibodies, are very common. One half of SCLE patients have four or more of the diagnostic criteria for SLE, but a less severe disease. Still, some SCLE patients may manifest SLE symptoms; hence, look for pleuritis, pericarditis, neurologic involvement, and renal impairment. They also may have nonspecific cutaneous manifestations of lupus erythematosus, such as livedo reticularis, palpable purpura, urticaria, ischemic changes of the distal fingertips (from Raynaud’s phenomenon), or mucosal ulcerative lesions.

240 Can any drugs elicit SCLE skin lesions?

Mostly hydrochlorothiazide, but also calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and griseofulvin.

241 What is the association with discoid lupus erythematosus (DLE)?

Some SCLE patients can have lesions of DLE. Some may even develop small vessel vasculitis.

242 What is discoid lupus?

The chronic cutaneous form of lupus erythematosus. It is also the most common form, accounting for 50–85% of all cutaneous manifestations of LE.

243 What is the difference between DLE and the discoid lesions of SLE?

DLE occurs in the absence of other systemic involvement and in patients who rarely develop SLE. It affects middle-aged subjects with low ANA titers and absence of more SLE-specific antibodies, such as anti-native DNA and anti-Sm. DLE may also occur in 20% of patients with SLE, and indeed some DLE patients (<5%) may progress to SLE. Yet, the two are fundamentally separate. DLE patients rarely fulfill four or more of the criteria for SLE, and serologic abnormalities are uncommon. Still, some DLE patients may also have lesions of SCLE, and some may even have a malar rash.

244 How does DLE present?

As a chronic, scarring, and atrophy-producing photosensitive dermatosis. Discoid lesions begin as sharply demarcated erythematous papules and plaques, with slight to moderate scaling, usually arising over a sun-exposed area, such as the cheeks, nose, ears, face, and scalp. In severe disease, however, they may involve the upper chest, back, and arms, and, on rare occasions, even the legs and unexposed skin. DLE lesions are mostly asymptomatic, although at times they may be pruritic and occasionally painful. Eventually, they spread centrifugally and may merge. As they do so, scales thicken and become adherent, causing hyperpigmentation at the active border and hypopigmentation in the central and inactive areas. As lesions age, dilation of follicular openings occurs with a keratinous plug, termed follicular plugging. There also may be telangiectasias. Resolution of the active lesion results typically in pink or white depressed scars and alopecia of the scalp. In fact, atrophy and disfiguring scarring are the hallmark of the disease. Hence, the term “lupus,” since, like a wolf, it devours the patient’s physiognomy.

245 What are localized and generalized DLE?

Patients with DLE can present with involvement that is either localized (i.e., affecting only the head and neck) or generalized (i.e., affecting other areas). The latter is associated with hematologic and serologic abnormalities, has greater progression to SLE, and is more difficult to treat.

246 What are the serologic markers of DLE?

One fifth of patients have positive ANA titers, 1–3% have anti-Ro (SS-A) autoantibodies, and <5% have anti–double-stranded DNA or anti-Sm antibodies. The latter usually reflect SLE.

247 Is skin involvement common in systemic lupus erythematosus?

It is present in 85% of patients, both as disease-nonspecific and disease-specific manifestations. The latter is acute, subacute, and chronic (discoid) lupus. The first sign of disease is usually an erythematous blush on the cheeks and nose (butterfly rash) or a maculopapular eruption above the waistline, similar to a drug reaction. Discoid lesions are also common.

248 What are the disease-nonspecific manifestations of SLE?

They are alopecia, panniculitis (lupus profundus), bullous lesions, urticarial vasculitis, and vasculitic purpura (i.e., palpable purpura that may result in ulceration). Patchy or generalized alopecia can occur independently of other manifestations, and may be associated with flares of disease. Livedo reticularis is also possible (especially in cases of antiphospholipid antibodies), as is mucosal ulceration of the hard palate and nasopharynx, like nasal septal perforation. These often reflect active disease. Raynaud’s phenomenon occurs in 20–30% of cases.

249 What is lupus profundus?

It is lupus involvement of adipose tissue. This is characterized by multiple subcutaneous nodules, usually with normal skin, but sometimes with overlying discoid lesions of the face, breasts, buttocks, trunk, or proximal arms and legs. These may ulcerate and typically heal with subcutaneous atrophy. Calcification may also occur. Many patients have a positive ANA and antibodies to double-stranded DNA. Yet, lupus profundus also may occur with CDLE or SLE.

250 Who develops lupus?

It depends. DLE affects 25- to 45-year-old subjects, women twice as often as men. SLE peaks instead at 30–40 years, although it may occur in children and even elderly patients. Women are eight times more affected, and so are African Americans. One tenth of patients have a genetic predisposition.

251 Can drugs trigger lupus erythematosus?

Yes. Hydralazine, procainamide, isoniazid, methyldopa, sulfonamides, phenytoin, and penicillamine may all induce a systemic lupus-like illness.

Syphilis

253 Who develops syphilis?

Early syphilis (primary and secondary disease) may occur in any age group, but more commonly in the sexually active years. Male-to-female ratio is 2:1. Recently, the incidence has increased, initially because of homosexual males, but with anti-HIV changes in sexual practices, because of inner-city, African-American heterosexuals involved in drug use.

254 What are the other clinical presentations of syphilis?

Insect Infestations

256 Who develops insect infestations?

Any age group. Still, pediculosis capitis is more common in children, pediculosis pubis in young adults (frequently spread by sexual contact), and scabies in nursing homes and hospitals, often as epidemics. They all spread by close physical contact with infected subjects or clothing.

257 What is Norwegian scabies?

It is “crusted” scabies, a much more politically correct term, since the only reason the poor Norwegians got stuck with this unfortunate association is a report that came out of their country during the mid-1800s. Whatever the name, this is a separate and very contagious form of scabies, characterized by extensive, widespread, and crusted lesions over the elbows, knees, palms, and soles. Thick, yellowish, and hyperkeratotic scales and plaques may almost suggest psoriasis, although the pruritus of scabies is typically much more intense. The condition is characterized by hundreds to millions of adult female mites infesting the host, who is usually immunocompromised (e.g., AIDS), but also elderly, or physically and/or mentally disabled and impaired. Hence, this is a particularly serious problem in institutionalized settings.

Necrobiosis Lipoidica

259 What is the presentation of NL?

The classic one is a series of asymptomatic and shiny 1–3   mm papules/nodules that are well circumscribed and slowly enlarging over months to years. Usually located over the pretibial areas, they also may affect the face, scalp, trunk, and upper extremities. Lesions eventually form waxy and atrophic round patches, red to brown in color. These may progress into depressed, atrophic, and yellowish plaques, 2–10   cm in diameter, scaly, and with violaceous borders that are due to skin atrophy, thus making underlying veins more visible. Multiple telangiectasias can also be seen on the thinning epidermis. Plaques may eventually ulcerate, especially after trauma, and occasionally become infected. Lesions tend to be multiple and bilateral, with a pronounced Koebner’s phenomenon. In 75% of the cases, they are painless (probably because of concomitant neuropathy), although they also may be extremely painful. Otherwise, the only complaint is usually cosmetic.

Porphyria Cutanea Tarda (PCT)

261 What is the presentation of PCT?

It is characterized by photosensitive lesions due to increased skin fragility to sun exposure. This results in full-thickness epidermal erosions and blistering, with painful indolent sores of sun-exposed areas, like the face, forearms, and back of the hands. These become thickly crusted and secondarily infected, eventually healing with hyperpigmentation and scarring. Milia (tiny epidermal white or yellow papules), hypertrichosis (over temporal and malar areas), scleroderma-like plaques, and excretion of port-wine urine rich in porphyrin pigments are other common features.

Sarcoidosis

263 What are the skin manifestations of sarcoidosis?

They are either nonspecific or specific, with only the latter being histologically characterized by noncaseating granulomas. The most common nonspecific manifestation is erythema nodosum, whereas the most common specific one (especially in African-American women) is a cluster of small, nonscaling, dome-shaped papules on the face, periorbital areas, nasolabial folds, and/or extensor surfaces. These may be skin colored or variously hued (violaceous, reddish-brown, or hyperpigmented). They are usually asymptomatic, indurated, and resolving without scarring.

264 What is “plaque” sarcoidosis?

A form of chronic cutaneous involvement (i.e., >2 years), usually reflecting more severe systemic disease. Plaques result from the coalescence of papules into larger lesions, which are round to oval, reddish to purple, flat topped, and infiltrated. They may have an annular appearance (as a result of central atrophy), large telangiectatic vessels, and they may even appear scaly, which often prompts a differential diagnosis with psoriasis or lichen planus. They are usually located on the scalp, back, buttocks, extremities, and face (where they can mimic discoid lupus, especially when central atrophy and scaling are present). They often heal with scarring. In fact, scalp plaques lead to alopecia.

265 What is lupus pernio?

The most characteristic of all specific sarcoid lesions. It is more common in African-American women with long-standing systemic involvement—usually pulmonary. It presents as chronic, indurated papules or plaques that resemble frostbite (pernio in Latin). Like other sarcoid lesions, they are variously hued (red to purple and at times violaceous), and usually located over the bridge and alae of the nose, even though they also can involve the cheeks, ears, and lips (and even the back of the hands, fingers, toes, and forehead). They are commonly associated with chronic uveitis and bone cysts. The course is chronic, often resulting in disfigurement (hence, the term lupus). If involving the nasal rim, lupus pernio has been associated with granulomatous disease of the upper respiratory tract and nasal mucosa, resulting in masses, ulcerations, or even life-threatening airway obstruction.

266 What is erythema nodosum (EN)?

The most common nonspecific (i.e., not granulomatous) cutaneous manifestation of sarcoid. EN is an acute, nodular, and erythematous hypersensitivity reaction that involves the panniculus of the shins. Often self-limited, it resolves with just a residual hyperpigmentation.

267 What are the characteristics of EN?

It afflicts predominantly young women (peak onset 18–34 years), presenting with flu-like symptoms, arthralgias and fever, followed by a painful rash that consists of large (2–6   cm in size), tender, nonscaling, and erythematous nodules/plaques on both pretibial areas (mostly shins and ankles). During the first week of rash, lesions are bright red, hard, tense, and painful. During the second week, however, they become bluish to livid and occasionally fluctuant (but never suppurative or ulcerative). Eventually, they fade to a yellowish hue, like a bruise, often leaving residual hyperpigmentation and desquamation of the overlying skin. Although each lesion lasts approximately 2 weeks, new lesions may continue to appear for 3–6 weeks. In one third of the idiopathic cases, the eruption may actually last for more than 6 months. After resolution of all lesions, achiness may persist for weeks.

268 Which sarcoid patients get EN?

Child-bearing women, especially those of North European lineage (particularly Scandinavians).

269 What is Löfgren’s syndrome?

A characteristic and febrile form of acute sarcoid that includes:

Acute and benign, the syndrome resolves spontaneously in 6–8 weeks.

270 Is erythema nodosum exclusive of sarcoid?

No. Currently, the most common cause of EN in children is streptococcal infection, while in adults it is streptococcal infection and sarcoid. Still, EN also may occur as a drug reaction, manifestation of systemic diseases, or idiopathic entity. Among drugs the usual culprits are oral contraceptives, sulfonamides, iodides, and bromides. Associated infections include instead tuberculosis, Mycoplasma pneumoniae, M. campylobacter, Yersinia enterocolitica, and all major mycoses. Autoimmune diseases comprise the inflammatory bowel disorders. Finally, other conditions (pregnancy, Hodgkin’s disease and lymphoma, Behçet disease) can do it, too.

Behçet’s disease

272 What is the presentation of BD?

Systemic symptoms (such as malaise, anorexia, weight loss) often precede the mucosal ulcerations by 6 months to 5 years. Of these, oral ulcers are the most common and earliest sign.

273 What is the apperance of oral ulcers?

They can be shallow or deep, with a central purulent base characterized by punched-out and clean margins. They are indistinguishable from common aphthae (canker sores), although usually larger (up to 3   cm in diameter), more painful, more frequent, and more rapidly progressing. The most common sites are the tongue, lips, buccal mucosa, and gums, with the tonsils, palate, and pharynx being instead less commonly affected. Ulcers appear singly or in crops, persist for 1–2 weeks, and subside without leaving scars. They tend to recur at least three times over a 1-year period, with the interval between recurrences ranging from weeks to months. Morphologically they can be divided into:

274 What are the eye lesions of BD?

Frequent. Eye involvement occurs in 47–65% of BD patients, occasionally progressing to blindness. The most common manifestation is posterior uveitis (i.e., retinal vasculitis), but other manifestations are possible. Hypopyon, once considered the hallmark of BD, is now uncommon.

275 Describe the skin lesions of BD.

Variously appearing. They occur in 58–97% of patients and include erythema nodosum-like manifestations (the most common), acneiform nodules, erythema multiforme-like lesions, and papulopustular eruptions. Often there is a positive pathergy test (see question 278).

276 What are the genital manifestations of BD?

They are aphthous ulcerations that may accompany oral ulcers in 50–100% of cases, often resembling them. In males, they usually occur on the scrotum, penis, and groin. In females, they occur instead on the vulva, vagina, groin, and cervix. They are recurrent and may heal with scarring.

277 What are the other manifestations of BD?

278 What is pathergy?

The tendency to develop new lesions after minor trauma. Due to nonspecific skin hyperactivity. Although not limited to it, pathergy strongly suggests BD. It consists of an erythematous papule that develops 48 hours after intradermal injection of saline, often evolving into a sterile pustule.

Dermatomyositis

280 What are the most typical manifestations?

The two most characteristic (and possibly pathognomonic) are the heliotrope rash and the Gottron papules. Malar erythema, poikiloderma in a photosensitive distribution, violaceous erythema on extensor surfaces, and periungual and cuticular changes are instead less specific.

281 What is the heliotrope rash?

A symmetric, violaceous to dusky, erythematous rash of the periorbital area—with or without edema. It can be subtle and only appear as a mild discoloration of the eyelid margins.

282 What are Gottron papules?

Slightly elevated, reddish/violaceous papules and plaques that can be found over bony prominences, especially the dorsal surfaces of knuckles (metacarpophalangeal, proximal interphalangeal, and distal interphalangeal), but also the elbows, knees, and/or feet. At times, these have a slight scale and, occasionally, a thick and psoriasiform one. In addition to psoriasis, they may resemble lesions of lupus erythematosus or lichen planus.

283 What is poikiloderma?

An erythematous disorder, first described by Civatte in 1923, that presents with atrophy, telangiectasia, and mottled pigmentation—both hypopigmentation and hyperpigmentation. It affects the cheeks and lateral sides of the neck of middle-aged women, sparing areas shaded by the chin. In addition to the “V” of the neck, it also may occur on other sun-exposed areas, such as the extensor surfaces of arms or the upper part of the back (shawl sign). It is characteristic but not specific of dermatomyositis.

Diabetes Mellitus

Scleroderma

286 What is sclerodactyly?

The symmetric thickening, tightening, and induration of the fingers. It has a 10-year survival rate of 71%.

287 What is proximal scleroderma?

Skin involvement proximal to metacarpophalangeal or metatarsophalangeal joints. Induration also may affect the entire extremity, face, neck, and trunk (thorax and abdomen). Proximal scleroderma that spares the trunk has a 58% 10-year survival, whereas diffuse skin induration has only a 21% 10-year survival.

288 What are the minor cutaneous manifestations of scleroderma?

As a result of ischemia, fingertips may be pitted, tapered, and with loss of the digital pad. Raynaud’s phenomenon also is quite common, with 70% of patients initially presenting with this complaint and 95% eventually developing it during the course of their disease. Skin pigmentary changes also are common. These may include a salt-and-pepper appearance, with areas of hyperpigmentation alternating with hypopigmentation, or an overall hyperpigmentation or hypopigmentation. Telangiectasias (dilated vessels located just beneath the dermis) are also frequent, and most obvious on the face, perioral area, and neck (but also the upper chest and arms).

289 What are the characteristics of the hand lesions of scleroderma?

Early in the disease, the skin of the hands may feel puffy to the patient as a result of edema. This eventually progresses to sclerosis, with rapidity of progression reflecting visceral involvement and severity of outcome. In the sclerotic phase, the skin appears tight and shiny, with loss of hair, decreased sweating, and inability to make folds. Thickening and induration of the skin begin distally on the fingers and advance proximally. Calcinosis may occur on the fingers and extremities, including the extensor side of the forearms and the prepatellar areas.

290 What is limited cutaneous scleroderma?

It is skin thickening of areas that are distal to the elbow and knee. It also may involve the face and neck. CREST syndrome (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) is an older term for this subset of limited cutaneous scleroderma.

291 What is diffuse cutaneous scleroderma?

It is skin thickening of proximal aspects of the extremities plus the trunk and face. Reduced oral aperture (microstomia) due to perioral involvement may occur. Measure incisor-to-incisor distance.

292 What about Raynaud’s phenomenon?

Raynaud’s phenomenon of the digits (but also the lips, nose, and ears) occurs in 5–15% of the general population and quite commonly in postmenopausal women. Of these, only 5% develop a connective tissue disease. In scleroderma, it may precede obvious skin changes by months or even years (see also Chapter 22, questions 5–9).

Hyperthyroidism

Pyoderma gangrenosum

295 How does PG look?

It usually begins as a tender erythematous nodule or a hemorrhagic pustule, which eventually undergoes necrosis, forming ulcers with tender, raised borders that extend into the dermis. These are often solitary, but if multiple may coalesce into a single large ulcer that can be very painful, with irregular and dusky margins and satellite lesions. Progression is often rapid. Lesions are mostly distributed over the lower extremities, but also can appear on the trunk, abdomen, and rarely the head and neck. There is also pathergy. Systemic symptoms of fatigue and fever may also occur.

296 What are the causes of PG?

About 25–50% of cases are idiopathic. The rest are associated with systemic disorders, such as ulcerative colitis, Crohn’s, various arthritic disorders, neoplasms, but also myelodysplastic syndromes, polycythemia vera, myelofibrosis, and essential thrombocythemia. All present with an atypical PG, often bullous and in unusual sites (such as the face and arms).

Sweet’s Syndrome

298 What are the skin lesions of Sweet’s syndrome?

They are edematous, tender, beefy-red or violaceous plaques or nodules that suddenly erupt over the face, neck, and extremities (Fig. 3-38). They often have a purulent base, with central clearing and ultimately ulceration. They also may be papular, pustular, vesicular, or bullous. Systemic signs and symptoms (such as fever, myalgias, arthralgias, or ocular involvement—like conjunctivitis) usually accompany the skin eruption. Neutrophilic leukocytosis and elevated sedimentation rate are common, too. Less common are pulmonary infiltrates and hepatic and renal involvement.

Figure 3-38 Sweet’s syndrome in an elderly man.

(From Fitzpatrick JE, Aeling JE: Dermatology Secrets. Philadelphia, Hanley & Belfus, 1996.)

299 What do these lesions appear like histopathologically?

They have a diffuse, neutrophilic infiltrate in the dermis without leukocytoclastic vasculitis. This is similar to erythema multiforme, but caused by a neutrophilic infiltrate.

300 How often is Sweet’s syndrome associated with an underlying malignancy?

In 20–50% of the cases. Hematologic disorders account for 90% of all cancers, with acute myelogenous leukemia being the most common, followed by lymphoma, multiple myeloma, and myelodysplastic syndromes. Association with solid tumors is rare, and most are genitourinary.

301 Is there anything unique in the Sweet’s syndrome of cancer?

Its cutaneous features are more severe, and lesions are more often bullous and on atypical sites, such as the trunk, mucosae (i.e., conjunctivitis), and internal organs (i.e., lungs, kidneys, and liver). Patients have less neutrophilia while having instead platelet abnormalities and anemia.

302 Which cancers metastasize to the skin?

Breast, GI, prostate, kidney, and head and neck. Melanomas, of course, and leukemias also may metastasize to the skin. Overall, autopsy studies reveal that 2–4% of all patients with internal cancer develop skin metastases. Once these have occurred, prognosis is generally poor.

303 How do skin metastases present?

As firm and rapidly growing skin nodules, often covered with fine telangiectasias (due to the neoplastic angiogenesis) and even ulcers (due to inability of the vasculature to catch up with the rapid growth of the tumor). Lesions are subcutaneous or intradermal, skin-colored but occasionally reddish and even bluish. Common on the anterior trunk, but also anywhere else.

304 What are the unusual patterns of skin metastases?

One interesting pattern is the ability of lesions to form a zosteriform pattern, with clusters of tumorlets merging into a zoster-like plaque. Other unusual presentations include:

Acknowledgment

The author gratefully acknowledges the contributions of Debra J. Grossman, MD, MPH; Cynthia Guzzo, MD; and Scott Bennion, MD, FAAD, FACP, to this chapter in the first edition of Physical Diagnosis Secrets.