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:

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