Chapter 358. Disorders of the Epidermis

Primary skin diseases that principally affect the epidermis may be categorized as either a dermatitis or a papulosquamous disorder. Dermatitis commonly denotes inflammation of the epidermis. Eczema generically denotes edema within the epidermis. Many primary dermatitides are eczematous in nature, although the term eczema is often misused interchangeably for atopic dermatitis. In its mildest or chronic form, edema is seen histopathologically as prominent, toothlike interconnections between keratinocytes (spongiosis). With more intracellular fluid accumulation, intraepidermal vesicles are formed. Vesicles are often subclinical in subacute or chronic eczemas where edema is mild but present as grossly evident vesicles and bullae in acute eczemas. Papulosquamous eruptions are characterized by the presence of erythematous papules or plaques with overlying scale. While eczematous processes clinically manifest with weeping or crusting, papulosquamous disorders are associated with little to no edema and thus clinically tend to be dry.

Atopic dermatitis is the most common chronic inflammatory childhood skin disease, characterized by intense itching, dry skin, inflammation, and exudation. The typical clinical finding is an ill-defined patch or plaque of scaling and erythema. Pruritus is a constant feature. Chronic scratching results in dramatic accentuation of the skin markings (lichenification), sometimes with postinflammatory hyperpigmentation, whereas the chronic eczematous process itself may result in hypopigmentation.

The exact prevalence of atopic dermatitis is not known but has been reported to be 15% to 20% lifetime prevalence. Symptoms begin during the first 6 months in 45% of children, first year of life in 60%, and before the age of 5 years in at least 85% of affected individuals.1

The pathogenesis of atopic dermatitis is not completely understood. It is likely multifactorial involving interplay between immune, genetic, metabolic, infectious, and environmental factors.2 Abnormalities of the epidermal barrier paired with immune dysregulation culminate in expression of this disease. A genetic basis for abnormal barrier function in some patients with atopic dermatitis has recently been linked to the FLG gene, the gene in which null mutations result in ichthyosis vulgaris, a scaly skin disorder in which 20% to 25% of people are also atopic.3 The FLG gene encodes filaggrin, a protein essential for epidermal barrier formation and hydration. The role of filaggrin (or of its absence) in the development of atopic dermatitis is not completely understood.

In infancy, involvement of the face, particularly the cheeks (Fig. 358-1), and of extensor surfaces of the extremities is typical, but involvement of the scalp and trunk is also common. In older children, atopic dermatitis favors the flexures such as the antecubital and popliteal fossae. Ankles, wrists, and dorsa of hands and feet are also commonly involved (eFig. 358.1). Occasionally, disease is widespread and severe. A papular variant may be seen, particularly in African American patients (eFig. 358.2). Several subtle physical findings may support the diagnosis, including accentuation of skin markings on palms and soles, double or triple creases under the lower eyelid (Dennie-Morgan folds), conspicuous sparing of the central face (“headlight sign”), and small fissures at the base of the ear lobe. Generalized xerosis (dry skin) is almost invariably present. Other primary skin diseases that can mimic atopic dermatitis include seborrheic dermatitis (particularly in infants), scabies, allergic contact dermatitis, psoriasis, ichthyoses, cutaneous lymphoma, and immunodeficiency. Atopic dermatitis is a clinical diagnosis because there are no specific diagnostic tests. Skin biopsy is not typically performed for atopic dermatitis, but it may help exclude other diseases in atypical cases. The histopathology is that of a subacute or chronic eczema and often is not distinguishable from other eczematous processes.

The treatment of infants and children with atopic dermatitis must be individualized and based on disease severity. It is useful to divide therapeutic strategies into those aimed at treating the rash and those aimed at preventing future disease. Parents tend to focus on identification of “the cause.” It is unusual, however, that one or a few environmental factors can be identified that, when eliminated, will lead to a “cure.” Rather, this is a condition of inherited skin “sensitivity”; that is, a variety of precipitating factors, such as dry skin (xerosis), heat, infection, specific allergens, topical irritants, and/or psychological state may be responsible, to varying degrees, for a given flare of the disease. Once established, the dermatitis tends to be self-perpetuating such that elimination of the original inciting factors may not lead to resolution of the rash. Therefore, it is important that initial efforts be directed toward treatment of the dermatitis and its complications.

The most significant aspect of preventive therapy is decreasing skin dryness. This aim may be achieved by the liberal and frequent (2–3 times daily) use of emollients (ointments are preferred to creams and particularly to lotions) and by avoidance of strongly alkaline soaps. Daily baths in warm (not hot) water can hydrate skin and débride crust and will not adversely affect disease, provided moisturizing cleansers are used and emollients are applied immediately after. Emollients are first-line agents in the management of atopic dermatitis and may be steroid sparing. In dry environments or during the winter months, room humidification, when not contraindicated by respiratory tract mold sensitivities, is also of benefit. Attention to other factors that induce pruritus, such as woolen or synthetic fabrics, heat, sweating, and stress, is also important in the management of atopic dermatitis. Most children respond to standard dermatologic therapy and do not require investigation of dietary triggers or food avoidance.

Topical corticosteroids are the first-line therapy for management of disease exacerbations. For most patients, atopic dermatitis can be adequately and safely controlled with low- and medium-potency topical corticosteroids (Table 358-1). Twice daily application is recommended; there is no evidence that more frequent application enhances efficacy.2 In general, the mildest corticosteroid that will be effective should be chosen. In more severe flares or on unresponsive lesions, a medium- to high-potency steroid may be indicated. Once control is achieved, patients should be switched to a milder corticosteroid; thereafter, use of higher-potency steroids should be limited to focal, resistant lesions.

Because of their better emolliency and greater potency, ointments are generally preferred over creams. However, some patients with atopic dermatitis may not tolerate ointment vehicles because of increased pruritus. The prolonged use of potent corticosteroids can result in local skin atrophy, manifested by transparent skin with prominent blood vessels, telangiectasia, and cigarette paper–like wrinkling, which is indicative of epidermal thinning. Atrophy, if unrecognized, may progress to permanent striae formation. Topical steroids must be used cautiously on the face and groin, where side effects are more common. Systemic effects depend on the inherent potency of the corticosteroid, its percutaneous transport, the relative surface area treated, and the surface area–body volume ratio. With appropriate use, topical corticosteroids are not associated with significant adverse effects (eg, suppression of the hypothalamic-pituitary-adrenal axis or growth).2

Topical calcineurin inhibitors, tacrolimus (0.03% and 0.1% ointment) and pimecrolimus (1% cream), are considered as second-line therapy for the management of atopic dermatitis. Topical tacrolimus 0.03% and pimecrolimus are approved for use in the treatment of atopic dermatitis in children over 2 years old. Application of these agents may be associated with a burning or stinging sensation, particularly at the beginning of therapy. Concern about potential long-term adverse effects exists, and these agents carry a warning from the US Food and Drug Administration (FDA) stating that rare cases of malignancy (eg, skin cancer and lymphoma) have developed in patients treated with these agents, although a causal relationship has not been established. With the current knowledge, a conservative approach is prudent. Prolonged continuous use of these medications is not recommended until further long-term safety data is available. Patients should be advised to employ photoprotective measures while using these agents given concerns for the potential development of cutaneous malignancy. Evidence of systemic immunosuppression resulting from topical application of calcineurin inhibitors has not been documented, and studies have shown normal response to immunizations and normal delayed-type hypersensitivity responses.4 Future studies examining systemic absorption of these agents in infants and young children and evaluating their long-term safety are needed to better define their role in the management of atopic dermatitis.

Oral antihistamines are useful adjuncts to therapy for control of pruritus. In acute flares, doses may need to be increased until sedation is achieved. With milder disease, a single nighttime dose is given to reduce scratching during the night. Nonsedating antihistamines are not particularly effective. Oral antibiotics may be indicated in children who show evidence of superinfection, such as serous crusting of lesions or follicular pustules, or in children who are not responding to therapy. Prophylactic antibiotic therapy is not advisable because of the potential for emergence of antibiotic resistance. Dilute bleach baths (1/4 to 1/2 cup of a 6% sodium hypochlorite solution in a bathtub of water) for 10 to 15 minutes, 2 to 3 times a week, may decrease bacterial colonization and need for systemic antibiotics.

Although systemic corticosteroids almost invariably result in rapid improvement, attempts to taper or discontinue the drug are very commonly associated with a severe rebound flare. Because of this problem, and in view of the numerous side effects associated with their long-term use, systemic corticosteroids should be avoided in the management of atopic dermatitis. Most patients experiencing a severe generalized flare will respond within 3 to 5 days to a course of intensive topical therapy using wet wraps. This treatment consists of application of the topical steroid to affected areas (typically triamcinolone 0.1% ointment) followed by wrapping the areas with soft cotton cloths soaked in warm tap water and then an outer occlusive plastic wrap, leaving the wraps in place for 20 to 30 minutes and repeating this 3 times a day. In cases of a severe flare, antihistamines should be given in sedative doses, and any secondary bacterial, fungal, or viral infections treated. Patients in whom this regimen fails at home will invariably respond in the hospital.

For older patients with moderate to severe disease recalcitrant to topical therapies, ultraviolet light therapy may be beneficial. Newer therapies with a narrower spectrum (UVA1 and narrowband UVB) may be safer than traditional broadband therapy and have been shown to be efficacious.5 Patients for whom this may be a viable option are often logistically limited by the requirement of treatments in a medical office 2 to 3 times weekly. Long-term concerns regarding the use of phototherapy include photodamage and the potential increased risk of skin cancer.

Systemic immunomodulators, including cyclosporine, azathioprine, and mycophenolate mofetil, can be effective for severe atopic dermatitis unresponsive to other therapies. Limited studies of their efficacy and safety in children exist. Use of these medications requires close monitoring for potential side effects and prevention of long-term sequelae.

Atopic individuals are at risk for widespread cutaneous infection with molluscum contagiosum and herpes simplex (eczema herpeticum). The latter presents as multiple vesicles or punched-out erosions that may be grouped or dispersed and are found on both normal and eczematized skin (eFig. 358.3). Whereas Staphylococcus aureus is not normally resident on skin, both uninvolved and involved areas in atopic individuals can be colonized with S aureus. Impetiginized lesions are a frequent complication of atopic dermatitis and manifest as serous crusting. Patients with severe impetigo may have fever, adenopathy, foul odor, and superficial erosions. Staphylococcal folliculitis should be considered in patients with marked pruritus and widespread excoriations. These lesions are extremely pruritic and soon excoriated; thus, a careful examination is needed to identify a follicular pustule.

Atopic dermatitis is characterized by frequent remissions and exacerbations. Parents and children must understand that the treatments outlined here suppress the disease process but do not result in cure. Fortunately, the majority of children improve with age, and most are free of disease by adolescence. A national support group, the National Eczema Association (http://www.nationaleczema.org), provides patient information and support.

Several other skin disorders are more common in children with atopic dermatitis or with a familial atopic diathesis. Pityriasis alba is common in school-aged children and is characterized by ill-defined areas of hypopigmentation, often with a fine scale (Fig. 358-2). It occurs most commonly on the cheeks but may be seen in other locations. The pathologic process is that of a mild eczema, often caused by overdrying of the skin, which may be subclinical, and is followed by postinflammatory hypopigmentation, most evident in dark-skinned children. While bland emollients are often helpful and important for maintenance, a mild topical corticosteroid ointment (eg, 1% hydrocortisone) may be used to treat the dermatitis; with time repigmentation will follow. Keratosis pilaris is also more common in atopic patients.

Contact dermatitis occurs when the skin adversely reacts with outside agents either from direct irritation (irritant contact dermatitis) or as a delayed-type hypersensitivity reaction (allergic contact dermatitis). Primary irritant contact dermatitis is caused by the direct effects of chemicals or physical substances on the skin. Irritant diaper dermatitis is the most common and classic example of a primary irritant contact dermatitis occurring from contact with urine and feces (see “Diaper Dermatitis” in this chapter). Lip-licker’s dermatitis is another common example of an irritant contact dermatitis that occurs as a result of repeated contact of saliva with perioral skin (eFig. 358.4). Other common primary irritants are detergents, acids, alkalis, and harsh soaps. It is uncommon to see frank vesiculation in irritant contact dermatitis compared to allergic contact dermatitis.

Historically, allergic contact dermatitis has been considered to be rare in children, but recent studies suggest it occurs more commonly than previously thought.6,7 A study of asymptomatic general pediatric patients under 5 years of age found a sensitization rate of 24.5% with sensitization demonstrated as young as 6 months.8 As a result of increased exposures and sensitization, the prevalence of allergic contact dermatitis generally increases with advancing age. It is a form of delayed T-cell hypersensitivity reaction (type IV).7 Development of allergic contact dermatitis requires 2 phases: sensitization and elicitation.7 After penetration of the skin, allergens are taken up by an antigen-presenting cell (Langerhans cell) and presented to a naïve T cell in the lymph node; proliferation of sensitized lymphocytes (memory T cells) subsequently occurs. On cutaneous reexposure to antigen, elicitation ensues with presentation to memory-effector T cells, release of lymphokines, and recruitment of mononuclear cells to the area of involvement.

Acute allergic contact dermatitis is characterized by intense pruritus, erythema, and vesiculation in contrast to chronic reactions, which are scaly rather than vesicular. An intensely pruritic eruption begins 7 to 14 days after exposure in primary sensitization reactions and after 1 to 4 days in subsequent exposures. Typically, the area of skin with greatest exposure correlates with the worst severity, but ectopic allergic contact dermatitis exists.7 These reactions occur with involvement of areas of thinner skin (ie, eyelids) as a result of allergen transfer from unaffected, thicker, and more protected skin (ie, fingers) (eFig. 358.5). A common example of this is with allergy to nail polish: Patients often present with involvement of their eyelids or neck. Transfer of antigen to areas of sensitive skin (eg, face and eyelids, penis and scrotum) may result in marked dermal edema and swelling. Widespread papular eruptions or “id” reactions characterized by pruritic papules in nonexposed areas can be triggered by a local atopic dermatitis. At times, the diagnosis of contact dermatitis may be evident by the presence of geometric shapes or linear configurations, which suggest an external cause, but it can often be difficult to distinguish from other eczematous conditions, such as atopic or irritant dermatitis.

The most common cause of acute allergic contact dermatitis among children in the United States is exposure to poison ivy, oak, or sumac, all members of the genus Toxicodendron (formerly, Rhus) (eFig. 358.6). Rash is most common on the lower extremities but may occur at any location. Nickel allergy is the most common cause of subacute or chronic allergic contact dermatitis and is usually localized to sites where earrings, bracelets, necklaces, or the metal clasp or zipper of a garment comes into contact with the skin (Fig. 358-3). Id reactions are particularly common with nickel-induced atopic dermatitis, developing in as many as 50% of affected children (eFig. 358.7).9 Earlobe involvement commonly presents with redness and oozing at the pierced site and can be mistaken for bacterial infection. Jewelry made of surgical stainless steel or 24-karat gold is usually tolerated. Other common causes of allergic contact dermatitis include preservatives and vehicle chemicals in topical preparations and cosmetics, fragrances, and adhesives in tapes or bandages. The worsening of any skin condition in the face of topical therapy should raise the possibility of an allergic contact dermatitis to a component of the medicament. Shoe allergy presents as a scaly, pruritic eruption on the dorsum of feet and toes (eFig. 358.8). The antigen may be rubber or rubber accelerators, adhesives, tanning agents, dyes, or leather. Neomycin and the “-caine” type of topical anesthetics are frequent sensitizers.

Determination of the offending agent often requires detective work, particularly given the delay between exposure and onset of symptoms. Patch testing is the gold standard for definitive diagnosis and identifies specific allergens to avoid for prevention of recurrence. With this testing, small amounts of common allergens are placed on the patient’s back and left on for 48 hours. The first reading to evaluate the patient’s response is performed at the time of removal, and the second typically occurs at 72 to 96 hours. In small children, this testing may be limited by the size of their back, and 2 separate tests may be necessary to evaluate all standard allergens. Given the difficulty in distinguishing contact dermatitis from other eczematous dermatitides, it has been argued that any child with difficult-to-control dermatitis should be patch tested to evaluate for contact allergens.10

Education about avoidance of known allergens to prevent recurrence is first-line management of patients with atopic dermatitis. Children with allergy to Toxicodendron should be taught to recognize the plants. Patients must learn to examine product labels carefully for hidden ingredients, a difficult task given that many allergens have multiple names. Relatively inexpensive, commercially available dimethylglyoxime nickel test kits can be obtained to identify the presence of nickel in clothing, jewelry, or other personal items. Treatment of mild contact dermatitis consists of cool soaks (when an acute, vesicular eruption is present) and topical corticosteroids. When involvement is extensive and severe, a 2- to 3-week course of oral prednisone should be considered (eg, 1 mg/kg/day for 5 to 7 days; then 0.5 mg/kg/day for 5 to 7 days). Shorter courses may result in a rebound flare of the dermatitis.

Juvenile plantar dermatosis is a recurrent skin disorder characterized by erythema and fissuring of the weight-bearing part of the plantar surface. It is somewhat more common in children with atopic dermatitis and is frequently misdiagnosed as tinea pedis. Sparing of the interdigital web spaces is typical in juvenile plantar dermatosis and helps to differentiate it from tinea pedis. Hyperhidrosis is often associated, and this condition develops as a result of repeated wetting and drying of the feet. Children with this condition should avoid occlusive shoes, such as rubber-soled sneakers, which may exacerbate the condition. Socks should be cotton and should be changed as soon as possible if damp. Treatment consists of repeated applications of petrolatum for lubrication and an absorbent powder. Occasionally, a moderate-strength topical corticosteroid ointment is helpful if symptomatic.

Dyshidrotic eczema (pompholyx) is a recurrent, acute eczematous eruption involving the hands and, less commonly, the feet. The development of small, firm vesicles on the lateral borders of the finger is characteristic. The disorder is intensely pruritic, and subsequent fissuring of the fingers and palms may be painful. Control of this disorder may be achieved by the use of emollients and potent topical corticosteroids.

Seborrheic dermatitis is a chronic skin condition whose presentation in infancy is quite different from that in adolescents and adults. While most practitioners and even parents easily recognize scalp scaling or “cradle cap” as a manifestation of this disease, its presentation can be variable and difficult to differentiate from other skin conditions. The etiology of seborrheic dermatitis is poorly understood; as its name implies, a relationship to sebaceous gland activity is recognized by the predilection for sites with high sebaceous gland density and its prevalence at times of increased hormone levels (first year of life and adolescence).11,12 A role for Pityrosporum ovale (a lipophilic yeast normally resident on the skin) in the pathogenesis of seborrheic dermatitis has been postulated, and clinical improvement with use of topical antifungal agents (eg, ketoconazole cream) has been noted.13

Seborrheic dermatitis, a common disorder of infancy, begins within 2 months after birth. In its mildest form, cradle cap, patches of greasy, yellowish scale, develop over the scalp vertex; in more severe cases, the scalp is erythematous, and papules spill over onto the forehead and cheeks. Intertriginous sites, particularly the axillae, neck, diaper area, and retroauricular folds, commonly show erythema and greasy scale. Rarely, the eruption may become generalized. Infantile seborrheic dermatitis is usually asymptomatic and resolves spontaneously during a period of several weeks to months. In adolescents, seborrheic dermatitis usually manifests as dandruff, or diffuse scalp scaling, which is often pruritic and may be accompanied by midfacial erythema and scaling. Relapse is common, and emphasis should be on controlling this condition rather than cure.

Seborrheic dermatitis is often difficult to differentiate with certainty from atopic dermatitis because there is considerable overlap.11 Pruritus and recurrence after therapy are usually indicative of atopic dermatitis. The differential diagnosis also includes Langerhans-cell histiocytosis (see Chapters 363 and 463) and psoriasis. Langerhans-cell histiocytosis must be excluded by skin biopsy in all patients with unusually severe seborrheic dermatitis, particularly if clinical signs of a destructive process, such as atrophy, ulceration, or purpura, are present. Psoriasis should be considered in infants with well-circumscribed and widespread lesions (see Fig. 358-4) but tends to be less treatment responsive, allowing it to be differentiated from seborrheic dermatitis. Other causes of scalp scaling and pruritus include tinea capitis and atopic dermatitis.

Infants with severe involvement may be treated with a low-potency topical steroid and daily shampooing of the scalp to hasten resolution. Application of oil to the scalp can help to loosen scales. While alopecia is unusual with seborrheic dermatitis, aggressive manipulation of the scale can create temporary hair loss. Scalp involvement in adolescents usually responds to antiseborrheic shampoos containing antifungals, selenium sulfide, zinc, tar, or salicylic acid. More severe involvement may warrant a topical corticosteroid; patients often prefer vehicles such as solutions, foams, or shampoos for scalp application. When thick scales are present, application of oils and keratolytics (eg, Derma-Smoothe, Baker’s P&S) overnight may be effective in removing scales and facilitating penetration of the topical steroid.

Diaper dermatitis is among the most common of all pediatric dermatologic disorders, resulting in more than a million office visits per year in the United States.14 More than 90% of these visits occur in pediatrician or family physician offices. In most cases, diaper rash begins as a nonallergic, irritant dermatitis caused by the combination of occlusion, friction, and wetness. The prevalence has been estimated to be 7% to 35%, with a peak incidence between 9 and 12 months. Irritant diaper dermatitis occurs more frequently in the setting of diarrhea. The causative factors are wetness, leading to edema of the stratum corneum and increased absorption of irritants, and stool proteases and lipases, which are most active at the higher pH created by a urine and stool mixture. Candida albicans commonly infects the diaper area, particularly if the irritant rash has been present for a few days or if the patient is being administered oral antibiotic therapy.

Irritant diaper dermatitis typically presents with erythema that is most prominent on the lower abdomen, inner thighs, and on the buttocks, and tends to spare the folds. In severe cases, erosions or ulcerated papules may develop (eFig. 358.9). The presence of satellite pustules, intense erythema, or involvement of the folds suggests Candida dermatitis (eFig. 358.10). Other common causes of dermatitis in the diaper area include seborrheic dermatitis and impetigo. Perianal streptococcal disease may present as mild erythema and scaling; it can be excluded by culture. Uncommonly, psoriasis, dermatophyte infection, and Langerhans cell histiocytosis (Chapters 363 and 463) may present as diaper rash.

Treatment involves frequent diaper changes, use of superabsorbent diapers, avoidance of aggressive cleaning, and application of a barrier cream. Culture can help assist in evaluation for secondary bacterial or yeast organisms, which may be contributory. For moderate to severe dermatitis, application of a low-potency topical steroid (Table 358-2) may be necessary for clearance. A topical antifungal should be instituted if there is suspicion of Candida. The antifungal-corticosteroid combinations, nystatin/triamcinolone (Mycolog) or clotrimazole/betamethasone dipropionate (Lotrisone), should be avoided because the potency of corticosteroids is inappropriately high for this location.

Nutritional and metabolic disorders should be considered in the infant with persistent dermatitis. Zinc deficiency results in a periorificial and acral dermatitis (see Fig. 408-7). Zinc deficiency may occur as an acquired or as an inherited disorder, acrodermatitis enteropathica. Acrodermatisi enteropathica is discussed in Chapter 408 and acquired zinc deficiency in Chapter 23. Acquired zinc deficiency is most commonly observed during prolonged total parenteral nutrition with inadequate zinc supplements but also may occur with malabsorption syndromes or chelation therapy. Premature infants are especially prone to zinc deficiency because of low stores and high requirements. Some mothers produce breast milk that is very low in zinc, and symptomatic zinc deficiency has been reported in this setting, particularly in premature infants. Lesions are typically sharply marginated, eroded, and crusted plaques but may be psoriasiform in nature. Secondary infection with Candida is common. Dermatitis and diarrhea are usually the first signs of zinc deficiency, but with time, these are accompanied by alopecia and irritability. The diagnosis is established by a low plasma zinc concentration. A trial of zinc therapy is indicated in all infants with a suggestive clinical phenotype, even if plasma zinc concentrations are normal. Response to zinc therapy (0.5–1 mg/kg/day elemental zinc; given as zinc sulfate or gluconate) is rapid (ie, 2–4 days) and dramatic.

Biotin deficiency may produce a cutaneous phenotype identical with zinc deficiency and occurs similarly in both acquired and genetic forms. The late infantile form of biotin-responsive multiple carboxylase deficiency, caused by biotinidase deficiency, commonly presents with rash and/or alopecia. Central nervous system symptoms, including ataxia, seizures, developmental delay, and acidosis, are present in most patients with time but may be episodic. Diagnosis is established by demonstration of decreased biotinidase activity in blood. Blood biotin concentrations are usually low, and urinary organic acid concentrations are increased, but values within the normal range do not exclude the diagnosis. A trial of biotin (at least 10 mg/d) is indicated for all patients with a suggestive clinical picture. The response is rapid and usually dramatic. Acquired biotin deficiency is rare and usually seen in patients undergoing prolonged parenteral nutrition that lacks biotin or who ingest large quantities of raw egg whites that contain avidin, which binds biotin and prevents intestinal absorption.

Eczematous and periorificial dermatitis has also been observed in essential fatty acid deficiency. Dry skin with eczematous changes in conjunction with hypopigmentation is seen in children with protein malnutrition (kwashiorkor).

Psoriasis is a chronic disease of exacerbations and remissions that affects approximately 1% to 2% of the population.16 Disease develops before the age of 20 years in 35% of patients.16 No gender prevalence has been detected overall, although a female predominance has been reported in childhood onset.17,18 Psoriasis is more common in Caucasians than in other races.

Development of psoriasis occurs as a result of both genetic and environmental factors. In greater than 50% of affected children, a positive family history is present.18,19 Early onset psoriasis has been linked to human lymphocyte antigen types B57, Cw6, and DR7.20 PSORS1 is the first gene linked to psoriasis, but several other loci have been identified.19 The lifetime risk of psoriasis is 4% if no parent is affected, 28% if 1 parent is affected, and 65% if both parents are affected.20 Environmental factors, such as trauma or infection (particularly streptococcal), are known triggers. Psoriasis is now recognized to be immune mediated. Activated T cells in psoriatic lesions release proinflammatory Th1 cytokines such as tumor necrosis factor-α (TNF-α) and interferon-γ. The importance of these cytokines in the development of psoriasis is supported by both the observation that inhibition of TNF-α with new biologic therapies is effective in treating psoriasis and the evidence of interferon-γ’s ability to induce psoriatic plaques.20

The prototypic lesion of psoriasis is a uniform erythematous papule or plaque, sharply delineated from the surrounding normal skin, and covered with tightly adherent, silvery scale (Fig. 358-4). A useful diagnostic feature, the Auspitz sign, is the presence of pinpoint bleeding after the removal of scale. Lesions vary in size from pinhead-sized papules to extensive plaques and show a predilection for the elbows, knees, scalp, penis, and gluteal cleft (“gluteal pinking”). Its distribution is characteristically symmetric. Some differences in the presentation of psoriasis in children compared to adults have been described. Facial involvement is more common in children than adults, with periorbital skin typicallybeing most affected. Lesions in children tend to be thinner and less permanent.18 The development of psoriatic lesions in areas of trauma is termed the Koebner phenomenon or isomorphic response. Nail involvement may take the form of numerous small pits arranged in vertical strips, detachment of the nail plate distally (onycholysis), or marked subungual hyperkeratosis. Characteristic nail changes are often valuable in making the diagnosis of psoriasis in patients with limited skin disease. A geographic tongue can be seen in psoriasis and is more common in children (eFig. 358.11).

Psoriasis during infancy is relatively rare but may be severe and generalized. The diaper area is often the presenting site, and the persistent rash may easily be confused with candidiasis or seborrheic dermatitis (eFig. 358.12). Psoriasis tends to be less responsive to therapy than seborrheic dermatitis, but their presentation can be nearly identical with involvement of the diaper, scalp, and trunk. Guttate psoriasis is particularly common in childhood and is characterized by the rapid development of numerous small, scaly papules and plaques on the trunk, face, and proximal extremities (eFig. 358.13). Streptococcal infections of the upper respiratory tract and perianal skin have been implicated as provocative factors for guttate psoriasis, and marked improvement in the skin is often seen with appropriate antibiotic therapy. The classic plaque form of psoriasis is the most common presentation in older children and adolescents, as it is in adults. Inverse psoriasis presents with lesions in the genital, axillary, inguinal, or periumbilical areas (eFig. 358.14). In intertriginous areas, lesions generally do not have their characteristic silvery scale and must be distinguished from candidal or dermatophyte infection. Pustular psoriasis and generalized psoriatic erythroderma are rare, severe forms of the disease that may occur occasionally during childhood (eFig. 358.15).

Although psoriasis is most often easily diagnosed on the basis of clinical appearance, skin biopsy is sometimes helpful. The most typical histologic features are acanthosis with evenly elongated rete ridges; neutrophilic spongiform pustules within the epidermis; parakeratotic stratum corneum containing neutrophils; and tortuous, dilated capillaries within dermal papillae.

While treatment modalities used in children mirror those for adults, most are not FDA approved for use in children given the paucity of pediatric studies. Topical therapies are most commonly used in the treatment of psoriasis and are often adequate for mild or limited disease. Topical steroids, calcipotriene, tar preparations, anthralin, tazarotene, salicylic acid, or a combination of these may be used. Medium- to high-potency topical corticosteroids (Table 358-1) are often used in conjunction with other therapies. In all chronic dermatoses, topical corticosteroids must be employed with caution because long-term use may be associated with local skin atrophy and striae. Use of anthralin and tar preparations is limited by their staining and irritation and has largely been replaced by calcipotriene and tazarotene as alternatives to steroids. Local irritation is a common side effect of these medications as well. Pulse dose treatment with calcipotriene during the week and topical steroids on weekends is often used to decrease the potential side effects of topical steroids. Topical tacrolimus and pimecrolimus, discussed earlier under “Atopic Dermatitis,” have shown efficacy in intertriginous and facial psoriasis and serve as an alternative to topical steroids in these areas that are more prone to steroids’ adverse effects.20 Scalp psoriasis is particularly difficult to control. The combination of a medicated shampoo containing corticosteroid, zinc, tar, or salicylic acid with a topical steroid solution or foam (Table 358-2) is a common regimen. Calcipotriene is also available in a liquid form for scalp application. Oil-based preparations can soften and help remove scale to allow increased penetration of the topical steroid.

For patients with severe erythrodermic or pustular psoriasis, more aggressive treatment regimens are warranted. The addition of phototherapy for widespread plaque-type involvement can augment the effects of topical therapy. Narrowband UVB has largely replaced the use of psoralens and ultraviolet light (PUVA) for the treatment of psoriasis, but PUVA remains an option for older children or adolescents. Other systemic medications that have been used off-label in children with psoriasis include methotrexate, acitretin, and cyclosporine. A newer class of medications, the biologic agents, including etanercept, infliximab, adalimumab, efalizumab, and alefacept, have proven to be quite effective in the treatment of psoriasis, but none are FDA approved for childhood psoriasis at this time. These include etanercept (a dimeric fusion protein which binds TNF-α), infliximab (a murine/human chimeric monoclonal antibody that binds TNF-α), adalimumab (recombinant human monoclonal antibody that binds TNF-α), efalizumab (a humanized anti-CD11a monoclonal antibody), and alefacept (a human fusion protein that inhibits T cells by antagonizing CD2).19 The anti-TNF-α agents do have FDA approval for use in children; etanercept and adalimumab are approved for polyarticular idiopathic arthritis and infliximab is approved for Crohn disease. Long-term safety of these medications remains unknown, particularly in regard to the potential risk for lymphoma. The potential toxicities associated with these treatments require supervision by an experienced physician. Systemic corticosteroids are contraindicated in psoriasis because of the risk of inducing a pustular, rebound flare.

The natural history of psoriasis is one of remissions and exacerbations over a patient’s lifetime. Flares may be triggered by infection, trauma to the skin, or stress. Avoidance of aggravating factors is a major component to psoriasis management to minimize flares. The role of trauma in the exacerbation of psoriasis should be emphasized with patients and families. Although usually a lifelong disease, prolonged remissions can occur. The National Psoriasis Foundation provides excellent information and support for patients at http://www.psoriasis.org.

Pityriasis rosea is a common, generalized, and self-limited dermatosis that most commonly presents in adolescence. Its cause is unknown, although an infectious trigger has been proposed. Support for an infectious etiology includes the occasional temporal and geographic clustering of cases, the prodrome of malaise or pharyngitis reported by some patients, and the rarity of recurrences throughout one’s lifetime. A single, larger, well-circumscribed area of erythema and scale on the trunk or extremities—the herald patch—commonly precedes the generalized rash by 2 to 21 days and may be commonly mistaken for a lesion of tinea corporis or nummular eczema. Pityriasis rosea is characterized by the progressive eruption of numerous round to oval, salmon-colored, 2- to 10-mm flat patches bearing a peripheral ring of scale (eFig. 358.16). Atypical lesions may be smaller, papular, or even vesicular (eFig. 358.17). Intense pruritus may occur. The lesions characteristically align along skin lines. On the back and chest, this arrangement resembles the sloping branches of a Christmas tree. The lesions favor the trunk, upper arms, legs, and, particularly, the axilla; the face is usually spared, except in young children. A recent study observed black American children to have more atypical presentations than characteristically described, with more papular lesions and more facial and scalp involvement.21-23

Pityriasis rosea must be distinguished from drug eruption (eTable 358.1), guttate psoriasis, pityriasis lichenoides chronica, and secondary syphilis. Involvement of palms and soles is unusual for pityriasis rosea and warrants evaluation for secondary syphilis. Its self-limited nature often distinguishes it from other chronic dermatoses, which it can mimic. The histopathology of pityriasis rosea is nonspecific, and while biopsy is rarely confirmatory, it can help eliminate other diagnoses.

Pityriasis rosea usually resolves in 4 to 6 weeks, and most patients require no treatment. Mild pruritus may be managed with topical antipruritics (calamine lotion, lotions containing menthol and/or camphor, lotions with pramoxine), oatmeal baths, low-potency topical steroids, and oral antihistamines.19 More severe, symptomatic cases may benefit from phototherapy.

Lichen planus is an uncommon dermatosis of unknown etiology that occurs most often in middle-aged adults; only 2% of cases develop before the age of 20.22 The etiology is unknown, but a cell-mediated autoimmune response has been suggested.19 The characteristic lesions of lichen planus are intensely pruritic, violaceous, sharply defined polygonal papules on the forearms, flexor surfaces of the wrists, and extensor surfaces of the lower extremities (eFig. 358.18). Lichen planus, like psoriasis, may demonstrate the Koebner phenomenon with development of lesions in areas of trauma. Oral involvement typically appears as a lacy array of white patches on the buccal mucosa or tongue. Painful erosive mucosal lesions may be seen less commonly. Nail changes, which may progress from longitudinal ridging to severe nail dystrophy, are seen in 10% of adult patients but are thought to be less common in children. In rare variants of lichen planus, there may be bullous, linear, atrophic, hypertrophic, or annular lesions as well as scarring alopecia. Many drugs can produce eruptions that resemble lichen planus (lichenoid drug eruption), and medications must be reviewed to exclude this possibility (eTable 358.1). On biopsy, the disease is distinguished by a bandlike infiltrate along the dermal-epidermal junction with partial destruction of the basal cell layer, in conjunction with hyperkeratosis and increased thickness of the granular layer. Lichenoid drug eruption has a similar histologic picture, but eosinophils are more numerous. Treatment consists of antihistamines and moderate-potency topical corticosteroid ointments. For severe or generalized cases, phototherapy or even systemic steroids may be necessary to gain control of the disease (see Table 358-1). The duration of lichen planus varies from months to years, and relapses or recurrences occur in 20% of patients. Postinflammatory hyperpigmentation is often quite striking after the eruption resolves.

Lichen striatus is a relatively common childhood skin disease, characterized by a linear array of small, violaceous, flesh-colored, or hypopigmented papules (eFig. 358.19). The arms and legs are most commonly affected. The differential diagnosis includes epidermal nevi, as both occur in Blaschko lines (see Chapter 357); however, epidermal nevi are usually more verrucous and do not involute. Lichen striatus is self-limited, resolving over several months to a year. Treatment is usually not required because most cases are asymptomatic and treatment does not generally speed resolution; however, a mild topical corticosteroid is useful for symptomatic patients. It typically results in postinflammatory hypopigmentation in contrast to lichen planus, but this eventually disappears.

Lichen nitidus is a benign, self-limited eruption of unknown etiology composed of minute, pink-red or flesh-colored papules that may be asymptomatic or extremely pruritic. It is most commonly seen in preschool and school-aged children.18 In black children, the papules of lichen nitidus are hypopigmented. Lesions favor the trunk, wrists, genitalia, and inner thighs but may be widespread. Papules tend to be grouped in patches or plaques; the presence of a linear array of papules within a scratch (the Koebner phenomenon) is a useful diagnostic finding (eFig. 358.20). The skin biopsy is diagnostic, showing a discrete nest of histiocytes and lymphocytes in the upper dermis surrounded by an epidermal lip. Lichen nitidus resolves spontaneously over several months to years; the cause is not known, and there is no effective therapy.

Pityriasis rubra pilaris is a rare skin disorder of unknown etiology. It typically develops as an acquired condition, but there are rare cases inherited as an autosomal dominant condition. At its onset, the lesions are composed of small, tapered follicular papules that are best appreciated on the dorsal surface of the proximal phalanges or over elbows or knees (eFig. 358.21). Scaling and erythema of the scalp and marked thickening of the palms and soles are also characteristic (eFig. 358.22). Over time, these papules coalesce into yellow to pink scaly plaques or a generalized exfoliative erythroderma that may contain islands of normal skin. Disease can be either mild and localized or, rarely, severe and generalized. The skin biopsy shows follicular plugging, perifollicular parakeratosis, and a superficial perivascular inflammatory infiltrate, features that are characteristic but not diagnostic.23 Mild disease may be improved by emollients or topical corticosteroids. Topical keratolytics (Table 358-2) may be used for palmoplantar hyperkeratoses. Systemic retinoids may be indicated in the severe cases and seems to be more effective than other therapies.24 Phototherapy, methotrexate, cyclosporine, and azathioprine have also been used to treat pityriasis rubra pilaris.19 These potent drugs should be prescribed only by experienced physicians. The majority of patients experience a complete remission within a few months to several years.23

Pityriasis lichenoides is a disorder of unknown etiology characterized by erythematous papules that evolve into scales, vesicles, pustules, and crusts, sometimes with central necrosis.25 This disease is a spectrum with an acute form referred to as pityriasis lichenoides et varioliformis acuta (PLEVA; Mucha-Habermann disease) and a chronic form referred to as pityriasis lichenoides chronica. Patients with lesions typical of both ends of this spectrum have been observed, demonstrating the overlap of these 2 forms. T-cell clonality has been demonstrated in the lesions, suggesting that this is a benign lymphoproliferative process being held in check by a strong immune response.19 In addition, rare cases of cutaneous T-cell lymphoma in patients with a history of pityriasis lichenoides et varioliformis acuta or pityriasis lichenoides chronica have been reported, suggesting that pityriasis lichenoides may be at the benign end of the spectrum of lymphoproliferative disorders.

Pityriasis lichenoides et varioliformis acuta is characterized by the rapid onset of numerous papules, macules, and papulovesicles, usually involving the trunk and extremities (eFig. 358.23). The face, scalp, palms, and soles are usually spared. The lesions of pityriasis lichenoides et varioliformis acuta evolve in crops, rapidly form hemorrhagic crusts, and often resolve with severe postinflammatory hypopigmentation, particularly in darker-skinned individuals. Some lesions may resolve with a varioliform scar. Pityriasis lichenoides chronica is characterized by scaly papules and small plaques rather than vesicles and crusts. The differential diagnosis of the acute form includes chickenpox, arthropod reaction, and impetigo; the chronic form must be distinguished from psoriasis, lichen planus, pityriasis rosea, and secondary syphilis.19,26 Skin biopsy reveals a mononuclear perivascular infiltrate, intraepidermal extravasation of erythrocytes, vacuolization, necrosis of the basal cell layer, and, occasionally, necrosis of the entire epidermis. Oral erythromycin appears to shorten the course of the disease in some children; typically a 2-month trial is initiated and, if successful, is subsequently tapered to maintain remission. Ultraviolet light therapy (narrowband UVB) is also effective in some patients. Pityriasis lichenoides is self-limited; untreated, pityriasis lichenoides et varioliformis acuta may persist for weeks to months, whereas pityriasis lichenoides chronica may persist for years.

Two well-recognized dermatitides that occur as a result of aquatic exposure are cercarial dermatitis (swimmer’s itch) and seabather’s eruption, which occur in freshwater and saltwater respectively. In addition, skin findings can be observed as a result of a large number of venomous marine animals a large variety of jellyfish, sea anemones, fire corals, and Portuguese man-of-war that cause mild, debilitating, or fatal envenomization. These most frequently are seen in tropical or temperate waters of North America and the Indo-Pacific region. Because of the marked increase in recreational water sports, especially scuba diving, exposure to marine animal envenomization is more frequent than in the past.

Cercarial dermatitis is an itchy, self-resolving inflammatory dermatosis that occurs from penetration of skin by nonhuman schistosome parasites found in freshwater lakes. The eruption occurs on exposed areas of skin as erythematous papules and papulovesicles. Seabather’s eruption, or “sea lice,” is a markedly pruritic eruption that results from stinging nematocysts of Cnidarian larvae most commonly found in saltwaters off of Florida and in the Caribbean.27 This self-limited eruption tends to involve covered areas (in contrast to cercarial dermatitis) and presents with erythematous papules, pustules, and papulovesicles. Treatment for both is supportive with antipruritics.

Cnidarian contact dermatitis and envenomization is caused by a large variety of jellyfish, sea anemones, fire corals, and Portuguese man-of-war. All of these marine animals, which are present in temperate, subtropical, and tropical environments, possess cnidae (ie, nematocysts) on the outer surface of their tentacles. These are spirally coiled, barbed, hollow threads through which toxin is forcibly injected when rubbed or touched into the skin. Depending on the particular species, amount of venom injected, age of the victim, and prior sensitization, mild to severe local and/or systemic reactions may ensue. In the United States, fire corals are among the most frequent causes of mild cnidarian stings. Immediately after contact, intense burning or a stinging sensation with central radiation appears, followed by severe pruritus and urticaria that may last for several days and leave an area of hyperpigmentation that gradually fades after several months. Hours after contact, a delayed reaction can appear, presenting as papules or hemorrhagic vesicles. At times, an erythema nodosum–like reaction can recur repeatedly over a period of several months.

Sea anemone stings usually occur in shallow water. Almost instantaneously, they produce severe burning followed by intense itching. An area of central pallor frequently appears, surrounded by erythema and petechial hemorrhage. The envenomized area becomes edematous, and in severe envenomization, it evolves to become ecchymotic and then hemorrhagic. The lesion may ulcerate and subsequently heal after eschar formation. Milder envenomizations usually resolve uneventfully within several days.

Portuguese man-of-war (ie, Physalia physalis and P utriculus) have long, hanging, and trailing nematocyst-containing tentacles in which an unwary swimmer can become enmeshed and severely stung. This causes an almost immediate, centripetally radiating, intense stinging sensation; subsequently, numbness or paresthesias may occur. The affected area usually has the appearance of deeply erythematous, vesicular, whiplike striations crisscrossing over one another and delineating the pattern of the tentacles on the skin.28 The lesions may become necrotic and ulcerate before healing and leave long-lasting hyperpigmentation. The seriousness of the systemic manifestations depends largely on the extent of the area involved, previous sensitization, and age. Muscle spasm, vomiting, renal and respiratory failure, and profound hypotension can occur in severely stung individuals.

Treatment of cnidarian stings is aimed at stopping further envenomization by inactivation and/or removal of the adherent cnidae and by treating the local and/or systemic reactions. All remaining adherent tentacles should be carefully lifted away, not brushed, with an instrument or gloved fingers, because this might discharge other cnidae. Freshwater should not be used to wash away loosely adherent tentacles and cnidae, because freshwater causes their discharge. Only seawater should be used for this purpose. If available, vinegar or 3% to 10% acetic acid should be poured over the entire affected area repeatedly for at least 30 minutes or until the pain abates. This inactivates the cnidae. It remains controversial whether 40% to 70% isopropyl alcohol should be used as an alternative to acetic acid, because alcohol causes discharge of cnidae in vitro. Removal of cnidae can be a problem. Some authorities recommend applying aerosol shaving cream and then shaving off the cnidae with a safety razor. Local and systemic reactions can be treated with antihistamines or corticosteroids; anaphylaxis may require epinephrine.