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ATOPIC DERMATITIS IN INFANTS AND CHILDREN
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PEDIATRIC DERMATOLOGY
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ATOPIC DERMATITIS IN INFANTS AND CHILDREN An Update Leonard Kristal, MD, and Peter A. Klein, MD, MPA
Atopic dermatitis is a common chronic or relapsing eczematous dermatitis characterized by intense pruritus and occurring primarily in infants and children. Commonly referred to as eczema, atopic dermatitis is but one disease in a group of eczematous diseases including nummular dermatitis, seborrheic dermatitis, and hand eczema. Approximately 10% of all children are affected by atopic dermatitisP, 30 typically in the setting of a personal or family history of atopy. Most cases manifest in infancy and early duldhood, with lesions initially affecting the scalp, face, and extensor surfaces. Flexural areas are affected most often in older children and adults. Atopic dermatitis may be severe and widespread, leading to significant morbidity and possible social isolation. Moreover, one study revealed the cost of treatment to be as high as $364 million.31Because the underlying pathophysiology of atopic dermatitis is unknown, therapy is directed at interruption of the itch-scratch cycle and control of antigenic and irritant triggers. EPIDEMIOLOGY
Nine percent to 12% of all children born after 1970 have had atopic derma30, 54 The prevalence has increased since before 1960, when 2% to 5% of titi~.2~, children were affected.z9* 54 The reasons for this increase are unknown. Changes in environmental pollutants, breastfeeding patterns, and diagnosis may be associated, but a general consensus does not exist. Despite differences in methodology, however, the balance of epidemiologic studies favors a true increase in prevalence. In children in whom atopic dermatitis develops, signs and symptoms most
From the Department of Dermatology, State University of New York at Stony Brook, Stony Brook, New York ~~~~~~
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PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 47 * NUMBER 4 * AUGUST 2000
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often manifest early in childhood. Thirty-five percent to 60% of symptoms manifest in the first year of life, and 47% to 85%, by 5 years of age.15,40 By the age of 10 years, the disease manifests in most susceptible children. The prevalence is higher in dry, mountainous regions because of a dry, disrupted epidermal barrier, and in urban areas, which have a higher prevalence for unknown reasons. A study of British sch~olchildren~~ showed a direct relationship between socioeconomic class and the prevalence of atopic dermatitis not attributable to increased medical awareness. GENETICS An inheritance pattern for atopic dermatitis has not been established. Genetic susceptibility to respiratory atopy has been identified on chromosome 11913 in asthmatic patients, but an association with atopic dermatitis has not been found.I3,61 Atopy has a familial basis for asthma and atopic dermatitis. Forty-two percent of first-degree relatives of patients with atopic dermatitis are affected, and 28% have respiratory atopyS4Fifty-six percent of patients with atopic dermatitis have one affected parent.55In cases in which both parents have atopic dermatitis, 81% of children also have the disease. Among monozygotic twins, 86% have atopic dermatitis if the sibling is affected. Interestingly, the risk is 21% in dizygotic twins, which equals that of nontwin siblingsj6 DIAGNOSIS AND CLINICAL FINDINGS Hanifin and Rajka2' codified major and minor criteria for atopic dermatitis in 1980. These criteria included? Must have three or more of the following primary features: Pruritus Typical morphology and distribution Flexural lichenification or linearity in adults Facial and extensor involvement in infants and children Chronic or chronically relapsing dermatitis Personal or family history of atopic dermatitis (e.g., asthma, allergic rhinitis, atopic dermatitis) Plus three or more of the following secondary features: Xerosis Ichthysosis, palmar hyperlinearity, or keratosis pilaris Immediate (type 1)skin test reactivity Elevated serum IgE level Early age of onset Tendency toward cutaneous infections (especially with Staphylococcus aureus and herpes simplex) or impaired cell-mediated immunity Tendency toward nonspecific dermatitis of the hand or foot Nipple eczema Cheilitis Recurrent conjunctivitis Dennie-Morgan infraorbital fold Keratoconus Anterior subcapsular cataracts Orbital darkening
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Facial pallor or facial erythema Pityriasis alba Anterior neck folds Itch when sweating Intolerance to wool and lipid solvents Perifollicular accentuation Food intolerance Course influence by environmental or emotional factors White dermographism or delayed blanch A modification of these criteria can be used to help assess atopic dermatitis in infancy47: Major features Family history of atopic dermatitis Evidence of pruritic dermatitis Typical facial or extensor eczematous or lichenified dermatitis Minor features Xerosis / ichthyosis / hyperlinear palms Perifollicular accentuation Chronic scalp scaling Periauricular fissures The presence of at least two major or one major and one minor criteria is needed for diagnosis. Hanifin has also made modifications to aid in making the diagnosis in children? Major features (must have three) Pruritus Typical morphology and distribution Facial and extensor involvement during infancy and early childhood Flexural lichenification and linearity by adolescence Chronic or chronically relapsing dermatitis Minor or less specific features Xerosis Ichthyosis/ palmar hyperlinearity/ keratosis pilaris IgE reactivity (increased serum IgE, RAST, or prick test positivity) Hand/ foot dermatitis Cheilitis Scalp dermatitis (e.g., cradle cap) Susceptibility to cutaneous infections (especially S. aureus and herpes simplex) Perifollicular accentuation (especially in pigmented races) The diagnosis of atopic dermatitis should be suspected in children having a personal or family history of atopy (i.e., asthma, allergic rhinoconjunctivitis, and atopic dermatitis) presenting with a chronic or relapsing pruritic dermatitis, distributed on the face and extensor surfaces in infants and young children, or involving flexural surfaces in older children and adolescents. The presence of primary lesions in patients with atopic dermatitis is a matter of debate. Some physicians regard pruritus as a primary phenomenon, but lesions have been found in infants less than 2 months of age, before the appearance of coordinated scratching. Moreover, xerosis has been found shortly after birth and may serve as the inciting and primary epidermal breach. In a setting where several patients were cleared and then rechallenged with inciting antigens, a pruritic morbilliform or, less commonly, urticaria1 eruption was
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observed, and, given continued allergen exposure, became eczematous within 48 hours.'* This suggests that atopic dermatitis may evolve from an intensely pruritic erythema or urticaria-like eruption. Lesions of atopic dermatitis are classified as acute, subacute, or chronic. Acute atopic dermatitis is characterized by intensely pruritic papules and papulovesicles with serous exudate on a background of erythema. The presence of fine, silvery scales surmounting erythematous grouped or scattered papules or plaques over variably erythematous skin characterize subacute eczema. The chronic changes of atopic dermatitis include thickened skin with lichenification (ie., increased skin markings) secondary to scratchng and rubbing. Fibrotic papules and nodules called prurigo nodularis may be present with a background of postinflammatory hyperpigmentation or hypopigmentation. In patients with subacute or chronic atopic dermatitis, seemingly unaffected skin may have a dry lackluster appearance. In darker-skinned patients, lesions may have a perifollicular distribution, giving the skin a pebbled appearance. The distribution of atopic dermatitis varies with age at presentation and may pose a diagnostic challenge. In infants, the eruption usually begins on the scalp and face (Fig. l), although the extensor surfaces of the extremities and trunk may also be involved (Fig. 2). The dermatitis on the face can be inflammatory and persistent. The increased drooling that occurs with teething can be further irritating to already inflamed skin. Although there may not be coordinated scratching in early infancy, parents usually note that children with extensive facial dermatitis tend to rub their faces on the sheets of the crib, or on the shoulder of someone holding them. A somewhat increased prevalence of diaper dermatitis has been reported in patients with e~zema.4~ Extensive and severe inflammation of the scalp rarely leads to alopecia, which is usually nonscarring and reversible. Atopic dermatitis of older children and adolescents is classically distributed on flexural surfaces, including the neck, antecubital or popliteal fossae, wrists,
Figure 1. Inflammation of the cheeks and forehead common in infants.
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Figure 2. Extensor dermatitis with excuriations. The pruritus is clearly evident by patient scratching.
and ankles. In school-aged children, the rash may develop on the crease between the buttock and the thigh. The eruption in children and adolescents usually consists of ill-defined, erythematous, scaly patches although acute flares can be inflammatory. With persistent scratching and rubbing, lichenification develops (Fig. 3). An inverse distribution on extensor surfaces, such as the elbows, knees, dorsal hands, wrists, and feet may occur and may portend a poorer pr0gnosis.5~ Involvement of the axillae, groin, and intergluteal areas is unusual and may indicate a concurrent disease process. Involvement of the hands as the initial presentation has been reported in approximately 30%, and 70% of patients have hand dermatitis at some time in their disease c o ~ r s eDermatitis .~ of the plantar or dorsal feet is also a manifestation of atopic eczema. Black children with atopic eczema tend to have a more papular dermatitis consisting of discrete skin-colored and erythematous papules. In addition, follicular accentuation is commmon. Comorbid Findings
Several comorbid disorders are diagnostic features and symptoms of atopic dermatitis. Atopic Diathesis
The presence of asthma, allergic rhinoconjunctivitis, or both is a risk factor for atopic dermatitis. Atopic dermatitis in one or both parents poses a significant risk for the child. In nearly 80% of patients, positive reactions to one or more allergens on immediate hypersensitivity skin testing develop.4l
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Figure 3. Lichenification seen secondary to chronic rubbing.
Xerosis
Dry skin, or xerosis, occurs in 48% to 98% of patients with atopic dermati ti^.^^ Xerosis leads to pruritus and scratching, which perturbs the epidermal barrier, leading to additional water loss. This cycle of water loss, scratching, and rubbing sustains and worsens atopic dermatitis. Xerosis is worsened during periods of low humidity and in dry geographic areas. lchthyosis Vulgaris
Ichthyosis vulgaris is a common disorder with autosomal dominant inheritance found in as many as 37% of patients with atopic dermatitis. The disease results from a defect in epidermal maturation and the formation of an intact epidermal moisture barrier. It is characterized by polygonal fishlike scales, most prominently on the extensor surfaces. The flexural surfaces and face are characteristically spared, although concurrent atopic dermatitis may obscure this distribution. Asymptomatic keratotic follicular papules distributed on the extensor surfaces of the upper arms, buttocks, and anterolateral thighs are found in patients with keratosis pilaris, a condition associated with ichthyosis vulgaris. Ichthyosis vulgaris and keratosis pilaris occur in the general population as an isolated finding without associated atopic dermatitis. Pigmentary Changes
Hypopigmented macular or slightly scaly patches called pifyriasis alba may be found on the cheeks, upper arms, or shoulders. These lesions may represent a subclinical dermatitis that results in abnormal tanning in the summer or
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merely postinflammatory hypopigmentation. Also, in patients with chronic atopic dermatitis, postinflammatory hyperpigmentation or hypopigmentation may develop at sites of scratching and rubbing. Pigmentary changes resolve within 9 months after treatment of the underlying dermatitis, although resolution may require more time in darker-skinned patients. Ocular Findings
Several ocular findings have been associated with atopic dermatitis. Patients may have periorbital dermatitis ranging from mild scaling to severe lichenification of the eyelids and ectropion. Conjunctival allergy also may lead to rubbing and a periorbital dermatitis. Infiltration of the palpebral mucosa with inflammatory cells may lead to a cobblestone appearance and a vernal conjunctivitis, which can abrade the cornea. An ophthalmologic consultation is indicated in this instance. The Dennie-Morgan fold, a single or double fold in the lower eyelid, has been found to have no diagnostic significance, especially in darkskinned children, in whom it may be a normal Allergic shiners (i.e., hyperpigmentation under the eyes) is likely caused by chronic edema, lichenification, and postinflammatory hyperpigmentation. Anterior and posterior subcapsular cataracts are increased in patients with atopic dermatitis. Anterior cataracts develop early in patients with severe disease. Posterior cataracts may be secondary to systemic steroids and topical steroids around the eyes." Patients using topical steroids around the eyes for extended periods should be followed up by an ophthalmologist. Differential Diagnosis
The criteria of Hanifin and Rajka (see previous lists) are helpful in the diagnosis of atopic dermatitis, but other eczematous conditions may lead to similar clinical presentations and include: Allergic contact dermatitis Dermatophytosis or dermatophytids Immunodeficiency syndromes Wiskott-Aldrich syndrome Hyper-IgE syndrome Neoplastic diseases Langerhans' cell histiocytosis Hodgkin's disease Nummular dermatitis Scabies Seborrheic dermatitis Lesions that are recalcitrant to, or worsened by, treatment may indicate a different or concurrent disease process. Seborrheic Dermatitis
Seborrheic dermatitis is the disease most often confused with atopic dermatitis in infancy. Seborrheic dermatitis typically develops at birth or within the first 2 months of age. An early appearance, however, cannot distinguish these diseases because lesions of atopic dermatitis have been observed at less than 2
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months of age despite a lack of coordinated scratching. Distinguishing seborrheic dermatitis of the scalp from atopic dermatitis may be especially difficult. The presence of pruritus indicates atopic dermatitis. Dermatitis of the axillary area and involvement of the diaper area indicate seborrheic dermatitis. Scabies
As with atopic dermatitis, patients with scabies may present with a severely pruritic eczematous dermatitis. Scabies, however, favors the axillae and genital regions, which typically are spared in patients with eczema. The index of suspicion for scabies is increased in patients living in institutionalized environment, especially when other children are similarly affected. The linear papulovesicular lesions of scabies are distinctive, and a microscopic examination of a scraped burrow confirms the diagnosis. Secondary eczematous changes may resemble atopic dermatitis. Allergic Contact Dermatitis
Allergic contact dermatitis should be considered when presumed atopic dermatitis presents in an unusual distribution or is refractory to treatment. Dermatitis of the hands or feet is seen in patients with atopic dermatitis, and its presence should not necessarily lead one to an alternative diagnosis. Nummular Dermatitis The chronic, papulovesicular, coin-shaped lesions of nummular dermatitis typically develop late in childhood or in adulthood, are idiopathic, and are unrelated to atopy. Coin-shaped lesions may be seen, however, in infants and children with atopic dermatitis, and their presence may be a manifestation of eczema given fulfillment of other appropriate diagnostic criteria. Dermatophytosisand Dermatophytids
Dermatophyte infections are common among children and may resemble atopic dermatitis. Dermatophyte infections are typically annular and well-circumscribed, with straightforward diagnosis by means of a potassium hydroxide preparation. The presence of hyphae does not necessarily rule out underlying atopic dermatitis. The presence of erythema, scale, and vesicles involving the palms and soles should raise the possibility of fungal infection. Id reactions are secondary inflammatory reactions occurring at cutaneous sites distant from a severe allergic or irritant contact dermatitis or a fungal infection. The immunologic mechanism is unknown, but in the case of a fungal infection systemically absorbed fungal antigens lead to a response at a distant site. Because dermatophytes are not present in the lesions of an id reaction, potassium hydroxide preparations and cultures are negative. Id reactions may have a varied appearance, including follicular papules, vesicles of the hands and feet, erythema nodosum, an erysipelas-like eruption, erythema annulare centrifugum, or urticaria. Id reactions may appear similarly to atopic dermatitis, and a primary fungal infectious cause must be recognized for correct diagnosis. ImmunodeficiencySyndromes
Wiskott-Aldrich syndrome is a disorder of X-linked recessive inheritance characterized by an atopiclike dermatitis, dysfunctional small-platelet dysgam-
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maglobulinemias, and recurrent infections. Patients may present in early cluldhood with an eczematous eruption of the face, scalp, or flexural extremities, with a history of recurrent and severe infections. The presence of hemorrhagic crusts secondary to platelet dysfunction and hemorrhage suggest the diagnosis. High levels of IgE may be present. Hyper-IgE syndrome is a heterogenous group of immunodeficiencies (e.g., Job’s syndrome) characterized by elevated levels of IgE and susceptibility to candidiasis and staphylococcal infections. Patients typically present with deep furuncles and carbuncles with potential involvement of the respiratory tract. A fine papular erythematous eruption with superficial vesicles and pustules may be localized to the face, scalp, or body folds, especially the axillae and groin. These areas are typically spared in patients with atopic dermatitis. As in patients with Wiskott-Aldrich syndrome, high levels of IgE may be present. Other immunodeficiency syndromes may have eczematous skin eruptions associated with them. The eruption is usually seen in conjunction with recurrent infections and is usually refractory to traditional topical treatment. Neoplastic Diseases
The cutaneous manifestations of mycosis fungoides and Hodgkin’s disease may be similar to those of atopic dermatitis, but these diseases are uncommon in children. Langerhans’ cell histiocytosis, presents as an indurated, sometimes hemorrhagic, papular dermatitis with yellow, greasy scales. Morbidity
Many patients with atopic dermatitis develop bacterial, viral, or fungal skin infections that flare and complicate their disease, possibly because of disruption of the cutaneous barrier or impaired cutaneous immunity. Malfunctioning chemotaxis in these patients results in increased symptomatic presentation of staphylococcal, viral, and dermatophyte infections.” Treatment of concurrent infectious processes and colonization is essential to long-term control. Bacterial Infections
Bacterial infections typically are caused by S. aureus, a pathogen that colonizes patients with atopic dermatitis. The colonization rate of the anterior nares with S. aureus in the general population ranges from 10% to 45%;” 6o with less than 10% carrying staphylococci on the ~ k i n . 3 Most ~ patients with atopic dermatitis, however, are colonized. A recent study found a nasal carriage rate of S. aureus of 79% and a cutaneous colonization rate of 64% among 28 patients with atopic dem1atitis.2~Nine percent of the colonized anterior nares and 11% of the colonized cutaneous lesions contained methicillin-resistant S. aureus. Other studFlares ies have found higher cutaneous colonization rates of 85% to 100%.5,8,33 of atopic dermatitis often are associated with bacterial infection and the presence of honey-crusted weeping pustules. Viral Infections
Patients with atopic dermatitis are susceptible to viral infections with herpes simplex virus (HSV), vaccinia, molluscum contagiosum viruses, and papillomavirus (warts). The most severe viral complication of atopic dermatitis is
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eczema herpeticum secondary to HSV, also known as Kaposi's varicelliform eruption. HSV can masquerade as a generalized, severe flare with low-grade fever, lymphadenopathy, and superficial vesicles that evolve to form punched-out Although infection may be widespread and prolonged, these patients have a favorable outcome. Infants and immunosuppressed children are more likely to have widespread disease. Localized infections with HSV are also common, sometimes localized to one side of the face, mimicking herpes-zoster virus. A culture specimen should be obtained in these patients because a Tzanck smear is not diagnostic. Other viruses, such as those causing molluscum contagiosum, may not occur more frequently, but these infections are more widespread and difficult to treat. In patients with atopic dermatitis, a patchy eczema may develop around molluscum lesions 1 month or more after onset. Tlus eczema resolves once the lesions are removed.14 Fungal Infections
Superficial fungal infections may be more common in patients with atopic dermatitis than in those without eczema. Lobitz et a135were the first investigators to describe a severe atopic dermatitis patient with generalized Trichophyfon rubrum infection. Jones et alZ4subsequently reported that chronic T. rubrum infection is threefold more common among adults with atopic dermatitis than in those without eczema." Generalized flares also may occur secondary to localized recurrent dermatophyte infections. Concurrent dermatophyte infections should be treated in patients with atopic dermatitis. Exfoliative Erythroderma
Some patients may progress to an exfoliative erythroderma, which is characterized by generalized and confluent erythema, scaling, lymphadenopathy, fever, and systemic toxicity. Factors thought to trigger erythroderma are cutaneous infection (e.g., staphylococci) and withdrawal of systemic corticosteroids. Highoutput cardiac failure, sepsis, disorders of thermoregulation and heat loss, and protein depletion may complicate disease in patients with erythroderma. Growth and Psychosocial Factors
Chronic, generalized atopic dermatitis places patients in a catabolic state secondary to inflammation, serous transudation, and a high epidermal cell turnover. Children may suffer growth retardation, which ceases when the severe dermatitis is controlled.* These patients require an increased protein intake to keep up with their metabolic needs. The analogous effect in adults is weight loss and fatigue, which also resolves with treatment. The effect of atopic dermatitis on stature poses an emotional toll, especially given severe cutaneous disease. Affected children experience frustration, sadness, and anxiety, which are likely to exacerbate their disease and increase pruritus. Children also may suffer from sleep disturbances that can lead to chronic fatigue and poor school performance. Children with atopic dermatitis have more arousals and awakenings per hour during sleep than patients without atopic dermatitis. In addition, atopic children in remission have sleep disturbances unrelated to scrat&ng.4la Children may be ostracized and ridiculed, which can be addressed by alerting teachers to the problem. A supportive home environment from parents and siblings is essential.
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Prognosis Most affected children experience amelioration of atopic dermatitis with increasing age. Seventy-seven percent to 91% of teenagers having moderate or severe dermatitis, however, continue to have symptoms into adulthood.28 Individuals who have outgrown the typical manifestations of the disease may develop irritant dermatitis, which may be chronic and disabling, especially in the context of wet, dirty, or caustic condition^.^^ A significant proportion of occupational disease occurs in patients with atopy and atopic d e r m a t i t i ~ . ~ ~ Laboratory Findings
No laboratory test is diagnostic of atopic dermatitis, but several parameters may support the diagnosis. Although not specific for atopic dermatitis, blood eosinophilia tends to correlate with disease severity.23Serum IgE levels also tend to be elevated in as many as 80% of patients with atopic dermatitis and may 53 Although potential aeroallergen triggers may follow the course of di~ease.'~, be elucidated by immediate hypersensitivity skin testing,' such testing is not helpful in patient management except in cases of comorbid allergic rhinitis. Although biopsy is unnecessary in atopic dermatitis, lesions that are hemorrhagic, markedly infiltrated, or unresponsive to aggressive treatment should undergo biopsy. TREATMENT PRINCIPLES
Treatment of acute and chronic atopic dermatitis involves several approaches to basic skin care, medication, and allergen control. Hydration
Hydration is essential to treating atopic dermatitis. The basis of adequate hydration is increasing the water content of the skin by means of baths or soaks and applying a hydrophobic barrier to prevent evaporation. Bathing for 15 to 20 minutes two times a day is adequate, but hot water must be avoided. Oatmeal products added to the bathwater may be soothing but do not increase water absorption. Oils should not be added because they may interfere with optimal water penetration. Mild cleansers (e.g., Dove or Dial) or nonsoap cleansers ( e g , Cetaphil) may be used, although water alone is best. After bathing, excess water should be removed by patting with a soft towel. Water evaporates rapidly from the skin surface, and hydrophobic occlusion ( e g , petrolatum) must be applied within 5 minutes. Topical medications are also best applied after bathing because penetration is far greater in hydrated skin. Severe disease may require soaking after baths to maintain continuous hydration and further increase penetration of topical medications. Soaks also may be soothing to inflamed skin. From a practical standpoint, soaks and wraps are best applied at bedtime. Severely affected areas on the extremities may be dressed with gauze and bandage wraps. Total-body occlusion may be accomplished by using two pairs of cotton pajamas. The first pair is wetted, wrung out to dampness, and placed on the patient. The second pair is worn dry over the wet pair. Hands and feet may be occluded, with wet socks followed by dry
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socks. Soaking of the face may be accomplished by applying two layers of wet gauze followed by two layers of dry gauze held in place with Spandex netting. If crusts are present, Burow’s solution may be added to baths and soaks at a 1:40dilution (one packet of Domeboro powder per quart). This therapy provides astringent and antibacterial effects for localized weeping lesions, but use for more than 3 days may lead to excessive drying and cracking.12 There are patients in whom frequent bathing may exacerbate their pruritus leading to worsening dermatitis. It is important to recognize this and to limit bathing in these patients. These patients require liberal applications of emollients to maintain adequate hydration. In patients with chronic disease, liberal application three to four times daily is recommended with water-in-oil moisturizers (e.g., Eucerin, Aquaphor, Lubriderm, or Cetaphil). Lactic acid preparations (e.g., Lac-Hydrin) are useful in removing scales, especially in patients with ichthyosis vulgaris, but stinging may occur in areas containing fissures or areas with changes of acute dermatitis. Topical Corticosteroids
Topical corticosteroids impart anti-inflammatory, antipruritic, and vasoconstrictive effects. Some general guidelines apply to the use of topical corticosteroids in atopic dermatitis and include: Topical steroids should be applied immediately after baths or soaks to increase penetration. Topical steroids should not be applied more than twice daily because frequent application does not improve efficacy and increases the risk for side effects. Ointments provide the most occlusion but, in humid environments, may lead to folliculitis. Creams may be better tolerated in some instances. Lotions and sprays are most appropriate for hair-bearing areas. The lowest-potency effective agent should be used. Higher-potency, fluorinated agents may be necessary during an acute flare, but these should not be used on thin-skinned areas of the face, neck, axillae, or groin. Adverse effects of topical corticosteroids include atrophy, depigmentation, steroid acne, and rarely systemic absorption with suppression of the hypothalamicpituitary-adrenal axis.18 If a patient is bathing twice daily, after the baths, a low-potency or midpotency topical steroid ointment should be applied to all affected areas except the face, groin, or axillae. These areas may be treated with 1%hydrocortisone or 0.05% desonide. As the dermatitis improves, frequency of application should be decreased with the substitution of less-potent agents. When disease is controlled, topical corticosteroid therapy should be eliminated and treatment should center on hydration. Ointment-based occlusives, such as Aquaphor, petrolatum, Eucerin, or Crisco, should be applied after the topical steroids are applied and in the middle of the day. Systemic Corticosteroids
Oral corticosteroids typically are not indicated in the treatment of patients with atopic dermatitis, a chronic, non-life-threatening illness. Although they
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may be a "quick fix" resulting in a rapid improvement, severe flares often occur during steroid withdrawal. If a short course of oral steroid therapy is given, the dosage must be tapered slowly and intensive skin care must be instituted to prevent a flare of disease. Systemic corticosteroids have no role in the management of patients with chronic atopic dermatitis; the potential side effects far outweigh any benefits.
Systemic Antibiotics
Oral antibiotics are sometimes necessary because secondary bacterial infections may exacerbate and complicate an acute -flare. Infection is suggested by the presence of honey-colored crusts, extensive serous weeping, folliculitis, pyoderma, and furunculosis. Penicillin-resistant S. aureus cause most of these flares. Dicloxacillin or cephalexin may be used as first-line oral therapy because penicillin resistance is almost universal. For patients with a penicillin allergy, erythromycin is the first choice of therapy. Caution must be exercised, however, in asthmatic patients using theophylline because erythromycin slows metabolism. Chdamycin is an alternative agent, especially in penicillin-allergicpatients carrying erythromycin-resistant strains of S. aureus, which have been reported in 23% and 39% of isolates from the nares and skin, respectively. Culture and sensitivity testing are essential during acute flares, not only to identify resistance to erythromycin but also because methicillin-resistant S. aureus has been reported in 9% and 11%of isolates from the nares and skin, respecti~ely.~~ Antibacterial cleansers and topical antibiotics, with the exception of mupirocin (Bactroban), should not be used because they may sensitize patients. Long-term use of mupirocin may lead to bacterial resistance.
Antihistamines
Antihistamines are a standard therapy for atopic dermatitis and are recommended in many clinical treatment protocols. Despite frequent use, surprisingly few clinical studies have examined their efficacy. Moreover, atopic dermatitis and associated pruritus are not mediated primarily by histamine. A recent evidence-based reviewz6of 16 trials of oral antihistamines revealed that none fulfilled the criteria for a well-designed study that contained a sufficient number of subjects to permit definitive conclusions. Sedating antihistamines commonly are used for their soporific effect to facilitate peaceful sleep because itch intensity often increases at night. Unfortunately, daytime use is problematic for that reason, although some patients may acclimate to this effect. The development of nonsedating oral antihistamines (e.g., loratadine) has led physicians to prescribe these agents in the hope of providing daytime relief. Studies have failed, however, to demonstrate efficacy.z6 Moreover, compared with sedating agents, they are much more expensive. Oral hydroxyzine (Atarax) and diphenhydramine (Benadryl) are reasonable choices and should be used on a regular basis for optimal results. Topical antihistamines (e.g., doxepin) or anesthetic agents ( e g , benzocaine) are unhelpful in relieving pruritus and may cause allergic contact dermatiti~.~J 36
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Tars
Tars and extracts of crude coal tar have anti-inflammatory effects and are most useful in replacing topical corticosteroids in the management of chronic disease. Five percent liquid carbonis detergens in petrolatum (Aquaphor) may be prepared by a pharmacy and has acceptable cosmetic properties. Tar gel products (e.g., Estar Gel) are a formulation of crude coal tar that is conveniently commercially available and cosmetically acceptable. They frequently contain alcohol, however, and may cause stinging and irritation of inflamed skin. Tar gels are drying and are best applied under emollients. They may be used only at bedtime under pajamas, which maximizes compliance and minimizes staining of clothing. A new tar preparation (Micanol) contains tar encapsulated in a crystal form that stains far less than older preparations. Clothing and bed sheets should be washed in cool water because heating may lead to staining. The side effects of tars include folliculitis, photosensitization, and contact dermatitis. Ultraviolet Radiation
Ultraviolet radiation may be a useful therapy for patients with recalcitrant atopic dermatitis. Ultraviolet B or psoralens plus ultraviolet A (PUVA) are used three or four times weekly. In adolescents with severe atopic dermatitis, PUVA led to significant improvement in disease and growth responses on percentile curves.6 A subsequent study showed that PUVA twice weekly led to clearance or near-clearance in 39 of 53 children (aged 6-16 years) after a mean of 9 ~ e e k s . 4 ~ Patients who expose themselves to natural sunlight should be warned not to sunburn and to avoid hot or humid conditions that may flare their disease. Home lamp treatments may lead to overexposure and should not be used. Side effects of ultraviolet therapy include acute phototoxicity and an increased risk for skin cancers with prolonged treatment. Caution should be exercised in patients with fair skin. Leukotriene Inhibitors
Leukotriene inhibitors (e.g., zafirlukast) are a new class of medication in the treatment of asthma. A recent small serieslO of four patients with atopic dermatitis showed improvement with zafirlukast. Additional larger studies are needed to evaluate the role of this class of medication. IDENTIFICATION AND ELIMINATION OF EXACERBATING FACTORS
Atopic dermatitis commonly is exacerbated by environmental factors that, once identified and eliminated or controlled, lead to far better control of disease. Exacerbating factors include irritants; emotional stress; allergens, including food; and infections. Irritants
Atopic dermatitis is a condition of dry, sensitive skin that is extremely vulnerable to irritation with various agents. The most commonly used irritant is
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soap, which depletes the skin of natural moisturizers and water. To prevent irritation, drying soaps, solvents, and other compounds should be minimized. Gentle soaps include Dove, Dial, Tone, Alpha Keri, Basis, Lowila, and Neutrogena. Nonsoap cleansing agents, such as Cetaphil and Aveeno, may be least irritating. Soap should be used only in intertriginous areas to avoid drying of large areas of skin. Laundry soaps also may be irritating, and the authors recommend allergen-free detergents (e.g., Tide Free) and two rinse cycles. Bubble baths should be discouraged strongly. Clothing that may be irritating, especially wool, should be eliminated. Children do best with soft, cotton clothing and avoidance of coarse, thick fabrics. Open-weave, loose-fitting garments are preferred. Sweating also may irritate atopic skin, and activities should be modified accordingly. Patients should sleep in comfortable surroundings at a fairly constant. temperature (20-24°C) and humidity (45-55%). Swimming is recommended and well tolerated, but chlorine or bromine in pool water may be irritating. Showering with the application of occlusives after swimming minimizes this effect.
Emotional Stress Itching can be a direct result of emotional and social stress. Atopic dermatitis is a chronic disease, and families may unknowingly worsen disease by excessive attention on skin appearance and projection of their frustration. Classmates also may induce itching by taunting affected children. Parents can alert teachers to the nature of the disease and encourage them to address the problem openly with other children. The period after school, especially when children do not have close supervision, can be a vulnerable period for itching and scratching. Provision of diversions is better than merely warning a child not to scratch. Allergens Aeroallergens may exacerbate atopic dermatitis. Although potential aeroallergen triggers may be elucidated by immediate hypersensitivity skin testing, such testing is not helpful in management except in cases of comorbid allergic rhinitis. If patients are found to have positive skin or RAST tests, those identified allergens should be avoided. House dust mites and their feces may be allergens in atopic dermatitis. They thrive in settings of wall-to-wall carpeting and high humidity. Bedding and furniture also harbor dust mites, which feed on human scales. A standardized patch test to house dust mites is still in development, but suspected mite allergy can be addressed by using hypoallergenic mattress and pillow covers that are available commercially. Removal or frequent vacuuming of carpets and covered furniture, acaricidal treatment of carpets, and laundering linens with hot water may help to ameliorate disease. The role of food allergens is controversial. The most common inciting allergens are eggs, cow's milk, soy products, wheat, peanuts, and fi~h.4~ A review article*2on atopic dermatitis provided the following general guidelines regarding the role of diet: Breastfeeding in conjunction with maternal hypoallergenic diets seems to decrease the prevalence of atopic dermatitis in high-risk infants, but benefits may not be sustained.l6,51, 52
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Food allergy or intolerance may exacerbate disease in a small subgroup and may be appropriate to consider, given a history of provocation with food or when treatment is ineffective. Positive skin tests or a history of food allergy should prompt an elimination diet as long as nutrition is not compromised. The potential role of several foods should be addressed using double-blind, placebo-controlled food trials. With the exception of sensitivity to peanuts, most food allergies wane with time, and these foods may be returned to the diet after 1 year of age. Infection may flare atopic dermatitis. Many patients carry S. uureus on the skin and nares and, in children with frequent bouts of infection-associated flares, attempts should be made to eliminate colonizing pathogens. The use of oral antibiotics in conjunction with mupirocin (Bactroban) applied to the nares three times daily may eliminate colonizing staphylococci during episodes of infectionmediated flares. Allergy to pets is often suspected but seldom documented. In children with associated asthma, keeping pets outdoors, restricting pets from bedrooms, and frequent vacuuming are probably prudent. Flaring of atopic dermatitis when embracing a pet is the best approach to assessing the possibility of an allergy. Because triggers are usually multifactorial, discarding pets is not recommended. Therapeutic Advances
Topical FK506 ointment (tacrolimus) is likely to be available soon in the United States for the treatment of atopic dermatitis. Used historically for transplant rejection as Prograf, tacrolimus has been shown to be effective in clinical trials. The drug does not accumulate in the skin or in the systemic circulation after repeated topical administration? Side effects may include itching or buming at sites of application. Topical SDZ ASM 981, a macrolactam ascomycin, is an inflammatory cytokine inhibitor under development. When applied in a recent trial:7 it was as potent as clobetasol, without local side effects. Clinical efficacy and safety have been confirmed in short-term trials in patients with moderate atopic d e r m a t i t i ~ . ~ ~ Side effects include burning and stinging at sites of application. Oral cyclosporin A (Sandimmune) may provide a dramatic response in patients with severe atopic dermatitis, but rapid relapses occur after discontinua n ~ eSide . ~ ~effects include hypertension, increases in serum creatinine level, and paresthesias. A recent case series52of 24 patients treated with human interferon gamma for 2 years demonstrated safety and efficacy, but flares occurred rapidly after withdrawal? Also, phosphodiesterase inhibitors show promise, but these agents are early in development. Alternative Therapies
Chinese herbal formulations have generated interest based on small studies. Zemaphyte, a proprietary formulation containing 10 Chinese herbs, has been used successfully in several trials in Great Britain.@One double-blind, placebocontrolled, crossover studyI7 of 37 Chinese patients with recalcitrant atopic dermatitis, however, showed no improvement. Moreover, given an unknown
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mode of action and controversy regarding variations in formulations, Chinese herbal therapy is not recommended. Phase 2 multicenter trials are underway in the United States to assess the findings of studies conducted in Great Britain. Schachner et a145have reported that daily massage for 20 minutes resulted in improvements in redness, scaling, lichenification, excoriation, and pruritus over a I-month treatment period. Patients' activity levels and dispositions improved, and parents administering massages also reported diminished anxiety levels. A control group receiving topical treatment alone improved significantly only on the scaling measure.
SUMMARY The goal in treating patients with atopic dermatitis is to maintain adequate hydration while decreasing pruritus and idammation. It is also important to recognize factors that are responsible for flares. Although the etiology of atopic dermatitis remains unknown, therapies are being developed targeting immunologic defects in this disease.
References 1. Abrahamov A, Schifmann R, Goldstein R, et al: Growth failure due to protein loss in dermatitis. Eur J Pediatr 145223-226, 1986 2. Adinoff AD, Tellez P, Clark RAF: Atopic dermatitis and aeroallergen contact sensitivity. J Allergy Clin Immunol 81:736-742, 1988 3. Agrup G: Hand eczema and other hand dernatoses in South Sweden. Acta Derm Venereol Suppl (Stockh) 49:1, 1969 4. Alaiti S, Kang S, Fiedler VC, et al: Tacrolimus (FK506) ointment for atopic dermatitis: A phase I study in adults and children. J Am Acad Dermatol 38:69-76, 1998 5. Aly R, Maibach HI, Shinefield HR Microbial flora of atopic dermatitis. Arch Dermatol 113:780-782, 1977 6. Atherton DJ, Carabett F, Glover MT, et al: The role of psoralen chemotherapy (PWA) in the treatment of severe atopic eczema in adolescence. Br J Dermatol 118:791-795, 1988 7. Berth-Jones J, Graham-Brown R, Marks R, et aI: Long-term efficacy and safety of cyclosporin in severe atopic dermatitis. Br J Dermatol 136:7@1, 1997 8. Bibel DJ, Greenberg JH, Cook J L Staphylococcus aureus and the microbial etiology of atopic dermatitis. Can J Microbiol23:1062-1068, 1977 9. Boguniewicz M, Jaffe HS, Izv A, et al: Recombinant gamma interferon in treatment of patients with atopic dermatitis and elevated IgE levels. Am J Med 88:365-370, 1990 10. Carucci JA, Washshenik K, Weinstein A, et al: The leukotriene antagonist zafirlukast as a therapeutic agent for atopic dermatitis. Arch Dermatol 134:785-786, 1998 11. Castrow F F Atopic cataracts versus steroid cataracts. J Am Acad Dermatol 5:64-65, 1981 12. Clark RAF, Kristal L: Atopic dermatitis. In Sams WM Jr, Lynch PJ (eds): Principles and Practice of Dermatology, ed 2. New York, Churchill Livingstone, 1996, pp 403418 13. Coleman R, Trembath RC, Harper JI: Chromosome 22923 and atopy underlying atopic eczema. Lancet 341:1121-1122, 1993 14. De Ore0 GA, Johnson HH, Binkley GW: An eczematous reaction ssociated with molluscum contagiosum. Arch Dermatol 74:344-348, 1956 15. Diepgen TL, Fartasch M Recent epidemiological and genetic studies in atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 176:13-18, 1992 16. Falth-Magnusson K, Kjellman NI: Allergy prevention by maternal elimination diet during late pregnancy: A 5 year follow-up of a randomized study. J Allergy Clin Immunol 89:709-713, 1992
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17. Fung AYE', Look PCN, Chong LY, et al: A controlled trial of traditional Chinese herbal medicine in Chinese patients with recalcitrant atopic dermatitis. In J Dermatol 38:387-392, 1999 18. Garden JM, Freinkel RK: Systemic absorption of topical steroids: Metabolic effects as an index of mild hypercortisolism. Arch Dermatol122:1007-1010, 1986 19. Gurevitch AW, Heiner DC, Reisner R IgE in atopic derrmatitis and other common dermatoses. Arch Dermatol 107712-715, 1973 20. Hanifin JM Atopic dermatitis in infants and children. Pediatr Clin North Am 38763789, 1991 21. Hanifin JM, Rajka G: Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 9244-47, 1980 22. Hanifin JM, Rogge JL: Staphylococcal infections in patients with atopic dermatitis. Arch Dermatol 1131383-1386, 1977 23. Hellerstrom S, Lidman H: Studies in Besnier's prurigo (atopic dermatitis). Acta Derm Venereol Suppl (Stockh) 3611, 1956 24. Jones HE, Reinhardt JH, Rinaldi M G A clinical, mycological and immunological survey for dermatophytosis. Arch Dermatol 108:61-65, 1973 25. Karaz SS, Moeckli JK, Davis W, et al: Effects of topical doxepin cream on skin testing. J Allergy Clin Immunol 96:997-998, 1995 26. Klein PA, Clark RAF: An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch Dermatol 135:1522-1525, 1999 27. Klein PA, Greene WH, Fuhrer J, et al: Prevalence of methicillin-resistant Staphylococcus uureus in outpatients with psoriasis, atopic dermatitis, or HIV infection. Arch Dermato1 1333463-1465, 1997 28. Lammintausta K, Kalimo K, Raitala R, et al: Prognosis of atopic dermatitis: A prospective study in early adulthood. Int J Dermatol 30:563-568, 1991 29. Larsen FS, Hanifin J M Secular change in the occurrence of atopic dermatitis. Acta Dermatol Venereol Suppl (Stockh) 176:7-12, 1992 30. Larsen FS: Atopic dermatitis: A genetic-epidemiological study in a population-based twin sample. J Am Acad Dermatol28:719-723, 1993 31. Lapidus CS, Schwarz DF, Honig PJ: Atopic dermatitis in children: Who cares? Who pays? J Am Acad Dermatol28:699-703, 1993 32. Leyden JJ, Baker DA: Localized herpes simplex infection in atopic dermatitis. Arch Dermatol 115:311-312, 1979 33. Leyden JJ, Marples RR, Kligman A M Staphylococcus uureus in the lesions of atopic dermatitis. Br J Dermatol90525-530,1974 34. Linde MIV: Dry skin in atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 177913, 1992 35. Lobitz WC Jr, Honeyman JF, Winkler N W Suppressed cell-mediated immunity in two adults with atopic dermatitis. Br J Dermatol 86:317-328, 1972 36. Marks JG Jr, DeLeo VA. Evaluation and treatment of patients with contact dermatitis. In Contact and Occupational Dermatology, ed 2. St. Louis, Mosby, 1997, pp 14-29 37. Meingassner JG, Grassberger M, Fahmgruber H, et al: A novel anti-inflammatory drug, SDS ASM 981, for the topical and oral treatment of skin diseases: In vivo pharmacology. Br J Dermatol 137568-576, 1997 38. Mevorah B, Frenk E, Wietlisbach V, et al: Minor clinical features of atopic dermatitis: Evaluation of their diagnostic significance. Dermatologica 17736e364, 1988 39. Noble WC: Skin carriage of the micrococcaceae. J Clin Pathol22:249-253, 1969 40. Rajka G: Essential Aspects of Atopic Dermatitis. Berlin, Springer-Verlag, 1989, p 1 41. Rajka G: Prurigo Besnier (atopic dermatitis) with special reference to the role of allergic factors: 11. The evaluation of skin reactions. Acta Derm Venereol SuppI (Stockh) 41:363-395, 1961 41a. Reuventi H, Chapnick G, Tal A, et al: Sleep fragmentation in children with atopic dermatitis. Arch Pediatr Adolesc Med 153:249-253, 1999 42. Rothe MJ, Grant-Kels J: Atopic dermatitis: An update. J Am Acad Dermatol 35:l-13, 1996 43. Rystedt I: Work-related hand eczema in atopics. Contact Dermatitis 12:164-171, 1985
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44. Sampson HA: The role of food allergy and mediator release in atopic dermatitis. J Allergy Clin Immunol 81:635, 1988 45. Schachner L, Field T, Hernandez-Reif M, et al: Atopic dermatitis symptoms decreased in children following massage therapy. Pediatr Dermatol 15:390-395, 1998 46. Schultz Larsen F, Holm NV, Henningsen K: Atopic dermatitis: A genetic-epidemiologic study in a population-based twin sample. J Am Acad Dermatol 15:487494,1986 47. Seymour JL, Keswick BH, Hanifin JM, et al: Clinical effects of diaper types on the skin of normal infants and infants with atopic dermatitis. J Am Acad Dermatol 1798%997,1987 48. Sheehan MP, Atherton DJ: A controlled trial of traditional Chinese medicinal plants in widespread non-exudative atopic dermatitis. Br J Dermatol 126:179-184, 1992 49. Sheehan MP, Atherton DJ, Norris P, et al: Oral psoralen photochemotherapy in severe childhood atopic eczema: An update. Br J Dermatol 129;431-436, 1993 50. Shmunes E, Keil J: The role of atopy in occupational dermatoses. Contact Dermatitis 11:174-178, 1984 51. Sigurs N, Hattevig G, Kjellman 8 : Maternal avoidance of eggs, cow's milk, and fish during lactation: Effect on allergic manifestations, skin-prick tests, and specific IgE antibodies in children at age 4 years. Pediatrics 89735-739, 1992 52. Stevens SR, Hanifin JM, Hamilton T, et al: Long-term effectiveness and safety of recombinant humaninterferon gamma therapy for atopic dermatitis despite unchanged serum IgE levels. Arch Dermatol 134799-804, 1998 53. Stone SF,' Muller SA, Gleich GJ: IgE levels in atopic dermatitis. Arch Dermatol 108:806-811, 1973 54. Taylor B, Wadsworth J, Wadsworth M, et al: Changes in the reported prevalence of childhood eczema since the 1938-45 war. Lancet 2:1255-1257, 1984 55. Uehara M, Kimura C: Descendant family history of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 7362-63, 1993 56. Van Leent EJ, Graber M, Thurston M, et al: Effectiveness of the ascomycin macrolactam SDS ASM 981 in the topical treatment of atopic dermatitis. Arch Dermatol 1345305-809, 1998 57. Vickers CFH The natural history of atopic eczema. Acta Derm Venereol Suppl (Stockh) 92:113-115, 1980 58. White A, Smith J: Nasal reservoir as the source of extranasal staphylocci. Antimicrob Agents Chemother 16k679-683, 1963 59. Williams HC, Strachan DP, Hay RJ: Childhood eczema: Disease of the advantaged. BMJ 3081132-1135, 1994 60. Williams R E 0 Healthy carriage of StuphyIococcus uureus: Its prevalence and importance. Baderiol Rev 275671, 1963 61. Young Rp, Sharp PA, Lynch JR, et al: Confirmation of genetic linkage between atopic IgE responses and chromosome 21913. J Med Genet 29:236-238, 1992 62. Zeiger RS, HeIler 5 ' The development and prediction of atopy in high-risk children: Follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance. J Allergy Clin Imrnunol95:1179-1190, 1995
Address reprint requests to Leonard Kristal, MD 2035 Lakeville Road, Suite 202 New Hyde Park, NY 11040
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PEDIATRIC DERMATOLOGY
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ATOPIC DERMATITIS IN INFANTS AND CHILDREN An Update Leonard Kristal, MD, and Peter A. Klein, MD, MPA
Atopic dermatitis is a common chronic or relapsing eczematous dermatitis characterized by intense pruritus and occurring primarily in infants and children. Commonly referred to as eczema, atopic dermatitis is but one disease in a group of eczematous diseases including nummular dermatitis, seborrheic dermatitis, and hand eczema. Approximately 10% of all children are affected by atopic dermatitisP, 30 typically in the setting of a personal or family history of atopy. Most cases manifest in infancy and early duldhood, with lesions initially affecting the scalp, face, and extensor surfaces. Flexural areas are affected most often in older children and adults. Atopic dermatitis may be severe and widespread, leading to significant morbidity and possible social isolation. Moreover, one study revealed the cost of treatment to be as high as $364 million.31Because the underlying pathophysiology of atopic dermatitis is unknown, therapy is directed at interruption of the itch-scratch cycle and control of antigenic and irritant triggers. EPIDEMIOLOGY
Nine percent to 12% of all children born after 1970 have had atopic derma30, 54 The prevalence has increased since before 1960, when 2% to 5% of titi~.2~, children were affected.z9* 54 The reasons for this increase are unknown. Changes in environmental pollutants, breastfeeding patterns, and diagnosis may be associated, but a general consensus does not exist. Despite differences in methodology, however, the balance of epidemiologic studies favors a true increase in prevalence. In children in whom atopic dermatitis develops, signs and symptoms most
From the Department of Dermatology, State University of New York at Stony Brook, Stony Brook, New York ~~~~~~
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often manifest early in childhood. Thirty-five percent to 60% of symptoms manifest in the first year of life, and 47% to 85%, by 5 years of age.15,40 By the age of 10 years, the disease manifests in most susceptible children. The prevalence is higher in dry, mountainous regions because of a dry, disrupted epidermal barrier, and in urban areas, which have a higher prevalence for unknown reasons. A study of British sch~olchildren~~ showed a direct relationship between socioeconomic class and the prevalence of atopic dermatitis not attributable to increased medical awareness. GENETICS An inheritance pattern for atopic dermatitis has not been established. Genetic susceptibility to respiratory atopy has been identified on chromosome 11913 in asthmatic patients, but an association with atopic dermatitis has not been found.I3,61 Atopy has a familial basis for asthma and atopic dermatitis. Forty-two percent of first-degree relatives of patients with atopic dermatitis are affected, and 28% have respiratory atopyS4Fifty-six percent of patients with atopic dermatitis have one affected parent.55In cases in which both parents have atopic dermatitis, 81% of children also have the disease. Among monozygotic twins, 86% have atopic dermatitis if the sibling is affected. Interestingly, the risk is 21% in dizygotic twins, which equals that of nontwin siblingsj6 DIAGNOSIS AND CLINICAL FINDINGS Hanifin and Rajka2' codified major and minor criteria for atopic dermatitis in 1980. These criteria included? Must have three or more of the following primary features: Pruritus Typical morphology and distribution Flexural lichenification or linearity in adults Facial and extensor involvement in infants and children Chronic or chronically relapsing dermatitis Personal or family history of atopic dermatitis (e.g., asthma, allergic rhinitis, atopic dermatitis) Plus three or more of the following secondary features: Xerosis Ichthysosis, palmar hyperlinearity, or keratosis pilaris Immediate (type 1)skin test reactivity Elevated serum IgE level Early age of onset Tendency toward cutaneous infections (especially with Staphylococcus aureus and herpes simplex) or impaired cell-mediated immunity Tendency toward nonspecific dermatitis of the hand or foot Nipple eczema Cheilitis Recurrent conjunctivitis Dennie-Morgan infraorbital fold Keratoconus Anterior subcapsular cataracts Orbital darkening
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Facial pallor or facial erythema Pityriasis alba Anterior neck folds Itch when sweating Intolerance to wool and lipid solvents Perifollicular accentuation Food intolerance Course influence by environmental or emotional factors White dermographism or delayed blanch A modification of these criteria can be used to help assess atopic dermatitis in infancy47: Major features Family history of atopic dermatitis Evidence of pruritic dermatitis Typical facial or extensor eczematous or lichenified dermatitis Minor features Xerosis / ichthyosis / hyperlinear palms Perifollicular accentuation Chronic scalp scaling Periauricular fissures The presence of at least two major or one major and one minor criteria is needed for diagnosis. Hanifin has also made modifications to aid in making the diagnosis in children? Major features (must have three) Pruritus Typical morphology and distribution Facial and extensor involvement during infancy and early childhood Flexural lichenification and linearity by adolescence Chronic or chronically relapsing dermatitis Minor or less specific features Xerosis Ichthyosis/ palmar hyperlinearity/ keratosis pilaris IgE reactivity (increased serum IgE, RAST, or prick test positivity) Hand/ foot dermatitis Cheilitis Scalp dermatitis (e.g., cradle cap) Susceptibility to cutaneous infections (especially S. aureus and herpes simplex) Perifollicular accentuation (especially in pigmented races) The diagnosis of atopic dermatitis should be suspected in children having a personal or family history of atopy (i.e., asthma, allergic rhinoconjunctivitis, and atopic dermatitis) presenting with a chronic or relapsing pruritic dermatitis, distributed on the face and extensor surfaces in infants and young children, or involving flexural surfaces in older children and adolescents. The presence of primary lesions in patients with atopic dermatitis is a matter of debate. Some physicians regard pruritus as a primary phenomenon, but lesions have been found in infants less than 2 months of age, before the appearance of coordinated scratching. Moreover, xerosis has been found shortly after birth and may serve as the inciting and primary epidermal breach. In a setting where several patients were cleared and then rechallenged with inciting antigens, a pruritic morbilliform or, less commonly, urticaria1 eruption was
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observed, and, given continued allergen exposure, became eczematous within 48 hours.'* This suggests that atopic dermatitis may evolve from an intensely pruritic erythema or urticaria-like eruption. Lesions of atopic dermatitis are classified as acute, subacute, or chronic. Acute atopic dermatitis is characterized by intensely pruritic papules and papulovesicles with serous exudate on a background of erythema. The presence of fine, silvery scales surmounting erythematous grouped or scattered papules or plaques over variably erythematous skin characterize subacute eczema. The chronic changes of atopic dermatitis include thickened skin with lichenification (ie., increased skin markings) secondary to scratchng and rubbing. Fibrotic papules and nodules called prurigo nodularis may be present with a background of postinflammatory hyperpigmentation or hypopigmentation. In patients with subacute or chronic atopic dermatitis, seemingly unaffected skin may have a dry lackluster appearance. In darker-skinned patients, lesions may have a perifollicular distribution, giving the skin a pebbled appearance. The distribution of atopic dermatitis varies with age at presentation and may pose a diagnostic challenge. In infants, the eruption usually begins on the scalp and face (Fig. l), although the extensor surfaces of the extremities and trunk may also be involved (Fig. 2). The dermatitis on the face can be inflammatory and persistent. The increased drooling that occurs with teething can be further irritating to already inflamed skin. Although there may not be coordinated scratching in early infancy, parents usually note that children with extensive facial dermatitis tend to rub their faces on the sheets of the crib, or on the shoulder of someone holding them. A somewhat increased prevalence of diaper dermatitis has been reported in patients with e~zema.4~ Extensive and severe inflammation of the scalp rarely leads to alopecia, which is usually nonscarring and reversible. Atopic dermatitis of older children and adolescents is classically distributed on flexural surfaces, including the neck, antecubital or popliteal fossae, wrists,
Figure 1. Inflammation of the cheeks and forehead common in infants.
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Figure 2. Extensor dermatitis with excuriations. The pruritus is clearly evident by patient scratching.
and ankles. In school-aged children, the rash may develop on the crease between the buttock and the thigh. The eruption in children and adolescents usually consists of ill-defined, erythematous, scaly patches although acute flares can be inflammatory. With persistent scratching and rubbing, lichenification develops (Fig. 3). An inverse distribution on extensor surfaces, such as the elbows, knees, dorsal hands, wrists, and feet may occur and may portend a poorer pr0gnosis.5~ Involvement of the axillae, groin, and intergluteal areas is unusual and may indicate a concurrent disease process. Involvement of the hands as the initial presentation has been reported in approximately 30%, and 70% of patients have hand dermatitis at some time in their disease c o ~ r s eDermatitis .~ of the plantar or dorsal feet is also a manifestation of atopic eczema. Black children with atopic eczema tend to have a more papular dermatitis consisting of discrete skin-colored and erythematous papules. In addition, follicular accentuation is commmon. Comorbid Findings
Several comorbid disorders are diagnostic features and symptoms of atopic dermatitis. Atopic Diathesis
The presence of asthma, allergic rhinoconjunctivitis, or both is a risk factor for atopic dermatitis. Atopic dermatitis in one or both parents poses a significant risk for the child. In nearly 80% of patients, positive reactions to one or more allergens on immediate hypersensitivity skin testing develop.4l
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Figure 3. Lichenification seen secondary to chronic rubbing.
Xerosis
Dry skin, or xerosis, occurs in 48% to 98% of patients with atopic dermati ti^.^^ Xerosis leads to pruritus and scratching, which perturbs the epidermal barrier, leading to additional water loss. This cycle of water loss, scratching, and rubbing sustains and worsens atopic dermatitis. Xerosis is worsened during periods of low humidity and in dry geographic areas. lchthyosis Vulgaris
Ichthyosis vulgaris is a common disorder with autosomal dominant inheritance found in as many as 37% of patients with atopic dermatitis. The disease results from a defect in epidermal maturation and the formation of an intact epidermal moisture barrier. It is characterized by polygonal fishlike scales, most prominently on the extensor surfaces. The flexural surfaces and face are characteristically spared, although concurrent atopic dermatitis may obscure this distribution. Asymptomatic keratotic follicular papules distributed on the extensor surfaces of the upper arms, buttocks, and anterolateral thighs are found in patients with keratosis pilaris, a condition associated with ichthyosis vulgaris. Ichthyosis vulgaris and keratosis pilaris occur in the general population as an isolated finding without associated atopic dermatitis. Pigmentary Changes
Hypopigmented macular or slightly scaly patches called pifyriasis alba may be found on the cheeks, upper arms, or shoulders. These lesions may represent a subclinical dermatitis that results in abnormal tanning in the summer or
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merely postinflammatory hypopigmentation. Also, in patients with chronic atopic dermatitis, postinflammatory hyperpigmentation or hypopigmentation may develop at sites of scratching and rubbing. Pigmentary changes resolve within 9 months after treatment of the underlying dermatitis, although resolution may require more time in darker-skinned patients. Ocular Findings
Several ocular findings have been associated with atopic dermatitis. Patients may have periorbital dermatitis ranging from mild scaling to severe lichenification of the eyelids and ectropion. Conjunctival allergy also may lead to rubbing and a periorbital dermatitis. Infiltration of the palpebral mucosa with inflammatory cells may lead to a cobblestone appearance and a vernal conjunctivitis, which can abrade the cornea. An ophthalmologic consultation is indicated in this instance. The Dennie-Morgan fold, a single or double fold in the lower eyelid, has been found to have no diagnostic significance, especially in darkskinned children, in whom it may be a normal Allergic shiners (i.e., hyperpigmentation under the eyes) is likely caused by chronic edema, lichenification, and postinflammatory hyperpigmentation. Anterior and posterior subcapsular cataracts are increased in patients with atopic dermatitis. Anterior cataracts develop early in patients with severe disease. Posterior cataracts may be secondary to systemic steroids and topical steroids around the eyes." Patients using topical steroids around the eyes for extended periods should be followed up by an ophthalmologist. Differential Diagnosis
The criteria of Hanifin and Rajka (see previous lists) are helpful in the diagnosis of atopic dermatitis, but other eczematous conditions may lead to similar clinical presentations and include: Allergic contact dermatitis Dermatophytosis or dermatophytids Immunodeficiency syndromes Wiskott-Aldrich syndrome Hyper-IgE syndrome Neoplastic diseases Langerhans' cell histiocytosis Hodgkin's disease Nummular dermatitis Scabies Seborrheic dermatitis Lesions that are recalcitrant to, or worsened by, treatment may indicate a different or concurrent disease process. Seborrheic Dermatitis
Seborrheic dermatitis is the disease most often confused with atopic dermatitis in infancy. Seborrheic dermatitis typically develops at birth or within the first 2 months of age. An early appearance, however, cannot distinguish these diseases because lesions of atopic dermatitis have been observed at less than 2
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months of age despite a lack of coordinated scratching. Distinguishing seborrheic dermatitis of the scalp from atopic dermatitis may be especially difficult. The presence of pruritus indicates atopic dermatitis. Dermatitis of the axillary area and involvement of the diaper area indicate seborrheic dermatitis. Scabies
As with atopic dermatitis, patients with scabies may present with a severely pruritic eczematous dermatitis. Scabies, however, favors the axillae and genital regions, which typically are spared in patients with eczema. The index of suspicion for scabies is increased in patients living in institutionalized environment, especially when other children are similarly affected. The linear papulovesicular lesions of scabies are distinctive, and a microscopic examination of a scraped burrow confirms the diagnosis. Secondary eczematous changes may resemble atopic dermatitis. Allergic Contact Dermatitis
Allergic contact dermatitis should be considered when presumed atopic dermatitis presents in an unusual distribution or is refractory to treatment. Dermatitis of the hands or feet is seen in patients with atopic dermatitis, and its presence should not necessarily lead one to an alternative diagnosis. Nummular Dermatitis The chronic, papulovesicular, coin-shaped lesions of nummular dermatitis typically develop late in childhood or in adulthood, are idiopathic, and are unrelated to atopy. Coin-shaped lesions may be seen, however, in infants and children with atopic dermatitis, and their presence may be a manifestation of eczema given fulfillment of other appropriate diagnostic criteria. Dermatophytosisand Dermatophytids
Dermatophyte infections are common among children and may resemble atopic dermatitis. Dermatophyte infections are typically annular and well-circumscribed, with straightforward diagnosis by means of a potassium hydroxide preparation. The presence of hyphae does not necessarily rule out underlying atopic dermatitis. The presence of erythema, scale, and vesicles involving the palms and soles should raise the possibility of fungal infection. Id reactions are secondary inflammatory reactions occurring at cutaneous sites distant from a severe allergic or irritant contact dermatitis or a fungal infection. The immunologic mechanism is unknown, but in the case of a fungal infection systemically absorbed fungal antigens lead to a response at a distant site. Because dermatophytes are not present in the lesions of an id reaction, potassium hydroxide preparations and cultures are negative. Id reactions may have a varied appearance, including follicular papules, vesicles of the hands and feet, erythema nodosum, an erysipelas-like eruption, erythema annulare centrifugum, or urticaria. Id reactions may appear similarly to atopic dermatitis, and a primary fungal infectious cause must be recognized for correct diagnosis. ImmunodeficiencySyndromes
Wiskott-Aldrich syndrome is a disorder of X-linked recessive inheritance characterized by an atopiclike dermatitis, dysfunctional small-platelet dysgam-
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maglobulinemias, and recurrent infections. Patients may present in early cluldhood with an eczematous eruption of the face, scalp, or flexural extremities, with a history of recurrent and severe infections. The presence of hemorrhagic crusts secondary to platelet dysfunction and hemorrhage suggest the diagnosis. High levels of IgE may be present. Hyper-IgE syndrome is a heterogenous group of immunodeficiencies (e.g., Job’s syndrome) characterized by elevated levels of IgE and susceptibility to candidiasis and staphylococcal infections. Patients typically present with deep furuncles and carbuncles with potential involvement of the respiratory tract. A fine papular erythematous eruption with superficial vesicles and pustules may be localized to the face, scalp, or body folds, especially the axillae and groin. These areas are typically spared in patients with atopic dermatitis. As in patients with Wiskott-Aldrich syndrome, high levels of IgE may be present. Other immunodeficiency syndromes may have eczematous skin eruptions associated with them. The eruption is usually seen in conjunction with recurrent infections and is usually refractory to traditional topical treatment. Neoplastic Diseases
The cutaneous manifestations of mycosis fungoides and Hodgkin’s disease may be similar to those of atopic dermatitis, but these diseases are uncommon in children. Langerhans’ cell histiocytosis, presents as an indurated, sometimes hemorrhagic, papular dermatitis with yellow, greasy scales. Morbidity
Many patients with atopic dermatitis develop bacterial, viral, or fungal skin infections that flare and complicate their disease, possibly because of disruption of the cutaneous barrier or impaired cutaneous immunity. Malfunctioning chemotaxis in these patients results in increased symptomatic presentation of staphylococcal, viral, and dermatophyte infections.” Treatment of concurrent infectious processes and colonization is essential to long-term control. Bacterial Infections
Bacterial infections typically are caused by S. aureus, a pathogen that colonizes patients with atopic dermatitis. The colonization rate of the anterior nares with S. aureus in the general population ranges from 10% to 45%;” 6o with less than 10% carrying staphylococci on the ~ k i n . 3 Most ~ patients with atopic dermatitis, however, are colonized. A recent study found a nasal carriage rate of S. aureus of 79% and a cutaneous colonization rate of 64% among 28 patients with atopic dem1atitis.2~Nine percent of the colonized anterior nares and 11% of the colonized cutaneous lesions contained methicillin-resistant S. aureus. Other studFlares ies have found higher cutaneous colonization rates of 85% to 100%.5,8,33 of atopic dermatitis often are associated with bacterial infection and the presence of honey-crusted weeping pustules. Viral Infections
Patients with atopic dermatitis are susceptible to viral infections with herpes simplex virus (HSV), vaccinia, molluscum contagiosum viruses, and papillomavirus (warts). The most severe viral complication of atopic dermatitis is
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eczema herpeticum secondary to HSV, also known as Kaposi's varicelliform eruption. HSV can masquerade as a generalized, severe flare with low-grade fever, lymphadenopathy, and superficial vesicles that evolve to form punched-out Although infection may be widespread and prolonged, these patients have a favorable outcome. Infants and immunosuppressed children are more likely to have widespread disease. Localized infections with HSV are also common, sometimes localized to one side of the face, mimicking herpes-zoster virus. A culture specimen should be obtained in these patients because a Tzanck smear is not diagnostic. Other viruses, such as those causing molluscum contagiosum, may not occur more frequently, but these infections are more widespread and difficult to treat. In patients with atopic dermatitis, a patchy eczema may develop around molluscum lesions 1 month or more after onset. Tlus eczema resolves once the lesions are removed.14 Fungal Infections
Superficial fungal infections may be more common in patients with atopic dermatitis than in those without eczema. Lobitz et a135were the first investigators to describe a severe atopic dermatitis patient with generalized Trichophyfon rubrum infection. Jones et alZ4subsequently reported that chronic T. rubrum infection is threefold more common among adults with atopic dermatitis than in those without eczema." Generalized flares also may occur secondary to localized recurrent dermatophyte infections. Concurrent dermatophyte infections should be treated in patients with atopic dermatitis. Exfoliative Erythroderma
Some patients may progress to an exfoliative erythroderma, which is characterized by generalized and confluent erythema, scaling, lymphadenopathy, fever, and systemic toxicity. Factors thought to trigger erythroderma are cutaneous infection (e.g., staphylococci) and withdrawal of systemic corticosteroids. Highoutput cardiac failure, sepsis, disorders of thermoregulation and heat loss, and protein depletion may complicate disease in patients with erythroderma. Growth and Psychosocial Factors
Chronic, generalized atopic dermatitis places patients in a catabolic state secondary to inflammation, serous transudation, and a high epidermal cell turnover. Children may suffer growth retardation, which ceases when the severe dermatitis is controlled.* These patients require an increased protein intake to keep up with their metabolic needs. The analogous effect in adults is weight loss and fatigue, which also resolves with treatment. The effect of atopic dermatitis on stature poses an emotional toll, especially given severe cutaneous disease. Affected children experience frustration, sadness, and anxiety, which are likely to exacerbate their disease and increase pruritus. Children also may suffer from sleep disturbances that can lead to chronic fatigue and poor school performance. Children with atopic dermatitis have more arousals and awakenings per hour during sleep than patients without atopic dermatitis. In addition, atopic children in remission have sleep disturbances unrelated to scrat&ng.4la Children may be ostracized and ridiculed, which can be addressed by alerting teachers to the problem. A supportive home environment from parents and siblings is essential.
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Prognosis Most affected children experience amelioration of atopic dermatitis with increasing age. Seventy-seven percent to 91% of teenagers having moderate or severe dermatitis, however, continue to have symptoms into adulthood.28 Individuals who have outgrown the typical manifestations of the disease may develop irritant dermatitis, which may be chronic and disabling, especially in the context of wet, dirty, or caustic condition^.^^ A significant proportion of occupational disease occurs in patients with atopy and atopic d e r m a t i t i ~ . ~ ~ Laboratory Findings
No laboratory test is diagnostic of atopic dermatitis, but several parameters may support the diagnosis. Although not specific for atopic dermatitis, blood eosinophilia tends to correlate with disease severity.23Serum IgE levels also tend to be elevated in as many as 80% of patients with atopic dermatitis and may 53 Although potential aeroallergen triggers may follow the course of di~ease.'~, be elucidated by immediate hypersensitivity skin testing,' such testing is not helpful in patient management except in cases of comorbid allergic rhinitis. Although biopsy is unnecessary in atopic dermatitis, lesions that are hemorrhagic, markedly infiltrated, or unresponsive to aggressive treatment should undergo biopsy. TREATMENT PRINCIPLES
Treatment of acute and chronic atopic dermatitis involves several approaches to basic skin care, medication, and allergen control. Hydration
Hydration is essential to treating atopic dermatitis. The basis of adequate hydration is increasing the water content of the skin by means of baths or soaks and applying a hydrophobic barrier to prevent evaporation. Bathing for 15 to 20 minutes two times a day is adequate, but hot water must be avoided. Oatmeal products added to the bathwater may be soothing but do not increase water absorption. Oils should not be added because they may interfere with optimal water penetration. Mild cleansers (e.g., Dove or Dial) or nonsoap cleansers ( e g , Cetaphil) may be used, although water alone is best. After bathing, excess water should be removed by patting with a soft towel. Water evaporates rapidly from the skin surface, and hydrophobic occlusion ( e g , petrolatum) must be applied within 5 minutes. Topical medications are also best applied after bathing because penetration is far greater in hydrated skin. Severe disease may require soaking after baths to maintain continuous hydration and further increase penetration of topical medications. Soaks also may be soothing to inflamed skin. From a practical standpoint, soaks and wraps are best applied at bedtime. Severely affected areas on the extremities may be dressed with gauze and bandage wraps. Total-body occlusion may be accomplished by using two pairs of cotton pajamas. The first pair is wetted, wrung out to dampness, and placed on the patient. The second pair is worn dry over the wet pair. Hands and feet may be occluded, with wet socks followed by dry
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socks. Soaking of the face may be accomplished by applying two layers of wet gauze followed by two layers of dry gauze held in place with Spandex netting. If crusts are present, Burow’s solution may be added to baths and soaks at a 1:40dilution (one packet of Domeboro powder per quart). This therapy provides astringent and antibacterial effects for localized weeping lesions, but use for more than 3 days may lead to excessive drying and cracking.12 There are patients in whom frequent bathing may exacerbate their pruritus leading to worsening dermatitis. It is important to recognize this and to limit bathing in these patients. These patients require liberal applications of emollients to maintain adequate hydration. In patients with chronic disease, liberal application three to four times daily is recommended with water-in-oil moisturizers (e.g., Eucerin, Aquaphor, Lubriderm, or Cetaphil). Lactic acid preparations (e.g., Lac-Hydrin) are useful in removing scales, especially in patients with ichthyosis vulgaris, but stinging may occur in areas containing fissures or areas with changes of acute dermatitis. Topical Corticosteroids
Topical corticosteroids impart anti-inflammatory, antipruritic, and vasoconstrictive effects. Some general guidelines apply to the use of topical corticosteroids in atopic dermatitis and include: Topical steroids should be applied immediately after baths or soaks to increase penetration. Topical steroids should not be applied more than twice daily because frequent application does not improve efficacy and increases the risk for side effects. Ointments provide the most occlusion but, in humid environments, may lead to folliculitis. Creams may be better tolerated in some instances. Lotions and sprays are most appropriate for hair-bearing areas. The lowest-potency effective agent should be used. Higher-potency, fluorinated agents may be necessary during an acute flare, but these should not be used on thin-skinned areas of the face, neck, axillae, or groin. Adverse effects of topical corticosteroids include atrophy, depigmentation, steroid acne, and rarely systemic absorption with suppression of the hypothalamicpituitary-adrenal axis.18 If a patient is bathing twice daily, after the baths, a low-potency or midpotency topical steroid ointment should be applied to all affected areas except the face, groin, or axillae. These areas may be treated with 1%hydrocortisone or 0.05% desonide. As the dermatitis improves, frequency of application should be decreased with the substitution of less-potent agents. When disease is controlled, topical corticosteroid therapy should be eliminated and treatment should center on hydration. Ointment-based occlusives, such as Aquaphor, petrolatum, Eucerin, or Crisco, should be applied after the topical steroids are applied and in the middle of the day. Systemic Corticosteroids
Oral corticosteroids typically are not indicated in the treatment of patients with atopic dermatitis, a chronic, non-life-threatening illness. Although they
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may be a "quick fix" resulting in a rapid improvement, severe flares often occur during steroid withdrawal. If a short course of oral steroid therapy is given, the dosage must be tapered slowly and intensive skin care must be instituted to prevent a flare of disease. Systemic corticosteroids have no role in the management of patients with chronic atopic dermatitis; the potential side effects far outweigh any benefits.
Systemic Antibiotics
Oral antibiotics are sometimes necessary because secondary bacterial infections may exacerbate and complicate an acute -flare. Infection is suggested by the presence of honey-colored crusts, extensive serous weeping, folliculitis, pyoderma, and furunculosis. Penicillin-resistant S. aureus cause most of these flares. Dicloxacillin or cephalexin may be used as first-line oral therapy because penicillin resistance is almost universal. For patients with a penicillin allergy, erythromycin is the first choice of therapy. Caution must be exercised, however, in asthmatic patients using theophylline because erythromycin slows metabolism. Chdamycin is an alternative agent, especially in penicillin-allergicpatients carrying erythromycin-resistant strains of S. aureus, which have been reported in 23% and 39% of isolates from the nares and skin, respectively. Culture and sensitivity testing are essential during acute flares, not only to identify resistance to erythromycin but also because methicillin-resistant S. aureus has been reported in 9% and 11%of isolates from the nares and skin, respecti~ely.~~ Antibacterial cleansers and topical antibiotics, with the exception of mupirocin (Bactroban), should not be used because they may sensitize patients. Long-term use of mupirocin may lead to bacterial resistance.
Antihistamines
Antihistamines are a standard therapy for atopic dermatitis and are recommended in many clinical treatment protocols. Despite frequent use, surprisingly few clinical studies have examined their efficacy. Moreover, atopic dermatitis and associated pruritus are not mediated primarily by histamine. A recent evidence-based reviewz6of 16 trials of oral antihistamines revealed that none fulfilled the criteria for a well-designed study that contained a sufficient number of subjects to permit definitive conclusions. Sedating antihistamines commonly are used for their soporific effect to facilitate peaceful sleep because itch intensity often increases at night. Unfortunately, daytime use is problematic for that reason, although some patients may acclimate to this effect. The development of nonsedating oral antihistamines (e.g., loratadine) has led physicians to prescribe these agents in the hope of providing daytime relief. Studies have failed, however, to demonstrate efficacy.z6 Moreover, compared with sedating agents, they are much more expensive. Oral hydroxyzine (Atarax) and diphenhydramine (Benadryl) are reasonable choices and should be used on a regular basis for optimal results. Topical antihistamines (e.g., doxepin) or anesthetic agents ( e g , benzocaine) are unhelpful in relieving pruritus and may cause allergic contact dermatiti~.~J 36
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Tars
Tars and extracts of crude coal tar have anti-inflammatory effects and are most useful in replacing topical corticosteroids in the management of chronic disease. Five percent liquid carbonis detergens in petrolatum (Aquaphor) may be prepared by a pharmacy and has acceptable cosmetic properties. Tar gel products (e.g., Estar Gel) are a formulation of crude coal tar that is conveniently commercially available and cosmetically acceptable. They frequently contain alcohol, however, and may cause stinging and irritation of inflamed skin. Tar gels are drying and are best applied under emollients. They may be used only at bedtime under pajamas, which maximizes compliance and minimizes staining of clothing. A new tar preparation (Micanol) contains tar encapsulated in a crystal form that stains far less than older preparations. Clothing and bed sheets should be washed in cool water because heating may lead to staining. The side effects of tars include folliculitis, photosensitization, and contact dermatitis. Ultraviolet Radiation
Ultraviolet radiation may be a useful therapy for patients with recalcitrant atopic dermatitis. Ultraviolet B or psoralens plus ultraviolet A (PUVA) are used three or four times weekly. In adolescents with severe atopic dermatitis, PUVA led to significant improvement in disease and growth responses on percentile curves.6 A subsequent study showed that PUVA twice weekly led to clearance or near-clearance in 39 of 53 children (aged 6-16 years) after a mean of 9 ~ e e k s . 4 ~ Patients who expose themselves to natural sunlight should be warned not to sunburn and to avoid hot or humid conditions that may flare their disease. Home lamp treatments may lead to overexposure and should not be used. Side effects of ultraviolet therapy include acute phototoxicity and an increased risk for skin cancers with prolonged treatment. Caution should be exercised in patients with fair skin. Leukotriene Inhibitors
Leukotriene inhibitors (e.g., zafirlukast) are a new class of medication in the treatment of asthma. A recent small serieslO of four patients with atopic dermatitis showed improvement with zafirlukast. Additional larger studies are needed to evaluate the role of this class of medication. IDENTIFICATION AND ELIMINATION OF EXACERBATING FACTORS
Atopic dermatitis commonly is exacerbated by environmental factors that, once identified and eliminated or controlled, lead to far better control of disease. Exacerbating factors include irritants; emotional stress; allergens, including food; and infections. Irritants
Atopic dermatitis is a condition of dry, sensitive skin that is extremely vulnerable to irritation with various agents. The most commonly used irritant is
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soap, which depletes the skin of natural moisturizers and water. To prevent irritation, drying soaps, solvents, and other compounds should be minimized. Gentle soaps include Dove, Dial, Tone, Alpha Keri, Basis, Lowila, and Neutrogena. Nonsoap cleansing agents, such as Cetaphil and Aveeno, may be least irritating. Soap should be used only in intertriginous areas to avoid drying of large areas of skin. Laundry soaps also may be irritating, and the authors recommend allergen-free detergents (e.g., Tide Free) and two rinse cycles. Bubble baths should be discouraged strongly. Clothing that may be irritating, especially wool, should be eliminated. Children do best with soft, cotton clothing and avoidance of coarse, thick fabrics. Open-weave, loose-fitting garments are preferred. Sweating also may irritate atopic skin, and activities should be modified accordingly. Patients should sleep in comfortable surroundings at a fairly constant. temperature (20-24°C) and humidity (45-55%). Swimming is recommended and well tolerated, but chlorine or bromine in pool water may be irritating. Showering with the application of occlusives after swimming minimizes this effect.
Emotional Stress Itching can be a direct result of emotional and social stress. Atopic dermatitis is a chronic disease, and families may unknowingly worsen disease by excessive attention on skin appearance and projection of their frustration. Classmates also may induce itching by taunting affected children. Parents can alert teachers to the nature of the disease and encourage them to address the problem openly with other children. The period after school, especially when children do not have close supervision, can be a vulnerable period for itching and scratching. Provision of diversions is better than merely warning a child not to scratch. Allergens Aeroallergens may exacerbate atopic dermatitis. Although potential aeroallergen triggers may be elucidated by immediate hypersensitivity skin testing, such testing is not helpful in management except in cases of comorbid allergic rhinitis. If patients are found to have positive skin or RAST tests, those identified allergens should be avoided. House dust mites and their feces may be allergens in atopic dermatitis. They thrive in settings of wall-to-wall carpeting and high humidity. Bedding and furniture also harbor dust mites, which feed on human scales. A standardized patch test to house dust mites is still in development, but suspected mite allergy can be addressed by using hypoallergenic mattress and pillow covers that are available commercially. Removal or frequent vacuuming of carpets and covered furniture, acaricidal treatment of carpets, and laundering linens with hot water may help to ameliorate disease. The role of food allergens is controversial. The most common inciting allergens are eggs, cow's milk, soy products, wheat, peanuts, and fi~h.4~ A review article*2on atopic dermatitis provided the following general guidelines regarding the role of diet: Breastfeeding in conjunction with maternal hypoallergenic diets seems to decrease the prevalence of atopic dermatitis in high-risk infants, but benefits may not be sustained.l6,51, 52
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Food allergy or intolerance may exacerbate disease in a small subgroup and may be appropriate to consider, given a history of provocation with food or when treatment is ineffective. Positive skin tests or a history of food allergy should prompt an elimination diet as long as nutrition is not compromised. The potential role of several foods should be addressed using double-blind, placebo-controlled food trials. With the exception of sensitivity to peanuts, most food allergies wane with time, and these foods may be returned to the diet after 1 year of age. Infection may flare atopic dermatitis. Many patients carry S. uureus on the skin and nares and, in children with frequent bouts of infection-associated flares, attempts should be made to eliminate colonizing pathogens. The use of oral antibiotics in conjunction with mupirocin (Bactroban) applied to the nares three times daily may eliminate colonizing staphylococci during episodes of infectionmediated flares. Allergy to pets is often suspected but seldom documented. In children with associated asthma, keeping pets outdoors, restricting pets from bedrooms, and frequent vacuuming are probably prudent. Flaring of atopic dermatitis when embracing a pet is the best approach to assessing the possibility of an allergy. Because triggers are usually multifactorial, discarding pets is not recommended. Therapeutic Advances
Topical FK506 ointment (tacrolimus) is likely to be available soon in the United States for the treatment of atopic dermatitis. Used historically for transplant rejection as Prograf, tacrolimus has been shown to be effective in clinical trials. The drug does not accumulate in the skin or in the systemic circulation after repeated topical administration? Side effects may include itching or buming at sites of application. Topical SDZ ASM 981, a macrolactam ascomycin, is an inflammatory cytokine inhibitor under development. When applied in a recent trial:7 it was as potent as clobetasol, without local side effects. Clinical efficacy and safety have been confirmed in short-term trials in patients with moderate atopic d e r m a t i t i ~ . ~ ~ Side effects include burning and stinging at sites of application. Oral cyclosporin A (Sandimmune) may provide a dramatic response in patients with severe atopic dermatitis, but rapid relapses occur after discontinua n ~ eSide . ~ ~effects include hypertension, increases in serum creatinine level, and paresthesias. A recent case series52of 24 patients treated with human interferon gamma for 2 years demonstrated safety and efficacy, but flares occurred rapidly after withdrawal? Also, phosphodiesterase inhibitors show promise, but these agents are early in development. Alternative Therapies
Chinese herbal formulations have generated interest based on small studies. Zemaphyte, a proprietary formulation containing 10 Chinese herbs, has been used successfully in several trials in Great Britain.@One double-blind, placebocontrolled, crossover studyI7 of 37 Chinese patients with recalcitrant atopic dermatitis, however, showed no improvement. Moreover, given an unknown
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mode of action and controversy regarding variations in formulations, Chinese herbal therapy is not recommended. Phase 2 multicenter trials are underway in the United States to assess the findings of studies conducted in Great Britain. Schachner et a145have reported that daily massage for 20 minutes resulted in improvements in redness, scaling, lichenification, excoriation, and pruritus over a I-month treatment period. Patients' activity levels and dispositions improved, and parents administering massages also reported diminished anxiety levels. A control group receiving topical treatment alone improved significantly only on the scaling measure.
SUMMARY The goal in treating patients with atopic dermatitis is to maintain adequate hydration while decreasing pruritus and idammation. It is also important to recognize factors that are responsible for flares. Although the etiology of atopic dermatitis remains unknown, therapies are being developed targeting immunologic defects in this disease.
References 1. Abrahamov A, Schifmann R, Goldstein R, et al: Growth failure due to protein loss in dermatitis. Eur J Pediatr 145223-226, 1986 2. Adinoff AD, Tellez P, Clark RAF: Atopic dermatitis and aeroallergen contact sensitivity. J Allergy Clin Immunol 81:736-742, 1988 3. Agrup G: Hand eczema and other hand dernatoses in South Sweden. Acta Derm Venereol Suppl (Stockh) 49:1, 1969 4. Alaiti S, Kang S, Fiedler VC, et al: Tacrolimus (FK506) ointment for atopic dermatitis: A phase I study in adults and children. J Am Acad Dermatol 38:69-76, 1998 5. Aly R, Maibach HI, Shinefield HR Microbial flora of atopic dermatitis. Arch Dermatol 113:780-782, 1977 6. Atherton DJ, Carabett F, Glover MT, et al: The role of psoralen chemotherapy (PWA) in the treatment of severe atopic eczema in adolescence. Br J Dermatol 118:791-795, 1988 7. Berth-Jones J, Graham-Brown R, Marks R, et aI: Long-term efficacy and safety of cyclosporin in severe atopic dermatitis. Br J Dermatol 136:7@1, 1997 8. Bibel DJ, Greenberg JH, Cook J L Staphylococcus aureus and the microbial etiology of atopic dermatitis. Can J Microbiol23:1062-1068, 1977 9. Boguniewicz M, Jaffe HS, Izv A, et al: Recombinant gamma interferon in treatment of patients with atopic dermatitis and elevated IgE levels. Am J Med 88:365-370, 1990 10. Carucci JA, Washshenik K, Weinstein A, et al: The leukotriene antagonist zafirlukast as a therapeutic agent for atopic dermatitis. Arch Dermatol 134:785-786, 1998 11. Castrow F F Atopic cataracts versus steroid cataracts. J Am Acad Dermatol 5:64-65, 1981 12. Clark RAF, Kristal L: Atopic dermatitis. In Sams WM Jr, Lynch PJ (eds): Principles and Practice of Dermatology, ed 2. New York, Churchill Livingstone, 1996, pp 403418 13. Coleman R, Trembath RC, Harper JI: Chromosome 22923 and atopy underlying atopic eczema. Lancet 341:1121-1122, 1993 14. De Ore0 GA, Johnson HH, Binkley GW: An eczematous reaction ssociated with molluscum contagiosum. Arch Dermatol 74:344-348, 1956 15. Diepgen TL, Fartasch M Recent epidemiological and genetic studies in atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 176:13-18, 1992 16. Falth-Magnusson K, Kjellman NI: Allergy prevention by maternal elimination diet during late pregnancy: A 5 year follow-up of a randomized study. J Allergy Clin Immunol 89:709-713, 1992
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17. Fung AYE', Look PCN, Chong LY, et al: A controlled trial of traditional Chinese herbal medicine in Chinese patients with recalcitrant atopic dermatitis. In J Dermatol 38:387-392, 1999 18. Garden JM, Freinkel RK: Systemic absorption of topical steroids: Metabolic effects as an index of mild hypercortisolism. Arch Dermatol122:1007-1010, 1986 19. Gurevitch AW, Heiner DC, Reisner R IgE in atopic derrmatitis and other common dermatoses. Arch Dermatol 107712-715, 1973 20. Hanifin JM Atopic dermatitis in infants and children. Pediatr Clin North Am 38763789, 1991 21. Hanifin JM, Rajka G: Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 9244-47, 1980 22. Hanifin JM, Rogge JL: Staphylococcal infections in patients with atopic dermatitis. Arch Dermatol 1131383-1386, 1977 23. Hellerstrom S, Lidman H: Studies in Besnier's prurigo (atopic dermatitis). Acta Derm Venereol Suppl (Stockh) 3611, 1956 24. Jones HE, Reinhardt JH, Rinaldi M G A clinical, mycological and immunological survey for dermatophytosis. Arch Dermatol 108:61-65, 1973 25. Karaz SS, Moeckli JK, Davis W, et al: Effects of topical doxepin cream on skin testing. J Allergy Clin Immunol 96:997-998, 1995 26. Klein PA, Clark RAF: An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch Dermatol 135:1522-1525, 1999 27. Klein PA, Greene WH, Fuhrer J, et al: Prevalence of methicillin-resistant Staphylococcus uureus in outpatients with psoriasis, atopic dermatitis, or HIV infection. Arch Dermato1 1333463-1465, 1997 28. Lammintausta K, Kalimo K, Raitala R, et al: Prognosis of atopic dermatitis: A prospective study in early adulthood. Int J Dermatol 30:563-568, 1991 29. Larsen FS, Hanifin J M Secular change in the occurrence of atopic dermatitis. Acta Dermatol Venereol Suppl (Stockh) 176:7-12, 1992 30. Larsen FS: Atopic dermatitis: A genetic-epidemiological study in a population-based twin sample. J Am Acad Dermatol28:719-723, 1993 31. Lapidus CS, Schwarz DF, Honig PJ: Atopic dermatitis in children: Who cares? Who pays? J Am Acad Dermatol28:699-703, 1993 32. Leyden JJ, Baker DA: Localized herpes simplex infection in atopic dermatitis. Arch Dermatol 115:311-312, 1979 33. Leyden JJ, Marples RR, Kligman A M Staphylococcus uureus in the lesions of atopic dermatitis. Br J Dermatol90525-530,1974 34. Linde MIV: Dry skin in atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 177913, 1992 35. Lobitz WC Jr, Honeyman JF, Winkler N W Suppressed cell-mediated immunity in two adults with atopic dermatitis. Br J Dermatol 86:317-328, 1972 36. Marks JG Jr, DeLeo VA. Evaluation and treatment of patients with contact dermatitis. In Contact and Occupational Dermatology, ed 2. St. Louis, Mosby, 1997, pp 14-29 37. Meingassner JG, Grassberger M, Fahmgruber H, et al: A novel anti-inflammatory drug, SDS ASM 981, for the topical and oral treatment of skin diseases: In vivo pharmacology. Br J Dermatol 137568-576, 1997 38. Mevorah B, Frenk E, Wietlisbach V, et al: Minor clinical features of atopic dermatitis: Evaluation of their diagnostic significance. Dermatologica 17736e364, 1988 39. Noble WC: Skin carriage of the micrococcaceae. J Clin Pathol22:249-253, 1969 40. Rajka G: Essential Aspects of Atopic Dermatitis. Berlin, Springer-Verlag, 1989, p 1 41. Rajka G: Prurigo Besnier (atopic dermatitis) with special reference to the role of allergic factors: 11. The evaluation of skin reactions. Acta Derm Venereol SuppI (Stockh) 41:363-395, 1961 41a. Reuventi H, Chapnick G, Tal A, et al: Sleep fragmentation in children with atopic dermatitis. Arch Pediatr Adolesc Med 153:249-253, 1999 42. Rothe MJ, Grant-Kels J: Atopic dermatitis: An update. J Am Acad Dermatol 35:l-13, 1996 43. Rystedt I: Work-related hand eczema in atopics. Contact Dermatitis 12:164-171, 1985
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