Atopic dermatitis and the atopic march

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<ul><li><p>S118</p><p>Atopic dermatitis and the atopic march</p><p>Jonathan M. Spergel, MD, PhD,a and Amy S. Paller, MDb Philadelphia, Pa, andChicago, Ill</p><p>Atopic dermatitis (AD), one of the most common skin disor-ders seen in infants and children, usually has its onset duringthe first 6 months of life. The prevalence of AD is similar in theUnited States, Europe, and Japan and is increasing, similar tothat of other atopic disorders, particularly asthma. AD hasbeen classified into 3 sequential phases: infantile, childhood,and adult, each with characteristic physical findings. AD has atremendously negative effect on the quality of life of patientsas well as family, most commonly disturbing sleep. The condi-tion also creates a great financial burden for both the familyand society. The cutaneous manifestations of atopy often rep-resent the beginning of the atopic march. On the basis of sev-eral longitudinal studies, approximately half of AD patientswill develop asthma, particularly with severe AD, and twothirds will develop allergic rhinitis. Epicutaneous sensitizationhas been thought to be responsible, with subsequent migrationof sensitized T cells into the nose and airways, causing upperand lower airway disease. Animal models and human observa-tion concur with this theory. Preliminary prevention studieswith oral antihistamines provide evidence that early interven-tion might slow the atopic march. (J Allergy Clin Immunol2003;112:S118-27.)Key words: Atopic dermatitis, atopic march, quality of life, asth-ma, skin sensitization</p><p>Atopic dermatitis (AD), one of the most common skindisorders seen in infants and children, has its onset dur-ing the first 6 months of life in 45% of children, the firstyear of life in 60% of affected individuals, and before 5years of age in at least 85% of affected individuals.1Although the term eczema is frequently used, AD is amore precise term to describe this subset of dermatitis.The concept of atopy (derived from the Greek atopia,meaning different or out of place) originally wasproposed in 1923 to include asthma and allergic rhinitis,but AD was added to the group of atopic disorders in1933 on the basis of association of this form of eczemawith asthma and allergic rhinitis. In fact, AD is mostoften the first manifestation of this atopic triad.</p><p>The prevalence of AD in the US childhood populationis 17.2%2 and is similar to the 15.6% prevalencedescribed in European children3 and the 24% prevalence</p><p>in 5- to 6-year-old children in Japan.4 The manifestationof AD in such a sizable proportion of the pediatric popu-lation represents a marked increase during the past sev-eral decades. Studies performed before 1960 estimatedthe prevalence to be up to 3%.5 The subsequent steadyincrease has paralleled the increase seen in children withasthma, suggesting shared triggers and consistent withthe frequency of development of other atopic disorders inchildren with AD.6 AD occurs more frequently in urbanareas than in rural areas, in smaller families, and in high-er socioeconomic classes, suggesting that exposure toantigenic pollutants and lack of exposure to infectiousagents or other antigenic triggers (particularly that favora TH1 helper T-cell response) early in life might play arole in the development of the dermatitis. The prognosisof AD for an individual child is unpredictable. Recentstudies have shown complete clearing of the disorder atpuberty or shortly after puberty in 40% to 60% ofpatients, although patients who do not show clearancemight show improvement with advancing age.7,8</p><p>The clinical features of AD that allow diagnosis arethe chronicity of the disorder, its associated pruritus, andthe age-specific morphology and distribution of lesions(Table I).9 Extent of involvement might range from mildand limited, for example, mild flexural area involvementonly, to generalized and severe. AD has been divided into3 phases on the basis of the age of the patient and the dis-tribution of lesions: the infantile phase, the childhoodphase, and the adult phase.</p><p>THREE PHASES OF ATOPIC DERMATITIS</p><p>The infantile phase of AD reflects the manifestations ofAD from birth to 2 years of age (Fig 1). The erythematouspapules and vesicles typically begin on the cheeks, fore-head, or scalp and are intensely pruritic. Lesions mightremain localized to the face or might extend to the trunkor particularly the extensor aspects of the extremities inscattered, ill-defined, often symmetrical patches. Exacer-bation of facial dermatitis on the medial cheeks and chinis often seen concomitant with teething and initiatingsolid foods, probably because of the exposure to irritatingsaliva and foods, although contact urticaria might con-tribute to the localized reactivity. Characteristic of this</p><p>From the aDivision of Allergy and Immunology, The Childrens Hospital ofPhiladelphia, University of Pennsylvania School of Medicine, and bDe-partments of Pediatrics and Dermatology, Childrens Memorial Hospital ofChicago, Northwestern Universitys Feinberg School of Medicine.</p><p>Disclosure: Dr Spergel is a consultant to Novartis and Fujisawa, has receivedresearch support/grants from Merck, Novartis, Genetech, Tanox. DrSpergel is also a member of the speakers bureau for GlaxoSmithKline,Novartis and Fujisawa. Dr Paller is a consultant and speaker for Novartisand Fujisawa.</p><p>Reprint requests: Amy S. Paller, MD, Division of Dermatology #107, Chil-drens Memorial Hospital, 2300 Childrens Plaza, Chicago, IL 60614.</p><p> 2003 American Academy of Allergy, Asthma and Immunology0091-6749/2003 $30.00 + 0doi:10.1016/j.jaci.2003.09.033</p><p>Abbreviations usedAD: Atopic dermatitis</p><p>BAL: Bronchoalveolar lavageETAC: Early Treatment of the Atopic ChildISAAC: International Study of Asthma and Allergies in</p><p>ChildrenMAS: Mulitcenter Atopy Study</p></li><li><p>J ALLERGY CLIN IMMUNOL</p><p>VOLUME 112, NUMBER 6</p><p>Spergel and Paller S119</p><p>infantile phase is the tendency to show significant edemaof affected areas, leading to oozing and crusting unrelat-ed to secondary infection. Generalized xerosis is com-mon. By 8 to 10 months the extensor surfaces of the armsand legs often show dermatitis, perhaps because of therole of friction associated with crawling and the exposureof these sites to irritant and allergenic triggers such as incarpets. Although dermatitis of the antecubital andpopliteal fossae, periorbital areas, and neck is more com-monly involved in older children and adolescents, thesesites might also be affected in infants and young children.Typically, lesions of AD spare the diaper area during</p><p>infancy, which aids in the diagnosis. This sparing likelyreflects the combination of increased hydration in the dia-per area, protection from triggers by the diaper, and inac-cessibility to scratching and rubbing.</p><p>Not uncommonly, infants present with an initial pat-tern suggestive of seborrheic dermatitis, particularly dur-ing the first month or two of life. The associated pruritusand the dry character of the scaling either support thediagnosis of AD rather than seborrheic dermatitis or sug-gest the combination of both disorders. The skin changesof infants who exhibit this combination of features usu-ally evolve into a more classic picture of AD as the seb-</p><p>FIG 1. Facial involvement in affected infants with AD. The cheeks and chin often show edema and erythe-ma, exacerbated by exposure to saliva and foods.</p><p>TABLE I. Clinical criteria for AD in pediatric patients</p><p>Essential featuresPruritusEczematous changesChronic or relapsing courseTypical and age-specific patterns: face, neck, and extensor involvement in infants and children; flexural lesions, especially in olderchildren and adolescents; sparing of the groin and axillae</p><p>Important features (support the diagnosis but do not occur in all patients)Early age of onsetXerosisAtopy (IgE reactivity)</p><p>Exclusions: The diagnosis of AD depends on the exclusion of conditions such as scabies, allergic contact dermatitis, seborrheic dermatitis,psoriasis, and ichthyosis.</p></li><li><p>S120 Spergel and Paller J ALLERGY CLIN IMMUNOLDECEMBER 2003</p><p>orrheic component clears. In children 1 year of age orolder, nummular lesions (coin-shaped, sharply definedscaling erythematous plaques) might accompany themore typical dry scaling erythematous patches of AD.Nummular lesions tend to be more recalcitrant to topicaltherapy and are frequently secondarily infected.</p><p>The childhood phase of AD might follow the infantilestage without interruption and usually occurs during theperiod from 2 years of age to puberty. Children are lesslikely to have the exudative lesions of infancy and insteadexhibit more lichenified papules and plaques represent-ing more chronic disease. The classic areas of involve-ment in children are the hands, feet, wrists, ankles, andantecubital and popliteal regions (Fig 2). Although local-ization at flexural areas is more common, some childrenshow an inverse pattern with primarily involvement ofextensor areas. Facial involvement, when present, tendsto localize to periorbital and perioral areas, in contrast tothe relative sparing of these facial localizations in theinfantile face. In African American children the lesionsof AD are often more papular (follicular AD). Pruritus isfrequently severe, leading to sleep disturbances. Lym-phadenopathy might be a prominent feature in affectedchildren, reflecting the role of lymph nodes in handlinglocal infection and inflammation.</p><p>The adult phase of AD begins at puberty and fre-quently continues into adulthood. Predominant areas ofinvolvement include the flexural folds, the face andneck, the upper arms and back, and the dorsa of the</p><p>hands, feet, fingers, and toes. The eruption is character-ized by dry scaling erythematous papules and plaquesand the formation of large lichenified plaques fromlesional chronicity. Weeping, crusting, and exudationmight occur but usually as the result of superimposedstaphylococcal infection.</p><p>Regardless of the phase of AD, postinflammatoryhypopigmentation or hyperpigmentation might be seen,especially in darker skinned children. The pigmentarychanges are transient and are reversible when the under-lying inflammation is controlled; however, 6 months ormore might be required for repigmentation, and sunexposure will accentuate the differences between unin-volved and dyspigmented skin areas. Parents might mis-take the postinflammatory pigment change for scarringand need reassurance. AD is not usually a scarring disor-der, unless secondary infection or deep gouging oflesions occurs. Hyperpigmentation is predominantlynoted at sites of lichenification, because the thickenedepidermis, especially in darker skinned children, accu-mulates epidermal melanin pigment.</p><p>INFECTIONS AND OTHER CLINICALMANIFESTATIONS ASSOCIATED WITH AD</p><p>Several other clinical signs are seen with increasedfrequency in children with AD (Table II), although theymight appear in children without AD as well. Childrenwith AD also have an increased risk of developing cuta-</p><p>FIG 2. Fold areas are typically affected in the childhood phase, particularly antecubital and popliteal areas.</p></li><li><p>J ALLERGY CLIN IMMUNOL</p><p>VOLUME 112, NUMBER 6</p><p>Spergel and Paller S121</p><p>neous Staphylococcus aureus infection and cutaneousdissemination of the viral organisms herpes simplex andmolluscum contagiosum. S aureus can be cultured from93% of dermatitic lesions and 76% of uninvolved (nor-mal-appearing) skin of patients with AD.10,11 Theincreased adherence of S aureus to the epidermal cells ofindividuals with AD12 and a failure to produce endoge-nous antimicrobial peptides in the inflamed skin ofpatients with AD13 might account for the high rate of Saureus and infection. The pyoderma associated with ADis usually manifested by erythema with exudation andcrusting and occasionally by small pustules in theadvancing edge (Fig 3). This complication must be con-sidered whenever a flare of chronic AD develops or failsto respond to appropriate therapy. S aureus exacerbatesthe AD, because S aureus itself is a trigger for AD withheightened IgE and T-cell responses to staphylococcalantigens and superantigens.14 The higher risk of cuta-neous spread of molluscum and herpetic lesions has beenattributed to defects in TH1 cytokine generation and cyto-toxic T-cell function. Molluscum, a common cutaneousviral infection, usually affects the trunk, axillae, antecu-bital and popliteal fossae, and crural areas, manifestingas small, dome-shaped papules that often show a centralumbilication. The molluscum lesions tend to be most</p><p>numerous at sites of active dermatitis and can induce pru-ritus as well as dermatitis around the molluscum papules.Eczema herpeticum describes the extension of the typicalclustered vesiculopustules of herpes simplex virus in anatopic individual and also tends to involve sites of activedermatitis more readily.</p><p>QUALITY OF LIFE IN ATOPIC DERMATITIS</p><p>Whereas physicians note changes in the clinical signsof AD to gauge severity and response to therapy, patientsand their families are equally concerned about their qual-ity of life. When the dermatitis is active, the quality oflife in infants, children, and adolescents has clearly beenshown to be reduced, particularly in patients with mod-erate and severe disease. The resultant psychologicstress, as well as other stresses such as concurrent infec-tious illness, can clearly provoke AD. Recent studieshave shown that stress can induce immunologic changesin patients with AD, including increases in the levels ofeosinophils, subpopulations of T lymphocytes, and nat-ural killer cells. These increases are not seen in healthycontrol subjects or individuals with psoriasis.15</p><p>By using the Childrens Dermatology Life QualityIndex as a tool to assess the psychosocial effects of cuta-</p><p>FIG 3. Staphylococcal superinfection occurs frequently in children with AD, characterized by exudativepapules and pustules that rapidly crust and erode.</p><p>TABLE II. Clinical features seen with increased frequency in children with AD</p><p>Associated disorder Manifestations</p><p>Keratosis pilaris Follicular-based keratotic papules; lateral aspects of face, extensor aspects of arms, and anterior thighsLichen spinulosus Round collections of numerous, tiny, skin-colored to hypopigmented dry spiny papulesPityriasis alba 1 cm hypopigmented patches, sometimes with fine scale; especially on face, upper armsHyperlinear palms Accentuated markings on the palms and soles; distinguish from ichthyosis vulgarisAtopic pleats Groove of the lower eyelid; often present from infancyAllergic shiners Slate-gray to violaceous infraorbital discoloration with or without swelling</p></li><li><p>S122 Spergel and Paller J ALLERGY CLIN IMMUNOLDECEMBER 2003</p><p>neous disorders in children between the ages of 5 and 16years, AD was second only to scabies among dermato-logic disorders in its adverse effect on quality of life.16 Inparticular, the AD in children led to distress, anxiety,embarrassment, poor self-esteem, and lack of self-confi-dence. The discomfort led to sleep disruptions and areduced functional capacity, including as related to sportsactivities and social relationships. A more recent...</p></li></ul>