Atopic dermatitis and the atopic march

  • Jonathan M Spergel
    Division of Allergy and Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pa, USA
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  • Amy S Paller
    Reprint requests: Amy S. Paller, MD, Division of Dermatology #107, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614
    Departments of Pediatrics and Dermatology, Children's Memorial Hospital of Chicago, Northwestern University's Feinberg School of Medicine, Chicago, Ill, USA
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  • Author Footnotes
    1 Dr Spergel is a consultant to Novartis and Fujisawa, has received research support/grants from Merck, Novartis, Genetech, Tanox. Dr Spergel is also a member of the speakers' bureau for GlaxoSmithKline, Novartis and Fujisawa.
    2 Dr Paller is a consultant and speaker for Novartis and Fujisawa.


      Atopic dermatitis (AD), one of the most common skin disorders seen in infants and children, usually has its onset during the first 6 months of life. The prevalence of AD is similar in the United States, Europe, and Japan and is increasing, similar to that of other atopic disorders, particularly asthma. AD has been classified into 3 sequential phases: infantile, childhood, and adult, each with characteristic physical findings. AD has a tremendously negative effect on the quality of life of patients as well as family, most commonly disturbing sleep. The condition also creates a great financial burden for both the family and society. The cutaneous manifestations of atopy often represent the beginning of the atopic march. On the basis of several longitudinal studies, approximately half of AD patients will develop asthma, particularly with severe AD, and two thirds will develop allergic rhinitis. Epicutaneous sensitization has been thought to be responsible, with subsequent migration of sensitized T cells into the nose and airways, causing upper and lower airway disease. Animal models and human observation concur with this theory. Preliminary prevention studies with oral antihistamines provide evidence that early intervention might slow the atopic march.



      AD (Atopic dermatitis), BAL (Bronchoalveolar lavage), ETAC (Early Treatment of the Atopic Child), ISAAC (International Study of Asthma and Allergies in Children), MAS (Mulitcenter Atopy Study)
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        • Kay J
        • Gawkrodger DJ
        • Mortimer MJ
        • Jaron AG
        The prevalence of childhood atopic eczema in a general population.
        J Am Acad Dermatol. 1994; 30: 35-39
        • Laughter D
        • Istvan JA
        • Tofte SJ
        • Hanifin JM
        The prevalence of atopic dermatitis in Oregon schoolchildren.
        J Am Acad Dermatol. 2000; 43: 649-655
        • Schultz Larsen F
        • Diepgen T
        • Svensson A
        The occurrence of atopic dermatitis in north Europe: an international questionnaire study.
        J Am Acad Dermatol. 1996; 34: 760-764
        • Sugiura H
        • Umemoto N
        • Deguchi H
        • Murata Y
        • Tanaka K
        • Sawai T
        • et al.
        Prevalence of childhood and adolescent atopic dermatitis in a Japanese population: comparison with the disease frequency examined 20 years ago.
        Acta Derm Venereol. 1998; 78: 293-294
        • Schultz Larsen F
        • Hanifin JM
        Secular change in the occurrence of atopic dermatitis.
        Acta Derm Venereol Suppl (Stockh). 1992; 176: 7-12
        • Eichenfield LF
        • Hanifin JM
        • Beck LA
        • Lemanske Jr, RF
        • Sampson HA
        • Weiss ST
        • et al.
        Atopic dermatitis and asthma: parallels in the evolution of treatment.
        Pediatrics. 2003; 111: 608-616
        • Williams HC
        • Strachan DP
        The natural history of childhood eczema: observations from the British 1958 birth cohort study.
        Br J Dermatol. 1998; 139: 834-839
        • Wuthrich B
        Clinical aspects, epidemiology, and prognosis of atopic dermatitis.
        Ann Allergy Asthma Immunol. 1999; 83: 464-470
        • Hanifin JM
        • Rajka G
        Diagnostic features of atopic dermatitis.
        Acta Derm Venereol. 1980; 92: 44-47
        • Leyden JJ
        • Marples RR
        • Kligman AM
        Staphylococcus aureus in the lesions of atopic dermatitis.
        Br J Dermatol. 1974; 90: 525-530
        • Aly R
        • Maibach HI
        • Shinefield HR
        Microbial flora of atopic dermatitis.
        Arch Dermatol. 1977; 113: 780-782
        • Cole GW
        • Silverberg NL
        The adherence of Staphylococcus aureus to human corneocytes.
        Arch Dermatol. 1986; 122: 166-169
        • Ong PY
        • Ohtake T
        • Brandt C
        • Strickland I
        • Boguniewicz M
        • Ganz T
        • et al.
        Endogenous antimicrobial peptides and skin infections in atopic dermatitis.
        N Engl J Med. 2002; 347: 1151-1160
        • Leung DY
        Atopic dermatitis and the immune system: the role of superantigens and bacteria.
        J Am Acad Dermatol. 2001; 45: S13-S16
        • Schmid-Ott G
        • Jaeger B
        • Adamek C
        • Koch H
        • Lamprecht F
        • Kapp A
        • et al.
        Levels of circulating CD8(+) T lymphocytes, natural killer cells, and eosinophils increase upon acute psychosocial stress in patients with atopic dermatitis.
        J Allergy Clin Immunol. 2001; 107: 171-177
        • Lewis-Jones MS
        • Finlay AY
        The Children's Dermatology Life Quality Index (CDLQI): initial validation and practical use.
        Br J Dermatol. 1995; 132: 942-949
        • Paller AS
        • McAlister RO
        • Doyle JJ
        • Jackson A
        Perceptions of physicians and pediatric patients about atopic dermatitis, its impact, and its treatment.
        Clin Pediatr (Phila). 2002; 41: 323-332
        • Absolon CM
        • Cottrell D
        • Eldridge SM
        • Glover MT
        Psychological disturbance in atopic eczema: the extent of the problem in school-aged children.
        Br J Dermatol. 1997; 137: 241-245
        • Bender BG
        • Leung SB
        • Leung DY
        Actigraphy assessment of sleep disturbance in patients with atopic dermatitis: an objective life quality measure.
        J Allergy Clin Immunol. 2003; 111: 598-602
        • Dahl RE
        • Bernhisel-Broadbent J
        • Scanlon-Holdford S
        • Sampson HA
        • Lupo M
        Sleep disturbances in children with atopic dermatitis.
        Arch Pediatr Adolesc Med. 1995; 149: 856-860
        • Reuveni H
        • Chapnick G
        • Tal A
        • Tarasiuk A
        Sleep fragmentation in children with atopic dermatitis.
        Arch Pediatr Adolesc Med. 1999; 153: 249-253
        • Lewis-Jones MS
        • Finlay AY
        • Dykes PJ
        The Infants' Dermatitis Quality of Life Index.
        Br J Dermatol. 2001; 144: 104-110
        • Daud LR
        • Garralda ME
        • David TJ
        Psychosocial adjustment in preschool children with atopic eczema.
        Arch Dis Child. 1993; 69: 670-676
        • Lapidus CS
        • Honig PJ
        Atopic dermatitis.
        Pediatr Rev. 1994; 15: 327-332
        • Su JC
        • Kemp AS
        • Varigos GA
        • Nolan TM
        Atopic eczema: its impact on the family and financial cost.
        Arch Dis Child. 1997; 76: 159-162
        • Lawson V
        • Lewis-Jones MS
        • Finlay AY
        • Reid P
        • Owens RG
        The family impact of childhood atopic dermatitis: the Dermatitis Family Impact Questionnaire.
        Br J Dermatol. 1998; 138: 107-113
        • Whalley D
        • Huels J
        • McKenna SP
        • Van Assche D
        The benefit of pimecrolimus (Elidel, SDZ ASM 981) on parents' quality of life in the treatment of pediatric atopic dermatitis.
        Pediatrics. 2002; 110: 1133-1136
        • Harper JI
        • Ahmed I
        • Barclay G
        • Lacour M
        • Hoeger P
        • Cork MJ
        • et al.
        Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy.
        Br J Dermatol. 2000; 142: 52-58
        • Pei AY
        • Chan HH
        • Leung TF
        Montelukast in the treatment of children with moderate-to-severe atopic dermatitis: a pilot study.
        Pediatr Allergy Immunol. 2001; 12: 154-158
        • Drake L
        • Prendergast M
        • Maher R
        • Breneman D
        • Korman N
        • Satoi Y
        • et al.
        The impact of tacrolimus ointment on health-related quality of life of adult and pediatric patients with atopic dermatitis.
        J Am Acad Dermatol. 2001; 44: S65-S72
        • Staab D
        • von Rueden U
        • Kehrt R
        • Erhart M
        • Wenninger K
        • Kamtsiuris P
        • et al.
        Evaluation of a parental training program for the management of childhood atopic dermatitis.
        Pediatr Allergy Immunol. 2002; 13: 84-90
        • Lapidus CS
        • Schwarz DF
        • Honig PJ
        Atopic dermatitis in children: who cares? who pays?.
        J Am Acad Dermatol. 1993; 28: 699-703
        • Herd RM
        • Tidman MJ
        • Prescott RJ
        • Hunter JA
        The cost of atopic eczema.
        Br J Dermatol. 1996; 135: 20-23
        • Rhodes HL
        • Sporik R
        • Thomas P
        • Holgate ST
        • Cogswell JJ
        Early life risk factors for adult asthma: a birth cohort study of subjects at risk.
        J Allergy Clin Immunol. 2001; 108: 720-725
        • Rhodes HL
        • Thomas P
        • Sporik R
        • Holgate ST
        • Cogswell JJ
        A birth cohort study of subjects at risk of atopy: twenty-two-year follow-up of wheeze and atopic status.
        Am J Respir Crit Care Med. 2002; 165: 176-180
        • Gustafsson D
        • Sjoberg O
        • Foucard T
        Development of allergies and asthma in infants and young children with atopic dermatitis: a prospective follow-up to 7 years of age.
        Allergy. 2000; 55: 240-245
        • Oettgen HC
        • Geha RS
        IgE regulation and roles in asthma pathogenesis.
        J Allergy Clin Immunol. 2001; 107: 429-440
        • Schafer T
        • Heinrich J
        • Wjst M
        • Adam H
        • Ring J
        • Wichmann H
        Association between severity of atopic eczema and degree of sensitization to aeroallergens in schoolchildren.
        J Allergy Clin Immunol. 1999; 104: 1280-1284
        • Wuthrich B
        Serum IgE in atopic dermatitis: relationship to severity of cutaneous involvement and course of disease as well as coexistence of atopic respiratory diseases.
        Clin Allergy. 1978; 8: 241-248
        • Burrows B
        • Martinez FD
        • Halonen M
        • Barbee RA
        • Cline MG
        Association of asthma with serum IgE levels and skin-test reactivity to allergens.
        N Engl J Med. 1989; 320: 271-277
        • Kulig M
        • Bergmann R
        • Klettke U
        • Wahn V
        • Tacke U
        • Wahn U
        Natural course of sensitization to food and inhalant allergens during the first 6 years of life.
        J Allergy Clin Immunol. 1999; 103: 1173-1179
        • Lau S
        • Nickel R
        • Niggemann B
        • Gruber C
        • Sommerfeld C
        • Illi S
        • et al.
        The development of childhood asthma: lessons from the German Multicentre Allergy Study (MAS).
        Paediatr Respir Rev. 2002; 3: 265-272
        • Ohshima Y
        • Yamada A
        • Hiraoka M
        • Katamura K
        • Ito S
        • Hirao T
        • et al.
        Early sensitization to house dust mite is a major risk factor for subsequent development of bronchial asthma in Japanese infants with atopic dermatitis: results of a 4-year followup study.
        Ann Allergy Asthma Immunol. 2002; 89: 265-270
        • Anonymous
        Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC—The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee.
        Lancet. 1998; 351: 1225-1232
        • Buffum WP
        • Settipane GA
        Prognosis of asthma in childhood.
        Am J Dis Childhood. 1966; 112: 214-217
        • Cookson W
        • Ubhi B
        • Lawrence R
        • Abecasis GR
        • Walley AJ
        • Cox HE
        • et al.
        Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci.
        Nat Genet. 2001; 27: 372-373
        • Beyer K
        • Nickel R
        • Freidhoff L
        • Bjorkstein B
        • Huang SK
        • Barnes KC
        • et al.
        Association and linkage of atopic dermatitis with chromosome 13q12-14 and 5q31-33 markers.
        J Invest Dermatol. 2000; 115: 906-908
        • Dohi M
        • Okudaira H
        • Sugiyama H
        • Tsurumachi K
        • Suko M
        • Nakagawa T
        • et al.
        Bronchial responsiveness to mite allergen in atopic dermatitis without asthma.
        Int Arch Allergy Immunol. 1990; 92: 138-142
        • Lack G
        • Fox D
        • Northstone K
        • Golding J
        • Avon Longitudinal Study of Parents and Children Study Team
        Factors associated with the development of peanut allergy in childhood.
        N Engl J Med. 2003; 348: 977-985
        • Tinkle S
        • Antonini J
        • Rich B
        • Roberts J
        • Salmen R
        • DePree K
        • et al.
        Skin as a route of exposure and sensitization in chronic beryllium disease.
        Environ Health Perspect. 2003; 111: 1202-1208
        • Spergel JM
        • Mizoguchi E
        • Brewer JP
        • Martin TR
        • Bhan AK
        • Geha RS
        Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice.
        J Clin Invest. 1998; 101: 1614-1622
        • Woodward AL
        • Spergel JM
        • Alenius H
        • Mizoguchi E
        • Bhan AK
        • Castigli E
        • et al.
        An obligate role for T-cell receptor alphabeta+ T cells but not T-cell receptor gammadelta+ T cells, B cells, or CD40/CD40L interactions in a mouse model of atopic dermatitis.
        J Allergy Clin Immunol. 2001; 107: 359-366
        • Herrick CA
        • MacLeod H
        • Glusac E
        • Tigelaar RE
        • Bottomly K
        Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4.
        J Clin Invest. 2000; 105: 765-775
        • Herrick CA
        • Bottomly K
        To respond or not to respond: T cells in allergic asthma.
        Nat Rev Immunol. 2003; 3: 405-412
        • Kondo H
        • Ichikawa Y
        • Imokawa G
        Percutaneous sensitization with allergens through barrier-disrupted skin elicits a Th2-dominant cytokine response.
        Eur J Immunol. 1998; 28: 769-779
        • Wollenberg A
        • Kraft S
        • Hanau D
        • Bieber T
        Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema.
        J Invest Dermatol. 1996; 106: 446-453
        • Novak N
        • Kraft S
        • Bieber T
        IgE receptors.
        Curr Opin Immunol. 2001; 2001: 721-726
        • Semper A
        • Heron K
        • Woollard A
        • Kochan J
        • Friedmann P
        • Church M
        • et al.
        Surface expression of FcepsilonRI on Langerhans' cells of clinically uninvolved skin is associated with disease activity in atopic dermatitis, allergic asthma, and rhinitis.
        J Allergy Clin Immunol. 2003; 112: 411-419
        • Aleksza M
        • Lukacs A
        • Antal-Szalmas P
        • Hunyadi J
        • Szegedi A
        Increased frequency of intracellular interleukin (IL)-13 and IL-10, but not IL-4, expressing CD4+ and CD8+ peripheral T cells of patients with atopic dermatitis.
        Br J Dermatol. 2002; 147: 1135-1141
        • Lambrecht B
        • Carro-Muino I
        • Vermaelen K
        • Pauwels R
        Allergen-induced changes in bone-marrow progenitor and airway dendritic cells in sensitized rats.
        Am J Respir Crit Care Med. 1999; 20: 1165-1174
        • Iikura Y
        • Naspitz CK
        • Mikawa H
        • Talaricoficho S
        • Baba M
        • Sole D
        • et al.
        Prevention of asthma by ketotifen in infants with atopic dermatitis.
        Ann Allergy. 1992; 68: 233-236
        • Bustos GJ
        • Bustos D
        • Romero O
        Prevention of asthma with ketotifen in preasthmatic children: a three-year follow-up study.
        Clin Exp Allergy. 1995; 25: 568-573
        • Anonymous
        Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC—Early Treatment of the Atopic Child.
        Pediatr Allergy Immunol. 1998; 9: 116-124
        • Warner JO
        A double-blinded, randomized, placebo-controlled trial of cetirizine in preventing the onset of asthma in children with atopic dermatitis: 18 months' treatment and 18 months' posttreatment follow-up.
        J Allergy Clin Immunol. 2001; 108: 929-937