Reviews and Feature Articles: Current Perspectives
Allergic and nonallergic forms of atopic diseases,☆☆

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Abstract

Atopic dermatitis, allergic rhinitis, and asthma are atopic diseases that develop on a complex genetic background, the so-called atopic diathesis. Although they target different organs, in most patients they are characterized by the presence of elevated total serum IgE levels. However, a subgroup of atopic patients exhibits normal IgE levels and mechanisms contributing to the so-called “intrinsic” or “nonallergic form” have been the matter of intensive research work in the last years. Because of the rapid advancements in the research field of atopic diseases, it now becomes possible for the first time to delineate a new disease classification of allergic and nonallergic subtypes of atopic diseases, thereby bringing hope to the clinician for a more specific treatment approach for each subgroup of these patients. (J Allergy Clin Immunol 2003;112:252-62.)

Section snippets

The role of IgE

Since Prausnitz and Kustner described the existence of a human serum factor that reacts with allergens in 1921, much effort has been made to characterize the effector molecule of immunologic hypersensitivity responses in depth.6 Today, we know that the antibody called IgE, which was discovered in 1967 by Ishizaka et al7 is composed of 2 identical heavy and 2 identical light chains. These chains form the variable antigen binding and the constant Fc domain, through which the IgE molecule binds to

Allergic or nonallergic disease?

The term “allergy” was introduced in 1906 by Clemens P. Pirquet, who used it to describe the reactions of protective immunity and hypersensitivity.8 Later there was a tendency to use the word “allergy” to describe all kinds of unpredictable reactions in the skin and the mucosa.9 Today, the term “allergy” is frequently used synonymously with IgE-mediated allergic diseases and will be used in this sense here. However, it has also been observed that serum IgE levels might lie within the normal

Clinical parameters

With regard to the diagnosis of atopic dermatitis (AD), numerous scoring strategies and diagnostic criteria have been developed. The criteria of Diepgen et al,12 Hanifin,13 the United Kingdom Working Party's Diagnostic Criteria for Atopic Dermatitis,14 and the Millennium Criteria for the Diagnosis of Atopic Dermatitis15 are most often used. In the definition of Hanifin, an elevated serum IgE level is not essential for diagnosis, and it can be defined by a syndrome of skin lesions, which are not

Clinical parameters

In general, asthma can be subdivided into 3 forms: the extrinsic/allergic asthma, which is clearly caused by an allergen, the intrinsic/nonallergic asthma, which is not linked to such an allergen, and the mixed form. It is well accepted that in all 3 variants local phenomena occurring in the mucosal tissue, such as bronchoconstriction of the smooth muscles as a consequence of local or systemic inflammation of the airways, are the central pathophysiologic mechanisms of asthma.

The sensitivity of

Clinical parameters

Seasonal or perennial allergic rhinitis, which has an overall prevalence of 9% to 42%,78 arises in atopic individuals with an increased tendency to generate IgE antibodies against common environmental allergens, such as ragweed, pollen, or house dust mite. This form is characterized by mucosal infiltration and activity of plasma cells, mast cells, and eosinophils.78, 79 Typically, positive skin prick test reactions toward aeroallergens can be observed in these patients (Table III).

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Conclusion

The genetic, humoral, and cellular differences between patients with allergic and nonallergic forms of atopic diseases mirror a complex network of distinct properties, which together determine the outcome of the allergic or nonallergic variants of atopic diseases. As a common feature, local IgE production in the affected tissue and the relevance of allergic and nonallergic (infectious) inflammatory processes seem to play a major role in all subtypes of atopic diseases.

Perhaps the most

Acknowledgements

We thank Dr Thomas A. E. Platts-Mills for the critical revision and helpful discussion of the manuscript, Elisabeth Geiger for critically reviewing this manuscript, and Natalie McGauran for editorial support.

References (91)

  • R Valenta et al.

    Molecular characterization of an autoallergen, hom s 1, identified by serum ige from atopic dermatitis patients

    J Invest Dermatol

    (1998)
  • IV Heinisch et al.

    Functional CD137 receptors are expressed by eosinophils from patients with IgE-mediated allergic responses but not by eosinophils from patients with non-IgE-mediated eosinophilic disorders

    J Allergy Clin Immunol

    (2001)
  • B Wedi et al.

    Delayed eosinophil programmed cell death in vitro: a common feature of inhalant allergy and extrinsic and intrinsic atopic dermatitis

    J Allergy Clin Immunol

    (1997)
  • N Novak et al.

    Dichotomic nature of atopic dermatitis reflected by combined analysis of monocyte immunophenotyping and single nucleotide polymorphisms of the interleukin-4/interleukin-13 receptor gene: the dichotomy of extrinsic and intrinsic atopic dermatitis

    J Invest Dermatol

    (2002)
  • T Schafer et al.

    Association between severity of atopic eczema and degree of sensitization to aeroallergens in schoolchildren

    J Allergy Clin Immunol

    (1999)
  • TJ Williams et al.

    Fetal and neonatal IL-13 production during pregnancy and at birth and subsequent development of atopic symptoms

    J Allergy Clin Immunol

    (2000)
  • J Bousquet et al.

    Allergic rhinitis and its impact on asthma

    J Allergy Clin Immunol

    (2001)
  • M Humbert et al.

    The immunopathology of extrinsic (atopic) and intrinsic (non-atopic) asthma: more similarities than differences

    Immunol Today

    (1999)
  • C Bachert et al.

    IgE to Staphylococcus aureus enterotoxins in serum is related to severity of asthma

    J Allergy Clin Immunol

    (2003)
  • PJ Hauk et al.

    Increased T-cell receptor vbeta8+ T cells in bronchoalveolar lavage fluid of subjects with poorly controlled asthma: a potential role for microbial superantigens

    J Allergy Clin Immunol

    (1999)
  • S Ying et al.

    Local expression of epsilon germline gene transcripts and RNA for the epsilon heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma

    J Allergy Clin Immunol

    (2001)
  • JE Gern et al.

    The role of viral infections in the natural history of asthma

    J Allergy Clin Immunol

    (2000)
  • RJ Martin et al.

    A link between chronic asthma and chronic infection

    J Allergy Clin Immunol

    (2001)
  • K Zeibecoglou et al.

    Macrophage subpopulations and macrophage-derived cytokines in sputum of atopic and nonatopic asthmatic subjects and atopic and normal control subjects

    J Allergy Clin Immunol

    (2000)
  • M Kimura et al.

    IL-4 production by PBMCs on stimulation with mite allergen is correlated with the level of serum IgE antibody against mite in children with bronchial asthma

    J Allergy Clin Immunol

    (2000)
  • AT Kotsimbos et al.

    Upregulation of alpha GM-CSF-receptor in nonatopic asthma but not in atopic asthma

    J Allergy Clin Immunol

    (1997)
  • P Christodoulopoulos et al.

    TH2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression

    J Allergy Clin Immunol

    (2001)
  • DP. Skoner

    Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis

    J Allergy Clin Immunol

    (2001)
  • LA Cameron et al.

    Expression of il-4, cepsilon rna, and iepsilon rna in the nasal mucosa of patients with seasonal rhinitis: effect of topical cortico-steroids

    J Allergy Clin Immunol

    (1998)
  • M Kato et al.

    Serum-soluble Fas levels as a marker to distinguish allergic and nonallergic rhinitis

    J Allergy Clin Immunol

    (1999)
  • T Shiomori et al.

    Relationship of nasal carriage of Staphylococcus aureus to pathogenesis of perennial allergic rhinitis

    J Allergy Clin Immunol

    (2000)
  • C Bachert et al.

    Total and specific IgE in nasal polyps is related to local eosinophilic inflammation

    J Allergy Clin Immunol

    (2001)
  • AB. Kay

    Allergy and allergic diseases. First of two parts

    N Engl J Med

    (2001)
  • AB. Kay

    Allergy and allergic diseases. Second of two parts

    N Engl J Med

    (2001)
  • JW Steinke et al.

    Genetics of hypersensitivity

    J Allergy Clin Immunol

    (2003)
  • LB Bacharier et al.

    Regulation of IgE synthesis: the molecular basis and implications for clinical modulation

    Allergy Asthma Proc

    (1999)
  • K Ishizaka et al.

    Allergen-binding activity of gamma-E, gamma-G and gamma-A antibodies in sera from atopic patients. In vitro measurements of reaginic antibody

    J Immunol

    (1967)
  • SC. Bukantz

    Clemens von Pirquet and the concept of allergie

    J Allergy Clin Immunol

    (2002)
  • B. Wuthrich

    What is atopy? Condition, disease or a syndrome?

    Curr Probl Dermatol

    (1999)
  • FM. Rackemann

    Nervous factors in asthma

    Trans Am Clin Climatol Assoc

    (1969)
  • B. Wuthrich

    Atopic dermatitis flare provoked by inhalant allergens

    Dermatologica

    (1989)
  • JM Hanifin et al.

    Diagnostic features of atopic dermatitis

    Acta Derm Venereol

    (1980)
  • HC Williams et al.

    The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis

    Br J Dermatol

    (1994)
  • SG Johansson et al.

    A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force

    Allergy

    (2001)
  • P Schmid-Grendelmeier et al.

    Epidemiology, clinical features, and immunology of the “intrinsic” (non-IgE-mediated) type of atopic dermatitis (constitutional dermatitis)

    Allergy

    (2001)
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    This work has been supported by a grant from the Deutsche Forschungsgemeinschaft DFG FOR 423 and NO454 1-1.

    ☆☆

    Reprint requests: Natalija Novak, MD, Department of Dermatology, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.

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