Atopiform dermatitis: what's in a name?

The term ‘atopy’ was first coined by Coco and Cooke in 1923 for a condition believed to represent a familial hypersensitivity in the skin and mucus membranes against environmental allergens associated with increased IgE production.1 The term ‘atopic dermatitis’ was suggested by Wise and Sulzberger in 19332 to name a skin condition characterized by intense dryness of the skin, pruritus, chronic erythematous lesions and a relapsing course. The condition‘atopic dermatitis’ (AD), certainly as described by clinicians, has increased in incidence sharply during the 20th century with early studies showing an incidence of 2–3%,3 and recent surveys showing an incidence of 15–20% in a U.K. population,4−6 and rising has high as 31% in one Australian study.7 While there is no doubt that there is a strong genetic propensity to atopy, environmental and lifestyle factors undoubtedly have a bearing on the manifestation of AD.8 Suggested environmental factors include outdoor pollution (sulphur dioxide, nitrogen dioxide, diesel particles) and indoor factors such as house dust mite, pets and deteriorating air quality through poor ventilation.8, 9 The term AD, as used by many researchers, has probably been applied to a heterogeneous group of conditions that display, among other features, typical flexural eczema in the antecubital and popliteal fossae, the neck, wrists and ankles.1 However, when more scientific and quantifiable data are examined, such as the chromosomal linkto11q1310 or allergen-specific IgE,11 these features are not present in all patients with a clinical picture of AD. This led to the concept of two forms of AD: one form associated with sensitization to environmental allergens and increased serum IgE (extrinsic AD) and the other (intrinsic AD), where allergen-specific IgE is absent in some 10–30% of patients who, it may be argued, do not possess the classical atopic diathesis.11 Dichotomies such as this challenge the validity of studies based on a clinical picture of flexural dermatitis alone12, 13 and raise the importance of developing robust guidelines for the diagnosis of AD.14 In order to carry out valid and repeatable epidemiological studies, attempts have long been made to define AD and have provided sound diagnostic criteria that can be universally applied. By far the best known, and hitherto most applied diagnostic criteria for AD, was established by Hanifin and Rajka. These clinically based criteria were developed and published in 1980 and have remained the gold standard for diagnosis of AD in most scientific studies since.15 These criteria represented a milestone in describing the clinical entity of ADand ensured a degree of comparability of individuals in subsequent studies. Little validation of these criteria was carried out, especially in community-based studies16 where they have been considered to becumbersome, and they were not particularly designed specifically for children.17 While updated versions of the original Hanifin and Rajka criteria have been produced,17 they have remained difficult to apply in population-based studies.16 Further refinement and modification came from the work of Diepgen et al.,18 who applied statistical analysis to derive a scoring system that seemed to demonstrate good discrimination between cases of AD and controls in a hospitalpopulation, but specificity dropped in community-based studies. Despite this, the authors were able to devise a questionnaire, based on their scoring system, which examined the prevalence of AD in Northern Europe.19 However, again this modification did not discriminate between extrinsic and intrinsic AD.8, 10,11 A further attempt to refine the criteria was initiated by a U.K. Working Party that developed diagnostic criteria that were simple to apply, appeared repeatable,14, 20,21 and that had been validated in the U.K. hospital14 and community settings22 as well as in Asian23 and Romanian communities.24 Given the advances made in the definition of AD in thelast few decades, it would seem easy to become complacent and not wish further to refine the diagnostic criteria for AD in the light of new scientific evidence, such as our knowledge about the genetics and immunopathogenesis and the treatment of AD with immunomodulatory therapies, either in routine clinical use or under development. It was recent developments inthe immunology of atopy that lead Bos et al.25 to suggest that the production of allergen-specific IgE should become a mandatory criterion for the diagnosis of AD. Bos et al. proposed that in addition to the mandatory presence of allergen-specific IgE, two of the three principal criteria from Hanifin and Rajka should be present to make an irrefutable diagnosis of AD.25 In this edition of the journal, Professor Bos takes this a step further and proposes the name ‘atopiform dermatitis’ to describe patients who have the clinical features of AD, but by virtue of lacking detectable allergen-specific IgE, he contests that they are different from those patients who do.26 He suggests, for example, that we should use the term ‘atopiform dermatitis’ for the skin disorder seen in conditions such as Wiskott–Aldrich syndrome, Netherton's syndrome and Job's syndrome, where a clinical picture of AD may be present, but where allergen-specific IgE is absent. In an invited response to these proposals, Hanifin suggests that patients who have a limited or absent capacity to produce IgE may simply have a different genotype. He is comfortable that they be subcategorized for analysis, but suggests that they remain an important subgroup of AD itself.27 He argues that a weakly positive skin prick test or RAST may have littlesignificance, and that it would be difficult to draw the line between true atopy and the proposed atopiform dermatitis on the basis of these tests alone. Hanifin also points out that there is, as yet, no convincing cost-effective benefit accruing from allergen avoidance and points to the development of further molecular and genetic markers that may further help to define atopic dermatitis. It seems certain that the definition of AD will further evolve with the passage of time, but the editors hope that publishing these articles ‘side-by-side’ will stimulate debate.