From the Cosmetics’ Perspective: Can We Trust Current Criteria to Diagnose Atopic Dermatitis?

Why do some people with atopic dermatitis (AD) experience intolerance or even allergies to skin care products or cosmetics, while others who struggle with extensive atopic diseases, including dermatitis, asthma and rhinoconjuctivitis, seem to tolerate them?

Continuing the discussion on AD that began with a look at research about and causes of it (Cosmetics & Toiletries February 2015), we will study the definition AD and examine existing diagnostic criteria. Earlier investigations into possible pathophysiologies in atopy and AD will be revisited as we explore current procedures to investigate AD features to provide a sounder basis to quantify AD diagnostic criteria, because history and recent research has shown it is much more than a qualitative "atopy—yes or no?"

AD Criteria

Recently, Simpson et al.¹ examined the definition of AD used in new cases of diseases in 102 studies of primary prevention of AD; 27 (27%) did not describe criteria for defining such incident cases. Hanifin and Rajka criteria² were used in 28 (27%), whereas a disease definition unique to the particular study was used in 21 (21%). While these data clearly demonstrate the discrepancy of the diagnostic criteria used to study AD, history and clinical experience has emphasized that the complexity of AD is much more than just “atopy—yes or no?”

Hanifin and Rajka are pioneers of the first widely used diagnostic AD criteria, created in 1980.² The criteria, developed empirically according to practical experience, and suggested from various individuals and discussions during a symposium, comprise 27 features, both subjective and objective.

Hanifin and Rajka’s work is considered important—it was the 11th most cited article in dermatologic literature from 1945 to 1990.³ By June 2014, their work had more than 800 citations, according to Web of Science. More research groups have, over time, modified the criteria by reducing the number of features.

Considerable other work has been done on the subject through the years. The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire⁴ from 1994 was designed to conduct multicenter epidemiology research of asthma and allergic diseases and has the second most citations at 1,517. The well-conducted and extensive U.K. criteria,⁵ with the third-most citations at 418, was also designed to gather larger epidemiological studies and are the most-validated,⁶ with 19 validation studies, though with large variations in sensitivities (10-100%) and specificities (89-99%). Table 1 provides an overview of these diagnostic criteria, along with the development method.

These most widely used criteria consist of several features or questions, of which the atopic patient must satisfy to have AD. They must all be considered as qualitative criteria as they aim to diagnose the AD patient.

Quantitative Criteria and Studies

The 1996 criteria by Diepgen et al.⁷ are an exception to the other criteria. As also seen in earlier studies from Diepgen’s own study group and Svensson et al.,^{8, 9} they performed case/control studies of AD patients. Controls were based on anamnestic, subjective and objective AD features basically derived from Hanifin and Rajka criteria, along with laboratory tests. Via logistic regression and backward elimination of features, they developed an atopic score system corresponding to the diagnostic importance of features, of which 10 points qualified for a diagnosis of AD. Scores of less than 3 points indicated a diagnosis of AD was unlikely.

In general, Diepgen documented major features defined by the Hanifin and Rajka criteria, like personal or family history of atopic diseases, which were not unique for AD patients compared to the normal population. Minor criteria, including dry skin, itchiness when sweating and intolerance to wool, were frequent AD features. Figure 1, adapted from Diepgen’s 1989 study, shows the distribution of atopic points between AD patients and controls. Distinguishable subgroups were found, even within the atopic group, where the measured antibody IgE levels corresponded statistically to their level of atopic points.

The studies are excellent demonstrations of a score system that facilitates diagnosis of AD quantitatively, relative to severity, defining conditions that are: not AD, possible AD, likely AD and definite AD.

Eyeing the Data with Caution

There are, of course, matters of criticism of the studies, such as comparing AD patients from a hospital setting to the normal population without dermatological diseases. This provides an obviously clearer separation between cases and controls. Another point of discussion is the AD inclusion criterion: recurrent flexural and lichenified eczema. AD patients lacking this symptom were excluded. Patients without AD having flexural eczema were included and the importance of this feature in itself was not studied.

We have, since the Diepgen and Svensson’s era, developed improved tools to quantify many features of AD. Comparing types and severity degree within AD, but also comparing it to other atopic diatheses and dermatoses, including some of the same features as AD, can provide a sounder basis to define an AD case.

Well-performed studies will be a great help in investigating and providing answers to why certain AD subtypes are predisposed to intolerance of skin care products/cosmetics, whereas the remaining experience tolerance—areas we have stunningly little knowledge of.

What defines atopy/AD remains a major matter for the cosmetic/skin care industry, as the dermatologic and cosmetic universe has long considered atopy/AD the underpinning of much of cosmetic intolerances. The atopic patient and the cosmetic industry will benefit by having a clearer identification of atopy, so the framework for mechanistic studies and better tolerated products can be provided. 

References

1. E. L. Simpson, L. E. Keck, J. R. Chalmers, and H. C. Williams, “How should an incident case of atopic dermatitis be defined? A systematic review of primary prevention studies.,”J. Allergy Clin. Immunol., vol. 130, no. 1, pp. 137–44, Jul. 2012.
2. J. Hanifin and G. Rajka, “Diagnostic features of atopic dermatitis,”Acta Derm. Venereol., vol. Suppl 92, pp. 44–7, 1980.
3. D. Dubin, “Citation Classics in Clinical Dermatologic Journals,”Arch. Dermatol., vol. 129, no. 9, p. 1121, Sep. 1993.
4. M. I. Asher, U. Keil, H. R. Anderson, R. Beasley, J. Crane, F. Martinez, E. A. Mitchell, N. Pearce, B. Sibbald, and A. W. Stewart, “International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods.,”Eur. Respir. J., vol. 8, no. 3, pp. 483–91, Mar. 1995.
5. H. C. Williams, P. G. J. Burney, R. J. Hay, C. B. Archer, M. J. Shipley, J. J. A. Hunter, E. A. Bingham, A. Y. Finlay, A. C. Pembroke, R. A. C. Graham-Brown, D. A. Atherton, M. S. Lewis-Jones, C. A. Holden, J. I. Harper, R. H. Champion, T. F. Poyner, J. Launer, and T. J. David, “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., vol. 131, no. 3, pp. 383–396, Sep. 1994.
6. E. E. A. Brenninkmeijer, M. E. Schram, M. M. G. Leeflang, J. D. Bos, and P. I. Spuls, “Diagnostic criteria for atopic dermatitis: a systematic review,”Br. J. …, vol. 158, pp. 754–765, 2008.
7. T. L. Diepgen, W. Sauerbrei, and M. Fartasch, “Development and validation of diagnostic scores for atopic dermatitis incorporating criteria of data quality and practical usefulness,”J. Clin. Epidemiol., vol. 49, no. 9, pp. 1031–1038, Sep. 1996.
8. A. Svensson, B. Edman, and H. Möller, “A diagnostic tool for atopic dermatitis based on clinical criteria.,”Acta Derm. Venereol. Suppl. (Stockh)., vol. 114, pp. 33–40, Jan. 1985.
9. T. L. Diepgen, M. Fartasch, and O. P. Hornstein, “Evaluation and relevance of atopic basic and minor features in patients with atopic dermatitis and in the general population.,”Acta Derm. Venereol. Suppl. (Stockh)., vol. 144, pp. 50–4, Jan. 1989.