Atopic Dermatitis, Patch Testing, and House Dust Mites: A Brief Review

Alde Carlo P. Gavino; Glen R. Needham; Whitney A. High

Disclosures

Dermatitis. 2008;19(3):121-128. 

In This Article

Clinical Evidence for the Association of HDMs with AD and for the Utility of Patch Testing

Although the role of HDM allergens in asthma and allergic rhinitis has been studied and largely accepted by those in the field, the involvement of these same allergens in the pathophysiology of AD remains a matter of debate ( Table 2 ). Exacerbation of AD by HDMs was first proposed by Tuft in 1949.[56] Careful environmental analysis in Scotland has demonstrated increased exposure to HDMs among atopic adults[57] and several authors have described dramatic clinical improvement when mite elimination and avoidance strategies were employed.[58–61] In 1982, Mitchell and colleagues showed that purified Der p 1 could induce eczematous lesions when placed on the skin of atopic individuals allergic to HDMs.[62] More recently, Tupker and colleagues demonstrated the worsening and/or development of new plaques of dermatitis in atopic patients exposed to intrabronchial HDM allergens.[63]

Nevertheless, there are significant barriers to the acceptance of a major role for HDMs in AD. For instance, the study by Mitchell and colleagues is flawed in that they abraded skin prior to the application of Der p 1, and biopsy specimens of the lesions contained significant amounts of neutrophils, a finding that is not typical of the histology of eczema. It is therefore unclear whether the skin lesions in this study represented “true eczema” or were instead a result of inflammation (secondary to intensive local stimulation by abrasion). Likewise, the lesions induced in the study by Tupker and colleagues could not be ascertained to be those of AD because biopsies were not performed. Moreover, many of those lesions developed within a few hours after intrabronchial HDM exposure and then immediately resolved. In addition, like many of the aforementioned studies, that of Tupker and colleagues involved a relatively small number of subjects and did not include an appropriate control population. Association also does not necessarily imply causality. For example, increased transepidermal water loss and copious shedding of squamous cells (on which the mites feed) are common in severe AD and may support an enhanced mite population in the bedroom/mattress environment of these patients, independent of a causal relationship.[57,64,65] Still other experts have cited the following as evidence against direct involvement: (1) a lack of improvement of AD symptoms despite aggressive measures to eliminate and/or avoid exposure to HDMs (as demonstrated by at least five randomized controlled clinical studies)[66–70] (2) the failure of a group of AD patients sensitized to HDMs to show a positive patch-test result[54,55] or to develop lesions when challenged topically with Der p[71] and (3) the increased prevalence of AD in dry and northern latitudes, where HDM populations are sparse.[72,73] Moreover, some experts believe that positive patch-test results in AD patients are rarely indicative of a specific allergy to HDMs. Instead, they believe that such a response is an irritant reaction to the proteolytic activity of mite enzymes[74] in the setting of an intrinsically lowered irritancy threshold in AD patients.[75]

Before the advent of standardized HDM preparations for patch testing, and despite the inconclusive evidence linking HDMs to the causation of AD, several investigators performed epicutaneous tests on atopic patients with a variety of mite antigens, with positive results reported for 21 to 72% of patients.[76–78] Interestingly, when patients with an aeroallergen-type distribution (face, neck, hands, feet) were examined separately, a significantly higher percentage of patients had positive results.[79]

Recently, Chemotechnique Diagnostics (Malmö, Sweden) began the commercial marketing of a standardized HDM allergen mixture (Der p and Der f in a 50:50 mix) in petrolatum in concentrations of 20% and 30%.[80] Several investigators have since conducted studies to determine the optimal concentration of this allergen mix and the rate of positivity among atopic patients who are patch-tested with it. Jamora and colleagues[81] found the 20% formulation to have a very high false-positive rate (83%) as it elicited many decrescendo or persistent reaction patterns characteristic of irritant substances. However, when diluted to 0.1%, the allergen mix more appropriately differentiated rates of positivity among healthy controls, respiratory atopic patients, and those with AD. Davis and colleagues[82] performed a similar study and also found the 20% formulation to have a very high rate of positivity (55%). With the 0.1% concentration, a much lower rate of reaction was seen (6.8%), but it was still high when compared with the reaction rates of other allergens included in their study. Interestingly, the researchers did not find this reaction rate to be higher in atopic subjects than in healthy controls.

This latter finding was echoed by Brasch and colleagues[83] who reported that of 571 patients patch-tested with the HDM allergen mix in Germany, 188 had positive reactions that were deemed irrelevant; specifically, there was no association between positive patch-test reactions to mite allergens and an atopic diathesis. However, in this particular series, those reacting to HDM allergens were statistically more likely to have additional positive reactions to other allergens, suggesting that unidentified factors that contribute to positive reactions to HDM allergen may also predict enhanced generalized responsiveness to other substances.

Despite these contradictory findings, other investigators believe adamantly that HDM patch testing has an important place in the management of AD patients. In a study population consisting of AD patients in remission, patch testing more specifically correlated with a history of HDM-induced eczema flares reported by these patients than did skin-prick testing or specific serum IgE measurement.[84,85] Furthermore, it has been shown that patch testing, compared to skin-prick testing, has an apparent ability to identify relevant mite sensitization in AD patients in the absence of specific serum IgE.[86]

The value of HDM patch testing in the management of AD is also supported by accumulating evidence suggesting that specific immunotherapy (SIT) against HDM sensitization is an effective curative therapy against atopic diseases.[87] SIT involves subcutaneously or sublingually administered incremental doses of allergen extracts to which an individual is sensitized. Studies have shown that SIT results in improved clinical severity of AD[88–91] and reduction of specific IgE levels against HDM allergens[89–91] with concomitant increases in the serum levels of the Th1 cytokine IFN-γ[89] and the tolerogenic cytokine IL-10.[89,91] As promising as they might seem, these studies are flawed in that they were not controlled with a placebo group. Hence, the above data are of limited value and are not powerful enough to justify the routine use of SIT in the management of AD.

Like all patch-testing results, the relevance of positive reactions to HDM allergens must be determined, and this issue is far from being settled. Many studies from different investigators hailing from disparate parts of the world have reported conflicting data. With the availability of the standardized allergen mix and a now standardized patch-test technique developed by the European Task Force on Atopic Dermatitis[84] scientists from different parts of the world may employ uniform materials and reproducible methodologies in their studies. There is no question that additional investigation into the relevance of positive patch-test reactions to mite allergens is needed to move beyond anecdotal evidence in regard to the role of HDMs in the pathogenesis of AD and the utility of allergen avoidance and other novel therapeutic strategies like allergen-specific immunotherapy in improving AD.

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