Effects of dupilumab treatment on patch test reactions: A retrospective evaluation

Abstract

Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are complex immunological conditions. ACD is a type IV T cell-mediated hypersensitivity reaction that is usually diagnosed through epicutaneous patch testing.1 Although varying reproducibility rates are reported (56%–96%), it is thought that allergy patch testing is reasonably reproducible as long as methodologic inconsistencies are minimized.2, 3 The relation between AD and ACD is complex and multifactorial.4 Factors that might play a role include the potentially shared immunological pathways and the downstream effects of Th2 cytokines.5 Recently, dupilumab, the first biologic for the treatment of AD which inhibits the effects of IL-4 and IL-13, has been approved. Literature about the impact of dupilumab on patch testing is sparse and controversial.6 However, the reliability might be of clinical relevance in patients developing a paradoxical head and neck erythema during dupilumab treatment.7 Distinction of ACD from other causes of the erythema (e.g., dupilumab-induced skin reactions; or Malassezia furfur and Demodex associated dermatitis) in these patients and patients with a general sub-optimal response to dupilumab treatment might be of great clinical interest.7 Here, we report on the reliability of patch testing in dupilumab treated AD patients. We conducted a retrospective cohort study in the Erasmus MC (Rotterdam) and Northwestern Medicine (Chicago). This study was not subjected to evaluation by the local Medical Research Ethics Committees because all data were collected as part of the standard of care. Adult AD patients who had at least 1 positive reaction in a PT conducted before the start of dupilumab treatment, elicited by an allergen that was re-tested during dupilumab treatment (≥12 weeks) were eligible. Detailed results of both PTs including strength of reactions (ICDRG criteria: +++; ++; +;?+; −) had to be available. Patients were treated with dupilumab according to the product label. Patients were excluded if they used systemic glucocorticosteroids or had sun(bed) exposure 2 weeks prior to patch testing; used topical therapy on the test site 48 h prior to testing; or when having eczema on the intended PT area. The use of any other relevant concomitant drugs was recorded. All PTs during dupilumab treatment (second PT), were conducted in our clinics. Allergens that tested positive in the first PT are reported. Details on the allergens and materials that were used can be found in Appendix S1. All tests were interpreted by the same medical team (i.e., ACD-experienced dermatologist and specialized nurses). Possible reactions were read on day 2 and day 3, in accordance with ICDRG recommendations. On day 2, the patches were removed and readings were performed. Patients with patches on their arm could optionally remove the patches themselves. They were asked to mark the patch sites and e-mail standardized photographs directly after removing the patches. On day 3, all patients consulted our dermatologist who determined present reactions. Test results defined as ?+ were considered indeterminate. Patients were informed of the possibility of a delayed reaction and were instructed to make an appointment for day 7 or to (let someone) check the tested sites on day 5–7 and visit our dermatologist the same day in case of (doubtful) signs or symptoms (e.g., itch/burning sensations/erythema/papules/vesicles). Additionally, patients were instructed to continue allergen avoidance during dupilumab treatment, even if all reactions turned negative in the second PT. Patient characteristics of the 20 patients that were included in our study are shown in Table 1. In the first PT, a total of 37 different allergens elicited 56 positive reactions (+ or stronger), with a median number of 2.5 positive reactions per patient (Table 2, Appendix S2). The median time between PTs was 5.5 years. During the first PT, 2 patients were treated with systemic immunosuppressants (patients 2 and 7). In the second PT, a total of 13 different allergens elicited a total of 16 positive reactions in 10 patients, with a median number of 0.5 positive reactions per patient (delayed reactions: n = 1, Appendix S2). These allergens included bacitracin, balsam of peru, carbamix, colophony, fragrance mix I and II, mercaptobenzothiazole, mercapto mix, methyldibromo glutaronitrile, methylisothiazolinone, nickel sulphate hexahydrate, potassium dichromate and sesquiterpene lactone (Appendix S2). The second PT was conducted after a mean of 36 weeks of dupilumab treatment, with 3 patients using concomitant systemic immunosuppressants (patient 4, 7 and 15). During the second PTs, 11 patients had recalcitrant eczematous lesions, mainly located in the head-neck area (Table 1). Table 2 shows that 37 (/56 = 66%) reactions that were initially positive turned negative at re-testing. Twelve of these reactions changed from ++ to −, and 25 reactions showed a change from + to −. More than 75% of the reactio