Sequential patch testing in a patient treated with dupilumab then with upadacitinib: Differences in patch test results as well as in disease control

When allergen avoidance is not feasible, treatment options for allergic contact dermatitis (ACD) include topical and systemic corticosteroids, phototherapy, systemic immunosuppressants and immunomodulators.1 Positive reactions to patch testing can be maintained on dupilumab.2 The effects of systemic JAK inhibitors on treatment of ACD and results of patch testing are still uncertain. A 54-year-old male working as an industrial mechanic in a pulp and paper industry presented at the ACD clinic for patch testing. Medical history included severe dermatitis with vesiculobullous lesions of the hands and feet, prurigo-like lesions, and leg ulcers since 2016. He had no history of atopic dermatitis. Treatment with topical and systemic corticosteroids (up to 1.5 mg/kg/day for 6 months) as well as with cyclosporine (4 mg/kg/day for 8 months) were ineffective. Patient was started on dupilumab in January 2020, with partial improvement of dermatitis but with persistent leg ulcers. Baseline clinical parameters were as follows: DLQI = 24, EASI = 16.9 and BSA = 20%. Patch testing with the North American standard series, cosmetic, corticosteroid and medicament series (Chemotechnique) was performed under dupilumab. A diagnosis of ACD was made with polysensitization to multiple allergens found to have clinical relevance (Table 1; Figure 1A). The patient's severe dermatitis persisted despite dupilumab therapy and attempts to avoid contact allergens. Dupilumab was stopped 1 year after its initiation due to inefficacy. Topical treatments containing allergens were discontinued but complete avoidance of shoe and rubber allergens was difficult. The patient was then started on upadacitinib 15 mg/day (DLQI = 17; EASI = 16.2; BSA = 11%), which was increased to 30 mg/day 2 months later. Complete clearance of dermatitis was observed 1 month after increased dosage, without adverse effect. The patient was able to return to work on a full-time basis after being on sick leave related to his skin disease for the past 2 years. Patch testing was repeated with the North American standard series, cosmetic, corticosteroid, rubber and medicament series (Chemotechnique) 4 months after being on upadacitinib at 30 mg/day. Remarkably, all positive patch test reactions disappeared except for reactions to lanolin and fusidic acid which remained strongly positive (Table 1; Figure 1B). Upadacitinib and abrocitinib are selective JAK1 inhibitors approved for the treatment of atopic dermatitis. Their use in the treatment of severe ACD is off-label. To our knowledge, patch testing under JAK inhibitors was never reported previously. Our patient had proven ACD to the ‘core molecule’ of corticosteroids, lanolin, thiuram mix and 4-tert-butylphenolformaldehyde resin. Repeated patch testing under upadacitinib did not exhibit sensitization to corticosteroids, rubber accelerators, nor formaldehyde resin. Interestingly, the weakest reactions (1+) to allergens under dupilumab were also the ones that were not reproducible when patch tested under upadacitinib. Conversely, positive patch testing results with fusidic acid and lanolin were reproduced under upadacitinib. Our case shows that upadacitinib can induce false negative reactions when patch testing selected allergens as well as completely resolve ACD to those allergens, possibly indicating different pathophysiological ways for some allergens. Consequently, we hypothesize that corticosteroids, thiuram and 4-tert-butylphenol formaldehyde resin allergy to be mediated via the JAK pathway, while lanolin and fusidic acid allergy to be mediated via another pathway. These findings bring possible clinical insights and relevance to prior laboratory findings that showed biomarkers to differ in ACD versus irritant contact dermatitis, as well as between different allergens.3 Moreover, upadacitinib could be considered in the treatment of severe recalcitrant ACD when complete avoidance of some allergens, including corticosteroids, thiurams and 4-tert-butylphenol formaldehyde resin, is not possible. Laurence Mainville has no conflict of interest to declare. Marie-Claude Houle received speaker's fees from Sanofi. Hélène Veillette received speaker's fees from AbbVie, Janssen, Novartis, Sanofi Genzyme, Bausch Health and Sun Pharma. She worked on advisory committees (Novartis, Sandoz, Pfizer, Sanofi Genzyme, Sun Pharma and UCB), and contributed to clinical trials (Sanofi, GlaxoSmithKline, Bellus Health, AnaptysBio, Boehringer-Ingelheim, Abbvie and Moderna). Informed written consent was obtained regarding included images.

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