Allergic Contact Dermatitis: Treatment With Dupilumab and Concurrent Patch Testing

Atopic dermatitis (AD) is a multifactorial disease of cutaneous xerosis, often the result of mutations in structural elements of the skin such as filaggrin, cutaneous microbial dysbiosis, and immune dysregulation, which skews toward T helper 2 (T_H2). Together, these result in cutaneous infl ammation, itch, and eczematous rash. Specifically in the inflammatory pathway, the ligands IL-4 and IL-13 act through the IL-4/IL-13/IL-4R axis to stimulate T_H2, leading to inflammation. Dupilumab is a human monoclonal antibody against the IL-4 receptor that acts to diminish this proinflammatory pathway. It is approved for the treatment of moderate to severe AD in patients aged 6 months and up.¹

Allergic contact dermatitis (ACD) is a type IV hypersensitivity reaction that results in a cutaneous eczematous eruption after cutaneous contact to an allergen to which one has been sensitized. Unlike AD, ACD is thought to be mediated largely through the T_H1 pathway, with some interaction with the T_H2, T_H17, and T_H22 pathways.^2-5 Common allergens include certain plants, fragrances, surfactants, rubber, preservatives, and metals. Patch testing is the gold standard diagnostic test for the identifi cation of allergens causing ACD. Ideal therapeutic management of ACD is full avoidance of identified allergens.⁶ Topical and systemic steroids, as well as nonsteroidal immunosuppressants, such as methotrexate, cyclosporine, and mycophenolate mofetil, can also help in managing dermatitis.

Dupilumab has been reported as beneficial in the treatment of ACD and noninterfering with the process of patch testing. Both cannot be true. In this article, we investigate the use of dupilumab in the context of ACD and patch testing.

Dupilumab and ACD

How is it that dupilumab, which interrupts the T_H2-mediated pathway, can treat ACD, a predominantly T_H1-mediated disease? The current thinking is that ACD may not be strictly T_H2-mediated and the degree to which an allergen stimulates one immune branch or the other differs based on the allergen itself. For example, different allergens stimulate T_H2 or T_H1 to varying levels. Fragrance and rubber are primarily T_H2-mediated, whereas nickel is primarily T_H1-mediated.⁷ Patients with more T_H2-skewed allergies may be more likely to achieve clearance with dupilumab than those with a T_H1-oriented allergy.⁷

ACD can clear with the use of dupilumab.^8-10,11 Dermatitis in 15 patients improved 85% on average with dupilumab use; however, repeat patch testing was not performed, which would be the true determinant of ACD resolution.¹² Similarly, ACD patient cohorts of 32 and 3 improved with dupilumab; however, many of the patients had ACD with concurrent AD.^9,13 And although ACD can improve with dupilumab, results are inconsistent.^10,13

Dupilumab and Patch Testing

Numerous studies have assessed the effect of dupilumab on patch tests.^9,10,14-16 Of 125 patch testing sets before and during dupilumab use, 13 reactions were lost (10.4%),⁹ including fragrances (balsam of Peru and fragrance mix 1), metals (vanadium [III] chloride and phenylmercuric acetate), select preservatives, topical medicaments, surfactants/emulsifiers (propylene glycol 10% and 100%, amerchol, and dimethylaminopropylamine), sunscreens (sulisobenzene and phenylbenzimidazole-5-sulfonic acid), and resins (tosylamide formaldehyde). No specific allergen was blocked by dupilumab. Conversely, out of 56 positive reactions before dupilumab use, only 16 (29%) could be replicated during dupilumab use, and 66% of initial positive reactions were lost once dupilumab treatment was initiated.¹⁰

The effect of dupilumab on patch tests appears inconsistent.^14,16 In a systematic review of 28 patients with 144 pre- and duringdupilumab treatment patch testing pairs, 17 of the pairs were lost, 71 were replicated, and 8 were newly positive.¹⁶

Reservations and Recommendations

This topic has been, and will remain, hotly debated as the field awaits the result of an ongoing clinical trial investigating dupilumab’s impact on ACD (ClinicalTrials.gov identifier NCT03935971).^17-21 Although patch testing on dupilumab may not affect all reactions, the effect may depend on the offending allergen and patient milieu. There is sufficient dampening and potentially the complete loss of reactions that warrant caution. This risk of erroneous testing is problematic when we recognize that many patients with AD have concomitant ACD, where the best treatment for the latter is allergen identification and avoidance. ^22,23 One could imagine a scenario in which a patient is appearing to fail dupilumab, is sent for patch testing, and the results are falsely negative. Thus, best practice is to perform patch testing before the initiation of dupilumab to minimize any risk of pharmacologic suppression. For patients who have already been on the medication, the amount of time needed to be off it before patch testing can be performed is not known but is likely somewhere around 5 half-lives (roughly 12 weeks).^24,25

Overall, it is reassuring that dupilumab does not appear to make ACD worse, as might be expected if the immune balance was shifted between T_H2 and T_H1. In many cases, improvement can be observed. Nevertheless, dupilumab does not appear to be a silver bullet for ACD or a substitute for allergen avoidance.

In Minneapolis, MN, Morgan Dykman is a third-year medical student at the University of Minnesota Medical School and Dr Hylwa is a faculty physician in the department of dermatology at Hennepin Healthcare and Park Nicollet Contact Dermatitis Clinic and an assistant professor at the University of Minnesota.

Disclosure: Dr Hylwa is a paid lecturer for SmartPractice. The authors report no other relevant financial relationships.

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