Negative patch test findings after initiation of upadacitinib: A case report

Abstract

Upadacitinib is a systemic Janus kinase inhibitor currently approved for the treatment of atopic dermatitis. Many patients with atopic dermatitis have a concomitant diagnosis of allergic contact dermatitis. The utility of Janus kinase inhibitors for the treatment of allergic contact dermatitis and the effect on patch testing results remains unclear. We present a case of a woman in her 30s with atopic dermatitis and allergic contact dermatitis who was patch test negative after initiating therapy with upadacitinib.

Introduction

Janus kinase (JAK) inhibitors are small molecule medications that interrupt the JAK-STAT (signal transducer and activator of transcription) signaling pathway which mediates cellular responses involved in inflammation. ¹ Upadacitinib is a selective JAK1 inhibitor approved for treatment of atopic dermatitis (AD). Allergic contact dermatitis (ACD) commonly co-occurs in patients with AD and is a delayed-type IV hypersensitivity reaction with a complex pathophysiology involving activation of T cells and cytokines. ² Given the successful use of JAK inhibitors in the treatment of AD, there is potential that the utility of these medications may also extend to treatment of ACD and have important implications for patch test results given their immunosuppressive effects. ³ Here we present a patient with AD and ACD who was patch tested before starting upadacitinib and during therapy.

Case report

A woman in her 30s was being followed in the dermatology clinic for a longstanding history of severe AD described as ill-defined erythematous patches as well as papulovesicular eruption involving the lateral fingers, palms, dorsal hands, scalp, medial upper eyelids, antecubital fossa, neck, back, retro-, and pre-auricular areas. She worked as a sonographer and her past medical history was significant for asthma and allergic rhinitis. She had failed multiple topical therapies, cyclosporine, and dupilumab. She had previously undergone patch testing in 2014 and was found to be positive for multiple allergens, including rosin 2+, dimethylaminopropylamine amine 2+, methylisothiazolinone 3+, methylchloroisothiazolinone 3+, oleamidopropyl dimethylamine 3+, and glutaraldehyde 3+. She was started on upadacitinib 30 mg daily in April 2022 with significant improvement of her dermatitis. She underwent patch testing again in October 2022. Her upadacitinib was discontinued during testing and she was found to be positive for lanolin 2+, fragrance mix 1 2+, decyl glucosides 2+, limonene 1+, fuyuhun cream 1+, and formaldehyde releasers ± diazolidinyl urea, imidazolidinyl urea, DMDM hydantoin. Interpretation of these patch test results was difficult as she was flaring from an AD perspective. She was referred for repeat patch testing again in September 2023 while on upadacitinib therapy and tested to the North American Contact Dermatitis Group standard series, new extended cosmetic series, and steroid series. Patch test findings were negative at 48 and 96 h.

Discussion

Use of upadacitinib in patients with ACD is currently off-label and the effects of systemic JAK inhibitors on the treatment of ACD as well as patch test results have not been well-documented to date. Generally, it has been recommended to avoid patch testing in patients receiving immunosuppressive medications due to concerns over the validity of patch test results. A recent systematic review found that dupilumab, cyclosporine, low-dose prednisone for dermatitis, tumor necrosis factor α inhibitors, ustekinumab, and methotrexate for psoriasis, were associated with positive patch test results for various allergens, suggesting that patients were still able to mount an acute allergic response despite these immunosuppressive therapies. ⁴

While there have been several case reports describing the improvement of ACD with JAK inhibitors,^5–7 to our knowledge, there is only one other case report examining JAK inhibitor treatment for ACD and patch testing results while on therapy specifically. ⁸ The authors report a case of a 54-year-old male with severe dermatitis, but no history of AD, who was patch test positive to multiple allergens. After initiating upadacitinib, the patient had complete clearance of their dermatitis and all positive patch test reactions disappeared except for reactions to lanolin and fucidic acid, which remained strongly positive. Our patient was patch test positive for multiple allergens on two separate occasions. Repeat patch testing while on upadacitinib yielded negative results at both 48 and 96 h, even for allergens that had strong positive reactions on prior testing.

This case highlights the results of patch testing before and post-initiation of upadacitinib therapy, suggesting that systemic JAK inhibitors may impair delayed-type hypersensitivity responses, and thus influence patch test results. At this time, the data remains very limited, and the clinical relevance of dampening effects or complete loss of allergic responses on patch testing is yet to be clarified. Clinicians should therefore assess the risks and benefits of patch testing while on systemic JAK inhibitors on an individual patient basis. Moreover, while the mainstay of the management of ACD is allergen identification and avoidance, this case demonstrates the potential for upadacitinib use in patients with recalcitrant ACD or where strict allergen avoidance may be challenging. Further research is needed to better understand the utility of upadacitinib in the treatment of chronic ACD and to clarify the impact of therapy on patch test results.