Development of Acne/Folliculitis Secondary to Tofacitinib Treatment for Alopecia Areata

Abstract

Several Janus kinase (JAK) inhibitors (JAKIs) have demonstrated efficacy for dermatologie conditions. However, major adverse events have been observed with the use of JAKIs, including JAKI-induced acne1. Some clinical trials, retrospective studies, case series, and case reports have reported acne/folliculitis in patients with alopecia areata (AA) using JAKIs, including tofacitinib, ruxo-litinib, baricitinib, ritlecitinib, and brepocitinib2-4. Tofacitinib was associated with JAKI-associated acne/folliculitis in 7.8% to 69.2% of patients, ruxolitinib in 2.6%, baricitinib in 5.1% to 5.6%, ritlecitinib in 10%, and brepocitinib in 11% (Table 1). However, information on anatomical distribution, time of occurrence, risk factors, and course of treatment was unavailable. Herein, we report the characteristics and treatment outcomes of patients who developed acne/folliculitis secondary to tofacitinib treatment for AA. We retrospectively identified 49 patients who underwent off-label treatment with tofacitinib for AA in our clinic. The patients received 5 mg of tofacitinib once or twice daily. Twenty-four (49.0%) were male and 25 (51.0%) female. The median age of patients was 30 (range, 18 ~ 54 years). The median initial Severity of Alopecia Tool (SALT) score was 100 (range, 5.2~100.0). Acne/folliculitis developed in eight patients (16.3%) after a median of 161 days of treatment (range, 29 ~ 290 days) (Table 2). One (12.5%) of these eight patients had preexisting acne/folliculitis, and the lesions were aggravated after taking tofacitinib; the other seven patients (87.5%) acquired new acne/folliculitis after tofacitinib treatment. Among them, three (37.5%) were male and five (62.5%) were female. The median age and initial SALT score of the patients who developed acne/folliculitis was 26 years (range, 18~31 years) and 96.68 (range 68.4~100.0), respectively. Similarly, patients without acne/folliculitis had a median age of 23 years and an initial SALT score of 100, suggesting that their age or AA severity may have not influenced development of acne/folliculitis. All cases were mild to moderate in severity. One patient (12.5%) did not need treatment, five (62.5%) were treated with topical agents such as clindamycin, benzoyl peroxide, and adapalene, and two (25.0%) required systemic treatment, such as doxycycline. Under these treatments, all patients experienced alleviation of symptoms, and none of the patients discontinued tofacitinib therapy because of acne/folliculitis. One patient (12.5%) with pre-existing acne/folliculitis showed persistent lesions after discontinuation of tofacitinib. Currently, the pathogenesis of JAKI-associated acne/folliculitis remains unknown. A previous study showed that JAK1 and JAK3 were overexpressed in acne lesions, suggesting that JAK signaling could be a novel therapeutic target for patients with acne5. However, this contradicts the current observation of acne/folliculitis development and exacerbations in patients treated with JAKIs. Hair follicle stem cell activation induced by JAKIs or the paradoxical activation of other inflammatory pathways may be involved in this phenomenon. In conclusion, our findings provide the prevalence, timing, clinical presentation, treatment option, and response to tofacitinib-induced acne/folliculitis in patients with AA in a real-world clinical setting. Acne/folliculitis is a relatively common side effect of JAKIs, but it remains underexplored. Larger studies are needed to identify the mechanisms, characteristics, and risk factors as well as their management.