BH02 (P100) Critically appraised topic: is dupilumab a cause or a treatment for alopecia areata? A case series and literature review to guide discussions in clinical practice
Authors: Alramthan Anwar , Kreeshan Firas , Hunter Hamish , Harries Matthew , Asfour Leila 
Published: June 2024

Abstract
Dupilumab is licensed in adult and paediatric patients with atopic dermatitis (AD). A suggested temporal association between dupilumab and alopecia areata (AA) exists. However, there is evidence to suggest improvement of pre-existing AA with dupilumab. Although AA has been classified as a T helper (Th)1-driven process, findings of genomic susceptibility loci and cytokine activation support Th2 pathway involvement. It is hypothesized that dupilumab downregulates the Th2 pathway, which may amplify the Th1 pathway and promote AA. However, concurrent AD confers an increased risk of AA. We present a case series of AA during dupilumab treatment and review the literature in a critically appraised topic. Out of 156 patients receiving dupilumab in our department, we identified five cases of AA, including three male and two female patients with a mean age of 25.8 years. The mean duration of dupilumab exposure to AA development was 15.5 weeks. One patient discontinued dupilumab. The others showed regrowth while on dupilumab. A literature search was performed on 1 January 2024. Our methodology followed the critically appraised topic recommendations of Callander et al. (Callander J, Anstey AV, Ingram JR et al. How to write a Critically Appraised Topic: evidence to underpin routine clinical practice. Br J Dermatol 2017; 177: 1007–13). The risk of bias was assessed based on the EQUATOR website. In total 103 papers were identified, with 42 excluded. The 61 papers included 48 case reports, six case series, two randomized controlled trials, one VigiBase review, one meta-analysis, one case–control study, one retrospective cohort study and a postmarket review. From the literature, AA after dupilumab initiation was reported in 20 adult patients, and dupilumab-induced reactivation or worsening of AA was seen in six. Certain new-onset cases of AA demonstrated histological features atypical of AA, including parakeratosis or sebaceous gland atrophy. Most patients with new-onset alopecia regrew their hair while still on dupilumab therapy (13 of 20), as seen in our patients with AA therapies. Fifty-six patients with AA in real-world studies, who had hair regrowth after dupilumab, had previous treatment-resistant AA. A phase II study reviewing use of dupilumab in AA suggested a response correlation to IgE levels. However, this has not been reproduced in other reports. There are no paediatric reports of dupilumab-induced new-onset AA. One case of AA recurring with dupilumab initiation was reported, which resolved while on dupilumab. Sixteen children with pre-existing AA regrew hair while on dupilumab. Although reports suggested a male predominance in developing dupilumab-induced AA, a large pharmacovigilance dupilumab database highlighted a female preponderance. In total there were 44 cases of AA detected. The ‘paradoxical effect’ of dupilumab on AA has been widely discussed in the literature and with patients. Our results demonstrate the limited number of these cases reported. We ponder whether cases are under-reported or poorly characterized or if there is a weak association? Reassuringly, hair regrowth is seen despite dupilumab continuation.