Alopecia Areata Related Paradoxical Reactions in Patients on Dupilumab Therapy: A Systematic Review

Dupilumab is the first targeted biologic approved for the treatment of moderate-to-severe atopic dermatitis (AD). ¹ Despite its safe efficacy profile, recent studies have reported both worsening and improvement in alopecia areata in patients receiving dupilumab. ² To further explore these paradoxical findings, we conducted a systematic review to summarize alopecia areata (AA) related outcomes after initiating dupilumab.

EMBASE and MEDLINE searches were conducted on June 23, 2020, using PRISMA guidelines. Overall, 14 studies highlighted AA related complications, while 10 studies reported AA improvement after initiating dupilumab for AD (Supplemental Table S3 and Figure S1).

Alopecia Areata Complications

A total of 17 patients (mean age: 34.1 years), who were predominantly male (70.6%, n = 12/17), reported new onset (82.4%, n = 14/17), reactivation (11.8%, n = 2/17) and exacerbation (5.9%, n = 1/17) of AA after dupilumab use (Supplemental Table S1). The mean latency period between dupilumab initiation and AA complications was 17.6 weeks. Complete resolution (CR) of AA was achieved in 41.2% of cases (n = 7/17), while 35.3% (n = 6/17) experienced partial resolution (PR) within 14.0 weeks. Of the 7 CR cases, 3 were after dupilumab discontinuation and no treatment, 2 after dupilumab discontinuation and treatment, and 2 after treatment while remaining on dupilumab. Of the 6 PR cases, 2 discontinued dupilumab and all cases received AA specific treatments (Supplemental Table S1). It has been hypothesized that Th2 inhibition induced by dupilumab may amplify alternative immune pathways, such as Th1 or Th17, that are implicated in AA adverse outcomes. ^3,4 Additionally, increased prevalence of atopic diseases, such as allergic rhinitis and atopic dermatitis, are documented in patients with alopecia areata, suggesting a common pathway. ² However, these pathways warrant further investigation.

Alopecia Areata Improvements

Eleven patients (mean age: 35.0 years), who were predominantly male (n = 6), reported hair regrowth after dupilumab use within the mean duration of 2.3 months (Supplemental Table S2). CR and PR of AA was reported in 36.4% (n = 4/11) and 63.6% (n = 7/11) of patients, respectively, after receiving dupilumab for AD. The mean resolution period for CR and PR of AA was 15 weeks and 6.3 weeks, respectively. It has been hypothesized that IL-4 results in the production of inflammatory mediators (ie, IgE, mast cells, and eosinophils) implicated in both AA and AD. ⁵ Dupilumab, by inhibiting IL-4 and IL-13, dampens the downstream effect of these inflammatory mediators, potentially leading to concomitant improvement in AA and AD. ⁵

Limitations include small sample size and predominantly male study population (64.3%), making it difficult to generalize findings. However, the sex-based variance in the activity and distribution of CD4 +T cells may contribute to the greater incidence of alopecia in males. ² Additionally, a temporal relationship between dupilumab use and AA does not ensure causality (mean Naranjo—4 [probable]). Genetics, comorbidities, physical, and emotional stress can be associated with AA. ^2,5 Also, the phase-3 trials of dupilumab did not mention alopecia as a significant side effect. ¹ Lastly, the severity of AD was not reported in some studies. Although we have highlighted the paradoxical effect of dupilumab use and AA, further studies are required to better understand this phenomenon.

Supplemental Material

Supplementary Material 1 - Supplemental material for Alopecia Areata Related Paradoxical Reactions in Patients on Dupilumab Therapy: A Systematic Review

Supplemental material, Supplementary Material 1, for Alopecia Areata Related Paradoxical Reactions in Patients on Dupilumab Therapy: A Systematic Review by Muskaan Sachdeva, Adrian Witol, Asfandyar Mufti, Khalad Maliyar and Jensen Yeung in Journal of Cutaneous Medicine and Surgery