Alopecia areata (AA) is an immune-mediated, nonscarring alopecia that affects approximately 2% of the general population and can occur in both children and adults, with varying severity among individuals.1 It is associated with a negative impact on quality of life.2

Genetic and immunologic factors contribute to the development of AA. Key mediators include IFN-γ, IL-15, and IL-2, which promote CD8+ T-cell proliferation around the hair follicle bulb, loss of hair follicle immune privilege, and overexpression of major histocompatibility complex (MHC) class I, ultimately leading to hair follicle dystrophy.1,3

Antihistamines have been proposed as unconventional therapies in AA due to their ability to decrease the production of IFN-γ by T cells and proinflammatory cytokines, including IL-4 and IL-5, as well as the expression of ICAM-1 on epithelial cells.4

We conducted a systematic review of the safety and efficacy profile of antihistamines for alopecia areata or androgenetic alopecia according to our published protocol (PROSPERO CRD420251063593). Searches were performed on July 3, 2025, in PubMed, Embase, the Cochrane Skin Group Specialized Register, and the Cochrane Central Register of Controlled Trials, with no language restrictions. A total of 637 records were identified; 132 duplicates were removed, resulting in 505 articles. Two reviewers (NG, SM) independently screened abstracts of all retrieved studies in Covidence for inclusion, followed by full-text screening. Disagreements were resolved by a third reviewer (CS). Studies were grouped according to alopecia type (AA or androgenetic alopecia). A total of 3 studies met the inclusion criteria for antihistamines in AA.5–7Table 1 summarizes the study characteristics.

All studies included both children and adults, with mean ages of 30, 32, and 44 years, and included both male and female participants,5–7 with a higher proportion of females in 2 studies.5,7 In the study by Iraji et al., the proportions of females and males were similar.6 The most frequent comorbidity was atopy, present in 54.5% of patients in the study by Inui et al.5 and in 12.5% of patients in the other two studies.6,7

The severity of AA varied across studies. The study by Iraji et al. included only patchy alopecia (≤3 patches on the scalp or beard measuring ≤3×3cm).6 The study by Lee et al. reported that most patients (91.7%) had a Severity of Alopecia Tool (SALT) score of 0–30.7 The study by Inui et al. included only patients with ≥50% scalp involvement.5

All 3 studies assessed oral antihistamines in combination with other therapies.5–7 In 2 studies, oral antihistamines (desloratadine in the study by Iraji et al. and fexofenadine or ebastine in the study by Lee et al.) were administered with topical corticosteroids and cryotherapy.6,7 In the remaining study, fexofenadine was administered with contact immunotherapy.5 Intervention and control groups are described in Table 1.

Oral antihistamines combined with topical corticosteroids and superficial cryotherapy showed mixed efficacy results. In the study by Lee et al., the group receiving antihistamines demonstrated significantly greater major hair regrowth compared with controls (P=.045).7 In contrast, in the study by Iraji et al., although there was an increase in terminal hair regrowth and patient satisfaction scores with each additional therapy, no significant differences were observed between groups.6

In the study by Inui et al., fexofenadine was associated with significantly improved regrowth in patients with atopic AA, whereas no significant difference was observed in nonatopic AA. This suggests that fexofenadine may enhance the therapeutic effect of contact immunotherapy in patients with an atopic background.5

Overall, antihistamines were well tolerated. No adverse events led to treatment discontinuation.6,7 In the clinical trial, 31.25% of patients in the antihistamine group experienced side effects (12.5% transient erythema and 18.75% pain with transient erythema); however, there was no significant difference vs the topical corticosteroid and cryotherapy group.6 One study did not report adverse events.5

In conclusion, current evidence suggests that oral antihistamines may be an effective and safe adjunctive treatment for AA. However, limitations include the small number of available studies and potential publication bias. Further studies are needed to confirm the efficacy and role of antihistamines in AA.