Topical immunotherapy with diphenylcyclopropenone in patients with alopecia areata: A large retrospective study of 757 patients

Dear Editor, Alopecia areata (AA) is an autoimmune disorder of hair follicles, which counts for approximately 0.1% to 0.2% of hairloss. A number of 14% to 25% of cases with patchy AA can progress to diffuse alopecia that spontaneous hair regrowth is less than 10%. Treatment of AA totalis and universalis is so challenging and topical sensitizers such as squaric acid dibutylester and diphenylcyclopropenone (DPCP) are considered effective treatment modalities. A retrospective study was conducted on 757 AA patients who underwent topical DPCP therapy at alopecia clinic in the Department of Dermatology, RAZI Hospital, from 2012 to 2017. The study was approved by Ethic Committee of Tehran University of Medical Sciences (IR.TUMS.MEDICINE.REC.1398.101). The patients were categorized into four subtypes: (a) universalis, (b) totalis, (c) ophiasis, and (d) patch type. Severity of the scalp involvement was determined with the Severity of Alopecia Tool (SALT) scoring system. The response rate was categorized into four categories: (a) excellent (>75%), (b) good (50%-75%), (c) moderate (25%-50%), and (d) poor (<25%) hair regrowth. Patients' demographic information is summarized in Table 1. The overall response rate either terminal or vellus hair regrowth was recorded in 454 patients (60.1%), but in 136 patients (29.5%) the pull test was still positive. The response rate as SALT score was recorded as 74 (16.3%) excellent, 70 (15.4%) good, 90 (19.8%) moderate, and 220 (48.4%) poor response. So, over 50% hair regrowth was seen in 31.7% (Table 1). Statistical analysis established a significant correlation between the treatment response and extent of alopecia (73.5 ± 28.8 vs 82.4 ± 27.6, Spearman's ρ = 0.324, P value <.0001) and also subtypes of alopecia (odds ratio [OR] = 2.56, 95% confidence interval [CI] = 1.48-4.42, P value = .001), which patients with patchy AA had 2.56 times higher response rate in comparison to other subtypes. Conversely, universalis AA had 2.6 time lower chance of hair regrowth (OR = 2.6, 95% CI = 1.72-3.93, P value < .0001). Treatment response was also significantly associated with treatment duration (15.4 ± 13.5 vs 8.9 ± 6.8, P value < .0001) and nail involvement (OR = 2.02, 95% CI = 1.17-3.5, P value = .011), which the chance of response to treatment was two times higher in patients without nail involvement. Moreover, disease duration had a statistically significant relationship with treatment response (6.84 ± 8.0 vs 9.06 ± 9.03, P value = .007), patients with shorter disease duration had higher chance of hair regrowth. Factors that were not associated with treatment response include family history of AA, sex, history of atopy, DPCP concentration, age, and age at disease onset. Complications were observed in 28.1% of patients including bullous reaction, hyperpigmentation, lymphadenopathy, generalized eczema and pruritus, and vitiligo. The literature review illustrated a wide range of response rate to DPCP in AA patients from 4% to 85% with a mean response rate of 65.5% in a recent systematic review and metanalysis of 2227 patients (74.6% in patchy and 54.5% in alopecia totalis/universalis). This difference in treatment response could be explained by different study designs, disease severity, different duration of therapy, and concentration of DPCP (Table 1). Our patients were mostly (43.1%) totalis or universalis subtypes, and 75% of our patients had alopecia more than 50% of scalp area. Studies have indicated that extensive alopecia is one of the poor prognostic factors associated with treatment response. As a comparison, Chiang et al in a 3-year study of 50 patients reported a response rate of 71% in totalis and 56% in universalis subtypes. Their higher response rate may be due to longer duration of therapy in comparison to our study that the mean duration was 12 months. Conclusively, our study on large number of AA patients showed that topical DPCP therapy is a good and safe treatment option with 60.1% response rate. The most important prognostic factors could be the severity of disease, type of alopecia, duration of illness, and nail involvement. Received: 6 April 2020 Revised: 29 May 2020 Accepted: 6 June 2020