Abstract

• Background: The combination of topical diphenylcyclopropenone (DCP) and anthralin may possess a synergistic effect in the treatment of chronic extensive alopecia areata (AA).

• Objective/Methods: The investigators conducted a study to compare the efficacy of topical DCP combined with 0.5% anthralin versus DCP alone. The study enrolled 10 patients diagnosed with alopecia totalis (AT; n=1), severe AA (>50% hair loss; n=2), and alopecia universalis (AU; n=7). A split-scalp treatment protocol was implemented for 6 months. One side of the scalp was treated with DCP alongside 0.5% anthralin, while the contralateral side was treated with DCP alongside a cream base. Efficacy was evaluated monthly utilizing the Severity of Alopecia Tool (SALT) score, and adverse effects were assessed at every follow-up visit.

• Results: The therapeutic efficacy between the two treatment sides showed no statistically significant difference (P = 0.59). Regarding adverse effects, the side treated with DCP plus anthralin exhibited a significantly higher incidence of excessive dermatitis compared to the DCP-alone side (7 patients vs. 2 patients, P = 0.02). Transient hyperpigmentation was observed on the dual-therapy side in 8 patients, whereas none was observed on the DCP-alone side (P < 0.001).

• Conclusion: The combination of DCP and 0.5% anthralin did not yield superior clinical outcomes compared to DCP alone and resulted in a higher incidence of adverse effects (dermatitis and hyperpigmentation).

Introduction

• Alopecia Areata (AA) is a non-scarring form of hair loss triggered by an autoimmune response against the hair follicles. Pathogenically, it is characterized by peribulbar T-lymphocyte infiltration that targets hair follicles during the anagen (growth) phase. Severe manifestations include Alopecia Totalis (AT), defined as complete loss of scalp hair, and Alopecia Universalis (AU), defined as complete loss of all body hair.

• Diphenylcyclopropenone (DCP) is a topical contact immunotherapy agent. It induces a mild allergic contact dermatitis, which is theorized to downregulate T-cell reactivity surrounding the hair follicles.

• Anthralin (Dithranol) exhibits anti-inflammatory properties by inhibiting pro-inflammatory cytokines, such as TNF-α and IFN-γ.

• Given their distinct mechanisms of action, the researchers hypothesized that a combination therapy might enhance therapeutic efficacy, particularly in patient cohorts that demonstrate recalcitrance to conventional treatments.

Methodology

• Patient Selection: Ten patients, aged ≥18 years, presenting with chronic severe AA, AT, or AU were enrolled. A minimum washout period of 4 weeks from any prior treatments was mandatory prior to study initiation.

• Treatment Protocol:

  • Week 1: Immunological sensitization was performed using 2% DCP applied to the vertex of the scalp.

  • Week 3 (2 weeks post-sensitization): Low-concentration DCP (0.0001%) was applied bilaterally once a week, left on for 48 hours, and subsequently washed off. The concentration was gradually titrated upward until a mild contact dermatitis was achieved.

  • Remaining 3 days of the week: 0.5% anthralin was applied to one side of the scalp, and a cream base was applied to the contralateral side. Applications occurred once daily at bedtime and were washed off in the morning. This regimen was maintained continuously for 6 months.

• Evaluation: The SALT score was utilized, dividing the scalp into four quadrants to calculate the percentage of hair regrowth.

Results

• Patient Attrition: Two patients withdrew from the study. One patient experienced a severe allergic reaction to DCP during the sensitization phase, and the other developed severe dermatitis during the DCP concentration upward titration.

• Efficacy in Completers (n=8):

  • Severe AA Group (n=1): Achieved 100% hair regrowth on both sides of the scalp.

  • AT Group (n=1): Achieved 50% hair regrowth on the dual-therapy side, compared to 30% on the DCP-alone side.

  • AU Group (n=6): Displayed minimal to no therapeutic response.

• Mean SALT Scores:

  • Baseline: Dual-therapy side = 47.1 | DCP-alone side = 47.3

  • At 6 months: Dual-therapy side = 38.62 | DCP-alone side = 40.7

  • There was no statistically significant difference in SALT score reduction between the two groups (P = 0.59).

• Adverse Effects:

  • Excessive Dermatitis: Documented in 77.8% of the dual-therapy side versus 22.2% of the DCP-alone side (P = 0.02).

  • Hyperpigmentation: Documented in 88.9% of the dual-therapy side versus 0% of the DCP-alone side (P < 0.001).

Discussion and Conclusion

• The combination therapy did not produce superior outcomes when compared to DCP monotherapy. This lack of significance may be attributed to the relatively short follow-up duration (6 months) and the high proportion of AU patients in the cohort, which is clinically recognized as the most recalcitrant subtype to treat.

• The concurrent topical application of both agents led to cumulative cutaneous irritation. Furthermore, given Thailand’s tropical climate, ultraviolet (sun) exposure likely served as an aggravating factor for post-inflammatory hyperpigmentation.

• Study Limitations: The study is limited by a small sample size (n=10) and a short follow-up duration.

• Final Conclusion: The addition of 0.5% anthralin to DCP in the treatment of AA does not demonstrate a clear therapeutic advantage and significantly increases the incidence of adverse effects. Larger-scale, randomized controlled trials are required to definitively validate these clinical findings.