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My fair-weather therapeutic friends for alopecia areata

DII small banner By Warren R. Heymann, MD
April 25, 2017

Type C clinical pattern of alopecia. A, Patchy hair loss on a background of a diffuse hair loss with (B) occipital involvement in an ophiasis-like pattern. C, Biopsy specimen obtained from the vertex of the scalp. Histopathology of vertical sections shows an atrophic epidermis with miniaturized hair follicles in the dermis and subcutaneous tissue with numerous end-stage fibrous tracts and a dysmophic telogen hair follicle (inset). D, Detail of the end-stage avascular obliterated fibrous tracts with solar elastosis–like appearance. (Hematoylin–eosin stain; original magnification: C, ×40; inset and D, ×200.)
Credit: JAAD
We were never best of friends, but we got along well most of the time. The relationship seemed to work, with rare moments of ecstasy, but was irritating all too often. There were no major conflagrations; we just drifted apart.

Such has been my relationship with anthralin for alopecia areata (AA). We all know how difficult treating AA can be, handling both the physical and emotional aspects. The current darlings of the AA world are the JAK inhibitors, which we have discussed recently (Tofacitinib for Adolescent Alopecia Areata: Balancing the Risk-Benefit Ratio. January 17th, 2017).
I was intrigued by the study by Özdemir and Balevi of 30 children with chronic, severe, treatment-refractory, extensive AA who were treated with 1% anthralin ointment. One side of the scalp was treated with anthralin for 12 months and the other side was left untreated. Outcomes were evaluated according to the Severity of Alopecia Tool (SALT) score. The mean time to first response in terms of new hair growth was 3 months and the mean time to maximal response was 9 months. In the first 12-month period, 10 patients (33.4%) achieved complete response to treatment and 11 patients (36.6%) had a partial response. Of the 11 patients with partial response at the end of the first year, 6 achieved a complete response before the end of the study. Total SALT scores for the entire scalp decreased from the end of the first year to the end of the 2-year period. No serious adverse events were observed. The authors concluded that anthralin 1% is a safe and effective therapy for AA and should be continued at least 9 months. At 9 months of topical anthralin therapy, the patients with at least a 50% reduction in their pretreatment SALT scores should continue the same treatment for at least 1 year (1).
While researching prior data about anthralin and alopecia, I came across the following article, which changed my focus and perspective.

Sasmaz and Arican studied 31 subjects with patchy AA who did not receive any treatment for at least 1 month prior to the study. Subjects were randomized to apply either 20% azelaic acid (15 subjects) or 0.5% anthralin (16 subjects) for 12 consecutive weeks. In a subsequent 8-week follow-up period no cream was applied. Two independent investigators performed an efficacy evaluation with clinical examination using a terminal hair regrowth score (RGS) with a scale ranging from 0 (inadequate response) to 2 (complete response) at week 20. Partial response was accepted as score 1. Both groups were well matched for the relevant demographic and clinical indicators affecting treatment response at baseline. All subjects completed the trial. A complete response was observed in 53.3% of cases in the azelaic acid group (8 of 15) compared with 56.2% (9 of 16) in the anthralin group (p > 0.05). No serious adverse events were observed in either group during the study. The study demonstrated that the use of azelaic acid gave similar results to anthralin regarding hair regrowth, and that it can be an effective topical therapy for patchy AA.  The authors recommended that more extensive trials would be necessary to reach a definitive conclusion (2). I certainly agree with that. Since that article was published in 2005, no such studies have been performed.

Azelaic acid is available as a 20% cream (Azelex) or as a 15% formulation (Finacea gel or foam). Azelaic acid has been shown to exhibit multiple pharmacologic effects, which may correlate with its varied clinical uses. A variety of anti-inflammatory and antioxidant properties have been reported, the former including downregulation of cathelicidin (LL-37) activation via inhibition of serine protease (kallikrein-5). At least some of these effects are believed to correlate with therapeutic activity in papulopustular rosacea and possibly acne vulgaris (3). Why shouldn’t azelaic acid work in AA (as well as anything else)?

The pathogenesis of AA is unknown, but the widespread belief is that it is an autoimmune process of cytotoxic T-lymphocytes reacting with follicular autoantigens in genetically predisposed patients.  Kassira et al analyzed 40 studies on treating alopecia totalis and alopecia universalis including: topical immunotherapy, steroids, photodynamic therapy, immunosuppressive agents, TNFα inhibitors, and other therapies, such as sulfasalazine, bexarotene, JAK inhibitors, and simvastatin/ezetimibe. They found that although certain treatments showed significant hair regrowth, no treatment was completely effective (4).

Perhaps anthralin and I will get reacquainted. Until then, I think I’ll date (or is it hook up with, these days?) azelaic acid for AA, to see whether it becomes my new BFF.

1. Özdemir M, Balevi A. Bilateral half-head comparison of 1% anthralin ointment in children with alopecia areata. Pediatr Dermatol 34(2): 128-32.
2. Sasmaz S, Arican O. Comparison of azelaic acid and anthralin for the therapy of patchy alopecia areata: A pilot study. Am J Clin Dermatol 2005; 6L 403-6.
3. Del Rosso JQ. Azelaic acid topical formulations: Differentiation of 15% gel and 15% foam. J Clin Aesthet Dermatol 2017; 10: 37-40.
4. Kassira S, et al. Review of treatment for alopecia totalis and alopecia universalis. Int J Dermatol 2017; Apr 5 [Epub ahead of print]

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