Comparative evaluation of the efficacy of topical tacrolimus 0.03% and topical calcipotriol 0.005% mixed with betamethasone dipropionate versus topical clobetasol 0.05% in treatment of alopecia areata: A clinical and trichoscopic study

Alopecia areata (AA) is a common non‐scarring hair loss disorder that affects children and adults with a great psychological burden because of its recurrent and sometimes treatment‐refractory nature.

1,25 (OH)2 D3 receptors (VDRs) were found to be strongly expressed in human hair follicles implicated in regulating cellular differentiation and that AA patches demonstrates lack of their expression. 6 Based on such background, calcipotriol, a vitamin D analogue, has been used topically to treat AA in some studies and showed good results 6,7 and even in comparison to phototherapy 8 and topical steroids. 9 So, we thought of researching the double effect of combined vitamin D analogue together with steroid.
According to the Italian guidelines in AA management, the biphasic nature of the disease necessitates using immunosuppressive agents, for example, steroids for the acute phase and immunomodulatory agents for the chronic phase. Tacrolimus, being an immunomodulatory drug with a wide spectrum of application in dermatology, has drawn attention to be used in AA. [10][11][12] So, we tried to investigate its efficacy in treating mild to moderate chronic alopecic patches.

| PATIENTS AND ME THODS
A total of 60 patients with mild to moderate patchy AA, either stable or progressive, were included and randomized into three groups each of 20 subjects. Patients in group I used topical calcineurin inhibitor (tacrolimus 0.03%, Tarolimus®), patients in group II used topical mixed vitamin D analogue with potent-steroids (calcipotriol 0.005% and betamethasone dipropionates, Daivobet®) while patients in group III used topical superpotent steroids (clobetasol dipropionate 0.05%, Dermovate®). Treatment was applied twice daily for 3 months, and patients were followed for 3 other successive months.
TA B L E 1 Demographic data of the studied groups. significant decrease in the frequency of a positive test in each group posttreatment compared to pretreatment by 60%, 65% and 75% for groups I, II, and III, respectively ( Table 2).

Variable
There were no statistically significant differences among the studied groups in estimated SALT scores pretreatment compared to posttreatment. But there was a statistically significant decrease in SALT scores in all groups posttreatment compared to pretreatment by 24.16%, 53.57%, and 48.57% for groups I, II, and III, respectively ( Table 3).
Regarding the AAPS results, a score of 2 means a 98% chance of hair regrowing on the current therapy, 1 means 89%, 0 means 13%, −1 means 2%, and −2 and -3 means less than 1% chance. Dermovate therapy (group III) achieved a score of 2 (mean 1.5 ± 0.76) based on their trichoscopic findings. The other two groups achieved a score of 1 (mean for Daivobet was 1 ± 1.08 and that for Tarolimus was only 0.6 ± 0.88) ( However, being a superpotent steroid, its use allows a higher chance of undesirable side effects such as skin atrophy, folliculitis, and telengectasia.
The efficacy of topical vitamin D analogues in treating AA, despite proven in few studies. 6,7,8,9,14 is still under researched. Aside from their ability to regulate hair follicle keratinocytes' proliferation and differentiation, their immunomodulatory properties evident in shifting immune response from Th1 to Th2 phenotype, inhibiting Th17 cells and enhancing Treg cells give them a strong base to be able to suppress the autoimmune causality of AA. 6 Topical application of calcipotriol (a vitamin D analogue) to AA patches was associated with a faster regrowth of hair and later tendency for relapse when compared to clobetasol-treated patches. 14 The same study highlighted the superiority of calcipotriol over clobetasol in terms of availability, affordability, efficacy, and a better side effects profile. All these studies failed to prove a good efficacy of tacrolimus in treating AA. They attributed that to the high molecular weight of its ointment formula which hinders its penetration through an intact epidermal barrier of the alopecic patches.
Regarding our results, tacrolimus could achieve a terminal hair growth in some cases achieving a statistically significant difference in group I, treated with Tacrolimus. However, the reduction of SALT score caused by using Tacrolimus in group I is nearly half that caused by using Dermovate in group III.
Our study was limited by the small sample size and inability to do long-term statistical evaluation as many patients dropped the follow up and did not return our calls. We recommend it would be done on a large cohort of selected patients with a certain trichoscopic phase.
In conclusion, we found that combining a vitamin D analogue with a topical steroid of medium potency was of comparable efficacy to a superpotent topical steroid but with a wider safety profile and less side effects and thus would be more suitable for long term use that suits a disease with a persistent and recurrent nature such as AA. We do not believe Tacrolimus is eligible to be recommended as a candidate in the armamentarium of AA.

CO N FLI C T O F I NTE R E S T
None declared.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

E TH I C A L A PPROVA L
Study approved by the Institiutional review board (IRB) of Zagazig University #5925/12-2-2020.