Introduction
Alopecia areata (AA) is a common, chronic, inflammatory disease that causes non-scarring hair loss. The severity ranges from small patches of hair loss, which usually recovers spontaneously to complete alopecia where the prognosis for hair regrowth is poor.[ 1 ] The exact etiopathogenesis of AA is still clearly unknown but there is abundant evidence that it is an autoimmune disease. The diagnosis of AA is mostly clinical aided by peculiar dermatoscopic findings.
Although there are various treatment options for AA, there is no good trial evidence that any treatment provides long-term benefit to patients with AA.[ 2 ] Most commonly used first line drugs in patchy AA like potent topical and intralesional steroids have various side effects and the injection is painful. A study by Zaher et al .[ 3 ] has shown that bimatoprost, a prostaglandin analogue, is effective and safe in the treatment of scalp AA. Moreover, the onset of hair regrowth is faster, the chance of relapse is less, and regrown hairs are pigmented from the beginning of therapy compared to the topical steroid group. There are many studies that have used prostaglandin analogues in AA of eyelashes and eyebrows[ 4 , 5 ] and few in androgenetic alopecia (AGA),[ 6 , 7 ] but very few studies have compared prostaglandin analogues like latanoprost and bimatoprost with topical steroids in AA of scalp .[ 3 , 8 ]
This study aims to compare the efficacy and safety of topical bimatoprost 0.01% solution with the standard treatment topical steroid (clobetasol propionate 0.05% cream).
Materials and Methods
A prospective non-randomized comparative clinical trial was conducted from March 2018 to February 2019. Sample size was calculated using Power Analysis and Sample Size Software (PASS) Version 15.0.4. and calculated as 50 i.e., 25 patients in each group using convenient sampling technique. Group A applied bimatoprost 0.01% solution and Group B applied clobetasol propionate 0.05% cream, twice daily, using a cotton tip applicator.
A predesigned proforma was used for data collection. Informed written consent was taken from the patients prior to the study and ethical clearance was taken from the Institutional Review Committee (IRC).
All patients attending the dermatology out patient department (OPD) diagnosed as scalp AA by a registered dermatologist with SALT score S1 (<25% hair loss) and stationary or progressive course were included in this study. Exclusion criteria included i) Patients <13 years of age ii) Patients with alopecia totalis (AT)/alopecia universalis (AU) and ophiasis iii) Patient who received any form of systemic steroid or prostaglandin analogue within 4 weeks and topical treatment within 7 days prior to the study iv) Patients who reported spontaneous hair regrowth v) Patients with associated autoimmune diseases vi) Patients who had AA in areas other than the scalp vii) Pregnant and lactating mothers viii) Patients not willing to follow-up and not consenting to participate.
Data entry and statistical analysis was done using independent sample t-test, paired t-test and ANOVA in SPSS version 20 (Statistical Package for the Social Sciences; SPSS Inc., Chicago, IL, USA)
According to SALT I scoring system, the scalp was divided broadly into 4 different areas. According to SALT II scoring system, these 4 areas were further subdivided into 100 parts of 1% each. About 1% of the scalp was equivalent to 7 square cm.[ 9 ]
The SALT score at one site was calculated by [(length × breadth) × (% hair loss)/100]/7.[ 9 ] The baseline, 4, 8, and 12 weeks SALT scores were calculated and analyzed. Post treatment SALT score and hair regrowth were also calculated by comparing serial photographs of patients. Standard tools for objective and global assessment and subjective assessment included in the proforma was used for that purpose.[ 10 ] Side effects and color of regrown hair were also recorded. Initial response was considered positive if there was a cosmetically significant hair regrowth (i.e., >25% regrowth) and was recorded in weeks.
Results
Out of 50 patients, 27 were males and 23 were females with a mean age of 28.5 ± 9.34 years and mean duration of disease of 18.67 ± 46.1 weeks. The baseline characteristics between the two groups were comparable in terms of age (p = 0.521), sex (p = 0.395), duration of disease (p = 0.358), family history (p = 0.609), past treatment history (p = 0.059), past treatment modalities (p = 0.235), number of alopecia patches (p = 0.451), and size of patches (p = 0.779). The mean baseline SALT score was 1.928 ± 1.29%. The mean baseline SALT score in group A was 2.06 ± 1.50% and in group B was 1.95 ± 1.16%. The difference was not statistically significant (p = 0.761). The difference in mean salt score between the two groups was statistically not different at 4 weeks (p = 0.865), 8 weeks (p = 0.298), and 12 weeks (p = 0.246). Within the group, there was statistically significant reduction in SALT score at 12 weeks compared to baseline in both the groups (p = 0.00) [Figure 1 ].
Figure 1: Reduction in SALT score at 4, 8, and 12 weeks in both groups
Out of 50 patients who received treatment, 39 (78%) had cosmetically acceptable hair regrowth at 12 weeks i.e., >25%. Eighteen patients (72%) in group A vs. 20 (80%) in group B had cosmetically acceptable hair regrowth [Figure 2 ]. The difference is statistically not significant (p = 0.508). Mean regrowth in group A is 50.69 ± 33.55; while, in group B it is 61.57 ± 37.18. Although cosmetically acceptable hair growth is seen in both groups, the absolute regrowth is more in clobetasol group. However, the difference is statistically not significant (p = 0.282).
Figure 2: Hair regrowth according to grades at 12 weeks in both groups
Initial response was considered positive if there was cosmetically significant hair growth (i.e., >25%) during follow up at 4, 8, and 12 weeks. Mean duration of onset of initial response in group A was 4.8 ± 2.9 weeks while in group B it was 7.2 ± 3.7 weeks. In group A, majority of patients i.e., 10 (40%) had response at 2–4 weeks while in group B, majority i.e., 7 (28%) had response within 6 to 8 weeks. The difference was statistically significant (p = 0.017).
When examined for color of regrown hair, 38 (76%) had black hair, 9 (18%) had grey hair, while 3 (6%) had mixed colored hair. A larger proportion of patients (92%) in bimatoprost group had black colored hair on regrowth as compared to 60% in clobetasol group. The difference was statistically significant (p = 0.024) [Figure 3 ].
Figure 3: Nature of terminal hair in both groups
A total of 16 (32%) patients developed various side effects. In clobetasol group, 13 patients (52%) developed various side effects, while only 3 patients (12%) developed side effects in bimatoprost group. The difference in side effects was statistically significant (p = 0.002).
The most common overall side effect was pruritus 11 (22%) followed by erythema and folliculitis in 8 (16%) and 6 (12%) patients, respectively. There was statistically significant difference in side effect erythema (p = 0.002) and pruritus (p = 0.017) while there was no statistically significant difference in folliculitis (p = 0.189), atrophy (p = 1.00) and telangiectasia between two groups [Table 1 ].
Table 1: Different side effects noticed in both groups
Discussion
Bimatoprost is a prostaglandin F2 alpha analog and has been found to have hair growth-stimulatory effect by increasing the percentage of anagen follicles, promoting anagen reentry of telogen hair follicles, and increasing hair bulb diameter. Further, activation of the prostaglandin F receptor results in potent stimulation of human melanocyte dendricity and increases melanogenesis.[ 11 ] Corticosteroids reduce inflammation by suppressing T cells around the hair follicle and allow it to return to the normal growth cycle.[ 2 ]
The mean 12 weeks SALT score showed reduction post treatment was more in clobetasol group, the difference was not statistically significant (p = 0.246), while in study done by Zaher et al .[ 3 ] there was greater reduction of SALT score in bimatoprost group compared to mometasone group but it was not statistically significant (p = 0.084). The higher reduction in SALT score in clobetasol group than in bimatoprost group in our study and vice versa in previous study could be because they used mid potent topical steroid i.e., mometasone once daily while in our study super potent steroid (clobetasol) was used twice daily. However, study done by El-Ashmawy et al .[ 8 ] showed significant reduction in SALT score in latanoprost group (p = 0.044), in betamethasone group (p = 0.032) and in combination of betamethasone and latanoprost group (p = 0.04). The higher reduction in SALT score in this study might be because they had treated for slightly longer duration i.e., 20 weeks.
Our study showed mean hair regrowth after 12 weeks was higher in clobetasol group but the difference was not statistically significant (p = 0.282). However, study done by Zaher et al .[ 3 ] showed significantly higher regrowth in bimatoprost group compared to mometasone group (p = 0.001). Although the absolute regrowth was comparable in bimatoprost group in both studies, it was less in steroid group in his study. The reason for this could be because we used super potent steroid (clobetasol propionate cream 0.05%) twice daily while they used mid potent steroid (mometasone furoate cream 0.1%) once daily and lower concentration (0.01%) of bimatoprost in our study versus 0.03% in other studies.[ 3 , 8 , 12 ]
Cosmetically acceptable hair regrowth was seen more in clobetasol group, and the difference was statistically not significant (p = 0.508). Comparable results were seen in study done by El-Ashmawy et al .[ 8 ] using betamethasone and latanoprost.
Our study showed that a statistically significant larger proportion of patients in bimatoprost group had black colored hair on regrowth versus clobetasol group (p = 0.024). Similar results were seen in study done by Zaher et al .[ 3 ] which showed 100% pigmented hair in bimatoprost group and 100% non-pigmented hair in mometasone group but it was just an observation finding and no objective evaluation was done. A large proportion of patients in clobetasol group (13, 52%) developed various side effects while only 3 (12%) developed side effects in bimatoprost group.
Erythema was seen in 8 (32%) of our patients compared to 7 (23.3%) who used mometasone in Zaher et al .[ 3 ] study. El-Ashmawy et al .[ 8 ] showed folliculitis in 2 (10%) patients who had applied betamethasone valerate and Tosti et al .[ 13 ] showed folliculitis in 11 (39.28%), while our study showed higher incidence of folliculitis in clobetasol group (5, 20%). Higher incidence of side effects compared to El-Ashmawy et al .[ 8 ] might be because of the use of super potent steroid in our study, while higher incidence in Tosti et al [ 13 ] . could be because of occlusion of scalp after application.
Telangiectasias and atrophy were observed in 2 (7.1%) and 1 (3.5%) patients, respectively, in study done by Tosti et al .[ 13 ] No such side effects were reported in studies done by Kuldeep et al. ,[ 14 ] El-Ashmawy et al. ,[ 8 ] and Sardesai et al .[ 15 ] Our study did not show telangiectasia in any of the patients. Atrophy was seen in 1 (4%) patient in clobetasol group in our study.
Our study reported pruritus (2, 8%) and folliculitis (1, 4%) in bimatoprost group. Side effects reported in clinical trials of bimatoprost include dryness (6.56%), irritation (7.69%), contact dermatitis (7.69%), and pruritus (11.48%);[ 16 , 17 ] however, study done by Roseborough et al .[ 18 ] and Zaher et al .[ 3 ] did not report any side effects to latanoprost in eyelashes and bimatoprost in scalp alopecia areata, respectively.
Conclusions
There is no significant difference in hair regrowth between clobetasol and bimatoprost in the treatment of AA on scalp at the end of 12 weeks, but bimatoprost has an advantage of lesser side effects, more rapid response, and growth of more pigmented hairs.
Limitations
Some of the limitations of this study are lack of control group and shorter follow-up period.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Allergan, Inc. for Bimatoprost and H and H pharmaceutical LLP for Clobetasol.
Conflicts of interest
There are no conflicts of interest.
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