Bimatoprost: a potential therapeutic tool for alopecia areata of the scalp : Journal of the Egyptian Women’s Dermatologic Society

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Original articles

Bimatoprost

a potential therapeutic tool for alopecia areata of the scalp

Zaher, Hesham; Gawdat, Heba

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Journal of the Egyptian Women's Dermatologic Society 11(2):p 123-127, May 2014. | DOI: 10.1097/01.EWX.0000444330.33581.2f
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Abstract

Introduction

Alopecia areata (AA) is a common autoimmune disease whose target is the hair follicle. It is often clinically characterized by nonscarring and patchy hair loss. The scalp is the most frequent location of the disease, but any hair-bearing area can be affected 1.

Many therapeutic modalities have been used to treat AA, with variable efficacy and safety profiles. Among these modalities are corticosteroids (topical, intralesional, and systemic), topical immunotherapy (e.g. diphenylcyclopropenone), photochemotherapy (systemic and topical psoralen plus ultraviolet A light), and others (e.g. cyclosporine, methotrexate, and biologics) 2. Unfortunately, none of these agents is curative or preventive 3.

Prostaglandin and prostamide analogs (e.g. latanoprost, travoprost, and bimatoprost) are effective and widely used medication in the treatment of open-angle glaucoma 4. This treatment was incidentally found to treat hypotrichosis of the eyelashes, and this observation was first reported by Johnstone 5. Since then, there have been several reports about the use of prostaglandin and prostamide analogs in the treatment of AA of the eyelashes 1,6–11. However, the results demonstrated by these reports concerning the efficacy and safety of such treatment were conflicting and none of them have tested this medication for AA of the scalp.

In December 2008, the US Food and Drug Administration (FDA) approved the use of 0.03% bimatoprost solution (Latisse©), identical to the ophthalmic solution for glaucoma treatment (Lumigan©), for increasing eyelash length, thickness, and darkness in patients with hypotrichosis of the eyelashes or in persons who desire lengthy eyelashes 10.

This prompted us to conduct the current prospective study to evaluate the use of bimatoprost 0.03% solution as a new therapeutic modality for scalp AA.

Patients and methods

The current prospective study was approved by the Dermatology Research Ethical Committee (REC), Kasr Al Aini Hospital, Cairo University.

Fifteen AA patients (10 men and five women), with ages ranging between 20 and 45 years, who had no systemic or other dermatological diseases, were recruited from the Dermatology Outpatient Clinic, Faculty of Medicine, Cairo University. Written informed consents were retrieved from all participants.

Detailed history was retrieved from each patient with regard to age, sex, family history, course, and duration of the disease. Clinical examination was performed for all patients using the ‘Severity of Alopecia Tool’ (SALT) score 12 to determine the extent of surface area involvement of the scalp. Patients with SALT score greater than S1 (S1≤25% hair loss) and those with associated nail affection, atopic dermatitis, and an ophiasis pattern or reported spontaneous hair regrowth were excluded from the study. In addition, patients receiving systemic or topical immunomodulatory treatment for AA within 3 months before the study were also excluded.

Treatment protocol

Each patient was instructed to apply bimatoprost 0.03% solution (Lumigan©, Allergan Inc., Irvine, California, USA) to a single patch of AA (the longest dimension ranging from 5 to 10 cm) using a cotton-tipped applicator twice daily for a period of 3 months.

Patient assessment

Each patient was assessed at regular intervals (every 3 weeks) by a fixed senior investigator throughout the treatment period (3 months of bimatoprost therapy) for the extent and the density of hair regrowth in AA lesions using the SALT scoring system for regrowth, which is categorized as follows: A0=no change or further loss, A1=1–24% regrowth, A2=25–49% regrowth, A3=50–74% regrowth, A4=75–99% regrowth, and A5=100% regrowth 12.

Photographic documentation of the expected response was performed for all patients using the same digital camera (Sony Cyber-shot digital camera, DSC-HX5V; Sony Corp., Tokyo, Japan) at baseline, when hair regrowth first occurred (as reported by the patients) and at the end of the treatment period (3 months).

Patients were asked to report their opinion of the medication used (satisfied or unsatisfied) with regard to efficacy, rapidity of the response (when hair regrowth first occurred), and the occurrence of any side effects in the form of erythema, pruritus, and pigmentation of the skin of the scalp 13.

Follow-up

All patients who showed improvement (hair regrowth) were followed up for a period of 3 months after cessation of treatment to determine the incidence of recurrence of AA.

Statistical analysis

Data were statistically described in terms of mean±SD, median and range, or frequencies (number of cases) and percentages when appropriate. Comparison of numerical variables was performed using the Wilcoxon signed-rank test. The exact test was used instead when the expected frequency was less than 5. P values less than 0.05 were considered statistically significant. All statistical calculations were performed using computer program SPSS version 15 (Statistical Package for the Social Science; SPSS Inc., Chicago, Illinois, USA).

Results

The current study included 15 patients with AA of the scalp [10 men (66.7%) and five women (33.3%)], whose age ranged from 20 to 45 years (24.50±7.794 years). All included patients had no family history of AA, and 53.3% of the patients (n=8) had a progressive course, whereas 46.7% (n=7) had a stationary one. The disease duration of the included patients was 1.80±1.785 years.

Patient assessment

According to the physician’s assessment of recruited patients, which was performed by comparing clinical photographs of AA lesions taken at baseline and 3 months after therapy with bimatoprost, the results were as follows: the mean SALT score of AA lesions in 86.7% of the included patients (n=13) was significantly reduced after 3 months of treatment by bimatoprost, where the mean SALT score at baseline was 7.604±5.291, whereas the mean SALT score after therapy was 3.607±4.573 (P=0.01). The mean extent of hair regrowth according to the SALT scoring system for regrowth was 47.850±29.185%, where three patients (20%) had 50–74% regrowth (A3), six patients (40%) had 25–49% regrowth (A2), 26.7% of the patients (n=4) had 1–24% regrowth (A1), and two patients (13.3%) showed no response (no change or further loss=A0). Hair regrowth started to occur after a mean time of 2.870±1.541 weeks as reported by the patients and documented by clinical photography (Figs 1 and 2). No correlation was found between the SALT score after treatment and the age of the patients or the disease duration.

F1-9
Figure 1:
A 40-year-old male patient with alopecia areata (AA) of the scalp (occipital region). (a) AA patch at baseline; (b) AA patch after 2 weeks of bimatoprost therapy (when hair regrowth started to occur); (c) AA patch after 3 months of bimatoprost therapy (A3=50–74% regrowth).
F2-9
Figure 2:
A 30-year-old male patient with alopecia areata (AA) of the scalp (vertex). (a) AA patch at baseline; (b) AA patch after 3 weeks of bimatoprost therapy (when hair regrowth started to occur); (c) AA patch after 3 months of bimatoprost therapy (A2=25–49% regrowth).

Patient satisfaction

Eleven patients (73.3%) were satisfied with the response achieved after 3 months of bimatoprost therapy, whereas four patients (26.7%) [two patients who did not respond to treatment and two patients who showed 1–24% regrowth (A1)] were unsatisfied with this therapeutic modality.

Side effects

Regarding side effects, none were experienced by the patients or were observed by the physician throughout the study period (3 months) or during the follow-up period (3 months after cessation of therapy).

Follow-up

One out of 13 patients (responders) (7.7%) experienced recurrence during the follow-up period (3 months after stoppage of treatment) in the form of hair loss in AA lesions that responded to bimatoprost therapy. This patient showed 1–24% regrowth (A1) according to the SALT scoring system for the extent and the density of hair regrowth, and he was shifted to another therapeutic modality.

Discussion

Bimatoprost is a synthetic prostamide initially designed pharmacologically to reduce the intraocular pressure for the treatment of glaucoma. It is structurally similar to other prostaglandin F (PGF) analogs, including latanoprost and travoprost 14. Hypertrichosis of eyelashes has been reported as a regular phenomenon associated with ophthalmic prostaglandin and prostamide analogs 5.

Prostaglandins are probably involved in a specific and complex network in hair growth and differentiation control. Most of the hair cell types are endowed with prostaglandin metabolism machinery and are able to produce PGE2 and/or PGF, and all prostaglandin receptors are present in the hair follicle 15–17. Furthermore, minoxidil, a known inducer of hair growth, was reported to act through stimulation of PGE2 synthesis 18, thus supporting the theory of the augmented efficacy of the direct use of prostaglandins for the treatment of hair loss.

There are several suggested mechanisms related to prostaglandin-induced hair growth such as (a) transition from telogen to anagen follicles, (b) stimulation of follicular hypertrophy early in the anagen phase, (c) delay in cessation of anagen (increasing its duration) and accordingly increasing hair length, (d) induction of a mitogenic stimulus that is required to trigger cell division at the initiation of anagen, and (e) upregulation of cell adhesion molecules and proteases that are involved in enlargement, remodeling, and downward migration of the hair follicle 19.

The current study provides further demonstration of such efficacy, where 13 patients (86.7%) have shown a statistically significant reduction of the mean SALT score of AA lesions after 3 months of bimatoprost therapy, whereas two patients (13.3%) showed no response. These results are in agreement with other studies that utilized both bimatoprost and latanoprost in the treatment of AA of eyelashes, where they reported an acceptable cosmetic response (total and moderate regrowth) in ∼45% of the patients 1,7,10. Cosmetically acceptable hair regrowth was achieved in 40% of the recruited patients (n=6). The difference in the number of patients with cosmetically acceptable hair regrowth could be attributed to the different sites (scalp and eyelids, respectively) and the surface area upon which treatment was applied.

In contrast, such results were contradicted by a number of studies that demonstrated a lack of efficacy of either latanoprost or bimatoprost in inducing hair regrowth in the AA of eyelashes 6,8,9. The frequency of application, which was twice in the current study and once in other studies, might be an explanation for the conflicting results. In addition, the medication might be washed out by tear secretion in case of application on the eyelids. The extent and severity of AA at baseline could offer another reason for the lack of efficacy of prostaglandin or prostamide analogs as illustrated by these studies 9.

The mean time after which hair regrowth started to occur was ∼2 weeks. This relatively short period might explain the satisfaction of 73.3% of patients (n=11) with bimatoprost therapy, inspite of the fact that acceptable hair regrowth was achieved by 40% of patients (n=6). The rapidity of response of prostaglandin and prostamide analogs was not discussed by other studies that utilized these agents for the treatment of AA of eyelashes. This observation requires further analysis and comparison with other therapeutic modalities of AA.

Regarding side effects, none were observed by the physician or the patients. The relatively high safety profile of bimatoprost and latanoprost was agreed upon by other studies that reported absence of side effects in patients treated by such agents apart from some transient conjunctival hyperemia and irritation 1,6–10.

A recent study by Khidhir et al. 20 has demonstrated the efficacy of bimatoprost in stimulating human scalp follicles in culture and rodent pelage follicles in vivo, mirroring eyelash behavior, and has shown that scalp follicles contain bimatoprost-sensitive prostamide receptors, which, when blocked by a prostamide antagonist, resulted in the inhibition of follicle growth. They concluded that their findings highlight a new follicular signaling system and confirm that bimatoprost offers a novel, low-risk therapeutic approach for scalp alopecias.

In accordance to the results of the current study, it could be concluded that bimatoprost represents a potentially effective therapeutic modality for AA of the scalp. Large-scale studies, a longer treatment duration, and modified formulations and concentrations of such medication are required for better interpretation of its possible role in the treatment of such a distressing condition.

Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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Keywords:

alopecia areata; bimatoprost; efficacy; safety

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