Treatment of Frontal Fibrosing Alopecia

Beyzaee, Amir Mohammad; Goldust, Mohammad; Patil, Anant; Ghoreishi, Bahare; Ghahremanloo, Tahoora; Rahmatpour Rokni, Ghasem

doi:https://doi.org/10.1155/2023/3856674

Dermatologic Therapy

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Abstract Introduction Methods Results Discussion Conclusion Data Availability Conflicts of Interest Authors’ Contributions References Copyright Related Articles

Review Article | Open Access

Volume 2023 | Article ID 3856674 | https://doi.org/10.1155/2023/3856674

Treatment of Frontal Fibrosing Alopecia

Amir Mohammad Beyzaee,¹Mohammad Goldust,²Anant Patil,³Bahare Ghoreishi,⁴Tahoora Ghahremanloo,⁴and Ghasem Rahmatpour Rokni⁵

Academic Editor: Nawaf Al Mutairi

Received23 Dec 2022

Revised26 Jan 2023

Accepted03 Feb 2023

Published16 Feb 2023

Abstract

Introduction. Frontal fibrosing alopecia (FFA) is known as a lymphocytic primary cicatricial alopecia. The main characteristic of FFA is progressive frontotemporal hairline recession. The pathogenesis of FFA is not completely understood. Destructing the stem cells of the epithelial hair follicles causes permanent hair loss and seems to be the main cause of FFA. Studies have reported significantly decreased quality of life in patients with hair loss. On the other hand, late diagnosis and treatment of FFA can decrease the success rate of the treatment. In this regard, different topical and systemic therapies have been developed to resolve the symptoms; however, only a partial response to treatment is usually achieved. We conducted a systematic review of the literature to identify the effectiveness of the available treatment modalities used for FFA patients and the related outcomes. Methods. On April 2022, we made a wide systematic computer-assisted search of PubMed and Google Scholar databases, using “frontal fibrosing alopecia” and “treatment” keywords. We scanned 1,514 articles. All the studies concerning a therapeutic regimen for FFA were included. After removing duplicate studies, 50 studies containing the therapeutic regimen of 1,478 FFA patients were included in this review. Results. The 5-alpha-reductase inhibitors (oral finasteride/dutasteride) were the most used medications (usually prescribed as a combination therapy with other medications). Topical corticosteroids were the second commonly used medication for the treatment of FFA. Systemic corticosteroids seem to be ineffective in improving FFA progression. Oral isotretinoin (or alitretinoin) had the most promising effect on improving facial papules of FFA patients with a 92% rate of facial papule improvement. Conclusion. In our review, intralesional corticosteroid injection and 5-alpha-reductase inhibitors (finasteride/dutasteride) were reported as the most effective treatment modalities. Oral isotretinoin (or alitretinoin) is considered as the most promising treatment for improving facial papules in the context of FFA. However, it had minimal effects on hair regrowth or stabilization of hairline recession in FFA patients.

1. Introduction

Frontal fibrosing alopecia (FFA), first described by Kossard in 1994, is known as a lymphocytic primary cicatricial alopecia [1]. As reported in the literature, most of the patients affected by FFA are postmenopausal women [2], although it has also been reported in men and premenopausal women [1, 3–5]. The main characteristics of FFA are progressive frontotemporal hairline recession, eyebrow hair loss, body hair loss, and perifollicular erythema and hyperkeratosis [1], which are commonly accompanied by itching, burning, or pain [6]. In FFA, infundibulum and isthmus of the hair follicles are surrounded by lymphocytic infiltration and fibrosis, often with sebaceous gland loss. According to the histological presentation, FFA is assumed to be a variant of lichen planopilaris (LPP), which is known by multifocal patches of alopecia, pruritus, burning, and tenderness in the affected area [3]; however, this assumption is still controversial.

The pathogenesis of FFA is not completely understood. The destruction of the stem cells of the epithelial hair follicles, where the infiltration of the inflammatory cells primarily happens, causes permanent hair loss, and seems to be the main cause of FFA. The proinflammatory cytokines such as interferons, the increased apoptotic response, and the collapse of the relative immune privilege of the hair follicle could be considered as trigger to an ongoing inflammatory response, leading to the mentioned stem cell destruction [7]. Also, the possible pathogenetic role of androgens has been proposed, as well as the theory that the melanocyte of the upper hair follicle might represent the antigenic target in FFA [8].

Beside this, studying gene expressions has indicated a defective lipid metabolism signaling pathway in LPP, which is a vital part of sebaceous gland function [9].

Studies have reported a significantly decreased quality of life in patients with hair loss. Loss of self-confidence and low self-esteem are the most common psychosocial findings in women with alopecia [10]. On the other hand, late diagnosis and treatment of FFA can decrease the success rate of the treatment [11].

In this regard, different topical and systemic therapies have been developed to resolve the symptoms [11]; however, only a partial response to treatment is usually achieved [12].

Numerous studies have tried to represent a better insight into or management of FFA. We conducted a systematic review of the literature to identify the effectiveness of the available treatment modalities used for FFA patients and the related outcomes.

2. Methods

On April 2022, we made a wide systematic computer-assisted search of PubMed and Google Scholar (Embase, Scopus) data base, using “frontal fibrosing alopecia treatment” keyword. We scanned 1,514 studies (Figure 1).

All types of studies, including case reports, case series, case-control studies, randomized controlled trials, cohort and cross-sectional studies, and retrospective and prospective observational studies, were reviewed. Furthermore, we checked the references of included studies and also review articles concerning the FFA, and related studies were included. On data acquirement, no language limitation was applied.

The studies reporting no treatment or outcome of the treatment, no histopathological diagnosis of FFA, or those concerning different topic were excluded. All the studies concerning a therapeutic regimen for FFA were included.

After removing duplicate studies, 50 studies containing the therapeutic regimen of 1,478 FFA patients were included in our review. The characteristics of studies, including the name of the first author, type of study, number of patients, mean age of the patients, diagnosis, evidence of histology, the mean of disease duration, administered therapeutic regimens, outcome evaluation criteria, response to treatment, and follow-up duration, are summarized in Table 1 [1, 3, 4, 13–59].

When first a treatment modality was administered, and later another one, both of these treatments were included.

There are no standard criteria for measuring the treatment outcome of FFA. So, the studies used different qualitative and quantitative indices for measuring the treatment outcomes of the patients. In order to evaluate the response to treatments, we classified the results of studies as “improved,” “stabilized,” and “worsened” groups, according to the hired outcome measurement index. When patients experienced improvement, including hair regrowth, symptom recovery, or any improvement in the course of disease, it was classified as “improved.” When a halt in hair loss or a steady state of the disease was observed, it was classified as “stabilized.” When no improvement or stabilization was achieved or worsening of the disease course was reported, it was classified as “worsened.”

In Table 1, where the “response to treatment” chart is reporting one outcome or the “Duration” chart is reporting a single period of time, it refers to the combination of administered treatment modalities; if not, the period of consumption and outcome of each treatment modality is noted separately.

3. Results

Various criteria were hired to evaluate the outcome of therapeutic regimens used for FFA treatment; however, response to treatment was different among the studies (summarized in Table 1). The efficacy of treatment modalities hired for treating FFA is summarized in Table 2.

Overall, 1,478 FFA patients were described. They received different therapeutic regimens as monotherapy or combination therapy.

Oral finasteride (1, 2.5, or 5 mg per day) or dutasteride (0.5 mg per day) were the most used medications (508 patients) (usually prescribed as a combination therapy with other medications; most often with topical treatments (topical steroids, topical minoxidil, topical retinoids, topical tacrolimus or pimecrolimus) or intralesional corticosteroids), of which, about 47% with monotherapy and 5% with combination therapy reported improvement, and 48% with monotherapy and 73% with combination therapy reported stabilization of the disease status after a course of 6–18 months of treatment.

Topical corticosteroids were the second prevalent medication used in FFA patients (312 patients); however, they were always utilized in combination with other treatment modalities and made it difficult to evaluate their effectiveness individually.

Systemic corticosteroids seem to be ineffective in improving FFA progression. All the 6 cases treated with oral corticosteroids as monotherapy or combination therapy experienced worsening of the disease status, as well as the patients taking intramuscular triamcinolone acetonide.

Intralesional corticosteroid injection was reported as one of the most effective treatments; 27% with monotherapy and 27% with combination therapy reported improvement, and 64% with monotherapy and 58% with combination therapy reported stabilization of the disease status.

Although topical calcineurin inhibitors (tacrolimus/pimecrolimus) were always prescribed with other treatment modalities as combination therapy, satisfactory results were reported (60% improved and 37% stabilized).

Improvement was reported in 28% and 19% of the patients taking oral antimalarial drugs (hydroxychloroquine/chloroquine) as monotherapy and combination therapy, respectively, as well as stabilization in 37% and 51% of the mentioned patients.

Oral isotretinoin (or alitretinoin) had the most effect on improving the facial papules of FFA patients, with a 92% rate of facial papule improvement.

Low-dose oral minoxidil was prescribed only once in the literature for the purpose of eyebrow regrowth in 7 patients [22]. The results were satisfactory, as complete regrowth in 2 patients and partial regrowth in 5 patients were achieved. Moreover, topical bimatoprost ophthalmic solution 0.03% was reported as a hopeful medication for eyebrows regrowth in FFA patients [27, 35]; as well as light-emitting diodes (LEDs) therapy [53].

Also, using the Nd:YAG nonablative laser was reported as an effective method to improve disease symptoms [54].

Platelet-rich plasma (PRP) injection was hired to achieve stabilization of hair loss and improvement of hairline recession in 8 FFA patients, which showed noticeable positive results [28, 29].

Tildrakizumab (interleukin-23 monoclonal antibody) was administered to a recalcitrant FFA patient who had not responded to various topical and systemic medications; however, symptomatic improvement at week 16 and objective clinical and dermoscopic improvement at week 28 were observed with no adverse effects [31].

FFA patients who hired the hair transplantation technique achieved complete satisfaction; however, the result was temporary. Most of the transplanted hair follicles did not survive 2–4 years after transplantation.

4. Discussion

As no definitive therapeutic regimen is specified for FFA, we searched the literature for utilized FFA treatments and their effects.

Currently, no standardized criteria are identified to evaluate the treatment efficacy in FFA patients.

Recently, some authors used the LPPAI (Lichen Planopilaris Activity Index), which is calculated by assessing subjective symptoms (pruritus, burning, and pain) and objective signs (erythema, perifollicular scaling, and hair loss) of the disease [42, 43]. Authors hiring other criteria than LPPAI mainly focus on the improvement of hair loss by various methods like counting hair shafts, serial photographical evaluation, or assessing the frontotemporal hair line resection according to the patient reports (represented in Table 1).

As the main complaint of FFA patients is permanent hair loss [1], we propose that improvement or stabilization of hair loss should be considered for outcome measurement of FFA treatment.

In our review, intralesional corticosteroid injection and 5-alpha-reductase inhibitors (finasteride/dutasteride) were reported as the most effective treatment modalities, according to the disease improvement or stabilization rate. Some authors have revealed the accompanying role of androgenetic alopecia in FFA [45]. Perhaps, it might be an explanation for antiandrogenic drugs’ efficacy.

Oral isotretinoin (or alitretinoin) is considered as the most promising treatment for improving facial papules in the context of FFA; however, it had minimal effects on hair regrowth or stabilization of hairline recession in FFA patients.

Also, topical calcineurin inhibitors (tacrolimus/pimecrolimus) can be considered a useful adjuvant treatment in combination therapies.

Oral antimalarial drugs (hydroxychloroquine/chloroquine) cannot be proposed to FFA patients as a hopeful and effective treatment, according to the low rate of disease improvement or stabilization with either monotherapy or combination therapy; neither can topical corticosteroids be recommended.

Tildrakizumab, oral minoxidil, topical bimatoprost ophthalmic solution 0.03%, LED therapy, Nd: YAG nonablative laser therapy, and PRP injection are newly introduced therapeutic methods for FFA and have shown satisfactory results. They can be administered cautiously for FFA patients with progressive disease status despite taking standard medications; however, more clinical trials and investigations are needed to prove their effectiveness and propose them as promising treatments for FFA.

Although hair transplantation results are satisfactory in the first 2 years, the long-term outcome is disappointing.

We propose hair transplantation for FFA patients with at least 2 years of disease stabilization. The donor region should be observed carefully in terms of follicular inflammation. Also, close postoperative follow-up sessions are highly recommended (every 4–6 months). In case of existence of any sign of perifollicular hyperkeratosis or erythema after the transplantation, medical treatment must be prescribed. These patients should be followed up for a long time.

Finally, a complete justificatory discussion should be conducted with the patients in terms of the duration of the results and the risk of hair loss in the long term follow-up.

Limitations of this study were the various doses and durations of therapeutic regimens with different follow-up periods and different scales to assess treatment outcome, which made it difficult to evaluate the true efficacy of medications.

5. Conclusion

Intralesional corticosteroid injection and 5-alpha-reductase inhibitors (finasteride/dutasteride) were reported as the most effective treatment modalities. Oral isotretinoin (or alitretinoin) is considered the most promising treatment for improving facial papules in the context of FFA; however, it had minimal effects on hair regrowth or stabilization of hairline recession in FFA patients. Also, topical calcineurin inhibitors (tacrolimus/pimecrolimus) can be considered as a useful adjuvant treatment in combination therapies. Oral antimalarial drugs (hydroxychloroquine/chloroquine) cannot be proposed to FFA patients as a hopeful and effective treatment. Tildrakizumab, oral minoxidil, topical bimatoprost ophthalmic solution 0.03%, LED therapy, Nd: YAG nonablative laser therapy, and PRP injection are newly introduced therapeutic methods for FFA and have shown satisfactory results. They can be administered cautiously for FFA patients with progressive disease status despite taking standard medications. Although hair transplantation results are satisfactory in the first 2 years, the long-term outcome is disappointing.

Data Availability

The data are available on request.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

A.M.B. performed the research. M.G. and G.R.R. designed the research study. A.M.B. and T.G. contributed essential reagents or tools. A.M.B. and B.G. wrote the paper. G.R.R., M.G., and A.P. revised the paper.

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Copyright © 2023 Amir Mohammad Beyzaee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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