Use of Hydroxychloroquine in Hair Disorders

Abstract

Hydroxychloroquine (HCQ) is an antimalarial that is utilized to treat a range of dermatologic and autoimmune disorders. With its ability to alter immunologic mechanisms, it has been used to slow or halt the progression of hair loss in conditions secondary to autoimmune dysfunction. Lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and alopecia areata (AA) are hair disorders with underlying autoimmune components and no standardized treatment guidelines. We summarized the available literature on the use of HCQ to treat LPP, FFA, and AA. For all three conditions, HCQ showed variable efficacy from halted hair loss to no improvement. While patients did show success with HCQ treatment, there were no clear treatment patterns. Regimens ranged from HCQ monotherapy to combination treatments with other agents like steroids. Overall, HCQ should certainly be considered by clinicians as a treatment option for patient suffering from these hair disorders. While there is no standardized treatment, incorporation of HCQ should take into consideration individual patient characteristics, clinical judgment, and risks of side effects.

Plain Language Summary

Hydroxychloroquine (HCQ) is an antimalarial drug that acts on the immune system. Lichen planopilaris, frontal fibrosing alopecia, and alopecia areata are all disorders that result in hair loss secondary to immune dysfunction. HCQ has been used to treat these conditions, so publications addressing HCQ use for such hair loss disorders were collected, and the findings were summarized. Overall, HCQ showed mixed efficacy but can be a successful treatment option for some patients. Various treatment patterns were seen from using only HCQ to combination therapy plans with HCQ and steroids, for example. Treating these hair loss conditions can be challenging, and while there are no standardized guidelines, HCQ should be considered in the treatment arsenal for patients.

Introduction

Hydroxychloroquine (HCQ) is a versatile drug that has been employed for treating a variety of conditions, especially those autoimmune in nature. Its origin can be traced back to World War II when the rheumatologic benefits of antimalarials were realized with soldiers placed on malaria prophylaxis exhibiting reduced arthritic symptoms [1]. While originally classified as an antimalarial, HCQ has since been utilized for dermatologic diseases like lupus erythematous, dermatomyositis, granuloma annulare, cutaneous sarcoidosis, and lichen planus among others [2].

The exact mechanism of action of HCQ is not well understood, but it is believed to play an immunomodulatory role with anti-lymphocytic properties [3]. The drug regulates the immune system through blocking major histocompatibility complex class II (MHC II) antigen presentation, inhibiting cytokines, and preventing pathways involving B- and T-cell signaling [1, 3]. HCQ was recently found to inhibit endosomal Toll-like receptor (TLR) activation, masking the TLR binding site and blocking downstream immune activation [4]. Due to its ability to modulate immunologic systems, it is believed that HCQ can slow or halt the progression of hair loss in autoimmune scarring and non-scarring alopecias [4].

The current literature on HCQ for hair pathology demonstrates a mixed picture of efficacy with no clear standardized guidelines. There is a body of literature including retrospective reviews and case series that report efficacy in conditions such as frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) [2, 5, 6]. However, there are also contrasting studies which found that HCQ was not an effective treatment [7–9]. Few clinical trials exist on the matter, with just one trial registered with the National Institute of Health (NIH) for HCQ use in alopecia areata (AA) and alopecia totalis (AT).

While HCQ has shown positive clinical outcomes, it is not risk-free, causing the decision-making calculus regarding its use a complex one. Serious adverse effects of HCQ use include retinopathy, agranulocytosis, leukopenia, gastrointestinal conditions, hypoglycemia, and cardiac involvement such as QT interval prolongation, severe arrhythmias, and cardiomyopathy [10–14]. The goal of our paper was to synthesize the literature on HCQ use for hair disorders including LPP, FFA, AA, and lupus alopecia to understand current evidence and the landscape of clinical practice patterns.

Methods

A comprehensive search was performed using PubMed to identify articles discussing HCQ as a treatment for hair loss up until January 2023. Search terms included “hydroxychloroquine,” “antimalarial,” “hair loss,” “cicatricial alopecia,” “alopecia,” “lichen planopilaris,” “frontal fibrosing alopecia,” and “cutaneous lupus.” This initial search yielded 346 articles, each of which was reviewed for inclusion. Papers judged appropriate for inclusion were required to utilize HCQ for treatment of a hair loss condition and provide patient outcome data. Institutional IRB approval was not necessary for this study as this was a review of publicly available, de-identified case reports and articles.

Lichen Planopilaris

There have been multiple case reports and retrospective studies examining outcomes of HCQ treatment for LPP. Babahosseini et al. [15] performed a large retrospective review and found HCQ to have a clinical response rate of 59% for LPP with a good safety profile. Another retrospective review by Nic Dhonncha et al. [6] reported similar success in 23 patients with LPP. They found that 60.9% of patients had a full clinical response consisting of improved signs and symptoms and decreased progression of hair loss [6]. A case series performed with 46 patients identified HCQ to be the most effective treatment modality for LPP with the highest rate of remission when combined with topical corticosteroids [16]. Although Chiang et al. found that only 14% of their patients were full responders to 200 mg of HCQ twice a day, 72% of patients had at least a partial response [1]. There were three other studies that reported clinical improvement of LPP with HCQ [17–19].

While the previously mentioned studies had success with HCQ, there have also been reports of mixed or suboptimal results of HCQ for LPP. Two separate studies found that roughly 20% of their LPP sample population responded to HCQ therapy, indicating the treatment did not work for a significant portion of the other patients [20, 21]. Limited success or no clinical improvement with HCQ has also been noted in some cases in the literature. Mirmirani et al. [22] reported that all 3 of their patients failed treatment with HCQ but showed better outcomes with cyclosporine. In the only randomized controlled study, Naeini et al. [23] concluded that methotrexate was a more effective treatment option than HCQ for LPP. Methotrexate resulted in significant improvement of patient pruritus, erythema, scaling, spreading, and follicular keratosis, while HCQ only resulted in significant improvement of erythema [23]. Other reports also did not have success using HCQ to treat LPP [24, 25].

Frontal Fibrosing Alopecia

There have been many publications that have found HCQ a beneficial treatment modality for FFA. A retrospective study by Samrao et al. [5] reported that 73% of their FFA patients showed a reduction in signs and symptoms with the use of HCQ after 6 months. Zhang et al. [26] found similar results with 62.5% of patients responding to HCQ. Their cohort showed 1 patient with regrowth, while nine others showed disease stabilization [26]. Panchaprateep et al. [27] studied 58 females who were all Asian and reported similar findings. Sixty percent of their patients on HCQ stabilized, and 30% continued to improve [27]. Maldonado et al. [28] found 100% of their patients achieving stabilization with 200–400 mg per day of HCQ in conjunction with topical treatments. Suchonwanit et al. [29] conducted a retrospective study with 56 patients and found HCQ combined with topical steroids was the most successful regime compared to HCQ monotherapy. They reported that 79.3% of patients had disease stabilization with combination therapy [29]. A few other articles we encountered demonstrated either a majority of patients responding to HCQ treatment or FFA stabilization [2, 17, 20, 30–33]. Lastly, a study that exclusively examined men with FFA also found halted disease progression with HCQ [34].

However, there is also the literature on FFA treatment with HCQ showing mediocre or dissatisfactory findings. Babahosseini et al. [15] only reported a 10% response rate to HCQ and determined 5-α reductase inhibitors and systemic retinoids, alone or in combination, were superior treatment options for FFA. A retrospective study with 54 patients found some stabilization and improvement with HCQ but determined that oral 5-α reductase inhibitors were the most effective treatment option, followed by intralesional corticosteroids [35]. Starace et al. [36] studied 65 FFA patients and reported similar findings with steroids being the treatment of choice followed by 5-α reductase inhibitors or HCQ as maintenance therapy, but 5-α reductase inhibitors seemed to be more effective. In addition to these larger studies, there have been case series and case reports on HCQ use showing no improvement or continued hairline recession [7–9, 37–39].

Alopecia Areata

HCQ is not a traditional therapeutic for AA patients, but there have been reports of its use in this population. In 2013, Stephan et al. [40] were the first to report excellent results of HCQ monotherapy for patients with AT who failed multiple other therapeutic agents. Since then, there have been other cases with varying results. Yun et al. [41] saw that 5 out of 9 children with AA were responding to HCQ therapy with improvements following 6 months of treatment. Of note, the two most common side effects experienced were gastrointestinal intolerance and headache [41]. One patient with alopecia universalis (AU) showed signs of hair regrowth after roughly 1 month with a combination of azathioprine and HCQ [42]. The most recent case report published in 2023 found another AU patient exhibiting positive clinical outcomes on HCQ [4].

However, there were also studies that found minimal hair regrowth or no response to HCQ [43, 44]. A case series with 8 patients did not find improvement with HCQ, and five patients discontinued the treatment due to lack of regrowth [43]. Another case series found that HCQ was ineffective in 5 out of 6 patients and recommended against its use in treatment-resistant AU [44]. There was one clinical trial conducted on HCQ use for AA and AT; however, no results of the study were posted on the NIH site.

Lupus Alopecia

A full review of the use of HCQ as treatment for cutaneous lupus erythematosus (CLE) is beyond the scope of this paper; however, HCQ has been widely used for treating CLE [45, 46]. A retrospective study of 35 Japanese patients found HCQ an effective treatment particularly for non-scarring alopecia secondary to CLE [47]. Patients exhibited complete improvement, although a clinical response took time to elicit [47]. Classic lupus panniculitis/lupus profundus are rarer forms of scarring alopecia specific to lupus [48]. Cases of lupus panniculitis have shown positive responses and complete resolution in some patients with HCQ treatment [48–57]. A retrospective cohort study found 66.7% of discoid lupus erythematosus patients responding to HCQ [20]. Two reports of discoid lupus erythematosus patients taking HCQ also exhibited hair regrowth [58, 59]. Other cases have shown optimistic outcomes for lupus-associated alopecia treated with HCQ [60–63].

Other Forms of Alopecia

Follicular mucinosis is a rare disorder that causes accumulation of mucin in the pilosebaceous unit and sebaceous glands, leading to follicular degeneration and hair loss [64, 65]. Currently, there is no consensus on the most effective treatment [66]. For some patients, expectant management is adopted as follicular mucinosis can resolve spontaneously within 2 years [66]. Topical, intralesional, or systemic corticosteroids are some of the more commonly used treatments in addition to phototherapy, indomethacin, and isotretinoin [64]. Data regarding HCQ use are limited to case reports with varying results of efficacy. Schneider et al. [66] reported HCQ use in 6 patients with idiopathic follicular mucinosis and found improvement in all patients without any relapse. However, use in pediatric patients has shown inconsistent results [67, 68].

Aside from lupus, there are other systemic autoimmune disorders that can precipitate alopecia. Dermatomyositis can present with scalp involvement and lead to non-scarring alopecia [69, 70]. In a retrospective study, Tilstra et al. [70] saw no improvement in any patients on HCQ and suggested the use of methotrexate or mycophenolate mofetil. Sarcoidosis is another systemic condition that can involve the scalp leading to alopecia [71]. While topical steroid therapy is the most common treatment for cutaneous sarcoidosis, extensive disease may call for HCQ which has shown partial improvement in a handful of patients [71].

Side Effects

HCQ is considered relatively safe within standard dosing ranges of 200–400 mg/day, but there are some notable side effects that should be considered [72]. Retinopathy is one of the most highlighted risks of HCQ use, and providers frequently recommend ophthalmologic screening [73]. The guidelines set forth by the American Academy of Ophthalmology recommend a baseline eye exam within the first year of starting HCQ with annual eye screenings suggested after 5 years of use [73]. The drug can also be cardiotoxic, leading to cardiomyopathy or conduction abnormalities [73]. While there are no standard screening guidelines, the risk of cardiomyopathy seems to be linked to prolonged use of HCQ and the cumulative dose [74]. Routine ECG monitoring is not included in standard clinical guidelines for patients on HCQ; however, a baseline ECG prior to treatment might be beneficial for patients at higher risk for arrhythmic abnormalities [75]. In addition, for laboratory follow-up, a complete blood count and complete metabolic panel are important, but there are no clear guidelines for monitoring intervals [73].

Cutaneous side effects can be common with patients experiencing pruritus, urticaria, and rashes [72]. Adverse effects involving the gastrointestinal system such as nausea, vomiting, and diarrhea can occur [73]. However, these symptoms are usually temporary and resolve with decreasing the dose of HCQ [73]. Other side effects that have been noted include HCQ-induced myopathy, blood dyscrasias like agranulocytosis, hemolytic anemia, and hepatic dysfunction [73]. While these are typically rare adverse effects, the medical history of patients should be carefully assessed to determine potential risks so that prevention and screening strategies can be employed.

Discussion

Available evidence suggests HCQ can be a relatively successful therapeutic option. According to authors and consistent with our review, first-line treatments for LPP include topical/intralesional steroids early on and oral HCQ between 200 and 400 mg [76]. Several alternatives are also available including short-term systemic prednisolone, methotrexate, cyclosporine, and mycophenolate mofetil with methotrexate showing the strongest evidence and a relatively well-tolerated safety profile. While HCQ remains a viable therapy for FFA, 5-α reductase inhibitors have shown more success, such as dutasteride if postmenopausal and finasteride if pre-menopausal. Other agents include topical calcineurin inhibitors, retinoids, pioglitazone, naltrexone, tofacitinib, and excimer lasers. These should be considered in conjunction with topical or intralesional corticosteroids and topical minoxidil solution as androgenetic alopecia is associated with FFA. Lastly, data on HCQ use in AA are restricted to a handful of cases with variable results but can be considered since some reports showed success.

With a lack of standardized guidelines and clinical trials, it is hard to extrapolate the exact efficacy of HCQ as a treatment option for patients with these conditions. Other challenges include low prevalence rates, inconsistent disease progression, and a lack of standardized assessment tools. Spontaneous resolution of LPP and FFA has been reported, which can cloud the assessment of different therapeutic agents [77]. In general, patients’ expectations should be to aim for slowing or halting disease progression, with treatment starting as early as possible to maximize the potential for hair regrowth.

There is also a lack of objective measures to determine treatment progress. Recent studies have adopted the Lichen Planopilaris Activity Index (LPPAI) as a metric to determine treatment response, which relies on objective and subjective symptoms such as burning, pruritus, and pain [2, 5]. However, the LPPAI might be more appropriate for identifying symptomatic control rather than clinical progression of the disease. Progression of hair loss has been suggested as a superior assessment metric for treatment effectiveness [78].

A common thread with all these hair disorders is the spectrum of clinical outcomes noted when patients were treated with HCQ. This conglomeration of results indicates that HCQ should always be considered for patients. However, its use may ultimately rely on a clinician’s judgment along with patient expectations and goals of care. While risk factors are always considered, HCQ is relatively well-tolerated among patients with a low incidence of adverse effects at appropriate doses [46, 79].

Conclusion

HCQ is a versatile drug that continues to be used in a variety of medical conditions including alopecia. Hair disorders such as LPP, FFA, and AA have been treated with HCQ, and patient results have been variable. While the literature does not show a clear outcome pattern, HCQ is an agent that should be included within treatment arsenals as it does demonstrate some efficacy for a range of conditions. HCQ may be used as monotherapy but is frequently combined with other treatments such as steroids. Treatment plans should ultimately consider individual patient factors and a physician’s clinical judgment to determine the incorporation of HCQ.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

No funding to report.

Author Contributions

A.R., M.R., and W.A.S. participated in collection of the literature, synthesizing all relevant articles, and writing the manuscript. A.T. provided leadership on the project and edited all manuscript iterations.

Funding Statement

No funding to report.