Alopecia Areata Barbae in a Nutshell

• Beard alopecia areata’s patho-etiology differs from alopecia areata’s and warrants different evaluation and treatment.

Alopecia areata is the second most prevalent hair loss in men, after androgenetic alopecia [1]. Beard alopecia areata (BAA) affects the beard, moustache, and sideburn areas in men. It has a lifetime risk of 2% [1] and carries immense psychological burden on patients [2, 3]. The average age of onset for BAA is 31 ± 8 years, compared to a mean age of 22 years for nonbeard alopecia areata [4]. Alopecia areata is a T-cell mediated autoimmune disorder whereby there is a loss of the hair follicle immune privilege (HFIP) that leads to bulbar inflammation and temporary anagen arrest [5]. Currently, it remains unclear whether unique features of the beard morphology may contribute to the BAA’s pathogenesis. The objective of this review is to summarize the current pathogenetic, dermoscopic, and clinical findings of BAA and provide updates on its evaluation and treatment options.

We applied a modified PRISMA guideline to our literature review and performed a PubMed, ProQuest, and Embase database to identify relevant articles. We identified 215 records and excluded articles that were not focused on BAA, articles that did not discuss beard morphology, or whose treatment discussions were not applicable to alopecia areata or BAA. We also excluded articles that did not provide relevant information on immunology or the pathology of the disease. We included only English language articles.

Reviewed articles included qualitative and quantitative peer-reviewed studies such as cohort studies and case reports, literature reviews, book chapters, which had been published online and written in English. Our target population included post-pubescent men globally, who had experienced alopecia areata.

Papers were excluded if they were written in a non-English language, were not peer reviewed, were not directly relevant to our aims and objectives, or provided outdated information.

To narrow our search to the most relevant articles, we applied the following keywords and made use of MeSH terms and Boolean operators such as “and”, “or”, “MAJR” to obtain relevant results. Bibliographies and journal content pages were also searched manually. Terms included “hair follicle biology” and “beard”; “beard hair follicles”; “graying of hair”; “alopecia areata barbae”, “beard alopecia areata,” “trichoscopy and beard,” “hair diseases/pathology” and “barbae”; “alopecia areata/diagnostic imaging,” “beard loss.”

All quantitative studies were evaluated using EBLIP Critical Appraisal Tool [6] for assessment of validity.

Twenty-five articles were included in the review among which were 11 reviews, 11 clinical studies, and 3 case reports.

The beard hair follicle has a distinct morphology. It is elliptical with a diameter twice larger and 1,000 times stiffer than the scalp follicle. Compared to the adult scalp’s density of 615 follicles per cm², the beard density contains between 20 and 89 follicles per cm² [7]. All beard hairs contain a medulla, though there are some ethnic variations: for example, blond and grey hairs lack medullae and significant melanocytes in the outer root sheath and bulb regions [8, 9]. The medulla predominately expresses trichohyalin protein [9], which shows some autoimmune reactivity. However, trichohyalin is not autoreactive to the extent of nonmedullary proteins such as keratins and melanocytes, located in the IRS and ORS, respectively [9]. These nonmedullary proteins have been implicated in antigen reactivity [10] following a breakdown of the HFIP [11‒13]. Some phenotypic ethnic differences include a denser network of hair follicles around the mouth in Asian men [7], and a companion layer mutation in the k6hf gene that can increase by 6-fold the onset of chronic inflammatory conditions like pseudo-folliculitis barbae in African-American men [14, 15].

The beard follicle has a shorter anagen phase of 4–14 weeks and grows at 10 mm per month, compared to scalp hair’s anagen phase of 2–6 years and slower growth rate of 1.5 mm per day [10, 16]. Since anagen inhibition is the major pathogenic feature of AA, the shorter growth cycle of the beard HF may explain why BAA is more persistent.

Certain hormonal changes are unique to the physiology of the beard hair follicle. During puberty, the hormonal composition of the beard hair follicle changes such that previously quiescent sebaceous glands become active with androgen production and in some adolescents, a third superficial bulge emerges to form apocrine glands [10]. Additionally, the beard has a denser arrangement of androgen receptors and increased gene expression of type 1 and 2 5α-reductase compared to scalp dermal papilla cells [17], which convert testosterone to 5α-dihydrotestosterone. In the beard HF, testosterone leads to increased autocrine growth factors that are secreted by the beard papilla cells [18]. Therefore, the abundance of testosterone receptors and enzymes may offer a protective and hair sparing effect in the beard hair follicles in androgenetic alopecia compared to the scalp [19], which is described as the “androgen paradox” [20]. In BAA, as with scalp AA, the beard hair follicle hosts a reservoir of mast cells, which secrete other chemoattractant for T cells and cytokines and drive the T-cell-mediated inflammatory response [21]. With regard to differences in expression of biomarkers in the scalp and beard dermal papillae, four unique genetic markers (sfrp2, mn1, atp1β1, fibulin-1d) have been isolated [17]. Of note, the atp1β1 is a potassium-channel protein whose mechanism of action involves opening potassium channels and is a possible target of minoxidil therapy [22].

Although the collapse of the immune privilege in the bulb region is a key factor in the pathology of AA and BAA, the etiology is not as clear: there is still debate about whether AA is a true autoimmune condition whereby its triggers are purely endogenously gene mediated as in the case of thyroiditis, or whether AA merely embodies mechanisms of autoimmune diseases triggered by exogenous pathogens such as viruses. The literature consents that IFN-γ and IL15 are the key cytokine mediators in the collapse of immune privilege [21, 23, 24]. These cytokines induce a reciprocal upregulation of Th1 (CD4+) cells and CD8+ NKG2D + T cells that are key regulators of AA pathogenesis. Other pathogenic factors involved in the loss of immune privilege include nerve growth factor, which is a stress neurotrophin, as well as substance P [25]. Both have been linked to the premature termination of anagen/early onset of catagen by activating the p75 NTR receptor and upregulating MHC-1 expression in the hair follicle [25]. These factors simultaneously repress immunomodulators and markers of immune privilege in the bulb region, such as transforming growth factor-β (TGβ 1 and 2) as well as transmembrane glycoprotein CD200 [25‒28].

BAA has been associated with other autoimmune conditions of viral, gastric, and rheumatoid etiology, though the bases for these associations are typically from case reports and may be anecdotal. These associations include COVID-19, influenza, EBV, atopic dermatitis, thyroiditis, psoriasis, lichen planopilaris, idiopathic thrombocytopenic purpura, vitiligo, Crohn’s disease, and ulcerative colitis [2, 5, 29‒31]. Thyroiditis is particularly prevalent in patients with AA (8–28%) and BAA, such that screening of patients presenting with BAA is advised [32]. Bacterial and viral pathogens cause molecular mimicry and create an enabling environment for auto-reactive CD8+ and CD4+ T cells to attack the hair follicles [29]. It is thus important to eliminate these pathogens as this may promote spontaneous remission in some cases of BAA. For example, in a case report of a 43-year-old man presenting with BAA and H. Pylori infection, it was only after complete eradication of H. Pylori that his BAA remised, following a failed course of treatments with topical steroids and minoxidil [33].

BAA patches are well-circumscribed, oval, round, or elliptical with white hairs in the periphery [5, 34]. Most patients present first with more than one patch along their lower jaw line and neck (shown in Fig. 1c). The sideburn area appears to be least affected by alopecia areata, in contrast to frontal fibrosing alopecia which also usually presents with bilateral involvement of the eyebrows as a distinguishing clue [35]. The sideburns contain hairs that are more likely to be grey, white, or lack pigmentation and these hairs are characteristically spared by alopecia areata [36]. Approximately 50% of patients with active BAA present with extra-beard patches within 12 months with the scalp being the most affected region, followed by the limbs and eyebrows. Progression to extra-beard regions is associated with a longer duration of active BAA [30, 34].

Patients presenting with BAA lack accompanying nail changes such as pitting and striations that are characteristically seen in alopecia areata [30, 34]. Additionally, while alopecia areata has a genetic pattern of inheritance, BAA does not demonstrate genetic predisposition [37, 38], although the data are not unanimous. For example, a multicenter review in Caucasians in Spain found an association between a family history of alopecia areata [34] while another study of South-Asian men found no familial association at all [30].

The beard loss percentage can be objectively evaluated using the Alopecia Barbae Severity (ALBAS) score, a beard-specific version of the standard Severity of Alopecia Tool (SALT) for alopecia areata [39] (shown in Fig. 1). The ALBAS tool considers effect modifiers such as grooming preferences, pre-existing scars, atrichia and shows high inter-rater confluence scores. The ALBAS tool shows that the neck region was most affected, having a median score of 6.8/10 followed by the left and right beard regions (combined median score of 5.2/10) [40]. This finding corroborates with findings in other studies that showed the neck and beard sides to be the most visibly affected by BAA [7, 30, 36].

Common findings include tapered hairs, nonfollicular white dots, thin regrowing hairs, yellow dots, and black dots. Exclamation mark hairs, vellus hairs, and skirt-like epithelial structures are also seen [5, 10, 34, 41] (shown in Fig. 2). The most common differential diagnoses, their trichoscopic, histologic findings, and updated treatment options are summarized in Table 1.

BAA is rarely biopsied. On histology, the hallmark of active alopecia areata is the “swarm of bees inflammatory infiltrate pattern,” seen in the matrix, and the bulbar outer root sheath. This pattern depicts the T-cell lymphocytic infiltrate following collapse of HFIP. Other morphological changes in BAA include an edematous elliptical beard follicle, devoid of a medulla and melanocytes [10, 12, 42].

Most published treatment studies for BAA are retrospective cohorts based on small sample sizes (n < 70), or case reports. Most utilized treatments include topical and oral corticosteroids, minoxidil, and anthralin.

In a study of 55 BAA patients, 44% of participants who received intralesional steroids achieved >75% regrowth; 29% of the topical steroid treatment group achieved >75% regrowth, while no treatment group and topical 5% minoxidil treatment group achieved 25% and 18% regrowth, respectively; intralesional steroids had the highest regrowth rate (44%) compared to topical steroids (30%) and topical mindoxidil (18.8%). Relapses within 4 months after stopping the treatment are common. Spontaneous remission occurred in 16% of cases [34]. In a BAA patient with underlying diabetes mellitus and hypothyroidism, treatment with topical 0.1% triamcinolone acetonide cream twice daily for 6 months led to complete regrowth of his beard after 6 months [43].

One study found anthralin combined with diphenylcyclopropenone as an effective treatment for BAA in 6/67 patients [44]. However, these patients presented first with severe alopecia areata (>50% of the scalp), then with extra scalp involvement such as the eyebrow and beard. Diphenylcyclopropenone was applied to the scalp while topical 0.5–1% anthralin was applied daily on the beard for 10 min to 1 h, provided there was no dermatitis, for up to 30 weeks [44, 45]. Laser therapies such as 308 nm excimer laser for BAA yielded inconsistent results across studies: one study reported success in some beard cases [46] and another reported improved results only for patients with alopecia areata of the scalp [47].

Newer therapies include the janus kinase (JAK) inhibitors, which target inflammatory cytokines to reduce inflammation. The FDA recently approved oral baricitinib (Olumiant) for AA following two phase 3 randomized control trials involving 1,200 AA patients [48, 49]. Baricitinib reversibly inhibits JAK1 and JAK2 signaling pathways. Patients with a SALT score of ≥50 were administered either 4 mg or 2 mg of oral baricitinib once daily and achieved 38.8% and 22.8% scalp regrowth, respectively, at 9 months [48]. With regard to BAA specifically, the JAK inhibitor tofacitinib has shown positive results [50], and it has also improved severe forms of alopecia areata, such as AA totalis [51]. Lower doses of tofacitinib, such as 5 mg twice daily, are commonly used in the AA studies. Tofacitinib, in contrast to baricitinib, inhibits JAK1 and JAK3 signaling and the key cytokines for the activation of autoreactive T cells in the bulge region of the beard [48, 52]. A study of 45 patients with active BAA showed oral tofacitinib successfully regrew the beard [50] and 5 mg oral tofacitinib administered twice daily sustained regrowth and remission of hair around the body [51]. The mean SALT score before tofacitinib therapy was 62 ± 38 and after tofacitinib was 41.7 ± 38.5 [50]. Interestingly, the degree of regrowth in the beard was also an indicator for the degree of regrowth in extra-beard regions: for example, 22% of men achieved complete beard regrowth after an average of 16 months, and 60% of these men also achieved complete scalp regrowth. By contrast, 19% of men achieved partial beard regrowth and of these only 1% achieved complete scalp regrowth by the end of 3 years [50].

There are limited data on topical JAK inhibitors for BAA. A retrospective study showed topical tofacitinib to be a potent alternative to oral tofacitinib, especially where systemic therapy had failed or was contraindicated for BAA treatment. The average age of the 9 men studied was 30 years, and prior to receiving treatment, the median duration for facial loss was 18 months. Topical tofacitinib was compounded at 2% into a poloxamer gel and administered twice daily for a range of 3–22 months, and 22% of the men achieved complete regrowth, while 55% achieved partial regrowth of beard hair [53]. Ruxolitinib is another JAK1/JAK3 inhibitor which has been studied to a lesser extent for the treatment of AA. In a case of an ultraorthodox Jewish man, for whom the loss of the beard had a significant effect on the social life, treatment with ruxolitinib 20 mg twice daily for 4 months resulted in complete regrowth [54].

In one case report, a patient with BAA showed full beard regrowth when PRP was injected three times at 6-week intervals [55]. Other emerging therapies include anti-Notch-1. It is being explored for melanomas but may also prove viable for BAA because the Notch family plays a role in development of hair follicle layers and stem cell differentiation. In particular, the Notch-4 T1297C allele was most upregulated in the severe forms of AA, such as AA totalis [56, 57].

Systemic immunomodulatory therapies such as disease-modifying antirheumatic drugs (DMARDs) have been used successfully in AA. Although it has not yet been used in BAA, DMARDs such as sulfasalazine target similar BAA markers mentioned above such as NFkB and IL-1. In fact, treatment with sulfasalazine 1–3 mg daily for 6 months showed >60% regrowth in 57% of patients with alopecia areata [58]. The DMARDs also had improved relapse time compared to steroids (10 months compared to 4 months) [58].

Our review provides an updated diagnostic toolkit for clinicians seeking to better understand, diagnose, and treat BAA. Further data from cohort studies and randomized controlled trials are necessary to better characterize and manage BAA, respectively.

An ethics statement is not applicable to this review article.

The authors have no conflicts of interest to declare.

The authors have no funding sources to declare.

Adaeze Nwosu made substantial contributions to the analysis, interpretation of the literature in this manuscript, and the design of Figure 1 listed and all tables in the work. She drafted and revised the manuscript critically for important intellectual content and gave final consent for the version to be published. She agrees to be accountable for all aspects of the work. Dr Mariya Miteva made substantial contributions to the acquisition, analysis, and interpretation of data for the work and the acquisition of Figure 2 listed in this work. She revised the manuscript critically for important intellectual content and gave final consent for the version to be published. She agrees to be accountable for all aspects of the work.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.