Frontal Fibrosing Alopecia Demographics: A Survey of 29 Patients

Comment

Frontal fibrosing alopecia is a form of cicatricial alopecia considered to be a clinical subset of LPP. Although the pathogeneses of both diseases are poorly understood, LPP is the better-studied model and is generally considered to be an autoimmune disease specific to the hair follicle, involving a cell-mediated inflammatory response to epithelial hair follicle stem cells.¹² In support of this hypothesis, FFA and LPP have been frequently associated with autoimmune diseases, particularly with hypothyroidism.^6,13-15 We found that 55% of our patients had a history of autoimmune disease, including 35% with hypothyroidism, 28% with mucocutaneous lichen planus, 7% with psoriasis, 3% with vitiligo, 3% with systemic lupus erythematosus, 3% with iritis, 3% with Sjögren syndrome, and 3% with ulcerative colitis. The link between FFA and hypothyroidism has been the best studied, with a large study by Atanskova Mesinkovska et al¹⁴ finding that 34% of 166 patients with LPP and FFA have some kind of thyroid disease and 29% have hypothyroidism. Frontal fibrosing alopecia also has been associated with mucocutaneous lichen planus,^8,15,17 vitiligo,^15,18 Sjögren syndrome,¹⁹ and lichen sclerosus et atrophicus^15,19 in other studies, but the current study also identifies less frequently reported associations between FFA and psoriasis, iritis, and ulcerative colitis.

Although FFA has been classically described to affect postmenopausal women, recent studies have consistently identified that premenopausal women^4-6,8,16,17 and men^14,16 also can be affected by the condition. In our patient cohort, there was 1 male patient (3%), and a substantial number of the female patients were premenopausal (19%) and menopausal (19%) at the time of disease onset. Most of the patients studied were white; Asian and black patients were a consistent minority across FFA studies,^5,13-16,25 highlighting the importance of screening for FFA in all demographics.

In our study, FFA patients also appeared to be more affluent than the general population and were predominantly nonsmokers (76%). These statistics are consistent with the United Kingdom population studied by MacDonald et al,⁶ which demonstrated a higher socioeconomic status and higher incidence of nonsmoking in their cases of FFA. Another large retrospective study of FFA patients in Spain found that 87% of their FFA cases (N=355) were nonsmokers, though they did not note a difference from the general unaffected population.¹⁵ In our study, we replicated these trends, finding an above average affluence level and a high but not statistically significant incidence of nonsmokers. Although it is not clear how socioeconomic status or smoking factors into the pathology of FFA, these studies may show a general trend in the environmental demographics of the disease.

Clinically, patients with FFA typically present with hair loss of the scalp as well as other sites. The eyebrows are the most common site to be affected outside of the scalp, affecting 86% of our patients, whereas eyelashes are the least commonly affected, presenting in only 3% of our patients. Body hair loss also is common, with almost two-thirds of our cohort reporting hair loss on the limbs and more than one-third reporting loss of axillary and pubic hair. These findings are consistent with those of other studies.^3-6,8,13,15 Eyelash loss, body hair loss, and facial papules have been found to be associated with more severe forms of FFA,¹⁵ though we did not investigate these forms in our study. Inflammatory symptoms are common, with pruritus affecting 66% of our patients and pain affecting 10% of patients, consistent with the published literature.^3,13,15,17

Multiple studies have shown that female FFA patients have a higher incidence of hysterectomies in their medical history.^5,8,15 This observation has been used to further support the hypothesis that a change in sex hormone balance may trigger the initial onset of disease.^5,8,15 A considerable number of the female patients in our study had also undergone hysterectomies (29%). Only 2 patients (7%) underwent premature surgical menopause through bilateral removal of the ovaries, and neither of these patients had abnormally early onset of FFA (age at onset, 52 and 65 years). Many patients in our study also reported a history of pharmacologic manipulation of sex hormones with hormone replacement therapy (43%) and oral contraceptive use (43%). However, patients with FFA have not been identified to have abnormal hormone levels compared to unaffected postmenopausal women.¹ Additionally, the disease does not exclusively affect androgen-dependent hair, as indicated by the high prevalence of eyebrow hair loss. We hypothesize that the link between increased prevalence of hysterectomy and FFA is not due to hormonal changes but rather from the stresses related to the hysterectomy or associated conditions that required the surgery. In our study, 35% of patients identified stress as the inciting event prior to their onset of hair loss, with 17% specifically referring to health-related stress such as surgery or new diagnoses as the cause. Although this pattern is purely observational, it is valuable to consider that stress could contribute to the initial onset of FFA as with alopecia areata.²⁶

A dental history was obtained in 24 patients to explore the possibility of FFA as a manifestation of contact allergy secondary to exposure to metal dental implants. Contact allergies to metal amalgam and gold alloy dental implants/fillings frequently have been described as presenting as oral lichen planus in the literature.^27-34 Given the histologic overlap between oral lichen planus and LPP/FFA, it is worth exploring the possibility that LPP and FFA are other manifestations of contact allergic response. In our study, 100% of the patients who provided a dental history had metal amalgam implants and 33% had gold alloy implants. It is an interesting observation, but it should be noted that none of the patients in our study had undergone patch testing for contact allergies to the metals in their dental implants, and further studies are required to explore this hypothesis.

Frontal fibrosing alopecia is a difficult condition to treat. In our study, patients tried an average of 3 different treatments, the most common being topical steroids (72%), hydroxychloroquine (55%), and intralesional steroids (38%). 5α-reductase isozymes were rarely utilized for patients in this study. Treatment response was noted in most patients using topical steroids, hydroxychloroquine, topical calcineurin inhibitors, and excimer laser therapy. Intralesional steroids also were efficacious in about 36% of patients treated. Little to no treatment response was reported in patients using doxycycline, minocycline, and topical minoxidil.

A PubMed search of articles indexed for MEDLINE using the terms randomized control trial and frontal fibrosing alopecia yielded no randomized controlled trials that have been performed to demonstrate the most efficacious treatments of FFA. However, one systematic review of 114 patients found 5α-RIs, antimalarials, and intralesional corticosteroids to yield the best responses in treating FFA.²² Another large, multicenter, retrospective study of 355 patients also demonstrated that 5α-RIs and intralesional corticosteroids minimized hair loss most effectively across treatment modalities.¹⁵ One treatment that was not discussed in either study but was utilized in ours was the UVB excimer laser, which has been demonstrated to induce T-cell apoptosis and decrease inflammation in psoriasis but has been infrequently studied in the use of FFA or LPP. In one study of 13 patients with LPP, excimer laser treatment was successful in reducing inflammatory symptoms and improving hair loss.³⁵ Our results reaffirm that laser therapy could be considered more frequently as a treatment of FFA.

This study is subject to several limitations. The study size was comprised of a relatively small number of patients with the condition. Additionally, only one-third of patients contacted agreed to participate in the study, and therefore the responses received may not be completely representative of all FFA patients. With a retrospective study, there is potential for recall bias in the data that are collected. Physician chart correlation to patient responses could not be reliably performed due to inconsistent documentation, care received outside our medical system, and prolonged or loss to follow-up. Another concern is that not all diagnoses of FFA in this study were biopsy confirmed. In one patient with systemic lupus erythematous who declined biopsy, it cannot be confirmed that her etiology of scarring alopecia was FFA rather than discoid lupus erythematous. Finally, because patients were treated with multiple medications, often concurrently, it was difficult to parse out which medications were efficacious and which were not. Despite these limitations, the findings in the study add to the growing literature about a rare but increasingly prevalent presentation.

Conclusion

Frontal fibrosing alopecia is a condition that predominantly affects white postmenopausal women but should not be overlooked in other demographics; higher socioeconomic status and nonsmoking are consistent with cases of FFA worldwide. Alopecia frequently involves other body hair, particularly the eyebrows, and is commonly associated with pruritus and pain. Many patients can identify an inciting event, usually stress, a health crisis, or new external exposures that they believe to have triggered the event. Consistent with data about LPP, FFA is frequently associated with autoimmune conditions, particularly hypothyroidism. A substantial portion of patients with FFA have had metal amalgam or gold alloy dental implants placed, though no patch testing was done to confirm that these patients have a contact allergy to these metals. Treatment for the condition is difficult, but topical and intralesional steroids, hydroxychloroquine, calcineurin inhibitors, and excimer laser therapy are efficacious in a large proportion of patients. Nevertheless, further research through prospective randomized trials is necessary to determine the best treatment modalities for FFA. Frontal fibrosing alopecia is a scarring form of hair loss that causes substantial emotional distress; therefore, it is critical to continue to investigate its etiology and treatments to improve patient care.