Patients meeting criteria for FFA were mailed a study consent form, as well as a 2-page survey to assess demographics, clinical features of hair loss, medical histories, social and family histories, and treatments utilized. After receiving consent from patients, survey results were collected and summarized. If there was any need for clarification of answers, follow-up questions were conducted via email prior to any data analysis that was performed.
For analysis of treatment response, patients were asked what treatments they had utilized and about the progression of their hair loss. Patients reporting stabilization of hair loss or hair regrowth were classified as treatment responsive. Patients who underwent multiple treatments were included in the analyses for each of those treatments. Physician records for treatment response were not correlated with patient responses due to inconsistent documentation, care received outside of our medical system, and prolonged or loss to follow-up. Physician-reported data were only used to identify qualifying patients and their biopsy results, as described above.
Results
Patient Demographic
Between October 2013 and May 2014, 29 patients with FFA were recruited into the study. Patients were diagnosed between January 2006 and December 2013. There were 28 female patients (97%) and 1 male patient (3%). The average age of disease onset was 55.4 years (range, 29–75 years). Twenty-five patients (86%) self-identified as non-Hispanic white, 3 patients (10%) as Asian, and 1 patient (3%) as black. Patients also appeared to be a more affluent group than the general St. Louis County population, with a median household income between $75,000 and $100,000. In comparison, the median household income reported in St. Louis County from 2008 to 2012 was $58,485.23 The patient population was primarily composed of nonsmokers, with 22 (76%) patients who had never smoked, 6 (21%) who were present smokers, and 1 (3%) smoked in the past. These results were comparable to the reported number of female smokers in Missouri.24
Clinicopathologic Features
The clinical features of FFA are described in Table 1. All patients had frontotemporal recession of the hairline with some degree of scarring and perifollicular erythema (Figure 1). Most patients also reported hair loss at other sites, including 25 patients (86%) with eyebrow hair loss, 18 (62%) with limb hair loss, 11 (38%) with axillary hair loss, 11 (38%) with pubic hair loss, and 1 (3%) with eyelash hair loss. Patients also frequently reported inflammatory symptoms, including 19 patients (66%) with itching, 18 (62%) with redness, 3 (10%) with pain, 2 (7%) with papular lesions, and 1 (3%) with sores and erosions on the skin. Regarding progression of hair loss over time, 16 patients (55%) reported stabilization of hair loss, 11 (38%) reported progressive hair loss, and 2 (7%) reported some hair regrowth. Thirteen patients (45%) identified some inciting event that they believed to have triggered the disease. Ten patients (35%) identified stress as the inciting event, and 5 patients (17%) specifically referred to health-related stressors, including hip-replacement surgery, new diagnoses of systemic diseases, starting new medications, and stopping hormone replacement therapy. Furthermore, 2 (7%) patients reported exposure to chemicals and pesticides as suspected triggers.
Figure 1. Frontal fibrosing alopecia presents with frontotemporal recession of the hairline with scarring and perifollicular erythema.
Typical biopsy results showed a perifollicular lymphocytic infiltrate and fibrosis surrounding the infundibulum and isthmus of hair follicles (Figure 2). There were associated vacuolar changes in the basal layer and scattered dyskeratosis throughout the follicular epithelium. As the disease progressed to end-stage scarring, there was marked reduction in the number of hair follicles, which were replaced by fibrous tracts, and a disappearance of the previous inflammatory infiltrate.
Figure 2. Frontal fibrosing alopecia demonstrates a moderately dense lymphocytic infiltrate surrounding the infundibula of hair follicles. Scattered necrotic keratinocytes also can be noted within the follicular epithelium (H&E, original magnification ×100).
Medical History
Of the 26 female patients who provided data about menopause status at time of disease onset, 16 (62%) were postmenopausal, 5 (19%) were menopausal, and 5 (19%) were premenopausal. Of the 28 female patients in the study, 8 (29%) had a history of hysterectomy and 2 (7%) also had surgically induced menopause through bilateral surgical oophorectomy. Twenty-four patients (86%) had a childbearing history, with an average of 2.3 children. Twelve patients (43%) reported use of hormone replacement therapy after menopause. Twelve patients (43%) also reported a history of oral contraceptive use.
Table 2 describes the comorbidities of all 29 patients. A history of autoimmune disease was prominent, found in 16 patients (55%). Thirteen patients (45%) reported thyroid disease, including 10 patients (35%) with hypothyroidism. Additionally, 8 patients (28%) had a history of mucocutaneous lichen planus, 2 (7%) of psoriasis/psoriatic arthritis, 1 (3%) of vitiligo, 1 (3%) of systemic lupus erythematosus, 1 (3%) of iritis, 1 (3%) of Sjögren syndrome, and 1 (3%) of ulcerative colitis. Six patients (21%) also reported a history of breast cancer.
A dental history was obtained in 24 patients. All 24 patients reported having some dental implant or filling placed. Twenty-four patients (100%) had a history of metal amalgam implants, 8 (33%) had gold alloy implants, 4 (17%) had composite resin implants, and 3 (13%) had porcelain implants. Two patients had metal amalgam implants that had since been replaced by nonmetal implants. Both patients reported no change in their clinical conditions with removal of the metal implants. Six of 8 patients (75%) with mucocutaneous lichen planus reported having dental implants. Of them, all 6 patients (100%) reported having metal amalgam implants, and 3 patients (50%) additionally reported having gold alloy implants.
Treatments
On average, patients were treated with 3 different therapies for FFA (range, 0–14). The treatments utilized are listed in Table 3, and responses to treatments are summarized in Table 4. Topical steroids were the most popular treatment modality and were used by 21 patients (72%). Approximately half of those patients reported treatment response with stabilization of hair loss or regrowth (n=11; 52%). Hydroxychloroquine was the second most commonly used modality (16 patients [55%]), with 10 of those patients (63%) reporting treatment response. Intralesional steroids were used in 11 patients (38%), with a treatment response in 36% (4/11) of those patients. Topical pimecrolimus and tacrolimus were used by 6 patients (21%), with 5 of those patients (83%) reporting treatment response. UVB excimer laser therapy was used on 3 patients (10%) with 100% treatment response.
Treatments with little or no treatment response to hair loss include doxycycline, minocycline, and topical minoxidil. Seven patients (24%) were treated with doxycycline or minocycline, all of whom reported no clinical response. Topical minoxidil was used by 3 patients (10%), with only 1 patient (33%) reporting stabilization of hair loss but no regrowth of hair. 5α-reductase inhibitors such as finasteride and dutasteride were only used by 1 patient (3%), who reported no treatment response. Other treatments that were rarely used include meloxicam (n=2), azathioprine (n=2), oral clindamycin (n=2), bimatoprost (n=1), quinacrine (n=1), cephalosporin (n=1), prednisone (n=1), isotretinoin (n=1), methotrexate (n=1), spironolactone (n=1), topical clindamycin (n=1), and laser hair removal (n=1). Of these, only meloxicam and quinacrine were anecdotally associated with stabilization of hair loss, while the rest of the treatments were associated with progressive hair loss despite therapy.