Are You Confident of the Diagnosis?
What you should be alert for in the history
Women with frontal fibrosing alopecia (FFA) note a rapid onset of frontal hair recession. This recession usually includes the temporal hairline; however, the emergence of hair loss can be subtle and slowly progressive. A useful clue to the diagnosis is frequently the loss of eyebrows, a loss that can precede the frontal recession.
Loss of hair over the limbs, pubic skin, and axillae may also be observed. By the time the medical consultation occurs, the process is often advanced.
Although most women with the disease are postmenopausal and elderly, premenopausal women have also developed FFA. This pattern has also followed oophrectomy. There are isolated reports of FFA in men.
Characteristic findings on physical examination
Physical examination reveals a symmetrical wide band of pale skin, lacking follicular orifices as a result of the receding hairline. The hair follicles immediately behind the receding hairline often have evidence of perifollicular erythema and an orificial scale (Figure 1).
The areas of fibrosing alopecia do not appear grossly scarred and there is an absence of mottled pigmentation, marked scaling, pustules, or groups of hairs forming tufts.
The hair loss over the limbs and axillae may appear nonscarring and can mimic alopecia areata, but the follicles are also permanently lost at these sites due to fibrous tract formation.
Expected results of diagnostic studies
Skin biopsy is the main diagnostic test, but is not always necessary because of the distinct clinical features. The biopsy should be taken at the receding hairline, within the area where there is evidence of perifollicular erythema. A 4mm punch biopsy is ideal, as it contains 30-40 follicles or fibrous tracts and allows quantitative analysis.
Histopathology characteristically shows perifollicular concentric fibrosis and lymphocytic inflammation targeting the infundibular area, isthmus, and also the underlying follicular canal associated with a fully keratinised internal root sheath (Figure 2).
The lichenoid reaction in FFA targets and destroys the follicular sheaths and stem cell region, but spares the interfollicular epidermis and also the lower follicle and hair bulb region. The follicles are progressively destroyed and replaced by fibrous tracts. Biopsies from the pale areas devoid of hair show only fibrous tracts and not the primary pathology. The finding of gross interfollicular scarring, panfollicular lymphocytic inflammation, or involvement of the interfollicular epidermis in a biopsy should prompt a search for an alternate form of scarring alopecia that may mimic FFA.
Laboratory investigations, including hormonal studies, thyroid function tests, and tests for connective tissue disease, have been unhelpful. A positive antinuclear antibody (ANA) may occur in elderly women, in the absence of clinical evidence for lupus erythematosus.
FFA has not been linked with any medications, and hormone replacement therapy has not prevented its development.
The differential diagnosis of FFA includes:
Frontal recession and loss of eyebrows may be seen in alopecia areata. Usually, there is a history of previous episodes of hair loss and recovery. In alopecia areata, multifocal patches of alopecia are often present, and the marginal involvement is often more prominent over the occipital and parietal areas. Preservation of follicular orifices, black dots, exclamation mark hairs, and small infundibular cystic structures are seen in alopecia areata and may be better appreciated with dermoscopy.
Lupus of the scalp usually results in multifocal areas of hair loss, with gross scarring, dyspigmentation, and lipoatrophy. Lupus is rarely confined to the frontal hairline or associated with total loss of the eyebrows. Signs of cutaneous lupus on sun-exposed sites is often helpful in the differential. Scalp biopsy and serological tests for lupus are helpful in difficult cases.
GENETICALLY BASED HIGH FRONTAL HAIRLINE
This condition usually has an earlier age of onset and a family history. The process is slow, without evidence of fibrosing hair loss or loss of eyebrows. This pattern is seen much more frequently in men.
This condition usually presents as a progressive thinning of the density of the hair, and does not have the symmetrical and often sudden progressive frontal hair loss and involvement of the eyebrows seen in FFA. In traction alopecia, the hair loss is often patchy and affects the temporal areas. In the frontal area, the loss may be more marked behind a preserved frontal hairline.
PUSTULAR SCARRING ALOPECIA
Rare presentations of scarring alopecia in the frontal hairline may be due to pustular scarring alopecia. Usually, this is associated with preceding gross erythema, scaling, and follicular pustules. Tufted groups of hairs and varioliform scars may emerge. Scalp biopsy and bacterial cultures will help to differentiate these cases.
Who is at Risk for Developing this Disease?
Frontal fibrosing alopecia was originally described in postmenopausal women, but now has been seen in premenopousal women. More rarely, younger women who have had oophorectomy have also developed FFA.
Isolated reports of men with this form of alopecia have also been documented.
Elderly women, often years after menopause, represent the main group who present with FFA.
What is the Cause of the Disease?
The etiology of FFA remains unknown. The process appears to be particularly linked to elderly women, in the years following menopause, and has a distinct pattern of distribution. Hormone replacement does not appear to prevent the appearance of FFA.
Hypothetically, a late onset of pattern alopecia in elderly women that involves recession of the frontal and temporal hairline may trigger an autoimmune lichenoid response in the setting of age-related diminished immune tolerance.
The relative rarity of FFA in men may reflect the earlier onset of this pattern of androgenic alopecia in men when immune tolerance is intact.
The induction of this reaction at the frontal hairline may subsequently trigger a more widespread destruction of the eyebrows and hair follicles at other sites. Scalp biopsy in FFA shows loss of follicles and perifollicular fibrosis with a lichenoid reaction that targets the infundibular and isthmus region of hair follicles, destroying the stem cell population.
Systemic Implications and Complications
There are no known systemic associations in FFA, and currently the process is best classified as a variant of lichen planopilaris, with a distinct clinical presentation linked by an identical histopathology.
The treatment options are limited, as therapies may potentially stabilize the process, but hair recovery does not occur after follicular destruction. Whether current therapy ultimately alters the course or severity of FFA has not been established.
Treatment in general is similar to that used for lichen planopilaris, but in view of the pattern of hair loss, finasteride or dutasteride have also been used to stabilize the process.
In the early accelerated phase of FFA, oral corticosteroids may be used to slow the process, commencing with prednisone 50mg daily, and gradually reducing to 12.5mg over a 6-week period. Hydroxychloroquine, at a dose of 200mg daily for a 6-12-month period, has also been used for progressive disease. Finasteride, at a dose of 2.5mg daily, has been used to stabilize FFA, and has been combined with topical minoxidil.
Topical corticosteroids, topical tacrolimus, or topical retinoids have not shown benefit.
Intralesional triamcinolone acetonide,10mg/ml, 0.125ml per eyebrow, resulted in positive hair regrowth in ten women who had partial eyebrow loss.
The main parameters for monitoring progress are the measurement of hairline recession, hair fall, and the presence of perifollicular erythema. Scalp biopsy may be required to assess ongoing lymphocytic destruction of follicles, as clinical progress may evolve slowly and be difficult to assess.
5% minoxidil lotion, twice daily (particularly in the presence of androgenic alopecia)
Triamcinolone acetonide injections, 10mg/ml (at sites of partial hair loss)
Hydroxychloroquine, 200-400mg daily for at least 6 months
Finasteride, 2.5mg daily (particularly in presence of androgenic alopecia)
Doxycycline, 50-100mg twice daily
Prednisone 50mg, reducing to 12.5mg over 6 weeks (in acute progressive phase)
Optimal Therapeutic Approach for this Disease
At present, the main treatment endpoint is stabilization of FFA, but the ultimate degree of recession and course varies considerably in individuals. Ultimately, the process tends to stabilize or is very slowly progressive, making assessment of therapeutic efficacy difficult, as hair regrowth is not achieved in areas of total loss.
Currently, the combination of finasteride and topical minoxidil (particularly in women with combined female pattern hair loss) or hydroxychloroquine are the main treatments that appear to help stabilize FFA. Intralesional steroids for partial hair loss may be helpful.
Photographic records are useful in monitoring FFA, as is measuring the depth of hairline recession. Dermoscopy may also be useful in detecting loss of follicles. Treatment can be discontinued if the process has stabilized, but relapses may occur.
A lichen planopilaris activity index scoring system that was also applied to FFA has been recently introduced, but needs further validation.
It is important to emphasize that the process often stabilizes. There are, however, women who may develop a more severe and extensive pattern, requiring a wig or consideration for hair transplantation, but this is rarely pursued.
Unusual Clinical Scenarios to Consider in Patient Management
FFA may be combined with more widespread oral or cutaneous lichen planus; this may alter treatment, if progressive symptomatic disease is present.
Female pattern alopecia may be seen together with FFA, in which case finasteride with minoxidil may be useful in stabilizing both forms of alopecia.
What is the Evidence?
Kossard, S, Lee, MS, Wilkinson, B. “Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris”. J Am Acad Dermatol. vol. 36. 1997. pp. 59-66. (Clinical evaluation, histopathology, and treatment of sixteen women with FFA, including an analysis of the immunophenotype of lymphocytes and comparison with lichen planopilaris. No positive benefit from treatment observed, but process usually stabilized.)
Moreno-Ramirez, D, Camacho-Martinez, F. “Frontal fibrosing alopecia: a survey of 16 patients”. J Eur Acad Dermatol Venereol. vol. 19. 2005. pp. 700-5. (Authors reviewed sixteen patients with FFA, three of whom were premenopausal and androgenic alopecia was present in seven. Although FFA tended to stabilize, intralesional and topical corticosteroids, and anti-androgens appeared to stop the progression of the disease. The authors found that relapse occured when treatment was discontinued.)
Tosti, A, Piraccini, BM, Iorizzo, M, Misciali, C. “Frontal fibrosing alopecia in postmenopausal women”. J Am Acad Dermatol. vol. 52. 2005. pp. 55-60. (Report of fourteen postmenopausal women with FFA. Four of the eight women receiving finasteride 2.5mg daily had their hair loss arrested.)
Tan, KT, Messenger, AG. “Frontal fibrosing alopecia: clinical presentation and prognosis”. Br J Dermatol. vol. 160. 2009. pp. 75-9. (Authors described eighteen women with FFA, three of whom were premenopausal, and three of whom had oral lichen planus [two also had lichen planus at other skin sites]. Most patients stabilized with or without treatment.)
Poblet, E, Jiminez, F, Pascual, A, Pique, E. “Frontal fibrosing alopecia versus lichen planopilaris: a clinicopathological study”. Int J Dermatol. vol. 45. 2006. pp. 375-80. (Authors compared biopsies from eight patients with FFA to eight patients with lichen planopilaris and found the histopathology was similar.)
Olsen, EA. “Female pattern hair loss and its relationship to permanent/cicatricial alopecia: a new perspective”. J Investig Dermatol Symp Proc. vol. 10. 2005. pp. 217-21. (A broad review of cicatricial alopecia developing in the setting of female pattern hair loss, including FFA.)
Stockmeier, M, Kunte, C, Sander, CA, Wolff, H. “Kossard frontal fibrosing alopecia in a man”. Hautarzt. vol. 53. 2002. pp. 409-11. (Authors describe a 69-year-old man with androgenetic alopecia who developed clinical and histopathologic findings of FFA, including eyebrow loss.)
Rallis, E, Gegoriou, S, Christofidou, E, Rigopoulos, D. “Frontal fibrosing alopecia: to treat or not to treat”. J Cutan Med Surg. vol. 14. 2010. pp. 161-6. (The authors reviewed the results of therapy in eighteen patients with FFA, thirteen of whom had stable disease. A combination of finasteride and 5% minoxidil was used in five patients with combined androgenic alopecia, systemic steroids were used in a patient with rapidly progressive disease, and topical clobetasol 0.25% lotion was used in six patients. No significant improvement was observed in any patient, as the progress had stabilized in the majority prior to therapy.)
Chiang, C, Sah, D, Cho, BK. “Hydroxychloroquine and lichen planopilaris: efficacy and introduction of lichen planopilaris activity index scoring system”. J Am Acad Dermatol. vol. 62. 2010. pp. 387-92. (The authors devised a lichen planopilaris activity index scoring system to better assess benefits of treatment with hydroxychloroquine in a group of forty patients with lichen planopilaris or FFA [or both] and found that at 12 months, 83% had improvement in signs and symptoms.)
Kossard, S, Trueb, RM, Tobin, DJ. “Post-menopausal frontal fibrosing alopecia”. Aging hair. 2010. pp. 33-9. (A review of the clinical features, differential diagnosis, and management of FFA. The author also proposes a hypothesis to address why this distinctive alopecia occurs predominantly in elderly postmenopausal women and rarely in men.)
Donovan, JC, Samrao, A, Ruben, BS, Price, VH. “Eyebrow regrowth in patients with frontal fibrosing alopecia treated with intralesional triamcinolone acetonide”. Brit J Dermatol. vol. 163. 2010. pp. 1142-4. (The authors describe positive hair regrowth in patients with FFA, and partial loss of eyebrows after intralesional corticosteroid injections.)
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