Frontal fibrosing alopecia: reflections and hypotheses on aetiology and pathogenesis

Abstract

Since first described by Kossard in 1994, frontal fibrosing alopecia (FFA) has been something of an enigma. The clinical heterogeneity of FFA, its apparent rarity and investigators' suboptimal access to phenotypically consistent patient cohorts may all have had a negative impact on delineating disease pathogenesis. Moreover, there is a relative paucity of epidemiological, interventional and basic research studies, and there have been no advances in translational therapeutics, unlike for other inflammatory dermatoses, such as alopecia areata (AA). Dermatologists anecdotally describe an increasing incidence in FFA over the last decade, which has led to the notion that the disorder may be induced by unknown environmental triggers. On the other hand, segregation of FFA in some families lends support to an unexplored genetic element implicated in disease pathogenesis. We herein review what is known about the pathobiology of FFA and formulate working hypotheses to advance insight into this intriguing hair disorder.

Examination of Clinical and Demographic Characteristics of 14 Cases with Frontal Fibrosing Alopecia

“…Itching was present in 21% of the cases (3 cases). While the ethiopathogenesis of the FFA is not exactly known, the key role is thought be played by T-cell mediated autoimmune reaction against hair follicles (2,(3)(4)(5)9,16). Another opinion regarding FFA ethiopathogenesis is the effect of androgen hormonal factors.…”

“…Another opinion regarding FFA ethiopathogenesis is the effect of androgen hormonal factors. While the facts that it usually affects postmenopausal women, involves frontal scalp, and responds to antiandrogens such as finasteride or dutasteride in some patients suggest this, a significant relationship is yet to be revealed (4,9,24). Today, FFA is regarded as a clinical variant of LPP which has selectivity for frontotemporal hairline, primarily affects postmenopausal women and is characterized by lymphocytic cicatricial alopecia (2,3,17).…”

“…To date, however, a complete genetic analysis has not been performed. Frequent occurrence in postmenopausal period and successful treatment with 5-alpha reductase inhibitors suggest that a hormone-induced trigger mechanism and androgenetic factors may also be responsible in pathogenesis (2,3,9).…”

Cicatricial Alopecia in Identical Twin Lumbee Native American Women

“…The genetic inheritance of LPP is poorly understood; there is one case report of a grandmother, mother and daughter having LPP [7]. Three pairs of identical twins were affected by frontal fibrosing alopecia, a possible variant of LPP, with a 67% concordance rate [8]. …”

Frontal fibrosing alopecia: when the treatment is worse than the disease

“…FFA is considered a variant of lichen planopilaris (LPP), mainly for the similar histopathological features, such as a reduced number of hair follicles and perifollicular lymphoid cell infiltrate with perifollicular fibrosis (2,8). Speculation about a hormonal origin, mainly affecting postmenopausal women or with a history of hysterectomy, and early menopause was questioned for the publication of cases in men and premenopausal women, but somewhat proposed again by the efficacy of 5-α reductase inhibitors and topical minoxidil treatment (9,10). No evidence-based treatment is recommended for FFA, and observational studies suggest similar efficacy for 5-α reductase inhibitors, antimalarials, calcineurin inhibitors, and intralesional steroids, which remain a very popular choice in daily practice (2,(11)(12)(13).…”