Version May 2024
INTRODUCTION — Frontal fibrosing alopecia (FFA) is a lymphocytic cicatricial (scarring) alopecia that classically presents with the progressive development of a symmetric, band-like patch of alopecia involving the frontal hairline (picture 1A-D). FFA is postulated to be a subtype of lichen planopilaris based upon the presence of similar histopathologic findings. (See "Lichen planopilaris".)
FFA most frequently occurs in postmenopausal women but occasionally occurs in other adults. Additional clinical features may include extension of alopecia to the posterior hairline, eyebrows, or other body areas. Patients may also exhibit facial papules, small, skin-colored papules on the cheeks, chin, or temples. A diagnosis of FFA is made based upon the presence of consistent clinical and histopathologic findings.
The pathogenesis, clinical manifestations, and diagnosis of FFA are reviewed here. Therapeutic management of FFA is discussed separately. Overviews of lichen planopilaris and the evaluation of patients with hair loss are also provided separately.
●(See "Frontal fibrosing alopecia: Management".)
●(See "Lichen planopilaris".)
●(See "Evaluation and diagnosis of hair loss".)
CLASSIFICATION — Classification of the various types of cicatricial alopecia is frequently based upon a system proposed by the North American Hair Research Society in 2001 [1]. FFA is classified as a primary lymphocytic cicatricial alopecia, a term used to describe a group of inflammatory scalp disorders that demonstrate a lymphocyte-predominant inflammatory infiltrate, follicular destruction, and permanent hair loss. (See "Evaluation and diagnosis of hair loss", section on 'Classification'.)
EPIDEMIOLOGY — Epidemiologic data on FFA are limited. FFA was first reported in 1994, and subsequently, reports of this diagnosis have continued to increase [2,3]. In a multicenter, retrospective study that included patients evaluated in specialist hair clinics in Europe, America, Africa, and Australia, FFA accounted for 11 percent of 3133 diagnoses of alopecia and 40 percent of 840 diagnoses of cicatricial alopecia [4].
FFA appears to be an adult-onset disorder; the disorder has not been reported in children. FFA is most frequently diagnosed in postmenopausal women between 55 and 70 years of age but may also occur in other adults [5-11]. In one of the largest series, a Spanish, multicenter, retrospective study, 83 percent of 355 patients with FFA were postmenopausal women [5]. Premenopausal women and men accounted for 14 and 3 percent of the patients, respectively. However, a review of 20 patients with histopathologically confirmed FFA in a single center in South Africa found a contrasting distribution; the patients included 5 postmenopausal women, 14 premenopausal women, and 1 man [8].
PATHOGENESIS — The pathogenesis of FFA is not well understood. Similar to lichen planopilaris (LPP), pathology specimens from FFA on the scalp typically demonstrate a dense, lymphohistiocytic, inflammatory infiltrate that targets the infundibular and isthmus regions of the hair follicle (figure 1) [12]. The follicular bulge, the site of stem cells involved in regeneration of hair follicles during follicular cycling, is within this region (figure 1). Damage to the follicular bulge is considered to contribute to the development of permanent alopecia.
Immune dysregulation, pathologic fibrotic pathways, and, as with LPP, downregulation of peroxisome proliferator-activated receptor-gamma gene expression have been postulated to play a role [13]. The reason for the preferential damage of follicles along the hairline in FFA is unknown. (See "Lichen planopilaris", section on 'Pathogenesis'.)
The stimuli that contribute to the onset of FFA remain unclear. A variety of factors have been proposed as contributors; examples include genetic predisposition, hormonal influences, and environmental factors:
●Genetics – Reports of familial occurrences of FFA suggest a genetic contribution [14-18]. An autosomal dominant pattern of inheritance has been suggested based upon an analysis of five individuals with FFA in one family [14]. In addition, a case-control study in which human leukocyte antigen (HLA) profiles of 13 patients with FFA in 6 families were compared with data from 636 healthy controls found linkage of the HLA class 1 haplotype F16A with CYP21A2 gene p. V28L, a potential genetic marker for familial susceptibility to FFA [19].
●Hormones – Suspicion for a hormonal contribution to FFA comes from the strong predilection for postmenopausal females, studies that suggest associations between FFA and alterations in estrogen or androgen levels, and apparent benefit of antiandrogen therapy. Reduced estrogen levels were postulated to contribute based upon a Spanish, retrospective study of 355 patients with FFA that found early menopause (≤45 years) in 14 percent of the women with FFA, a rate higher than estimated to occur in the general population, and a history of hysterectomy in 13 percent of women with FFA [5]. Moreover, 32 percent of 53 patients with FFA in a separate retrospective study had low adrenal androgen levels [20]. Lastly, inhibitors of 5-alpha reductase, antiandrogenic drugs, are thought to be beneficial treatments for FFA. (See "Frontal fibrosing alopecia: Management", section on '5-alpha reductase inhibitors'.)
●Environment – The onset of FFA in adulthood and the lack of recognition of this disease until 1994 has contributed to speculation regarding an environmental trigger for FFA. Sunscreen use has been proposed as one potential contributor, though a causative role for sunscreen has not been confirmed.
Data supporting a relationship between FFA and sunscreen use primarily comes from questionnaire-based, case-control studies and case reports [21]. One of the largest studies, a multicenter, case-control study of 664 women (335 with FFA and 329 controls) and 106 men (20 with FFA and 86 controls) in which subjects completed a questionnaire that assessed environmental, dietary, and other exposures, found associations between FFA and use of facial sunscreen (odds ratio [OR] 1.6, 95% CI 1.06-2.41 for females and OR 11.6, 95% CI 1.7-80.9 for males) [22].
There are conflicting data from retrospective studies regarding whether smoking has a protective effect against FFA [3,5,23]. Additional study is necessary to clarify the relationships among FFA, sunscreen and facial skin care product use, and smoking status.
CLINICAL MANIFESTATIONS — The clinical manifestations of FFA include a distinct pattern of hair loss on the scalp. Associated features may include hair loss on the eyebrows and/or other body sites and facial papules.
Scalp — Recession of the frontal and temporal hairline in a band-like pattern is the characteristic finding (picture 1A-D). The affected scalp shows a loss of follicular ostia [24], a finding consistent with cicatricial alopecia, and may also exhibit perifollicular hyperkeratosis and erythema, findings supportive of active inflammation (picture 2A-B) [25,26].
The "lonely hair" sign is an additional common finding. The sign describes the presence of one or a few remaining terminal hairs within a band of alopecia (picture 1A-B) [27,28].
Scalp hair loss typically manifests as slow, progressive recession of the anterior hairline. In one retrospective study, the average rate of hair loss was 1.05 cm per year (range 0.2 to 2.1 cm per year) among the 74 of 79 untreated patients who worsened during follow-up [5]. Occasionally, patients present with rapid hairline recession [29]. (See "Frontal fibrosing alopecia: Management", section on 'Prognosis'.)
A subset of patients with frontal hair loss due to FFA also develop alopecia on the occipital scalp or patchy alopecia (picture 3). In particular, occipital involvement may not be uncommon. Estimates of occipital involvement range from 7 to 32 percent of patients [3,5,30].
Associated symptoms may include pruritus, trichodynia (tenderness or burning), or tingling sensations on the scalp. In some patients, an evaluation for scalp pruritus leads to the discovery of frontotemporal hairline recession [31].
Other body sites — Manifestations of FFA can extend beyond the scalp, including hair loss involving eyebrows, eyelashes, or other body areas and facial lesions.
Hair loss — Cicatricial alopecia of the eyebrows is estimated to occur in 40 to 95 percent of FFA patients and ranges from partial to total loss of eyebrow hair (picture 4) [32]. Thinning of the lateral eyebrows is the common finding and may precede the onset of frontotemporal hairline recession [5,15,33]. Eyelash loss is less common [3,5,6,11,33].
Alopecia of other locations on the body, such as limbs, pubic area, and axillae, is estimated to occur in 6 to 53 percent of patients [32]. Findings of cicatricial alopecia in biopsies taken from the limbs of patients with FFA were documented in a case report [34].
Facial lesions — Facial papules, presenting as multiple small, noninflammatory papules on the temples, cheeks, or chin, are a common associated finding in FFA. Facial papules may be a manifestation of involvement of vellus hair follicles or another process [35,36]. (See 'Histopathology' below.)
Perifollicular erythema, with or without follicular keratosis, diffuse facial erythema, pigmented macules on the face, depression of frontal veins, and periauricular wrinkles have also been reported [36-38].
Frontal fibrosing alopecia/lichen planopilaris overlap — The term "frontal fibrosing alopecia/lichen planopilaris (FFA/LPP) overlap" has been used to refer to FFA occurring in association with patchy cicatricial alopecia with histopathologic findings consistent with LPP. Clinical findings include a smooth band of cicatricial alopecia across the frontal hairline and patches of cicatricial alopecia involving other locations on the scalp.
The overlap presentation occurs in a minority of patients with FFA. In one retrospective study, only 3 of 355 patients (1 percent) with FFA had findings consistent with LPP in other areas of the scalp [5]. A smaller, retrospective study found FFA/LPP overlap in 10 of 62 patients (16 percent) [5,10].
HISTOPATHOLOGY — Similar to lichen planopilaris (LPP), the histopathologic findings of FFA include perifollicular fibrosis and a lymphocytic infiltrate surrounding the isthmus and infundibulum of the hair follicle [7,39-41]. Although some subtle findings have been postulated to be distinct features of FFA (eg, sparing of the interfollicular epidermis and eosinophilic necrosis of cells of the external root sheath), there are no definitive distinguishing features [7].
Histopathologic findings in FFA-associated facial papules may vary; findings similar to the histopathology of LPP have been reported [35]. In contrast, one study found prominent sebaceous lobules with dilated ducts and an abnormal, elastic framework as the prominent features [42]. These findings were postulated to result from a preceding, subtle, inflammatory process.
DIAGNOSIS — A diagnosis of FFA may be strongly suspected based upon the history and physical findings; however, a biopsy is necessary to confirm the diagnosis.
FFA should always be considered when patients present with progressive recession of the frontotemporal hairline in a band-like distribution and a loss of visible follicular ostia within the area of alopecia. Additional supportive features may include:
●Postmenopausal female patient
●"Lonely hair" sign (picture 1A) (see 'Scalp' above)
●Perifollicular erythema or scale
●Scalp itching, tingling, burning, or tenderness
●Partial or total loss of eyebrow hair
●Facial papules
The absence of one or more of these supportive features does not exclude a diagnosis of FFA.
Dermoscopy may be a useful adjunctive tool for identifying characteristic findings. (See 'Dermoscopy' below.)
History and physical examination — The patient history should include:
●Assessment of the duration and course of hair loss and associated symptoms – Patients with FFA may complain of slow, progressive recession of their hairline. This may be associated with scalp tingling, burning, itching, or tenderness. (See 'Scalp' above.)
●Assessment for hair loss in other areas – Patients should be asked about eyebrow thinning and hair loss in other areas of the scalp or body, as these findings may accompany scalp involvement in FFA. (See 'Other body sites' above.)
The physical examination should include:
●Thorough examination of the scalp and scalp hair – The physical examination should include a thorough examination of the scalp and scalp hair, which can be aided by using the wooden end of a cotton-tipped applicator, one held in each hand, to part the hair. In particular, the frontotemporal hairline and posterior hairline should be examined thoroughly to detect loss of follicular ostia, the "lonely hair" sign, and perifollicular erythema or scale. (See 'Scalp' above and 'Dermoscopy' below and "Evaluation and diagnosis of hair loss", section on 'Physical examination'.)
●Examination of the face, eyebrows, and other hair-bearing areas – Cicatricial alopecia may be present in the eyebrows or other hair-bearing areas of patients with FFA. Facial papules are a common associated finding. (See 'Other body sites' above.)
Dermoscopy — Dermoscopic findings of FFA include a reduction of follicular ostia (consistent with cicatricial alopecia), perifollicular erythema, follicular plugging, and perifollicular hyperkeratosis (peripilar casts) (picture 5) [5,43-46]. Perifollicular erythema suggests active disease [43,47].
Biopsy — A 4 mm punch biopsy processed with transverse sectioning should be performed to assess for histopathologic features of FFA. Ideally, both a viable hair follicle producing a growing hair shaft and an area of scarring alopecia should be included in the specimen.
In our experience, a single biopsy processed with transverse sectioning is usually sufficient for the diagnosis of FFA. However, some dermatopathologists prefer the receipt of two punch biopsies (one sectioned transversely and the other sectioned vertically), as it allows for evaluation of the hair follicles in both horizontal and vertical sections. (See 'Histopathology' above and "Skin biopsy techniques", section on 'Biopsy techniques'.)
DIFFERENTIAL DIAGNOSIS — Other forms of alopecia share some clinical or histopathologic features with FFA. The recognition of key clinical or histopathologic findings can be useful for distinguishing FFA from other conditions:
●Traction alopecia – Traction alopecia is a form of temporary or permanent hair loss that results from extended periods of traction forces on the hair, which, for example, can occur with tight ponytails or braids. Alopecia commonly involves the frontotemporal scalp but may occur in other locations on the scalp.
The "fringe" sign, the persistence of vellus hairs at the frontal hairline, is a common finding in frontotemporal traction alopecia (picture 6) [48]. The "lonely hair" sign is more consistent with FFA (picture 1A).
Also, in contrast to the significant, perifollicular, lymphocytic infiltrate seen in skin biopsies of FFA, inflammation tends to be mild or absent in traction alopecia. Other histopathologic findings of traction alopecia include an increase in the proportion of catagen hairs and the presence of miniaturized hair follicles and pigmented hair casts. (See "Traction alopecia".)
●Female and male pattern hair loss (androgenetic alopecia) – Female and male pattern hair loss, also known as androgenetic alopecia, are slowly progressive, nonscarring alopecias that may involve the frontotemporal and/or vertex scalp (picture 7A-B). Hair loss typically follows characteristic patterns.
In female and male pattern hair loss, miniaturized hairs are easily visualized on dermoscopic or histopathologic examination. In contrast to FFA, loss of follicular ostia is absent. (See "Female pattern hair loss (androgenetic alopecia in females): Pathogenesis, clinical features, and diagnosis" and "Male pattern hair loss (androgenetic alopecia in males): Pathogenesis, clinical features, and diagnosis".)
●Alopecia areata – Alopecia areata is a nonscarring alopecia that presents with one or more well-demarcated, nonscarring patches of alopecia. The ophiasis pattern of alopecia areata, which is characterized by a band-like area of alopecia across the occipital scalp, may resemble occipital involvement of FFA (picture 8).
Unlike FFA, follicular ostia remain intact in alopecia areata. Dermoscopic findings of alopecia areata can include exclamation point hairs and yellow and black dots. A peribulbar lymphocytic infiltrate is seen on histopathologic examination. (See "Alopecia areata: Clinical manifestations and diagnosis".)
●Lichen planopilaris – Classic lichen planopilaris (LPP) typically presents with patches of alopecia with loss of follicular ostia, often involving the vertex and/or parietal areas of the scalp. Perifollicular erythema and follicular hyperkeratosis are usually present at the periphery of balding areas.
Classic LPP and FFA share similar histopathologic features. The frontal band-like pattern of hair loss distinguishes FFA. (See "Lichen planopilaris" and 'Histopathology' above.)
●Trichotillomania – Trichotillomania is a disorder in which individuals compulsively pull hair from the scalp or other areas, resulting in varying and often unusual patterns of hair loss. Broken hairs of varying lengths are typically present (picture 9A-B).
The history and physical examination are usually sufficient for diagnosis. If performed, a biopsy may demonstrate follicular damage and an increased number of catagen/telogen hairs. (See "Skin picking (excoriation) disorder and related disorders", section on 'Trichotillomania'.)
●Cutaneous sarcoidosis – Rarely, cutaneous sarcoidosis may present with clinical findings of anterior hairline recession (picture 10) [49]. Associated features may include alopecia in psoriasis-like plaques or atrophic, yellow plaques on the scalp. The detection of noncaseating granulomas on a skin biopsy supports the diagnosis. (See "Cutaneous manifestations of sarcoidosis", section on 'Special sites'.)
SUMMARY AND RECOMMENDATIONS
●Overview – Frontal fibrosing alopecia (FFA) is a lymphocytic cicatricial (scarring) alopecia that classically presents with progressive regression of the frontal hairline. FFA may represent a subtype of lichen planopilaris (LPP). (See 'Introduction' above and 'Classification' above.)
●Epidemiology – FFA is an adult-onset disorder that was first reported in 1994. The condition has primarily been reported in postmenopausal women but also occurs in other populations. (See 'Epidemiology' above.)
●Pathogenesis – The pathogenesis of FFA is not well understood. Permanent hair loss is thought to result from an inflammatory process that results in damage to the follicular bulge. Immune dysregulation, pathologic fibrotic pathways, and downregulation of peroxisome proliferated-activator receptor-gamma gene expression may play a role. Genetic, hormonal, and environmental factors are also postulated to play a role. (See 'Pathogenesis' above.)
●Clinical manifestations:
•Scalp – The classic clinical presentation of FFA consists of progressive recession of the frontal hairline in a band-line pattern (picture 1A-D). The area of alopecia exhibits a loss of follicular ostia, a finding consistent with cicatricial alopecia. Hair-bearing follicles near the areas of alopecia may demonstrate perifollicular erythema and scale (picture 2A-B). Scalp pruritus, tenderness, or burning is common. (See 'Clinical manifestations' above.)
•Other body sites – Frontal hair loss in FFA may be accompanied by other findings. Cicatricial alopecia of the occipital scalp is involved in a subset of patients. Patients may also exhibit loss of eyebrow or body hair (picture 4). Small facial papules on the temples, cheeks, or chin are common. (See 'Other body sites' above.)
●Diagnosis – The diagnosis of FFA is made based upon the detection of consistent clinical and pathologic findings. The pathologic findings of FFA are similar to findings in LPP. Typical findings are perifollicular fibrosis and a lymphocytic infiltrate surrounding the isthmus and infundibulum of the hair follicle. (See 'Diagnosis' above.)
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