10.5826/dpc.1201a80
Introduction: Frontal fibrosing alopecia (FFA) is a form of primary lymphocytic scarring alopecia characterized by a progressive recession of the fronto-temporal hairline. Although the clinical presentation of FFA is very typical, biopsy for histopathological examina­tion is still recommended to confirm the diagnosis. Currently, a growing number of skin and mucosal inflammatory diseases are diagnosed with modern noninvasive techniques such as dermoscopy without the necessity of a biopsy.
Objectives: The International Dermoscopy Society (IDS) aimed to test the ability of its members to diagnose classic FFA through clinical and dermoscopic parameters and to compare acquired data to the largest cohort studies published since 1994.
Methods: This is an observational, cross-sectional study describing patient demographics, clinical presentation and diagnostic tools used in a sample of FFA patients collected by IDS members. A literature search was then performed using Pubmed to review studies reporting more than 100 cases.
Results: IDS members submitted 188 cases demonstrating a predominant female population (98.4%). In 71.8% of the cases, the clinical presentation and the trichoscopic findings allowed for the diagnosis. Out of 24 revised studies, 13 showed that clinical and trichoscopic features were decisive for the diagnosis in almost all cases.
Conclusions: Demographic and clinical data of our cohort were mostly comparable to previous reported data on FFA. The relevant role of the clinical and trichoscopic features in diagnosing FFA was confirmed by our study and the reviewed literature. Trichoscopy could be considered a worldwide-acknowledged non-invasive technique for the diagnosis of FFA.
text/xml
2160-9381
1933
en
Bianca Maria  Piraccini
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
non-invasive
Clinical and Dermoscopic Approaches to Diagnosis of Frontal Fibrosing Alopecia: Results From a Multicenter Study of the International Dermoscopy Society
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Review
2022-02-02
2021-08-02
2022-02-02
2022-02-09
e2022080
Dermatol Pract Concept
Introduction: Frontal fibrosing alopecia (FFA) is a form of primary lymphocytic scarring alopecia characterized by a progressive recession of the fronto-temporal hairline. Although the clinical presentation of FFA is very typical, biopsy for histopathological examina­tion is still recommended to confirm the diagnosis. Currently, a growing number of skin and mucosal inflammatory diseases are diagnosed with modern noninvasive techniques such as dermoscopy without the necessity of a biopsy.
Objectives: The International Dermoscopy Society (IDS) aimed to test the ability of its members to diagnose classic FFA through clinical and dermoscopic parameters and to compare acquired data to the largest cohort studies published since 1994.
Methods: This is an observational, cross-sectional study describing patient demographics, clinical presentation and diagnostic tools used in a sample of FFA patients collected by IDS members. A literature search was then performed using Pubmed to review studies reporting more than 100 cases.
Results: IDS members submitted 188 cases demonstrating a predominant female population (98.4%). In 71.8% of the cases, the clinical presentation and the trichoscopic findings allowed for the diagnosis. Out of 24 revised studies, 13 showed that clinical and trichoscopic features were decisive for the diagnosis in almost all cases.
Conclusions: Demographic and clinical data of our cohort were mostly comparable to previous reported data on FFA. The relevant role of the clinical and trichoscopic features in diagnosing FFA was confirmed by our study and the reviewed literature. Trichoscopy could be considered a worldwide-acknowledged non-invasive technique for the diagnosis of FFA.
Bianca Maria  Piraccini
2022/02/02
10.5826/dpc.1201a80
e2022080
Department of Experimental, Diagnostic, and Specialty Medicine-Division of Dermatology, University of Bologna, Bologna, Italy
2160-9381
non-invasive
en
e2022080
Waśkiel-Burnat A, Rakowska A, Kurzeja M, et al. The value of dermoscopy in diagnosing eyebrow loss in patients with alopecia areata and frontal fibrosing alopecia. J Eur Acad Dermatol Venereol. 2019;33(1):213-219. DOI: 10.1111/jdv.15279. PMID: 30290016.
Clinical and Dermoscopic Approaches to Diagnosis of Frontal Fibrosing Alopecia: Results From a Multicenter Study of the International Dermoscopy Society
https://dpcj.org/index.php/dpc/article/download/1933/1479
                    Dermatology Practical & Conceptual


 Clinical and Dermoscopic Approaches to Diagnosis
    of Frontal Fibrosing Alopecia: Results From a
 Multicenter Study of the International Dermoscopy
                       Society
Michela Starace1, Gloria Orlando2, Matilde Iorizzo3, Aurora Alessandrini1, Francesca Bruni1,
    Victor Desmond Mandel4,5, Kelati Awatef6, Horacio Cabo7, Gabriella Fabbrocini13,
  Baybay Hanane8, Sven Lanssens9, Alejandro Lobato-Berezo10, Fatima Zahra Mernissi8,
    John Paoli11,12, Angela Patrí13, Emilia Noemi Cohen Sabban7, Martyna Sławińska14,
    Michał Sobjanek14, Oscar Zaar11,12, Giovanni Pellacani4,15, Bianca Maria Piraccini1


 1 Department of Experimental, Diagnostic, and Specialty Medicine-Division of Dermatology, University of Bologna, Bologna, Italy
 2 Department of Medicine - DIMED, Dermatology Unit, University of Padova, Italy
 3 Private Dermatology Practice, Bellinzona, Lugano, Switzerland
 4 Dermatology Unit, Surgical, Medical, and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative
   Medicine, University of Modena and Reggio Emilia, Modena, Italy
 5 Dermatology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy
 6 Dermatology Department, Cheikh Khalifa International University Hospital, Mohammed VI University of Health Sciences (UM6SS),
   Casablanca, Morocco
 7 Dermatology Division of the Instituto de Investigaciones Médicas Alfredo Lanari, University of Buenos Aires (UBA), Argentina
 8 Dermatology Department, UHC Hassan II. Fez, Morocco
 9 Dermatologie Maldegem – Maldegem, Belgium
10 Department of Dermatology, Hospital del Mar-Parc de Salut Mar, Barcelona, Spain
11 Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg,
  Gothenburg, Sweden
12 Region Västra Götaland, Sahlgrenska University Hospital, Department of Dermatology and Venereology, Gothenburg, Sweden
13 Department of Clinical Medicine and Surgery, Section of Dermatology, University of Naples Federico II
14 Department of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gdańsk, Poland
15 Dermatologic Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome,
  Rome, Italy



Key words: frontal fibrosing alopecia, trichoscopy, diagnosis, non-invasive, techniques
Citation: Starace M, Orlando G, Iorizzo M, et al. Clinical and dermoscopic approaches to diagnosis of frontal fibrosing alopecia: results
from a multicenter study of the international dermoscopy society. Dermatol Pract Concept. 2022; 12(1):e2022080. DOI: https://doi
.org/10.5826/dpc.1201a80
Accepted: October 18, 2021; Published: January 2022.
Copyright: ©2022 Starace et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Gloria Orlando, Dermatology Unit, Department of Medicine - DIMED, University of Padova, Italy.
E-mail: gloriaorlando@gmail.com




Review | Dermatol Pract Concept. 2022; 12(1):e2022080                                                                                       1
    ABSTRACT          Introduction: Frontal fibrosing alopecia (FFA) is a form of primary lymphocytic scarring alopecia
                      characterized by a progressive recession of the fronto-temporal hairline. Although the clinical presen-
                      tation of FFA is very typical, biopsy for histopathological examination is still recommended to confirm
                      the diagnosis. Currently, a growing number of skin and mucosal inflammatory diseases are diagnosed
                      with modern noninvasive techniques such as dermoscopy without the necessity of a biopsy.
                      Objectives: The International Dermoscopy Society (IDS) aimed to test the ability of its members to
                      diagnose classic FFA through clinical and dermoscopic parameters and to compare acquired data to
                      the largest cohort studies published since 1994.
                      Methods: This is an observational, cross-sectional study describing patient demographics, clinical pre-
                      sentation and diagnostic tools used in a sample of FFA patients collected by IDS members. A literature
                      search was then performed using Pubmed to review studies reporting more than 100 cases.
                      Results: IDS members submitted 188 cases demonstrating a predominant female population (98.4%).
                      In 71.8% of the cases, the clinical presentation and the trichoscopic findings allowed for the diagno-
                      sis. Out of 24 revised studies, 13 showed that clinical and trichoscopic features were decisive for the
                      diagnosis in almost all cases.
                      Conclusions: Demographic and clinical data of our cohort were mostly comparable to previous re-
                      ported data on FFA. The relevant role of the clinical and trichoscopic features in diagnosing FFA was
                      confirmed by our study and the reviewed literature. Trichoscopy could be considered a worldwide-ac-
                      knowledged non-invasive technique for the diagnosis of FFA.



Introduction                                                        that FFA correlates with the HLA-B*07:02 allele [19]. Lastly,
                                                                    it has been speculated that the disease was present even before
Frontal fibrosing alopecia (FFA), first described by Kossard in     Kossard’s first description, but somehow passed unnoticed [20].
1994 [1,2] is a form of primary lymphocytic scarring alope-            Due to the lack of randomized clinical trials and lack
cia characterized by a progressive band-like recession of the       of a control group in previous clinical studies, treatment of
fronto-temporal hairline and, in 50-75% of cases, by a partial      FFA is not evidence-based [21]. Lack of evidence doesn’t
or complete alopecia of the eyebrows. Whether FFA is only a         mean, however, lack of effectiveness. Disease control might
form of lichen planopilaris (LPP) or a more complex disorder        be achieved with topical, intralesional and oral treatments,
is still a matter of debate [3-5].                                  often combined together. The treatment aim is always to stop
    Thousands of cases have been described to date, with            disease progression [22].
increasing incidence of the disease worldwide. Postmeno-               At present, although the clinical picture of FFA is very
pausal women are still those primarily affected, but women          typical in most cases, a biopsy for histopathological confirma-
with childbearing potential and males can also present with         tion is still recommended to administer the correct treatment
this disease [6-8]. Scalp FFA can also present in atypical forms    [23]. In cases not involving the scalp, a biopsy is mandatory.
such as linear, diffuse, zig-zag, and pseudo-fringe patterns [9].   Scarring might be subtle and the fibrous tracts so thin that
Hair follicles on the occipital scalp and sideburns can also        the loss of follicular ostia might be missed. Thus, FFA can be
be involved as well as eyelashes, beard, axillae, limbs and         mistaken for a nonscarring alopecia, particularly alopecia
pubis [10-12]. Lichen planus pigmentosus, facial papules and        areata (AA) and androgenic alopecia (AGA). Moreover, due
facial erythema have also been described in patients with FFA       to the presence of the disease in cosmetically sensitive areas,
indicating that this is not necessarily a disease limited to the    patients do not always accept biopsy even if it is a 2-mm
scalp and eyebrows [13-15].                                         punch biopsy [24]. For these reasons, modern noninvasive
    The real incidence of FFA is unknown, but the important         techniques including dermoscopy [25-27], reflectance confo-
increase in the reported cases in recent years has led some         cal microscopy [28] and optical coherence tomography [29]
authors to refer to it as an epidemic disease [16] The etio-
                                                     .
                                                                    are increasingly used to diagnose several skin and mucosal
pathogenesis and the reason for the increasing incidence of         inflammatory diseases. The goal is to perform a diagnosis
FFA are still unknown. The fact that FFA develops later in life     without the necessity of a biopsy and to reserve it only for
suggests that triggering environmental factors might play a         early stages, doubtful cases and/or uncommon presentations.
role in the development of the disease. A genetic basis has also       Therefore, the International Dermoscopy Society (IDS)
been hypothesized since FFA has been diagnosed in siblings and      aimed to test the ability of its members to diagnose typical
members of the same family [17, 18]. Although FFA is thought        or classic FFA through clinical and dermoscopic parameters
to be a variant of LPP, there is no reported association with       and compare the acquired data to the largest cohort studies
HLA-DR1. A recent genome-wide association study showed              published since 1994.



2                                                                              Review | Dermatol Pract Concept. 2022; 12(1):e2022080
Methods                                                           Table 1. Clinical and Trichoscopy Data from 188
                                                                   Patients Affected by FFA and Collected Through
The study was launched by the IDS via an online call for          the International Dermoscopy Society Online Call
contributions published on the IDS website (www.dermosco-
                                                                               Characteristics
py-ids.org). From March 2018 to March 2020, IDS members
                                                                   Age (range)                          62 (40-84) years
were invited to submit cases of FFA. High quality clinical and
                                                                   Female patients                      98.4% (185/188)
dermoscopic images of the clinical presentations were manda-
                                                                   Post-menopausal patients             88.1% (163/185)
tory. Information on patient demographics and lesion char-
                                                                   Menopause onset, mean age (range)    44.3 (40-61) years
acteristics were also required including age, gender, involved
                                                                    FFA family history                  10.1% (19/188)
skin/scalp areas, time at onset, subjective symptoms and
                                                                    AGA family history                  42% (79/188)
trichoscopic features. Furthermore, information regarding
                                                                    AGA personal history                38.8% (73/188)
the diagnostic methodologies were also mandatory. The study
was conducted in accordance with ethical guidelines, and IRB        FFA onset, mean age (range)         58.6 (15-84) years

approval was obtained. All data were collected and analyzed.        Disease duration, mean (range)      4.4 (2 months –
                                                                                                        30 years) years
   A literature search for “frontal fibrosing alopecia” was
then performed on PubMed and returned 502 items (April             Clinical Severity

2021). Only papers reporting more than 100 cases were con-          Grade 1                             37 (19.6%)
sidered and revised. For each paper the year of publication,        Grade 2                             97 (51.6%)
the number of patients, the origin of the population, the type      Grade 3                             45 (23.9%)
of diagnostic methodology was collected.                            Grade 4                             7 (3.7%)
                                                                    Grade 5                             2 (1%)
                                                                   Clinical Data
Results
                                                                    Recession                           2.35 (0-10) cm
After the initial call, 206 FFA cases from 10 different centres     Glabella-hairline distance          7.57 (5-15)
were collected, but 18 cases were excluded from analysis due        Occipital area involvement          11.7% (22/188)
to misdiagnosis (8.7%). The clinical and trichoscopic data of       Parietal area involvement           70.2% (132/188)
all 188 included cases are presented in Table 1. The mean age       Eyebrows involvement                85.6% (161/188)
of the studied population was 62 years (range 40–84) with           Eyelashes involvement               27.6% (52/188)
a predominant female population (98.4%) and only 3 male
                                                                    Body hairs involvement              47,3% (89/188)
patients. The great majority of the female population were
                                                                    Armpits hairs involvement           42.5% (80/188)
post-menopausal (88.1%) with an average age of climacteric
                                                                    Pubis hairs involvement             36.1% (68/188)
onset at 44.3 years. The mean age at onset of the disease was
                                                                    Beard (*men only*)                  33.3% (1/3)
58.6 years, on average 11.2 years after menopause. However,
                                                                    Facial papules                      29.8% (56/188)
the disease was diagnosed up to 35 years after menopause.
                                                                   Scalp symptoms
Regarding the degree of disease at diagnosis, 51.6% of the
patients already showed grade 2 disease at that timepoint.          Pruritus                            65.9% (124/188)
When the frontal scalp was involved, the mean recession of          Trichodynia                         22.9% (43/188)
the hairline was 2.35 cm (0-10 cm) and the distance between        Trichoscopy
the glabella and the forehead was 7.57 cm (range 5-15 cm).          Empty follicles                     93.6% (176/188)
FFA also affected the parietal regions in 70.2% of cases            Absence of follicular ostia         92% (173/188)
(132/188), while the occipital region was involved in 11.7%         Perifollicular erythema             63.8% (129/188)
of cases (22/188). The sideburns were not affected in any of        Follicular hyperkeratosis           60.1% (113/188)
the patients.                                                       Lonely hairs                        54.8% (103/188)
   Reduction or complete loss of eyebrows was reported in          Clinical associations
85.6% of patients with partial loss in 104 patients (55.3%)         AGA                                 38.8% (73/188)
and total loss in 56 patients (29.8%). The beard was involved
                                                                    Lichen planopilaris                 18.6% (35/188)
only in one male patient, whereas involvement of eyelashes,
                                                                    Lichen planus (skin/mucosae/nails) 5.3% (10/188)
armpits and pubis were reported in 52 (27.6%), 80 (42.5%)
                                                                   Diagnostic methods
and 68 (36.1%) patients, respectively. In all cases with an
                                                                    Dermoscopy                          71.8% (135/188)
extra-scalp involvement, the eyebrows were also compro-
                                                                    Biopsy                              28.2% (53/188)
mised at the same time. Non-inflammatory facial papules
were observed in 56 patients (29.8%). In 48 patients, they        FFA=frontal fibrosing alopecia; AGA= androgenetic alopecia



Review | Dermatol Pract Concept. 2022; 12(1):e2022080                                                                        3
were localized on the face, in 6 patients on the limbs and in 2
patients simultaneously on the face, limbs and trunk.
    Concomitant signs of LPP on the scalp were present
in 35 patients (18.6%). Five of them showed diffuse hair
thinning in the crown area associated with trichoscopic and
histopathological features of LPP and were diagnosed with
fibrosing alopecia in a pattern distribution (FAPD). Ten out
of 188 patients (5.3%) had lichenoid changes on the skin,
mucous membranes and/or nails. The concomitant presence
of AGA was found in 73 patients (38.8%).
    A family history of FFA was reported in 19 patients
                                                                   Figure 1. Clinical presentation of a female with frontal fibrosing
(10.1%) with a mean age of onset at 56.4 years, while it was
                                                                   alopecia.
59.6 years in patients without a family history (P = 0.9).
    Trichoscopy reports showed signs of cicatricial alopecia
in all patients, with empty follicles in 93.6% of cases and
absence of follicular ostia in 92% of cases. The presence of
inflammatory signs such as perifollicular erythema and per-
ifollicular hyperkeratosis were present in 129 (63.8%) and
113 (60.1%) of the patients, respectively. One hundred and
three patients (54.8%) presented lonely hairs. Trichoscopic
signs were not associated with the degree of disease, but
clinical signs of inflammation such as perifollicular erythema
and perifollicular hyperkeratosis were associated with the
presence of pruritus (P = 0.049). Indeed, 124 patients (65.9%)
                                                                   Figure 2. Trichoscopy of a female affected by frontal fibrosing
complained of itching and 43 (22.9%) reported concomitant          alopecia.
trichodynia.
    In most cases (71.8%), the characteristic clinical presenta-      The literature search identified a total of 24 papers (all
tion (Figure 1) and the typical trichoscopic findings (Figure 2)   published between 2014 and 2021) with more than 100
made it possible to make the diagnosis of FFA without              included cases (Table 2) [19, 25-27, 30-49]. During 2014,
resorting to the use of invasive diagnostic techniques. Only       2015, and 2016 only one study was published per year
53 patients required a histopathological diagnosis.                [25,48,49]. Two and 5 studies were published in 2017 and


                   Table 2. Data of Published Studies on FFA Reporting more than 100 Cases

                       Number
                          of        Sex
                       patients     M/F           Population        Type of diagnosis                  Data collected
 Pindado-Ortega C      224         2/222     Spain                 Clinical                Retrospective observational study
 et al 2021 [30]                                                   (histopathological      on effectiveness of dutasteride in
                                                                   when needed)            FFA
 Muller Ramos P        451         18/433 Brazil                   NA                      Multicenter case-control study on
 et al 2021 [31]                                                                           risk factors for FFA
 Grassi S              119         8/111     Italy                 NA                      Retrospective observational
 et al 2021 [32]                                                                           monocentric study on epidemiology,
                                                                                           clinical and trichoscopic features
                                                                                           and comorbidities in FFA patients
 Trager MH             173         14/159 Colombia and USA         Clinical and            Retrospective cohort study on
 et al 2021 [33]                                                   histopathological       medical comorbidities and gender
                                                                                           distribution among patients with
                                                                                           LPP and FFA
 McSweeney SM          711         0/711     UK                    Clinical                Descriptive cross-sectional study on
 et al 2020 [34]                                                   (histopathological      clinical phenotype in women from
                                                                   when needed)            FFA UK GWAS cohort

                                                                                                                 Table 2 continues

4                                                                             Review | Dermatol Pract Concept. 2022; 12(1):e2022080
         Table 2. Data of Published Studies on FFA Reporting more than 100 Cases (continued).

                       Number
                          of         Sex
                       patients      M/F         Population       Type of diagnosis              Data collected
 Anzai A               151         0/151     Brazil/Italy         Histopathological    Retrospective and prospective study
 et al 2019 [27]                                                                       on trichoscopic findings of FFA of
                                                                                       the eyebrows
 Papanikou S           100         0/100     Greece               NA                   Observational study on the influence
 et al 2019 [35]                                                                       of social status on the prognosis of
                                                                                       FFA in female patients
 Mulinari Brenner      227         NA        Brazil               NA                   Observational study on reported
 F et al 2019 [36]                                                                     cases of FFA in a tertiary center
 Vañó-Galván et al     306         NA        Australia, Brazil,   NA                   Retrospective multicenter study on
 2019 [37]                                   Chile, Colombia,                          frequencies of alopecia types at 22
                                             Italy, Mexico,                            specialized hair clinics
                                             Norway, Poland,
                                             Portugal, South
                                             Africa, Spain,
                                             Switzerland,
                                             USAand UK
 Kanti V               490         25/465 France and              Clinical             Observational cross-sectional
 et al 2019 [38]                          Germany                 (histopathological   descriptive study on demographic
                                                                  when needed)         and clinical characteristics
                                                                                       associated with the severity of FFA
 Moreno-Arrones        278         0/278     Spain                Clinical             Multicenter cross-sectional study on
 OM                                                               (histopathological   factors influencing FFA severity
 et al 2019 [39]                                                  when needed)
 Tziotzios C           1016        0/1016 Greece and UK           NA                   Genome-wide association study on
 et al 2019 [19]                                                                       FFA
 Moreno-Arrones        335         20/315 Spain                   NA                   Multicenter case-control study on
 OM                                                                                    risk factors associated with FFA
 et al 2019 [40]
 Cranwell WC           130         0/130     Australia            NA                   Case-control questionnaire study on
 et al 2019 [41]                                                                       exposure to sunscreen or facial skin
                                                                                       care products and their association
                                                                                       with FFA
 Buendia-Castano       104         0/104     Spain                Clinical             Case-control study on hormonal
 D et al 2018 [42]                                                (histopathological   and gynecological risk factors for
                                                                  when needed)         FFA
 Imhof RL              148         0/148     USA                  Clinical             Retrospective study on
 et al 2018 [43]                                                  (histopathological   clinicopathological findings,
                                                                  when needed)         comorbidities and treatment
                                                                                       outcomes in women with FFA
 Saceda-Corralo D      103         0/103     Spain                Clinical             Descriptive cross-sectional study on
 et al 2018 [44]                                                  (histopathological   patients diagnosed with both FFA
                                                                  when needed)         and LPP
 Cervantes J           108         NA        USA                  Clinical             Retrospective study on trichoscopic
 et al 2018 [26]                                                  (histopathological   features of sideburns in FFA
                                                                  when needed)         compared to fronto-temporal scalp
 Pindado Ortega C      103         0/103     Spain                Clinical             Descriptive cross-sectional study
 et al 2018 [45]                                                  (histopathological   on relationship between FFA and
                                                                  when needed)         rosacea
 Donati A              149         NA        France               Clinical             Retrospective analysis on the use of
 et al 2017 [46]                                                  (histopathological   direct immunofluorescence in FFA
                                                                  when needed)

                                                                                                           Table 2 continues


Review | Dermatol Pract Concept. 2022; 12(1):e2022080                                                                         5
         Table 2. Data of Published Studies on FFA Reporting more than 100 Cases (continued).
                       Number
                          of        Sex
                       patients     M/F           Population        Type of diagnosis                 Data collected
 Moreno Arrones        242         0/242     Spain                 Clinical                Retrospective single-centre
 OM et al 2017                                                     (histopathological      observational study on clinical and
 [47]                                                              when needed)            prognostic classification of FFA
 Aldoori N             105         0/105     UK                    Clinical                Case-control study on the role of
 et al 2016 [48]                                                                           leave-on facial skin care products
                                                                                           and sunscreen in FFA
 Fernandez-            249         11/238 Spain                    Clinical and            Descriptive retrospective
 Crehuet P et al                                                   histopathological       observational multicenter study on
 2015 [25]                                                                                 trichoscopic features of FFA
 Vañó-Galván et al     355         12/343 Spain                    Clinical                Retrospective multicenter study on
 2014 [49]                                                         (histopathological      epidemiology, comorbidities, clinical
                                                                   when needed)            presentation, diagnostic findings,
                                                                                           and therapeutic choices in FFA

FFA = frontal fibrosing alopecia; F = females; M = ales; NA=not applicable.



2018, respectively [26,42-47]. Nine studies were released in          Navarro Belmonte et al reported that the age at onset of
2019 [19,27,35-41] and 5 studies were published in 2020            the disease in cases with relatives affected by FFA appears to
and 2021 [30-34]. In 13 studies, clinical and trichoscopic         be lower than in isolated cases [51]. Our study also showed an
features were decisive for the diagnosis in almost all FFA cases   earlier onset of about 3 years in subjects with a positive family
[26,30,34,39,42-49]. Invasive biopsies for histopathological       history. However, the difference between the two groups was
examinations were reserved for doubtful cases and confirmed        not significant in our cases.
the diagnosis in all cases.                                           In accordance with other small studies [8,52], our study
                                                                   reported an association between FFA and LPP (18.6% of

Conclusions                                                        cases) including 5 patients with FAPD. This observation sup-
                                                                   ports the theory that FFA could actually represent a clinical
Since its first description in 1994, FFA has shown a significant   variant of LPP despite the different symptoms. Although this
increase in incidence all over the world. In 2014, Vañó-Galván     association was not reported in larger studies, it is possible
et al published the first large cohort of patients diagnosed       that it is under-reported.
with FFA [49]. Subsequently, as confirmed by our review of            Consistent with previous studies [53,54], the presence
the literature, the number of published large cohort studies       of AGA was recorded in 38.8% of patients suggesting that
have increased over time, in particular during the last 3 years.   AGA may be at the root of a fibrotic process leading to FFA
Of note, Tziotzios et al published the largest cohort study        or that FFA and AGA may have a similar underlying patho-
in 2019, reporting more than 1,000 patients from Greece            genetic mechanism, for example a hormonal basis. The role
and UK [19]. Here, we report an additional large cohort of         of hormones is however still uncertain and debated as well
patients diagnosed with FFA collected through IDS members          as the link between FFA, LPP and AGA. One retrospective
who responded to our online call.                                  study associated FFA with androgen deficiency, while LPP
    The mean age at onset of the disease in our sample was         was more frequently associated with androgen excess [54].
58.6 years, which is comparable to the previously reported         Furthermore, no association with Lupus and AA was reported
data on FFA. The results support the current theory that           in our group of patients.
the disease mainly affects postmenopausal women (88.1%),              Interestingly, the diagnosis of FFA in our cohort was made
but also documents that it can be found in younger women           on average 4.4 years after the onset of the disease and in
(11.9%). The youngest patient was 15 years old at the onset        51.6% of cases already presented as grade 2 of severity with
of symptoms. Our sample also included 3 male subjects sup-         a mean frontal hairline recession of 2.35 cm, which in some
porting the fact that FFA can affect males as well. Cases of       cases reached 10 cm. This underlines the importance of aware-
FFA within multiple members of the same family have been           ness and education on this disease, not only among patients
reported in 5-8% of the cases [49, 50], a result that is a very    but also among health professionals, in order to diagnose
similar to the percentage observed in our study (10.1%).           and treat FFA at an earlier stage to stop the scarring process.



6                                                                             Review | Dermatol Pract Concept. 2022; 12(1):e2022080
   Alopecia of the eyebrows, found in 85.6% of cases, was         investigation of FFA to reduce the need of surgical biopsies
confirmed as the most frequent sign of the disease, while the     and histopathological confirmation of the disease.
loss of eyelashes and axillary, pubic and/or body hair was
documented with a lower rate. Some authors have raised the
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Review | Dermatol Pract Concept. 2022; 12(1):e2022080                                                                                              9
