Upregulation of caveolae-associated structural proteins in the hair follicle bulge of lichen planopilaris and frontal fibrosing alopecia.

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are primary cicatricial alopecia that cause a major impact on quality of life due to irreversible hair loss and symptoms as itching, burning and pain. They are characterized by permanent loss of hair follicle stem cells (HFSCs) by pathomechanisms still poorly understood, resulting in poor efficacy of currently available treatments. Caveolae are flask-shaped lipid rafts invaginated within the plasma membrane of multiple cell types. Although their role in the HF physiology and pathophysiology is relatively unknown, we have previously demonstrated that the primary structural component of caveolae (caveolin-1 or Cav1) is upregulated in FFA. Thus, we propose to investigate the expression and localization of caveolae-associated structural proteins (Cav1, Cav2, and Cavin-1) and HFSCs (identified by K15) in both LPP and FFA. We analyzed 4 patients with LPP biopsied in affected and non-affected (NA) scalp, 4 patients with FFA biopsied in affected scalp and 4 healthy controls. Affected scalp of LPP and FFA demonstrated increased levels of Cav1 and Cavin-1 compared with HC and LPP-NA. Moreover, Cav1, Cav2 and Cavin1 all exhibit high colocalization with K15 and their expression appears to be negatively correlated, supporting the hypothesis that these proteins are important players in LPP/FFA and may serve as therapeutic targets in future treatments.

Fenómeno infrecuente la co-localización de alopecia frontal fibrosante y vitiligo en un varón: informe de un caso / Infrequent phenomenon the co-localization of fibrosing frontal alopecia and vitiligo in a male: case repor

La alopecia frontal fibrosante es una alopecia cicatricial que se caracteriza por la recesión de la línea de implantación frontotemporal que afecta principalmente a mujeres caucásicas en edad posmenopáusica y rara vez a hombres. Actualmente los mecanismos específicos de desarrollo continúan en estudio; sin embargo hay varias hipótesis sobre la asociación de la alopecia frontal fibrosante con otros trastornos autoinmunitarios. Se comunica el caso de un paciente masculino de 58 años con alopecia frontal fibrosante en áreas comprometidas por vitiligo. (AU)

Frontal fibrosing alopecia is a cicatricial alopecic characterized by progressive regression of the frontotemporal hairline. It usually affects postmenopausal caucasian women, and rarely men. Currently the specific mechanisms of development remain unknown, however there are several hypotheses about the association of frontal fibrosing alopecia with other autoimmune disorders. The case of a 58-year-old male patient with frontal fibrosing alopecia in areas affected by vitiligo. (AU)

Frontal Fibrosing Alopecia: Is There a Link in Relatives?

Frontal fibrosing alopecia (FFA) is an acquired primary lymphocytic cicatricial alopecia characterized by frontotemporal hairline recession, leading to scarring alopecia with a band-like distribution. Prevalence is increasing worldwide, being the most frequent cause of primary scarring alopecia. The natural history of this condition is variable; however, slow progression with spontaneous remission is the most frequent reported outcome. The etiopathogenesis of FFA remains to be elucidated; numerous hypotheses concerning hormonal effects, environmental factors, and genetic predisposition have been proposed. Special interest on genetic basis has emerged since the first familial case was reported. Only a few more familial cases have been published. We report 6 additional cases of female patients with familial FFA (F-FFA) from 3 different families. Sixty-six percent had a family history of autoimmune disease in first-degree relatives; these same patients had a personal history of autoimmune disease. The families described in this cohort study plus the personal and family history of autoimmune disease, as well as the recently described involved genomic loci; reinforced the hypothesis of this disease being genetic. It is important to consider studying this entity since there are scarce data regarding familial cases and this might give us a better insight toward understanding its pathogenesis.

Eyebrow Regrowth in Patients with Frontal Fibrosing Alopecia Treated with Low-Dose Oral Minoxidil.

INTRODUCTION: The eyebrows are an important facial feature that shape one's physical appearance and play a role in non-verbal communication. Partial or complete eyebrow loss is seen in most patients with frontal fibrosing alopecia (FFA). Despite the scarring nature of FFA, eyebrow hair regrowth has been previously reported. Nevertheless, treatment options and supporting evidence remain scarce. CASE PRESENTATION: We report eyebrow regrowth in 7 patients with FFA treated with low-dose oral minoxidil (OM). CONCLUSION: Low-dose OM could be a promising adjunctive therapy for treatment of the eyebrows in patients with FFA, particularly in early disease.

Occipital Fibrosing Alopecia in a Young Male: A Case Report.

INTRODUCTION: Lichen planopilaris (LPP) is a primary lymphocytic cicatricial alopecia with 3 recognized clinical variants. Lately, LPP clinical spectrum has expanded with new and overlapping clinical variants. First considered as a subtype of LPP affecting postmenopausal women, the increasing worldwide incidence of FFA including atypical lesions in young female and male suggests a different pathomechanism for this disease. Although LPP-spectrum disorders may share similar histopathological findings, clinical features and prognosis are different. CASE REPORT: A 26-year-old Caucasian male presented with occipital scarring alopecia and pruritus for the last 6 months. The patient had been treated for an associated androgenetic alopecia and superficial recurrent scalp folliculitis over the vertex scalp for the last 5 years. Trichoscopy of the occipital scalp showed mild diffuse erythema, moderate peripilar scaling, and absence of follicular openings, suggestive of a scarring process. The patient underwent an occipital scalp biopsy that confirmed the diagnosis of a LPP-spectrum disorder. DISCUSSION/CONCLUSION: Both LPP and FFA mostly affect the anterior-mid scalp of females. However, recent reports on FFA also in premenopausal women and men should make physicians aware of atypical features of this disease and unusual clinical presentation.

Risk factors for frontal fibrosing alopecia: A case-control study in a multiracial population.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a chronic cicatricial alopecia with unknown etiology and a worldwide rising incidence. OBJECTIVE: The objective of this study was to evaluate the association of FFA with demographic and exposure factors in a Brazilian multiracial population. METHODS: A multicenter case-control study was conducted in 11 referral centers throughout Brazil. The study was a case-control study that prospectively recruited 902 participants (451 patients with FFA and 451 sex-matched control individuals). Study participants completed a thorough questionnaire comprising variables grouped as baseline demographics, environmental exposure, diet, hormonal factors, allergies, and hair and skin care. RESULTS: When adjusted by sex, age, menopause, and skin color, FFA was associated with hair straightening with formalin (odds ratio [OR], 3.18), use of ordinary (nondermatologic) facial soap (OR, 2.09) and facial moisturizer (OR, 1.99), thyroid disorders (OR, 1.69), and rosacea (OR, 2.08). Smokers (OR, 0.33) and users of antiresidue/clarifying shampoo (OR, 0.35) presented a negative association with FFA. There was no association with the use of sunscreen. LIMITATIONS: Recall bias. CONCLUSIONS: The association with moisturizers, ordinary facial soap, and hair straightening with formalin and the negative association with antiresidue/clarifying shampoo reinforce the possibility of an exogenous particle triggering FFA.

Frontal Fibrosing Alopecia and Autoimmune Disorders in a Hispanic Female.

Frontal fibrosing alopecia (FFA) is a cicatricial alopecia characterized by hairline recession. Multiple autoimmune pathologies have been reported in patients with FFA. Despite the fact that FFA etiology remains unknown, there has been described an association with autoimmune disorders probably caused by an altered activity of cytotoxic CD8 T lymphocytes. Moreover, other autoimmune pathologies develop TH1 and TH17 response. Genetics could be responsible, in part, for the role of multiple simultaneous autoimmune disorders. Herein, we describe a case of a female patient with vitiligo, lichen sclerosus, and autoimmune hypothyroidism who developed a pruritic band-like recession of the frontal hairline. More research is needed in this area since autoimmune events in these patients may not be a mere coincidence.

Frontal Fibrosing Alopecia Associated with Lichen Planus Pigmentosus: Not Only in Dark Phototypes.

The association between frontal fibrosing alopecia and lichen planus pigmetosus was first described in African women. Later, most reports about this association involved dark-skinned patients. Here, we describe 5 cases of frontal fibrosing alopecia associated with lichen planus pigmentosus in light-skinned women from Argentina. Our communication highlights the strength of both entities' association also in lower Fitzpatrick phototypes.

Pili Torti as a Sign of Eyebrow Involvement in Frontal Fibrosing Alopecia.

Frontal fibrosing alopecia (FFA) is a disease characterized by progressive band-like scarring alopecia involving the frontotemporal hairline and eyebrow hair loss. It affects mainly postmenopausal women. Trichoscopy features of FFA include absence of vellus hair, perifollicular erythema and scaling (peri-pilar casts), and absence of follicular openings. Trichoscopy of eyebrows in FFA patients shows tapered and broken hair, absence of follicular openings, black dots, and hair growing in different directions. We report a case of FFA with numerous pili torti in the eyebrows.

Frontal fibrosing alopecia: A new autoimmune entity?

Frontal fibrosing alopecia (FFA) is a rare type of cicatricial alopecic band, with bilateral and symmetric progressive regression of the frontotemporal hairline. The specific mechanisms of development of FFA remain unknown. Due to several clues, including the presence of lymphocytic infiltrates and the association of FFA with other autoimmune disorders, we hypothesised that FFA may be a new autoimmune condition, and future research must be focused on this possible origin.

Autologous Hair Transplantation in Frontal Fibrosing Alopecia.

We report a patient with frontal fibrosing alopecia (FFA), in whom autologous hair transplantation was successfully performed despite evidence of active disease. Since the underlying pathology of FFA is usually lichen planopilaris, reservations, and caveats have been expressed with respect to the risk of köbnerization phenomena following hair transplantation surgery. An important question that arises is how the lichenoid tissue reaction pattern is generated around the hair follicles in FFA. Follicles with some form of damage or malfunction might express cytokine profiles that attract inflammatory cells to assist in damage repair or in the initiation of apoptosis-mediated organ deletion. Alternatively, an as yet unknown antigenic stimulus from the damaged or malfunctioning hair follicle might initiate a lichenoid tissue reaction in the immunogenetically susceptible individual. Therefore, it might be expected that the transplantation of whole healthy hair follicles might less give rise to an inflammatory reaction than the disease itself, as revealed in our case report of successful hair transplantation in FFA.

Lichen Planopilaris Caused by Wig Attachment: A Case of Koebner Phenomenon in Frontal Fibrosing Alopecia.

Frontal fibrosing alopecia (FFA) represents a distinctive condition with a marginal scarring alopecia along the frontal and temporal hairline. Since its original description, the condition has been recognized to represent a more generalized than localized process, with extension beyond the frontotemporal hairline to include the parieto-occipital hairline and involve peculiar facial papules as evidence of facial vellus hair involvement and loss of peripheral body hair. Finally, the association of FFA with oral lichen planus, nail involvement, and concomitant lichen planopilaris (LPP) points to a close relationship to lichen planus. The Koebner phenomenon or isomorphic reaction has been described in lichen planus, LPP, and ultimately FFA, with face-lift procedures and hair restoration surgery having been implicated as the culprits in the latter. We report the first case of FFA in whom LPP developed at the sites of wig attachments, providing the evidence for Koebner phenomenon. Therefore, wigs are to be included to the list of procedures for hair restoration at risk of eliciting an isomorphic reaction in patients with FFA. Ultimately, the association of Koebner phenomenon with LPP-type lesions in FFA may provide further insight into the underlying pathology and nosology of the condition.

Frontal Fibrosing Alopecia Severity Index: A Trichoscopic Visual Scale That Correlates Thickness of Peripilar Casts with Severity of Inflammatory Changes at Pathology.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a scarring alopecia that mainly affects postmenopausal women characterized by recession of the frontotemporal hairline and eyebrow loss. Current techniques to assess FFA activity are limited and involve noninvasive tools that assess disease progression or an invasive technique such as scalp biopsies. However, since progression of FFA is very slow, it is very important to develop a noninvasive technique to assess disease activity to monitor treatment response. OBJECTIVES: To provide a standardized and objective method to assess FFA activity. METHODS: We evaluated the correlation between trichoscopy and pathological features (degree of lymphocytic infiltration) in 20 dermoscopy-guided biopsies of FFA. At trichoscopy, we divided the severity of peripilar casts into 3 grades according to their thickness. To validate the trichoscopic visual scale, we showed the images to 7 dermatologists with interest in hair diseases. Concordance was assessed using the Kendall Tau-b concordance test. RESULTS: A strong correlation between severity of peripilar casts at trichoscopy and degree of lymphocytic infiltrate was observed by the Kendall Tau-b test. Validation showed very good inter- and intraobserver agreement. CONCLUSION: The trichoscopic visual scale allows noninvasive assessment of scalp inflammation in FFA in different scalp regions and therefore provides optimal guidance for treatment.

Facial Papules in Frontal Fibrosing Alopecia: Beyond Vellus Hair Follicle Involvement.

BACKGROUND: Frontal fibrosing alopecia (FFA) is considered a variant of lichen planopilaris affecting mainly the frontotemporal hairline. Since the first report in 1994, several other clinical features have been associated with the disease, such as facial papules (FP). Even though FP have been linked to facial vellus hair follicle involvement, how this finding alone could lead to the formation of clinically evident FP in FFA patients had not yet been addressed. OBJECTIVE: To describe histopathological findings of FP in the context of FFA and to highlight features that may be linked to their clinical formation. METHODS: Cutaneous FP biopsies of FFA patients performed between January 2016 and May 2017 were retrieved from our pathology database and reexamined by 2 pathologists. RESULTS: Histological sections of thirteen 3.0-mm punch biopsy specimens (2 horizontally and 11 vertically oriented) were collected from 7 patients. Eleven specimens demonstrated prominent sebaceous glands and 10 dilated sebaceous ducts. Pinkus acid orcein staining revealed reduction and fragmentation of the elastic fibers in 12 samples and, in 7 of these, this finding was observed in both the papillary and reticular dermis, particularly around sebaceous lobules. Vellus hair follicle involvement was only seen in 2 samples. CONCLUSIONS: Prominent sebaceous lobules with dilated ducts associated with an abnormal elastic framework seem to be the main explanation for the formation of FP in the context of FFA.

Case Report of Connubial Frontal Fibrosing Alopecia.

Since its original report in 1994, frontal fibrosing alopecia has become increasingly common, attracting the attention of the medical community and giving rise to speculations on its etiology, specifically the possibility of environmental factors. Familial cases of frontal fibrosing alopecia point to the possible contribution of hereditary factors maybe related to androgenetic alopecia. We report thefirst case of connubial frontal fibrosing alopecia in a genetically unrelated couple pointing to the possibility of a common environmental exposure in the etiology of the condition. Our observation may be fortuitous, considering the high frequency of female frontal fibrosing alopecia. Nevertheless, the incidence of male frontal fibrosing alopecia has remained low with a consequently low statistical probability of random occurrence of the condition in a marital couple. We, therefore, suggest to systematically includes the hair condition of marital partners in the patient history of patients with frontal fibrosing alopecia, to elucidate the actual frequency of connubial frontal fibrosing alopecia and maybe a common causative agent or hair grooming practice.

Lichen planopilaris and frontal fibrosing alopecia cannot be differentiated by histopathology.

BACKGROUND: Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) represent 2 entities that cause primary cicatricial alopecia. These entities are clinically different; nevertheless, the literature suggests that FFA represents a form of LPP. The main argument in support of this hypothesis is that previous studies comparing the histologic findings have not found obvious differences between these diseases. METHODS: Our objective was to more critically compare and contrast 20 histologic findings of these diseases in a large number of patients in order to determine any significant histologic differences between LPP and FFA. RESULTS: We found 3 parameters that were statistically different, namely the presence of terminal catagen-telogen hairs (50% FFA vs 23.5% LPP; P = .020); a severe perifollicular inflammatory infiltrate (29.4% LPP vs 4.6% FFA; P = .010) and a zone of concentric lamellar fibroplasia (85.3% LPP vs 63.6% FFA; P = .041). CONCLUSIONS: Although a few histologic features differ between FFA and LPP, we believe that these differences are too subtle or non-specific to distinguish between them with confidence. Therefore, clinical correlation is essential to establish the diagnosis.

Trichoscopy of Dark Scalp.

Trichoscopy (dermoscopy of the hair and scalp) is a technique that improves diagnostic accuracy and follow-up with hair and scalp disorders. Although several studies of trichoscopy have been made in Caucasian and Asian populations, little has been published regarding trichoscopy findings in skin of color, despite the great prevalence of hair diseases in populations with this kind of skin. The aim of this review was to describe the trichoscopic features of normal scalp and of hair disorders in patients with dark skin phototypes. This will help dermatologists to distinguish between unique trichoscopic features of dark skin, and allow them to provide more accurate diagnoses and treatments for these patients.

Familial Cicatricial Alopecia: Report of Familial Frontal Fibrosing Alopecia and Fibrosing Alopecia in a Pattern Distribution.

Frontal fibrosing alopecia (FFA) and fibrosing alopecia in a pattern distribution (FAPD) as originally reported by Kossard in 1994 and by Zinkernagel and Trüeb in 2000, respectively, represent two distinct patterns of cicatricial pattern hair loss. Both share a patterned distribution and histological evidence of a lichenoid follicular inflammation with fibrosis. FFA is characterized by a marginal alopecia along the frontotemporal hairline, and FAPD by a progressive alopecia of the centroparietal scalp. Since the original reports, evidence has accumulated that there exists considerable clinical overlap among FFA, FAPD, and lichen planopilaris, with coexistence of features of the three conditions within the same individual. Moreover, familial cases of FFA have been reported, pointing to a possible genetic background to the condition. Our observation of familial occurrence of FFA and FAPD in daughter and mother, respectively, further underscore a nosologic relationship between the two conditions with respect to both an androgenetic background and the (lichenoid) inflammatory reaction pattern.