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Background/objectives Alopecia areata may occur at any age and is the third-most-common dermatosis in children. The objective of this study was to investigate the clinical and epidemiologic features of children and adolescents with alopecia areata based on the data of the National Alopecia Areata registry on children and adolescents. Methods Two thousand two hundred eighteen children and adolescents with alopecia areata self-enrolled in the National Alopecia Areata Registry and completed a web-based, self-administered, short-intake screening questionnaire (first tier). In the second tier, 643 patients participated in a clinical examination and completed a long-form questionnaire. Results Mean age of onset was 5.9 ± 4.1 years. With a female to male ratio of 1.5:1, alopecia areata was more prevalent in girls, but boys were significantly more likely to have a severe type (P = .009). One-fourth of all children had a positive family history, with 8% having more than three affected relatives. The disease most commonly associated with alopecia areata was atopic dermatitis (32.7%). Conclusion Childhood alopecia areata is more prevalent in girls than in boys, but boys have more extensive alopecia areata. Despite the low prevalence, congenital alopecia areata is an important differential diagnosis for neonatal hair loss. Alopecia areata runs in families, suggesting an underlying genetic background. One-quarter of the children reported at least one affected first-degree relative; 8% had more than three affected relatives.

Alopecia areata (AA) is an autoimmune disease in which cytotoxic T cells specifically target growing hair follicles. We used high-throughput TCR sequencing in the C3H/HeJ mouse model of AA and in human AA patients to gain insight into pathogenic T cell populations and their dynamics, which revealed clonal CD8+ T cell expansions in lesional skin. In the C3H/HeJ model, we observed interindividual sharing of TCRβ chain protein sequences, which strongly supports a model of antigenic drive in AA. The overlap between the lesional TCR repertoire and a population of CD8+NKG2D+ T cells in skin-draining lymph nodes identified this subset as pathogenic effectors. In AA patients, treatment with the oral JAK inhibitor tofacitinib resulted in a decrease in clonally expanded CD8+ T cells in the scalp but also revealed that many expanded lesional T cell clones do not completely disappear from either skin or blood during treatment with tofacitinib, which may explain in part the relapse of disease after stopping treatment.

This review presents a systematic approach to the diagnosis of hair loss. An accurate diagnosis is based on history, clinical examination, laboratory tests, and scalp biopsy. Whether the hair loss is a cicatricial or noncicatricial alopecia guides one's history taking. After assessing the patient's global appearance, the hair and scalp are evaluated, aided by a hair pull, hair tug, Hair Card, and hair mount. Scalp biopsies can confirm a diagnosis and are essential in all cases of cicatricial alopecia. In all patients with hair loss a complete blood count, ferritin, thyroid stimulating hormone, and vitamin D 25OH should be ordered.

Summary Background Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia with a distinctive clinical pattern of progressive frontotemporal hairline recession. Currently, there are no evidence-based studies to guide treatment for patients with FFA; thus, treatment options vary among clinicians. Objectives We report clinical findings and treatment outcomes of 36 patients with FFA, the largest cohort to date. Further, we report the first evidence-based study of the efficacy of hydroxychloroquine in FFA using a quantitative clinical score, the Lichen Planopilaris Activity Index (LPPAI). Methods A retrospective case note review was performed of 36 adult patients with FFA. Data were collected on demographics and clinical findings. Treatment responses to hydroxychloroquine, doxycycline and mycophenolate mofetil were assessed using the LPPAI. Adverse events were monitored. Results Most patients in our cohort were female (97%), white (92%) and postmenopausal (83%). Apart from hairline recession, 75% also reported eyebrow loss. Scalp pruritus (67%) and perifollicular erythema (86%) were the most common presenting symptom and sign, respectively. A statistically significant reduction in signs and symptoms in subjects treated with hydroxychloroquine (P

Alopecia areata (AA) is among the most highly prevalent human autoimmune diseases, leading to disfiguring hair loss due to the collapse of immune privilege of the hair follicle and subsequent autoimmune attack. The genetic basis of AA is largely unknown. We undertook a genome-wide association study (GWAS) in a sample of 1,054 cases and 3,278 controls and identified 139 single nucleotide polymorphisms that are significantly associated with AA (P

Lichen planopilaris (LPP) is a chronic inflammatory disorder that causes permanent scalp hair loss and significant patient discomfort.We sought to determine the efficacy and safety of mycophenolate mofetil (MMF) for treatment of LPP in patients who had failed prior topical, intralesional, or oral anti-inflammatory medications such as hydroxychloroquine or cyclosporine.We conducted a retrospective chart review of 16 adult patients with LPP treated with at least 6 months of MMF in an open-label, single-center study from 2003 to 2007. Subjective and objective end points were quantified using the LPP Activity Index (LPPAI) and scores before and after treatment were assessed using a paired t test. Adverse events were monitored.Patients who completed treatment with MMF had significantly decreased signs and symptoms of active LPP despite having failed multiple prior therapies (P.005). Five of 12 patients were complete responders (LPPAI score decreased85%), 5 of 12 patients were partial responders (LPPAI score decreased 25%-85%), and two of 12 patients were treatment failures (LPPAI score decreased25%). Four patients withdrew from the trial because of adverse events.Retrospective analysis and small sample size were limitations.MMF was effective at reducing the signs and symptoms of active LPP in 83% of patients (10 of 12) who had failed multiple prior treatments after at least 6 months of treatment.

Lichen planopilaris (LPP) and its variant frontal fibrosing alopecia (FFA) are primary lymphocytic cicatricial alopecias for which there is no evidence-based therapy.We assessed the efficacy of hydroxychloroquine in active LPP and FFA using the LPP Activity Index (LPPAI), a numeric score that allows quantification of the symptoms and signs of the condition for statistical comparison. In addition, we determined with the LPPAI if any improvement (reduction) in the numeric score pretreatment and posttreatment reached statistical significance.This was a retrospective, single-center chart review of 40 adult patients with LPP, FFA, or both who were treated with hydroxychloroquine for up to 12 months from 2004 to 2007 at the University of California, San Francisco Hair Center. Symptoms, signs, activity, and spreading were scored at each visit in the standardized cicatricial alopecia flow chart. A numeric score was assigned to these markers of disease activity and a numeric score was calculated at each visit.There was significant reduction (P.001) in the LPPAI at both 6 and 12 months. After 6 months, 69% had improved (reduced) symptoms and signs. At 12 months, 83% had improvement (reduction) in symptoms and signs.Retrospective analysis and uncontrolled study are limitations.Hydroxychloroquine is effective in decreasing symptoms and signs in LPP and FFA as shown by significant reduction in the LPPAI in 69% and 83% of patients after 6 and 12 months of treatment, respectively.

Primary cicatricial or scarring alopecias (CA) are a group of inflammatory hair disorders of unknown pathogenesis characterized by the permanent destruction of the hair follicle. The current treatment options are ineffective in controlling disease progression largely because the molecular basis for CA is not understood. Microarray analysis of the lymphocytic CA, Lichen planopilaris (LPP), compared to normal scalp biopsies identified decreased expression of genes required for lipid metabolism and peroxisome biogenesis. Immunohistochemical analysis showed progressive loss of peroxisomes, proinflammatory lipid accumulation, and infiltration of inflammatory cells followed by destruction of the pilosebaceous unit. The expression of peroxisome proliferator-activated receptor (PPAR) gamma, a transcription factor that regulates these processes, is significantly decreased in LPP. Specific agonists of PPARgamma are effective in inducing peroxisomal and lipid metabolic gene expression in human keratinocytes. Finally, targeted deletion of PPARgamma in follicular stem cells in mice causes a skin and hair phenotype that emulates scarring alopecia. These studies suggest that PPARgamma is crucial for healthy pilosebaceous units and it is the loss of this function that triggers the pathogenesis of LPP. We propose that PPARgamma-targeted therapy may represent a new strategy in the treatment of these disorders.

Tinea capitis is the most common dermatophyte infection in children. The clinical presentation varies from subtle asymptomatic scaling to inflammatory suppurative nodules and draining tracks. Both chronic and acute inflammatory infections may damage the hair follicle leading to secondary cicatricial alopecia. In rare instances, the initial presentation can mimic a primary cicatricial alopecia. We present three cases of tinea capitis in children masquerading as cicatricial alopecia and discuss the possible host immune and fungal antigenic factors that may influence the course of disease and its clinical presentation. An understanding of the clinical morphology of tinea capitis in the context of both host and fungal factors may improve treatment strategies and direct future paradigms of therapy.

The best outcome of current treatments of cicatricial alopecia is induction of a clinical remission with arrest of symptoms and signs, but the progression of hair loss may continue insidiously. Current treatments do not arrest the underlying disease process. A scalp biopsy is the first step in management. Selection of treatment described herein is guided by the histopathologic findings, including the type, location and extent of the predominant cellular inflammatory infiltrate, and clinical disease activity. Cicatricial alopecias with predominantly lymphocytic infiltrates are treated with immunomodulating agents, and those with predominantly neutrophilic infiltrates are treated with antimicrobial agents. Treatment selection may be challenging and requires flexibility, as histopathologic features frequently overlap, are not clear cut, or change over time. In the future, cellular and molecular biology studies will hopefully identify unique markers for the clinically distinct cicatricial alopecias and lead to better treatments and a cure.

Background: Primary cicatricial alopecias encompass a group of disorders characterized by permanent destruction of the hair follicle. The varied clinical features and differences in terminology have led to difficulties in defining consistent clinicopathologic correlation. Objective: We sought clinicopathologic correlation of 6 clinically distinct primary cicatricial alopecias: lichen planopilaris, frontal fibrosing alopecia, pseudopelade (Brocq), central centrifugal alopecia, folliculitis decalvans, and tufted folliculitis. Methods: We conducted prospective and blinded histopathologic evaluation of clinically typical primary cicatricial alopecias. Biopsy specimens were taken from early affected scalp lesions and paired with samples from clinically unaffected areas in the same patient. Results: The lymphocytic and neutrophilic groups were readily distinguished histologically. However, within the two groups clinically distinct primary cicatricial alopecias could not be distinguished with current histopathologic techniques. Conclusion: A descriptive, standardized histopathologic reporting of follicular architecture, type, location, and extent of the inflammatory infiltrate, and presence or absence of sebaceous glands, may be of greatest value in guiding the treatment of patients with primary cicatricial alopecias. ( J Am Acad Dermatol 2005;52:637-43.)

Alopecia areata is an immunologically mediated disease characterized by extreme variability not only in the time of initial onset of hair loss but in the duration, extent and pattern of hair loss during any given episode of active loss. These variables, as well as the unpredictable nature of spontaneous regrowth and lack of a uniform response to various therapies, has made clinical trials in alopecia areata difficult to plan and implement. In fact, there are currently no drugs FDA-approved specifically for the indication of alopecia areata. To help facilitate well-controlled clinical trials for alopecia areata, this National Alopecia Areata Foundation (NAAF) sponsored subgroup of investigators/clinicians experienced in clinical trials and/or in the clinical care of patients with alopecia areata has outlined some general principles and potential endpoints for clinical studies in alopecia areata.Theseguidelines buildontheAlopeciaAreata

Androgenetic alopecia (AGA), also known in women as female pattern hair loss, is caused by androgens in genetically susceptible women and men. The thinning begins between ages 12 and 40 years, the inheritance pattern is polygenic, and the incidence is the same as in men. In susceptible hair follicles, dihydrotestosterone binds to the androgen receptor, and the hormone-receptor complex activates the genes responsible for the gradual transformation of large terminal follicles to miniaturized follicles. Both young women and young men with AGA have higher levels of 5alpha reductase and androgen receptor in frontal hair follicles compared to occipital follicles. At the same time, young women have much higher levels of cytochrome p-450 aromatase in frontal follicles than men who have minimal aromatase, and women have even higher aromatase levels in occipital follicles. The diagnosis of AGA in women is supported by early age of onset, the pattern of increased thinning over the frontal/parietal scalp with greater density over the occipital scalp, retention of the frontal hairline, and the presence of miniaturized hairs. Most women with AGA have normal menses and pregnancies. Extensive hormonal testing is usually not needed unless symptoms and signs of androgen excess are present such as hirsutism, severe unresponsive cystic acne, virilization, or galactorrhea. Topical minoxidil solution is the only drug available for promoting hair growth in women with AGA. Efficacy has been shown in double-blind studies using hair counts and hair weight.

Alopecia areata (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the major histocompatibility complex, where we fine-map four independent effects, all implicating human leukocyte antigen-DR as a key aetiologic driver. Outside the major histocompatibility complex, we identify two novel loci that exceed the threshold of statistical significance, containing ​ACOXL/​BCL2L11(​BIM) (2q13); ​GARP (​LRRC32) (11q13.5), as well as a third nominally significant region ​SH2B3(​LNK)/​ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, transforming growth factor beta/Tregs and JAK kinase signalling, and support the causal role of aberrant immune processes in AA.

Alopecia areata is a common cause of nonscarring hair loss in children and adults. In newborns and very young infants, however, it is thought to be extremely rare. In this article we describe five cases of alopecia areata in patients less than 6 months of age and briefly discuss the pertinent differential diagnosis of infants and newborns with both patchy and complete hair loss. We propose that alopecia areata may be more common in this age group than the literature suggests.

Background: Androgenetic alopecia is a common condition of adult men. Finasteride, a type 2 5α-reductase inhibitor, decreases the formation of dihydrotestosterone from testosterone. Objective: Two separate clinical studies were conducted to establish the optimal dose of finasteride in men with this condition. Methods: Men from 18 to 36 years of age with moderate vertex male pattern hair loss received finasteride 5, 1, 0.2, or 0.01 mg/day or placebo based on random assignment. Efficacy was determined by scalp hair counts, patient self-assessment, investigator assessment, and assessment of clinical photographs. Safety was assessed by clinical and laboratory measurements and by analysis of adverse experiences. Results: Efficacy was demonstrated for all end points for finasteride at doses of 0.2 mg/day or higher, with 1 and 5 mg demonstrating similar efficacy that was superior to lower doses. Efficacy of the 0.01 mg dose was similar to placebo. No significant safety issues were identified in the trials. Conclusion: Finasteride 1 mg/day is the optimal dose for the treatment of men with male pattern hair loss and was subsequently identified for further clinical development.

Hair loss is a common and distressing symptom. With the approval of two drugs that promote hair growth — finasteride and minoxidil — we can now treat patients with some types of hair loss. Both drugs influence the hair-growth cycle and increase the length and diameter of existing hair, although their mechanisms of action differ. In this article, I will focus on the treatment of two common problems, androgenetic alopecia and alopecia areata, both of which involve a reversible alteration of the hair-growth cycle. The Hair-Growth Cycle Hair growth is cyclic, with phases of growth (anagen), involution (catagen), and rest . . .

From Duke University Medical Center, Durhama; University of Minnesota, Minneapolisb; Pontefract General Infirmaryc; University of California at San Franciscod; Northwest Cutaneous Research Specialists, Portlande; The University of British Columbia, Vancouverf; and Johnson & Johnson, Skin Biology Research Center, Skillman.g Reprint requests: Elise A. Olsen, MD, Professor of Medicine, Duke University Medical Center, Box 3294, Durham, NC 27710. J Am Acad Dermatol 1999;40:242-6. *Developed from the Alopecia Areata Consensus meeting sponsored by the National Alopecia Areata Foundation at the First Tricontinental Meeting of the Hair Research Societies, Brussels, Belgium, Oct 8, 1995. Participants are listed at the end of the guidelines. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/1/95940 I. PURPOSE To establish criteria for selecting and assessing subjects for both clinical and laboratory studies of alopecia areata, thereby facilitating collaboration, comparison of data, and the sharing of patient-derived tissue II. DEFINITION OF ALOPECIA AREATA Alopecia areata is a dermatologic disease characterized in its limited form by circumscribed round or oval patches of alopecia with well-demarcated borders between normal and affected scalp. There is no scale or induration of the scalp and no loss of follicular markings. Disease extent may progress from this limited form to complete loss of hair on the scalp and/or body. III. INCLUSION CRITERIA These guidelines apply only to terminal hair loss or growth on the scalp. These guidelines focus on the major forms of alopecia areata (patchy alopecia areata, alopecia totalis, and alopecia universalis) and their expression on the scalp. The terms alopecia totalis and alopecia universalis imply 100% scalp hair loss. Areas of hair loss other than on the scalp may be assessed and documented in the data collected on each patient. (See Section IV. B) IV. CRITERIA FOR MEASURING EXTENT OF INVOLVEMENT Those data items in boldface type should be filled out in toto. Those data items not in bold are optional and can be filled out as desired by the investigator. A. The proportion of scalp involvement is determined by dividing the scalp into 4 quadrants and estimating the percentage of the scalp surface that all the alopecic areas would occupy if placed together. The following groups will be used: S: Scalp hair loss _____S0 = No hair loss _____S4 = 76%-99% hair loss _____S1 = ≤ 25% hair loss _____a = 76%-95% hair loss _____S2 = 26%-50% hair loss _____b = 96%-99% hair loss _____S3 = 51%-75% hair loss _____S5 = 100% hair loss B. Other areas of alopecia or involvement by alopecia areata may be noted: B: Body hair loss _____B0 = No body hair loss _____B2 = 100% body (excluding scalp) hair loss _____B1 = Some body hair loss N: Nail involvement _____N0 = No nail involvement _____N1 = Some nail involvement _____a. Twenty-nail dystrophy/trachyonychia (must be all 20 nails) SPECIAL ARTICLE

Background. Recalcitrant scarring follicular disorders have been treated previously by removing hair follicles both surgically by scalp resection with skin grafting and with X-ray epilation. Laser-assisted hair removal may provide an alternate method of hair removal with less associated morbidity. Objective. The goal is to determine whether laser-assisted hair removal can be used to treat follicular inflammatory disorders by destroying hair follicles. Methods. Three patients with various scarring follicular disorders (dissecting cellulitis of the scalp, keratosis pilaris spinulosa decalvans, and pseudofolliculitis barbae) were treated with the long-pulse non-Q-switched ruby laser and followed clinically. Results. The patients tolerated the treatments well without significant side effects and noted improvement of their condition along with decreased hair growth in the treated area. Conclusion. Laser-assisted hair removal may provide a safe, effective means of treating recalcitrant follicular disorders.

Background: Androgenetic alopecia (male pattern hair loss) is caused by androgen-dependent miniaturization of scalp hair follicles, with scalp dihydrotestosterone (DHT) implicated as a contributing cause. Finasteride, an inhibitor of type II 5α-reductase, decreases serum and scalp DHT by inhibiting conversion of testosterone to DHT. Objective: Our purpose was to determine whether finasteride treatment leads to clinical improvement in men with male pattern hair loss. Methods: In two 1-year trials, 1553 men (18 to 41 years of age) with male pattern hair loss received oral finasteride 1 mg/d or placebo, and 1215 men continued in blinded extension studies for a second year. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, and review of photographs by an expert panel. Results: Finasteride treatment improved scalp hair by all evaluation techniques at 1 and 2 years ( P 2 ) of balding vertex scalp, were observed with finasteride treatment (107 and 138 hairs vs placebo at 1 and 2 years, respectively; P Conclusion: In men with male pattern hair loss, finasteride 1 mg/d slowed the progression of hair loss and increased hair growth in clinical trials over 2 years. (J Am Acad Dermatol 1998;39:578-89.)

Today there are new classes of hair growth promotors with proven efficacy. This article reviews the current state of the art agents for treatment of two of the most common forms of hair loss encountered in clinical practice, androgenetic alopecia and alopecia areata. Current therapeutic strategies are based on recent advances in the understanding of disordered hair growth. Practical treatment protocols are presented.

Alopecia areata (AA) is a nonscarring and recurrent disease characterized by hair loss that may significantly affect patient health-related quality of life (HRQoL). Given the lack of reliable and accurate reporting of HRQoL status in patients with AA, we analyzed data from 532 AA patients from the National Alopecia Areata Registry whose registry record included HRQoL assessments using three validated instruments: Skindex-16, brief version of the Fear of Negative Evaluation Scale, and Dermatology Life Quality Index. The mean HRQoL scores were compared with previously reported HRQoL levels from healthy controls and patients with other skin diseases. Two-step cluster analysis of Skindex-16 scales divided patients into two groups: 481 (57%) with good HRQoL and 361 (43%) with poor HRQoL. Multivariate logistic regression modeling revealed a set of risk factors for poor HRQoL: age

Alopecia areata is the only condition that can cause complete hair loss in 3 months without symptoms or signs.

The National Alopecia Areata Registry (NAAR) was established as a collaborative effort of five academic centers and was funded by the NIAMS (National Institute of Arthritis and Musculoskeletal and Skin Diseases) on 23 September 2000 and now has been transferred to the National Alopecia Areata Foundation (NAAF). The NAAR has an internet domain and website http://www.alopeciaareataregistry.com, which allows patients to self-register in the first tier. Patients were then invited to one of the five centers to have an examination and blood was drawn for samples of DNA, sera, and lymphoblast lines to be used for genetic studies. This will update the progress of the NAAR over the past 10 years and its emergence as a clinical trials network and biobank. At the time of the Summit, 6,153 of the 8,942 first-tier registrants had dermatologist-confirmed alopecia areata (AA), including 2,202 with alopecia areata persistent (AAP)41 year, 2,142 with alopecia universalis AU, 897 with alopecia totalis (AT), and 823 with transient AA (AAT)o1 year. There were 2,609 AA patients examined in tier 2, including 729 with AAP, 526 with AAT, 339 with AT, and 1,015 with AU as well as 396 unrelated controls and 463 related but unaffected. The distribution of age of onset is shown in Figure 1. We have identified 264 multiplex families and acquired 40 for linkage analysis. The Registry has been used for a number of projects relating to the pathogenesis and quality of life: (1) confirming the reported human leukocyte antigen associations; (2) studies of cytokine profiles in AA with or without atopy; (3) case-control study—incidence of autoimmunity in AA patients; (4) EBV (Epstein–Barr virus) as a trigger for AA in adolescents; (5) treatment practices in AA; (6) quality of life in adolescents and adults with AA; (7) self-reported trigger factors for AA; and last but not least (8) association and linkage studies—genomewide association studies revealing eight novel genes associated with AA that have been confirmed and being translated into clinical trials. The NAAR continues to accept patient registrations. NAAR is involved in an NIH (National Institutes of Health)-funded biomarker study to acquire scalp biopsies and DNA samples. The five centers in the Registry (University of Texas MD Anderson Cancer Center; Columbia University; University of Minnesota; University of Colorado; University of California, San Francisco) are a consortium for clinical trials, and the Registry sample collection represents an existing biobank for future translational studies.

Intralesional corticosteroid injections are a common treatment for patchy alopecia areata, the most prevalent subtype of this autoimmune hair disorder. To date, no studies have examined the potential adverse effects of this therapy on bone mineral density (BMD).In this retrospective, cross-sectional case series, 18 patients with patchy alopecia areata treated at 4- to 8-week intervals with intralesional triamcinolone acetonide for at least 20 months were evaluated for BMD using dual-energy x-ray absorptiometry (DXA). Follow-up DXA measurements were obtained in those with abnormal findings.Nine out of 18 patients (50%) had abnormal DXA results. Patients with the following risk factors were more likely to have abnormal BMD: age older than 50 years, body mass index less than 18.5 kg/m2, lack of weight-bearing exercise, smoking history, postmenopausal status, past stress fracture, family history of osteopenia or osteoporosis, and a cumulative intralesional triamcinolone acetonide dose of greater than 500 mg.Patients with patchy alopecia areata who receive chronic intralesional triamcinolone acetonide therapy should be counseled on preventive measures for osteoporosis and monitored for effects on BMD.

Background The biochemical bases for fragility in most of the rare brittle hair shaft syndromes are unknown. The hypothesis being investigated in several syndromes is that the hair cuticle cells show defects in cross-linked protein features. Since transglutaminases stabilize protein structures by cross-linking them, hair from autosomal recessive lamellar ichthyosis patients lacking keratinocyte transglutaminase was examined to find whether this enzyme participates in hair shaft stabilization. Methods Hair shaft samples from patients afflicted with lamellar ichthyosis or several brittle hair syndromes were examined ultrastructurally by transmission electron microscopy after vigorous extraction with detergent and reducing agent to reveal cross-linked protein features. Results In hair cuticle cells from three patients with lamellar ichthyosis the marginal band (A layer) was present but nonuniform and subject to breakage, while in a fourth sample it was missing altogether. The exocuticle appeared less dense than in normal hair, consistent with extensive protein loss during detergent extraction. In cuticle cells from trichothiodystrophy hair, the exocuticle layer was essentially fully extractable in one sample, while in two others (from siblings) the exocuticle appeared less dense and the A layer was absent or greatly reduced in thickness. A sample of proximal trichorrhexis nodosa also displayed defects in cuticle cells, in which the endocuticle layer appeared subject to rupture. The outer cuticle cells in monilethrix hair displayed a thinning of the A layer and less dense exocuticle, while the cortex exhibited regions lacking remnant cell borders. Pili annulati hair displayed large gaps in the cortex, presumably reflecting the air-filled cavities characteristic of this syndrome, and wavy borders of some cuticle cells. Conclusions Observations with autosomal recessive lamellar ichthyosis hair indicate that keratinocyte transglutaminase has a major role in maturation of the cuticle but appears unnecessary for stabilization of cell borders in the cortex. Defective cross-linking was also evident in cuticle cells of trichothiodystrophy and monilethrix. © 1996 Wiley-Liss, Inc.

Alopecia areata (AA) has been shown to be associated with the inheritance of HLA class II alleles. HLA-DQ3 appears to be the general susceptibility allele for AA. Patients with long-standing disease patterns, namely, long-term patchy AA and long-term alopecia totalis and alopecia universalis (AT/AU), can be differentiated by their particular HLA associations. Long-standing AT/AU patients have unique and highly significant associations with HLA antigens DR4, DR11, and DQ7. A complex of early onset, disease severity, family incidence, and associations with HLA DR antigens are characteristic of long-standing AT/AU as distinct from long-standing patchy AA.

Background: Trichothiodystrophy (TTD) is a rare, autosomal recessive disorder in which the hair identifies a group of genetic disorders with deficient high-sulfur matrix proteins, and a defect in excision repair of ultraviolet damage in fibroblasts of most patients. TTD patients may be grouped as follows: (1) the major group with defects in the excision repair cross-complementing gene ERCC2, the gene for xeroderma pigmentosum group D (XP-D); (2) those with defects in ERCC3, the gene for XP-B; and (3) those with a repair defect distinct from those in XP-D and XP-B. In contrast to XP patients, TTD patients have no increased frequency of skin cancers. Objective: The article explains the relationship of TTD and XP and helps clarify why TTD patients with defects in the same gene(s) as those with XP do not have increased skin cancers. Methods: Methods include biochemical studies, mutational analysis, and genomic sequence analysis of cell lines from skin biopsies of TTD and XP patients. Results: The ERCC2 gene is a component of the TFIIH complex which controls two distinct DNA-metabolizing processes, transcription initiation and nucleotide excision repair. Conclusion: In TTD, the major defect is in transcription initiation, whereas in XP-D, DNA repair is primarily altered.

Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders.

Traction alopecia is hair loss caused by prolonged or repetitive tension on the hair. Diagnostic challenges are encountered when the clinical suspicion is not high and when a history of traction is remote or not obtained. We have made the observation that the presence of retained hairs along the frontal and/or temporal rim, which we termed the "fringe sign," is a finding seen in both early and late traction alopecia, and may be a useful clinical marker of the condition.This was a retrospective single-center review to determine the frequency of the fringe sign in patients with traction alopecia.Over a 3.5-year period the diagnosis of traction alopecia was made in 41 women. Twelve of the 41 patients were Hispanic (29%). Thirty-five (85%) of all women and 100 percent of women who had traction involving the marginal hairline had the fringe sign. Fourteen biopsies (58%) were available for review. Histopathologic findings included retained sebaceous glands (100%), an increase in vellus-sized hairs (50%), a decrease in terminal hairs (100%), fibrotic fibrous tracts (100%), and sparse lymphocytic inflammation (57%).The fringe sign is a sensitive and specific clinical feature of traction alopecia when it involves the marginal hairline.

Background: Traction alopecia is hair loss due to prolonged or repetitive tension on the hair. Diagnostic challenges may be encountered if the clinical suspicion for traction is not high, or if the history of traction is remote or not obtained. Since pathologic features can vary dramatically with the stage of the disorder clinico-pathologic correlation is essential. We have made the observation that the presence of retained hairs along the frontal and/or temporal rim, which we termed the "fringe sign", is a finding that can be see in both early and late traction alopecia, and thus may be a useful clinical marker of the condition. Objective: To determine the frequency of the fringe sign in a series of patients with a diagnosis of traction alopecia. Methods: This was a retrospective single-center review. Results: Over a 3.5 year period the diagnosis of traction alopecia was made in 41women. Twelve of the 41 patients were Hispanic (29%). The average age of our cohort was 34. Thirty-five (85%) of all women and 100% of women who had traction involving the marginal hair line had the fringe sign. The majority of African American women (54%) compared to 17% of the Hispanic women had some clinical sign of scalp inflammation(most frequently scalp scaling). Fourteen biopsies(58%) were available for review. Histopathologic findings included retained sebaceous glands (100%) and an increase in vellus-sized hairs (50%), a decrease in terminal hairs (100%), fibrotic fibrous tracts (100%), and sparse lyphocytic inflammation (57%). Trichomalacia was only noted in only one of the biopsies. Limitations: Retrospective analysis, uncontrolled study. Conclusions: Hispanic women as well as African American women are at high risk for traction alopecia. The fringe sign was a sensitive and specific clinical feature of traction alopecia when it involved the marginal hair line. Retained sebaceous glands, decreased terminal hairs, and fibrotic fibrous tracts were noted in all histopathologic specimens.

The predominantly neutrophilic group of primary cicatricial alopecias includes folliculitis decalvans and tufted folliculitis. Clinically, the affected areas are much more inflamed than the lymphocytic cicatricial alopecias with crusting, pustules, draining, and erythema. There is usually considerable pain, tenderness, and itching. Histologically in the early stages, the inflammatory infiltrate consists predominantly of neutrophils. However, the infiltrate does not remain neutrophilic but rather becomes plasma-cell rich. What other histologic features can be used as clues to a neutrophilic cicatricial alopecia that is no longer predominantly neutrophilic? Scan the scalp biopsy with low-power light microscopy: the presence of four or more fused follicles, and dense interfollicular inflammation and fibrosis are diagnostically useful (see Chap. 3)

The patient with hair loss invariably complains “I am losing my hair,” which can mean vastly different things in different patients. Every patient with hair loss should have the following baseline lab studies: CBC, TSH, ferritin, and vitamin D 25OH because you do not want to miss other possible contributing factors of hair loss.

Until recently, primary cicatricial alopecias had received little attention in the clinical and research realm. With the dramatic increases in our knowledge of basic hair biology, new and powerful tools have become available to study these rare disorders in ways that were previously not possible. As we have moved from traditional clinical studies and histopathology to molecular biology, new paradigms regarding the pathophysiology of cicatricial alopecia have been developed. However, after clarifying many previously unanswered questions, we are faced with a series of new and unanswered ones. By the time this publication is completed, new information will be available, and we encourage the reader to stay tuned and engaged as research in cicatricial alopecia continues to unfold.

A 45-year-old man presents with extensive asymptomatic hair loss affecting most of the top of his scalp. Ten years earlier, he was seen by a dermatologist for patchy hair loss and he remembers having much pain and itching. Scalp biopsy at that time showed lichen planopilaris. His treatment included hydroxychloroquine 200 mg twice daily and intralesional triamcinolone acetonide. He was lost to follow up until his current visit. Scalp examination at the present time shows complete, confluent hair loss over the entire top of his scalp with absence of follicular markings and absence of any clinical inflammation (Fig. 9.1). Currently, there is no clinical clue regarding the diagnosis of his original patchy hair loss. A scalp biopsy is taken.

In this chapter, lichen planopilaris, Graham Little syndrome, frontal fibrosing alopecia (FFA), pseudopelade (Brocq), and central centrifugal cicatricial alopecia are described. Two additional entities that are not primary cicatricial alopecias are included, namely chronic cutaneous lupus erythematosus (CCLE) and keratosis follicularis spinulosa decalvans (KFSD) because they are important to recognize and differentiate.

Background : Several studies have examined the psychological impact of androgenetic alopecia on men but scientific evidence is absent regarding its effects on women. Objective: Our purpose was to determine the psychosocial sequelae of androgenetic alopecia in women and, comparatively, in men. Methods : Subjects were newly referred patients with androgenetic alopecia (96 women and 60 men) and 56 female control patients. Subjects completed standardized questionnaires to assess their psychological reactions to their respective conditions and to measure body image, personality, and adjustment. Results : Androgenetic alopecia clearly was a stressful experience for both sexes, but substantially more distressing for women. Relative to control subjects, women with androgenetic alopecia possessed a more negative body image and a pattern of less adaptive functioning. Specific correlates of the adversity of patients' hair-loss experiences were identified. Conclusion : The results confirm the psychologically detrimental effects of androgenetic alopecia, especially on women. The implications for patient care are discussed.