Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci.

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.

Health-Related Quality of Life (HRQoL) in alopecia areata patients-a secondary analysis of the National Alopecia Areata Registry Data.

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 <50 years (odds ratio (OR) 3.99, 95% confidence interval (CI) 1.66-9.58), female gender (OR 2.74, 95% CI 1.73-4.34), hair loss 25-99% (OR 2.47, 95% CI 1.12-5.45), family stress (OR 1.8, 95% CI 1.13-2.86), and job change (OR 2.01, 95% CI 1.02-3.94). The current analysis provides an overview of the HRQoL status of AA patients and may guide patient care in the future.

A single question can make the diagnosis.

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

What looks like alopecia areata is not always alopecia areata.

The differential diagnosis of a strongly positive and painless hair pull test includes alopecia areata and loose anagen syndrome. A hair mount examined with low power light microscopy easily clarifies the diagnosis.

Bone mineral density in patients with alopecia areata treated with long-term intralesional corticosteroids.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

How to diagnose hair loss.

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.

The "Fringe Sign" - A useful clinical finding in traction alopecia of the marginal hair line.

INTRODUCTION: 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. METHODS: This was a retrospective single-center review to determine the frequency of the fringe sign in patients with traction alopecia. RESULTS: 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%). CONCLUSIONS: The fringe sign is a sensitive and specific clinical feature of traction alopecia when it involves the marginal hairline.

The spectrum of hair loss in patients with mycosis fungoides and Sézary syndrome.

BACKGROUND: Alopecia can be a manifestation of mycosis fungoides (MF) and Sézary syndrome (SS), but the prevalence is unknown. OBJECTIVE: We sought to describe the clinicopathologic presentation and molecular features of alopecia in patients with MF/SS. METHODS: A retrospective chart review of a prospectively collected MF/SS database was used to identify patients with alopecia. The National Alopecia Areata Registry was used to identify patients with self-reported cutaneous T-cell lymphoma. RESULTS: Among 1550 patients with MF/SS, 38 patients with patchy, total-scalp, or universal alopecia were identified. Thirteen of 38 (34%) had patchy alopecia clinically identical to alopecia areata. Scalp biopsy specimens were available in 5 of the 13 patients. Specimens from 4 patients had atypical T lymphocytes within the follicular epithelium or epidermis, and that from two patients had a histology of follicular mucinosis. The remaining 25 of 38 (66%) patients with MF/SS included 20 with alopecia within discreet patch/plaque or follicular lesions of MF and 5 with total-body hair loss, which presented only in those with generalized erythroderma and SS. LIMITATIONS: This was a retrospective study done at one cancer center. Biopsy specimens of alopecia were not available for every patient. CONCLUSIONS: Alopecia was observed in 2.5% of patients with MF/SS, with alopecia areata-like patchy loss in 34% and alopecia within MF lesions in 66%.

Abnormal inner root sheath of the hair follicle in the loose anagen hair syndrome: an ultrastructural study.

BACKGROUND: Loose anagen hair syndrome (LAHS) is a disorder in which the hair pulls out easily and painlessly from the scalp. It first manifests in early childhood when the main concern of parents is that the sparse hair does not grow. The hair density and length improve with age, but the looseness persists into adulthood. OBJECTIVE: Light and electron microscopic studies of hair follicles were performed to better define the microscopic changes seen in LAHS. METHODS: Biopsy specimens were obtained from 4 patients, 3 children and 1 adult. The hair follicles were studied by light and electron microscopy. RESULTS: The most conspicuous structural changes were found in the inner root sheath complex of the anagen follicle. With light microscopy, the keratinized Henle cell layer showed a tortuous and irregular swelling. Irregular keratinization of the cuticle cells of the inner root sheath and a swollen appearance of Huxley cells were also found. With electron microscopy, the major pathological changes consisted of intercellular edema in the prekeratinized Huxley cell zone and dyskeratosis of Henle cells and cuticle cells of the inner root sheath. LIMITATIONS: The studies were done on a small number of patients. CONCLUSIONS: Structural abnormalities of the inner root sheath appear to disturb its normal supportive and anchoring function and result in a loose attachment of the hair shaft to the anagen follicle.

A practical, algorithmic approach to diagnosing hair shaft disorders.

The hair shaft is a unique structure composed of an inner cortex and a protective outer cuticle. Any defects in this normal structure due to genetics or the environment can lead to variations in physical properties. Thus one should suspect a hair shaft disorder if a patient presents with an abnormality or change in hair texture, appearance, manageability or ability to grow hair long. A key feature of the clinical evaluation is to determine whether there is hair breakage (increased fragility) by looking for broken hairs and performing a tug test. Once this determination is made, an algorithmic approach can be used to narrow the differential diagnosis: hair shaft disorders with and without fragility. A hair mount along with other directed questions and examination will almost always allow the clinician to make an in-office diagnosis. Common case scenarios, photographs, and practical tips are provided to illustrate the use of this algorithmic approach in the diagnosis of hair shaft disorders. We have also included a summary of the molecular defects where known, which can be helpful in providing a correlation with clinical findings, in counseling patients, and potentially offering treatment options.

Hydroxychloroquine and lichen planopilaris: efficacy and introduction of Lichen Planopilaris Activity Index scoring system.

BACKGROUND: Lichen planopilaris (LPP) and its variant frontal fibrosing alopecia (FFA) are primary lymphocytic cicatricial alopecias for which there is no evidence-based therapy. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: Retrospective analysis and uncontrolled study are limitations. CONCLUSIONS: 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.

Efficacy and safety of mycophenolate mofetil for lichen planopilaris.

BACKGROUND: Lichen planopilaris (LPP) is a chronic inflammatory disorder that causes permanent scalp hair loss and significant patient discomfort. OBJECTIVES: 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. METHODS: 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. RESULTS: 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 decreased>85%), 5 of 12 patients were partial responders (LPPAI score decreased 25%-85%), and two of 12 patients were treatment failures (LPPAI score decreased<25%). Four patients withdrew from the trial because of adverse events. LIMITATIONS: Retrospective analysis and small sample size were limitations. CONCLUSIONS: 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.