How not to get scar(r)ed: pointers to the correct diagnosis in patients with suspected primary cicatricial alopecia.

Primary cicatricial alopecias (PCAs) are a rare, but important, group of disorders that cause irreversible damage to hair follicles resulting in scarring and permanent hair loss. They may also signify an underlying systemic disease. Thus, it is of paramount importance that clinicians who manage patients with hair loss are able to diagnose these disorders accurately. Unfortunately, PCAs are notoriously difficult conditions to diagnose and treat. The aim of this review is to present a rational and pragmatic guide to help clinicians in the professional assessment, investigation and diagnosis of patients with PCA. Illustrating typical clinical and histopathological presentations of key PCA entities we show how dermatoscopy can be profitably used for clinical diagnosis. Further, we advocate the search for loss of follicular ostia as a clinical hallmark of PCA, and suggest pragmatic strategies that allow rapid formulation of a working diagnosis.

Central scalp alopecia photographic scale in African American women.

Central centrifugal cicatricial alopecia (CCCA) is a common but poorly understood cause of hair loss in African American women. A photographic scale was developed that captures the pattern and severity of the central hair loss seen with CCCA in order to help identify this problem in the general community and to potentially correlate clinical data with hair loss. The utility and reproducibility of this photographic scale was determined in a group of 150 African American women gathered for a health and beauty day who were evaluated by both four investigators experienced in the diagnosis of hair disorders and by the subjects themselves.

Management of primary cicatricial alopecias: options for treatment.

Primary cicatricial alopecias (PCAs) are a poorly understood group of disorders that result in permanent hair loss. Clinically, they are characterized not only by permanent loss of hair shafts but also of visible follicular ostia along with other visible changes in skin surface morphology, while their histopathological hallmark usually (although not always) is the replacement of follicular structures with scar-like fibrous tissue. As hair follicle neogenesis in adult human scalp skin is not yet a readily available treatment option for patients with cicatricial alopecias, the aim of treatment, currently, remains to reduce symptoms and to slow or stop PCA progression, namely the scarring process. Early treatment is the key to minimizing the extent of permanent alopecia. However, inconsistent terminology, poorly defined clinical end-points and a lack of good quality clinical trials have long made management of these conditions very challenging. As one important step towards improving the management of this under-investigated and under-serviced group of dermatoses, the current review presents evidence-based guidance for treatment, with identification of the strength of evidence, and a brief overview of clinical features of each condition. Wherever only insufficient evidence-based advice on PCA management can be given at present, this is indicated so as to highlight important gaps in our clinical knowledge that call for concerted efforts to close these in the near future.

The 'follicular trochanter': an epithelial compartment of the human hair follicle bulge region in need of further characterization.

Recent articles on hair follicle stem cells have summarized the current state of knowledge of what has been termed the hair follicle 'bulge'. During the course of immunohistological studies aimed at characterizing the expression of selected extracellular matrix proteins in the - as yet insufficiently characterized - niche of human bulge hair follicle stem cells, we have recently come across a largely forgotten, peculiar epithelial protrusion of the outer root sheath, which was visible in only a minority of all examined hair follicles. The morphology and immunoreactivity patterns of this structure, the 'follicular trochanter', are described herein.

Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss.

In androgenetic alopecia, or pattern hair loss, follicles undergo miniaturization, shrinking from terminal to vellus-like hairs. Traditionally, this process is thought to progress gradually over a number of follicular cycles. However, it is unlikely that miniaturization can be explained only by a series of progressively shorter anagen cycles. Simple calculations show that this process would take too long for significant miniaturization to occur secondary to shorter anagen cycles alone, especially in view of the latent lag period seen in pattern hair loss that occurs between the loss of a telogen hair and the appearance of an anagen hair. Evidence is presented to support a new concept that miniaturization is an abrupt, large-step process that also can be reversed in 1 hair cycle, as has been shown clinically, with confirmatory histologic evidence, in patients with pattern hair loss responding to finasteride treatment. It is hypothesized that the miniaturization seen with pattern hair loss may be the direct result of reduction in the cell number and, hence, size of the dermal papilla.

Human hair histogenesis for the mitochondrial DNA forensic scientist.

Analysis of mitochondrial DNA (mtDNA) sequence from human hairs has proven to be a valuable complement to traditional hair comparison microscopy in forensic cases when nuclear DNA typing is not possible. However, while much is known about the specialties of hair biology and mtDNA sequence analysis, there has been little correlation of individual information. Hair microscopy and hair embryogenesis are subjects that are sometimes unfamiliar to the forensic DNA scientist. The continual growth and replacement of human hairs involves complex cellular transformation and regeneration events. In turn, the analysis of mtDNA sequence data can involve complex questions of interpretation (e.g., heteroplasmy and the sequence variation it may cause within an individual, or between related individuals. In this paper we review the details of hair developmental histology, including the migration of mitochondria in the growing hair, and the related interpretation issues regarding the analysis of mtDNA data in hair. Macroscopic and microscopic hair specimen classifications are provided as a possible guide to help forensic scientists better associate mtDNA sequence heteroplasmy data with the physical characteristics of a hair. These same hair specimen classifications may also be useful when evaluating the relative success in sequencing different types and/or forms of human hairs. The ultimate goal of this review is to bring the hair microscopist and forensic DNA scientist closer together, as the use of mtDNA sequence analysis continues to expand.

Advances in the treatment of male androgenetic alopecia: a brief review of finasteride studies.

Finasteride is a type 2 5a-reductase inhibitor and therefore mimics the biochemical profile of inherited type 2 5a-reductase deficiency in men. It was developed to grow hair in androgenetic alopecia and shrink benign prostatic hyperplasia. Various clinical trials of finasteride have confirmed its beneficial effects in androgenetic alopecia in males, but not in females. It can produce visible hair growth in up to 66% of men with mild to moderate alopecia, but importantly can stop hair loss in 91% of patients. In long-term finasteride studies, placebo patients were characterized by significant and progressive hair loss. It can be concluded that finasteride prevents further hair loss by actually continuing to grow enough hair to preserve scalp coverage. This is confirmed by the loss of hair following withdrawal of finasteride in such cases. The proven preservative effect of finasteride, in addition to its restorative effect, is a strong indication for prescribing it in early cases of androgenetic alopecia before much hair has been lost.

Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia.

BACKGROUND: Finasteride, an inhibitor of type 2 5alpha-reductase, decreases serum and scalp dihydrotestosterone (DHT) by inhibiting conversion of testosterone to DHT and has been shown to be effective in men with androgenetic alopecia (AGA). The effects of finasteride in women with AGA have not been evaluated. OBJECTIVE: The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA. METHODS: In this 1-year, double-blind, placebo-controlled, randomized, multicenter trial, 137 postmenopausal women (41-60 years of age) with AGA received finasteride 1 mg/day or placebo. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, assessment of global photographs by a blinded expert panel, and histologic analysis of scalp biopsy specimens. RESULTS: After 1 year of therapy, there was no significant difference in the change in hair count between the finasteride and placebo groups. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. Similarly, patient, investigator, and photographic assessments as well as scalp biopsy analysis did not demonstrate any improvement in slowing hair thinning, increasing hair growth, or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. Finasteride was generally well tolerated. CONCLUSION: In postmenopausal women with AGA, finasteride 1 mg/day taken for 12 months did not not increase hair growth or slow the progression of hair thinning.

Purification and characterisation of epithiospecifier protein from Brassica napus: enzymic intramolecular sulphur addition within alkenyl thiohydroximates derived from alkenyl glucosinolate hydrolysis.

Epithiospecifier protein (ESP), a ferrous ion dependent protein, has a potential role in regulating the release of elemental sulphur, nitriles, isothiocyanates and cyanoepithioalkanes from glucosinolates. Two classes of ESP polypeptides were purified with molecular masses of 39 and 35 kDa, and we show that the previously reported instability was conditionally dependent. The 39 kDa polypeptide was made up of two distinct isozymes (5.00, 5.14) whilst several were present for the 35 kDa form of ESP (5.40-5.66). An anti-ESP antibody reacted with both the 39 and 35 kDa ESP forms in Brassica napus and strongly with a polypeptide corresponding to the 35 kDa ESP form in Crambe abyssinica, but did not detect any ESP in Sinapis alba or Raphanus sativus. A cytochrome P-450 mediated iron dependent epoxidation type mechanism is suggested for ESP.

Immunohistochemical localization of types 1 and 2 5alpha-reductase in human scalp.

The predominant form of 5alpha-reductase (5aR) in human scalp is 5aR1. None the less, clinical studies have shown that finasteride, a selective inhibitor of 5aR2, decreases scalp dihydrotestosterone and promotes hair growth in men with androgenetic alopecia. Immunolocalization studies were thus carried out to examine 5aR isozyme distribution within scalp and, in particular, to determine whether 5aR2 might be associated with hair follicles. 5aR2 was localized using both a rabbit polyclonal and a mouse monoclonal antibody. 5aR1 was detected with a mouse monoclonal antibody. The specificity of these reagents was demonstrated both by immunofluorescence and Western blot analyses of COS cells overexpressing human 5aR1 or 5aR2. When cryosections of scalp from men with androgenetic alopecia were stained with antibody against 5aR2, using immunoperoxidase avidin-biotin complex methodology, immunostaining was observed in the inner layer of the outer root sheath and, in more proximal regions of the follicle, in the inner root sheath. Staining was also prominent in the infundibular region of the follicle, with less intense staining extending throughout the granular layer of the epidermis. Some staining was also seen in sebaceous ducts. Similar results were obtained with both the polyclonal and monoclonal 5aR2 antibodies. In contrast, in scalp cryosections stained with antibody to 5aR1, no immunostaining was observed within hair follicles. Intense staining for the type 1 isozyme was, however, detected within sebaceous glands. Our immunolocalization data suggest that the results seen in clinical trials of men with male pattern hair loss treated with finasteride may be due, at least in part, to local inhibition of 5aR2 within the hair follicle.

Marie Unna congenital hypotrichosis: clinical description, histopathology, scanning electron microscopy of a previously unreported large pedigree.

Marie Unna congenital hypotrichosis (MUCH) is a rare autosomal dominant condition in which abnormalities are confined to hair shaft structure and hair density. We report a six-generation pedigree consisting of 59 members of whom 16 are affected; nine identified affected individuals are living. Affected individuals are born with adequate, normal to coarse hair. During early infancy the scalp hair becomes more coarse and wiry and stands out from the head. All affected individuals have sparse to absent eyebrows, eyelashes and body hair including secondary sexual hair. In some individuals, scalp hair is progressively lost beginning at puberty or beyond, until only a sparse fringe in the tonsorial distribution remains. The hair shafts are uniformly increased in diameter, measuring up to 0.12 mm. Individual hair shafts are deeply pigmented, variable in diameter, twisted, and bent at odd angles; some have a longitudinal groove visible on scanning electron microscopy. Cross-sectional shapes are variable and irregular, exhibiting oval, angular to reniform shapes. Multiple anagen hairs are extractable on gentle hair pull. Other ectodermal structures are unaffected except for exceptionally widely spaced upper incisor teeth seen in 50% of affected individuals. Histologically, there are dramatically reduced numbers of follicles per unit area, averaging nine total hairs per 4 mm cross-section as compared with a normal of 40. A mild to moderate inflammatory infiltrate is present, but little fibrosis and no scarring. The mechanism of progressive hair loss is unknown.

Measuring reversal of hair miniaturization in androgenetic alopecia by follicular counts in horizontal sections of serial scalp biopsies: results of finasteride 1 mg treatment of men and postmenopausal women.

Hair regrowth was evaluated by histologic analysis in men and women treated for androgenetic alopecia, by counting follicles in horizontal sections of scalp biopsies. Serial 4mm punch biopsies were taken at baseline and after 12mo of treatment from the transitional area of hair thinning between normal hair and vertex balding in men, and in an area of frontal/parietal thinning in women. Horizontal sections of reticular and papillary dermis were read by one observer, blinded to patient, treatment, and time. All terminal hair bulbs, terminal anagen and telogen hairs, and vellus and vellus-like miniaturized hairs were counted. Twenty-six men aged 18-41y, comprising 14 on finasteride 1 mg daily and 12 on placebo, and 94 postmenopausal women, aged 41-60y, comprising 44 on finasteride 1 mg daily and 50 on placebo, were evaluated. In the male study, the terminal hairs increased from a mean baseline count of 15.5-20.9 after 12mo of finasteride, versus 17.3-18.3 in the placebo patients. The miniaturized hairs decreased from 26.7 to 23.6 with finasteride versus 21.3-20.3 with placebo. The terminal-to-vellus ratio increased more in the finasteride than in the placebo patients, suggesting some reversal of the miniaturization process with finasteride. In the female study, no significant differences in follicular counts were found between the finasteride and placebo groups after 12mo of treatment. Follicular counts in horizontal sections provide an informative adjunct to noninvasive measures used in hair growth studies. Finasteride appears to be capable of reversing hair miniaturization in androgenetic alopecia in young to middle-aged men, but not in postmenopausal women.

Chronic telogen effluvium: increased scalp hair shedding in middle-aged women.

BACKGROUND: Diffuse loss of scalp hair is a common problem in middle-aged women. A segment of these cases represents idiopathic chronic telogen effluvium (CTE). OBJECTIVE: The purpose was to establish distinctive clinical and pathologic criteria for the diagnosis of CTE to facilitate its differentiation from androgenetic alopecia (AGA) and systemic causes of chronic diffuse hair loss. METHODS: A group of 355 patients (346 females, 9 males) with diffuse generalized thinning of scalp hair of unknown origin were classified as having CTE and were included in the study. Characteristically they presented with a history of hair loss with both increased shedding and thinning of abrupt onset and fluctuating course and showed diffuse thinning of hair all over the scalp, frequently accompanied by bitemporal recession. Two 4 mm punch biopsy specimens were taken mostly from the mid or posterior parietal scalp of these patients. The biopsies were performed at these same areas in 412 patients with AGA (193 male, 219 female). Similar paired biopsy specimens were also taken from 22 normal control subjects (13 males, nine females). Specimens were sectioned horizontally and vertically and were examined for terminal and velluslike (miniaturized) hairs, follicular stelae, follicular units, and perifollicular inflammation and fibrosis. RESULTS: In horizontal sections of 4 mm punch biopsy specimens from patients with CTE the average number of hairs was 39, the terminal/velluslike hair ratio was 9:1, 89% of the terminal hairs were in anagen, and 11% were in telogen. In AGA these values were 35, 1.9:1, 83.2%, and 16.8%, respectively, and in normal control subjects 40, 7:1, 93.5%, and 6.5%, respectively. Significant degrees of inflammation and fibrosis were present in only 10% to 12% of cases of CTE and normal controls, but occurred in 37% of cases of AGA. CTE ran a prolonged and fluctuating course in many patients. CONCLUSION: CTE, which usually affects 30- to 60-year-old women, starts abruptly with or without a recognizable initiating factor. It may be distinguished from classic acute telogen effluvium by its long fluctuating course and from AGA by its clinical and histologic findings.

Chronic telogen effluvium.

Chronic telogen effluvium is not uncommon. It is a form of diffuse hair loss affecting the entire scalp for which no obvious cause can be found. It usually affects women of 30 to 60 years of age who generally have a full head of hair prior to the onset of shedding. The onset is usually abrupt, with or without a recognizable initiating factor. The degree of shedding is usually severe in the early stages and the hair may come out in handfuls. Chronic telogen effluvium has distinctive clinical and histologic features that are usually diagnostic. Chronic telogen effluvium contrasts with classic acute telogen effluvium by its persistence and its tendency to fluctuate for a period of years. Patients are particularly troubled by the continuing hair loss and fear total baldness. Repeated reassurance that the condition represents shedding rather than actual hair loss and does not cause complete baldness is necessary. Chronic telogen effluvium does appear to be self-limiting in the long run.