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Lipedematous alopecia: a clinicopathologic, histologic and ultrastructural study.

Lipedematous alopecia is a rare condition of unknown etiology characterized by a thick, boggy scalp with varying degrees of hair loss that occurs in adult black females, with no clearly associated medical or physiologic conditions. The fundamental pathologic finding consists of an approximate doubling in scalp thickness resulting from expansion of the subcutaneous fat layer in the absence of adipose tissue hypertrophy or hyperplasia. Observations by light and electron microscopy detailed in this report suggest that this alteration principally manifests by localized edema with disruption and degeneration of adipose tissue. Some diminution in the number of follicles as well as focal bulb atrophy is noted. Aberrant mucin deposition such as that seen in myxedema or other cutaneous mucinoses is not a feature. The histologic findings bear some resemblance to those seen in lipedema of the legs, a relatively common but infrequently diagnosed condition. We present a case of lipedematous alopecia with emphasis on histologic and ultrastructural features. The etiology is unknown.

Adipose Tissue↗

Spontaneous alopecia areata-like hair loss in one congenic and seven inbred laboratory mouse strains.

Alopecia areata (AA) research has been hampered by the lack of suitable animal models for use in experimental procedures. AA-like hair loss has been observed in several species, including dogs, cats, horses, cattle, and nonhuman primates; however, these examples are isolated cases in outbred species of large size, limiting their use in AA research. Inbred rodent strains are ideal research models. C3H/HeJ mice can develop spontaneous AA-like hair loss and have previously been advanced as a suitable experimental model. The search for additional mouse strains with AA-like hair loss has continued. Nonscarring, inflammatory, spontaneously reversible hair loss has been observed in individual mice from several inbred mouse strains. Aside from C3H/HeJ mice, an AA-like phenotype has been observed in the substrain C3H/HeJBir, with an expression frequency of 5%. Up to 10% of individuals in an A/J mouse colony have been confirmed to develop patchy AA-like hair loss. Isolated examples of AA have also been identified in C3H/HeN/J mice, C3H/OuJ mice, HRS/J+/hr heterozygous normal mice, CBA/CaHN-Btk(xid)/J mice, and BALB.2R-H2h2/Lil mice, each with a colony frequency of less than 1%. BALB.2R-H2h2/Lil mice may also have severe nail defects. AA is regarded as rare in nonhuman species; however, nonscarring inflammatory based alopecia has been identified in several mouse strains. These examples may represent different subtypes of the heterogeneous AA phenotype. Pathologic and genetic analysis of different AA affected mouse strains may contribute to understanding AA pathogenesis and elucidating susceptibility genes.

Alopecia Areata↗

T cell repertoire in mice with alopecia areata.

It has become clear that skin infiltrating autoreactive CD4+ T helper cells play a crucial role in the initiation of alopecia areata. However, the natures of the pathogenic T cell clones as well as of the skin antigen they recognize remain obscure. Here, we analyzed the T cell receptor repertoire expressed in the spleen of diseased mice. We consistently observed the dominant expansion of a limited set of T cell clones expressing Vbeta8.2/Jbeta2.5 T cell receptor rearrangement. We conclude that T cell response in mice alopecia areata is markedly oligoclonal; a feature that may permit the design of selective immunotherapy.

Alopecia Areata↗

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.

5-alpha Reductase Inhibitors↗

Alopecia areata registry: an overview.

The National Alopecia Areata Registry was awarded as a five-year contract by NIAMS to promote research on the genetic basis of alopecia areata. The registry is Web based and can be accessed online at http://www. AlopeciaAreata Registry.org. Samples of DNA, lymphoblast lines, and sera, as well as epidemiology and quality-of-life data, are being collected from well-characterized individuals, multiplex families, and sib pairs for future research studies and investigators.

Alopecia Areata↗

Ichthyosis follicularis with alopecia and photophobia in a mother and daughter.

A mother and daughter having ichthyosis follicularis with alopecia and photophobia (IFAP) are reported, with histopathological and electron microscopic findings. We have followed the clinical course of the mother for 26 years since she was 5 years old, and the daughter since birth. They have had almost all the classical and some of the minor symptoms of IFAP, including severe photophobia, extensive non-inflammatory follicular hyperkeratosis, generalized non-scarring alopecia, hyperkeratosis of the extensor aspect of the four extremities, nail deformity and recurrent cheilitis. In addition, their facial appearance greatly resembles that of previously reported patients. A consistent feature in the mother was florid keratotic inflammatory eruptions on the genital region during each of her pregnancies, which rapidly improved after the delivery. Skin biopsy of the genital lesion showed marked acanthosis with dyskeratosis and spongiotic changes. The electron microscopic examination of diseased skin showed damaged desmosomes with spongiosis. No obvious changes were found in normal appearing skin.

Adult↗

Finasteride increases anagen hair in men with androgenetic alopecia.

BACKGROUND: The growth of scalp hair is a cyclical process of successive phases of growth (anagen) and rest (telogen). In previous clinical trials in men with androgenetic alopecia, treatment with finasteride increased scalp hair counts in a defined area (i.e. increased hair density). OBJECTIVES: The current study used a phototrichogram methodology to assess the effect of finasteride on the phases of the hair growth cycle. PATIENTS/METHODS: Two hundred and twelve men, age 18-40 years, with androgenetic alopecia were randomized to receive finasteride 1 mg daily or placebo for 48 weeks. At baseline and at 24 and 48 weeks, macrophotographs were taken to measure total and anagen hair count in a 1-cm(2) target area of the scalp. RESULTS: At baseline, mean total and anagen hair counts in the finasteride group were 200 and 124 hairs, respectively (% anagen = 62%) and the anagen to telogen ratio was 1.74 (geometric mean). In the placebo group, the respective values were 196 and 119 hairs (% anagen = 60%) and 1.57. At week 48, the finasteride group had a net improvement (mean +/- SE) compared with placebo in total and anagen hair counts of 17.3 +/- 2.5 hairs (8.3% +/- 1.4%) and 27.0 +/- 2.9 hairs (26% +/- 3.1%), respectively (P < 0.001). Furthermore, treatment with finasteride resulted in a net improvement in the anagen to telogen ratio of 47% (P < 0.001). In this study, treatment with finasteride 1 mg day(-1) for 48 weeks increased both total and anagen hair counts, and improved the anagen to telogen ratio. CONCLUSIONS: These data provide direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase. These data support that finasteride treatment results in favourable effects on hair quality that contribute to the visible improvements in hair growth observed in treated patients.

Adolescent↗

The hairless gene in androgenetic alopecia: results of a systematic mutation screening and a family-based association approach.

BACKGROUND: Genetic disposition and androgen dependence are important characteristics of the common patterned loss of scalp hair known as androgenetic alopecia (AGA). The genetic factors contributing to AGA are currently unknown. The human hairless gene (HR) has recently been cloned and mutations have been reported in families with autosomal recessive universal congenital alopecia and papular atrichia. The main feature of these disorders is persistent complete absence of hair at or shortly after birth. This suggests that HR is essential and specific for the development of hair. OBJECTIVES: To test the hypothesis that HR may be involved in AGA. METHODS: We systematically screened HR for genetic variability by means of single-strand conformation analysis (SSCA) in 46 unrelated men with AGA. To test for an involvement of HR in the development of AGA, seven common variants were genotyped in 61 families with 93 affected offspring. The results were analysed with the transmission/disequilibrium test (TDT). RESULTS: SSCA showed 15 single nucleotide substitutions: eight missense mutations, four silent mutations and three mutations in exon-flanking intronic sequences. TDT results showed a marginally significant association between AGA and variants 3379-29G/T (P = 0.024) and 2611-68C/T (P = 0.047). These results, however, did not remain significant after applying the conservative Bonferroni correction for multiple testing. CONCLUSIONS: Our results do not provide evidence for a strong involvement of HR in the development of AGA, although a minor role cannot be fully excluded.

Adult↗

Development of a health-related quality of life questionnaire for women with androgenetic alopecia.

Despite the negative effects of androgenetic alopecia (AGA), no standardized health-related quality of life (HRQOL) questionnaire which is both specific to women and suitable for use in clinical trials currently exists. A questionnaire to assess HRQOL in women with AGA, the Women's Androgenetic Alopecia Quality of Life Questionnaire (WAA-QOL), was recently developed. Aspects of life affected by AGA were generated from literature review, discussion with experts, and a focus group. The number of issues identified was reduced based on importance and relevance to women with AGA. A questionnaire was then constructed and pilot-tested for comprehension. The resulting 25-item instrument was later included in a double-blind, placebo-controlled clinical trial of finasteride 1 mg for the treatment of hair thinning in postmenopausal women (n = 137). Based on test characteristics, several questions were eliminated, resulting in a 16-item questionnaire. The WAA-QOL exhibited excellent test-retest reliability overall (intraclass correlation coefficient = 0.89), and for individual items (kappa = 0.66-0.85), as well as high internal consistency (Crohnbach's alpha = 0.98). Responsiveness of the questionnaire could not be assessed. The WAA-QOL is self-completed in about 10 min, exhibits good content validity, internal consistency, and test-retest reliability, and may be useful in assessing the impact of female AGA on HRQOL or in evaluating therapeutic effects in clinical trials.

Adult↗

Clinical relevance of hair microscopy in alopecia.

Hair microscopy can clarify the cause of hair loss in a range of diagnoses. Most of these are associated with hair breakage, the rest are related to lack of growth. Hair breakage may be due to excessive trauma or underlying susceptibility, where structural clues may be present. Lack of growth reflects follicular dynamics and represents the central mechanism of most common causes of alopecia. In such conditions, microscopy only reveals nonspecific confirmation of short anagen. Although this may assist clinical diagnosis, microscopy in alopecia only allows exclusion of diagnoses related to hair breakage. Confidence in the outcome of hair microscopy is based on the size of the sample of hairs, the length of the hair, the characteristics of the observations and the experience of the person undertaking the microscopy.

Alopecia↗

Cicatricial alopecia; a dermatopathologic and immunopathologic study of 33 patients (pseudopelade of Brocq is not a specific clinico-pathologic entity).

BACKGROUND: Pseudopelade of Brocq (PB) is a permanent progressive scarring alopecia characterized by numerous alopecic patches localized only in the scalp, that tend to coalesce into larger, irregular plaques with policyclic borders. PB can be considered either the final atrophic stage of several scarring disorders such as lichen planus pilaris (LPP) and discoid lupus erythematosus (DLE) (secondary PB) or an autonomous disease (primary PB). The aim of this study was to assess the incidence of primary vs. secondary PB by a combined histopathological and immunopathological study in a series of patients who fulfilled the clinical diagnostic criteria for PB set forth by Braun Falco et al. METHODS: We studied 33 patients (5 males and 28 females, whose age ranged from 24 to 75 years). The duration of the disease (from onset to biopsy) ranged from 3 months to 8 years. Serum samples were tested for circulating auto-antibodies (antinuclear antibodies anti ENA, anticentromere, anti-Scl70, antithyroid, antigastric parietal cells) circulating immune complexes, total and single fraction (C3, C4) complement activity. The skin biopsies taken from the active advancing margin of the more recent alopecic patch were bisected vertically, one was sent for histopathological examination, and the other for the immunofluorescence studies. RESULTS: In all patients the serum tests above were found to be negative or normal. Histopathologically, 11 biopsies (33.3%) displayed findings typical for LPP whereas seven cases (21.2%) showed typical DLE features. In the remaining 15 cases (45.5%) histopathological findings were not suggestive of any specific dermatosis. DIF investigations showed findings typical of LPP in six cases (18.1%) and typical of DLE in seven cases (21%). In three cases we did not find findings typical of LPP, DLE, or any other specific dermatitis. In 11 cases no immunological deposits could be detected and therefore were classified as negative. CONCLUSION: In conclusion, PB is a type of scarring alopecia of the scalp associated with a peculiar clinical presentation and evolution, which cannot be considered an autonomous nosologic entity because in 66.6% of patients it is the end stage of other inflammatory chronic diseases such as LPP and DLE. It is conceivable that even in those cases in which the histopathological and immunopathological findings did not allow for a specific diagnosis, LPP and DLE were also involved. It is noteworthy that in our study the histopathological and the immunopathological examinations did not conflict and often the results were even coincidental, thus confirming the compatibility of the combined histo-immunopathological approach in the diagnostic evaluation of PB.

Adult↗

Shortness of breath: an uncommon side-effect of cyproterone acetate in the treatment of androgenetic alopecia.

Cyproterone acetate is indicated for treatment of acne, hirsutism, seborrhea, and androgenetic alopecia in females. In general this medication is well tolerated in standard doses. Shortness of breath has been previously reported in men with prostatic carcinoma, receiving high-dose (200 mg/day) treatment with cyproterone acetate. We report a 66-year-old lady taking 50 mg/day of cyproterone acetate for biopsy proven androgenetic alopecia, who developed this unusual complication of shortness of breath. To our knowledge it has not been previously reported in women undergoing treatment for androgenization.

Aged↗

Vitamin D-dependent rickets Type II with alopecia: two case reports and review of the literature.

Vitamin D-dependent rickets Type II is a rare autosomal recessive disorder. It usually presents with rachitic changes not responsive to Vitamin D treatment with elevated circulating levels of 1,25-Dihydroxyvitamin D3, thus differentiating it from Vitamin D-dependent rickets Type I. Alopecia of the scalp or the body is seen in some families with Vitamin D-dependent rickets Type II. This is usually associated with more severe resistance to Vitamin D. We report two Saudi brothers with this disease, and review the salient features of this disease with emphasis on the associated alopecia.

Alopecia↗

The presence of trichodynia in patients with telogen effluvium and androgenetic alopecia.

BACKGROUND: Trichodynia refers to pain, discomfort, and/or paresthesia in the skin of the scalp or the hair. There may be an associated psychologic comorbidity. Although androgenetic alopecia (AGA) and telogen effluvium (TE) are different entities in terms of pathogenesis, etiology, and clinical picture, both may be influenced by psychologic stress and may be the cause of secondary stress. AIMS: To investigate the presence of trichodynia in patients with TE and AGA and to evaluate psychologic comorbidity in patients with trichodynia. MATERIALS AND METHODS: A total of 248 patients (153 females, 95 males), presenting with hair loss due to either TE or AGA, were enrolled in this study. The prevalence of trichodynia in these two groups was compared with that in controls (n = 184). In addition, psychiatric evaluation was performed in 25 patients with trichodynia (13 females, 12 males) and in 25 controls (16 females, nine males) without alopecia and trichodynia by a psychiatrist; Diagnostic and Statistical Manual of Mental Disorders (DSM)IV criteria were used for the assessment. RESULTS: Trichodynia was found in 72 patients (29%) with hair loss and in six controls (3.3%; P < 0.0001); 25 of the 72 patients with trichodynia underwent psychiatric evaluation and 19 of the 25 patients were found to have psychopathologic signs (76%). In the control group, only five patients had psychopathologic signs (20%; P = 0.0004). Of those with hair loss, trichodynia was more frequent in the TE group than in the AGA group (P < 0.0071). CONCLUSIONS: Trichodynia is a common symptom in patients with TE and AGA, and often coexists with psychopathologic findings, including depression, obsessive personality disorder, and anxiety.

Adolescent↗

Permanent alopecia following chemotherapy and bone marrow transplantation.

Alopecia can be a psychologically daunting prospect for people requiring cancer chemotherapy. Fortunately, most patients experience only temporary hair loss. We report the case of a 23-year-old woman with chronic myeloid leukaemia who developed permanent, near-total alopecia of her scalp, eyebrows, eyelashes, axillary and public hair following busulphan and cyclophosphamide chemotherapy which was used as conditioning prior to allogeneic bone marrow transplantation. The histology from a scalp biopsy revealed hair follicle destruction. Topical minoxidil failed to induce significant re-growth.

Adult↗

Frontal fibrosing alopecia associated with cutaneous lichen planus in a premenopausal woman.

A 45-year-old premenopausal woman presented with an 18-month history of a band-like area of fibrosing alopecia affecting the frontoparietal scalp. She also had marked thinning of the eyebrows. The histopathology was consistent with frontal fibrosing alopecia (FFA). Several months later she developed multiple pruritic papules on the wrists and feet. The clinical presentation and histopathology were consistent with cutaneous lichen planus. Although FFA has been reported to occur with mucosal lichen planus this is the first reported case of FFA associated with cutaneous lichen planus. This provides further evidence that FFA is a variant of lichen planopilaris.

Alopecia↗

Alopecia neoplastica caused by desmoplastic melanoma.

A 50-year-old man presented with a 6-month history of localized alopecia on the left frontal area of the scalp. Biopsy revealed desmoplastic melanoma with associated neurotropism. Wide excision was performed and showed desmoplastic melanoma extending to excision margins. Hair follicles were focally reduced in number and were infiltrated by melanoma cells. He has subsequently required multiple wide excisions, exenteration of the left eye and radiotherapy. He has had multiple recurrences and has developed involvement of the first division of the trigeminal nerve intracranially. To the authors' knowledge, this is the first reported case of desmoplastic melanoma presenting as alopecia.

Alopecia Areata↗

Reduction of intrafollicular apoptosis in chemotherapy-induced alopecia by topical calcitriol-analogs.

Chemotherapy-induced alopecia is thought to result from cytotoxic and apoptosis-related damage to the hair follicle. This study was designed to confirm whether keratinocyte apoptosis is indeed induced in growing (= anagen) hair follicles of C57 BL/6 mice after the injection of cyclophosphamide, using improved methods for histologic detection of apoptotic cells in murine skin. More importantly, we asked whether topical calcitriol-analogs are able to modulate cyclophosphamide-induced apoptosis in vivo, because there are conflicting reports on the effects of calcitriols on apoptosis in vitro. Anagen was induced in telogen mice on day 0 by depilation. Starting on day 5 post-depilation, the back skin of mice was topically treated with either 0.2 microg 1,25-dihydroxyvitamin D3, 2.0 microg calcipotriol, 0.02 microg KH 1060, or vehicle (ethanol) only. On the last day of treatment (i.e., day 9 post-depilation), all mice received 150 mg cyclophosphamide i.p. per kg as a single dose to induce alopecia, or vehicle (aqua dist.). Analysis of the treated skin by in situ-end labeling (using a modified terminal UTP nucleotide end labeling technique suitable for murine skin), by Hoechst 33342 stain, and by DNA electrophoresis on days 10 and 14, revealed the induction of massive apoptosis in cyclophosphamide-treated anagen hair bulbs, which was most prominent on day 10, whereas controls showed no follicular apoptosis. The calcitriol-pretreated groups demonstrated a significant reduction of apoptosis, with a maximal inhibition seen on day 14. This confirms that cyclophosphamide indeed induces massive keratinocyte apoptosis in anagen hair follicles, and provides evidence that topical calcitriol-analogs can suppress epithelial cell apoptosis in vivo. The mouse model employed here offers an excellent tool for dissecting the as yet poorly understood controls of keratinocyte apoptosis in situ and its pharmacologic manipulation.

Administration, Topical↗