Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene.

The xeroderma pigmentosum group D (XPD) protein is a subunit of transcription factor TFIIH with DNA helicase activity. TFIIH has two functions, in basal transcription and nucleotide excision repair. Mutations in XPD that affect DNA repair but not transcription result in the skin cancer-prone disorder, xeroderma pigmentosum (XP). If transcription is also affected, the result is the multi-system disorder trichothiodystrophy (TTD), in which there is no skin cancer predisposition, or in rare cases, XP combined with Cockayne syndrome. Up till now there have been no reports of combined clinical features of XP and TTD. We have now identified two patients with some features of both these disorders. One of these, XP189MA, a 3-year-old girl with sun sensitivity, mental and physical developmental delay, has XPD mutations not previously reported, and barely detectable levels of nucleotide excision repair. The other, XP38BR, a 28-year-old woman with sun sensitivity, pigmentation changes and skin cancers typical of XP, has a mutation that has been identified previously, but only in TTD patients with no features of XP. The level of repair of UV damage in XP38BR is substantially higher than that in other patients with the same mutation. With both patients, polarized light microscopy revealed a 'tiger-tail' appearance of the hair, and amino acid analysis of the hair shafts show levels of sulfur-containing proteins intermediate between those of normal and TTD individuals. Our findings highlight the complexities of genotype-phenotype relationships in the XPD gene.

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.

Changes in hair weight and hair count in men with androgenetic alopecia, after application of 5% and 2% topical minoxidil, placebo, or no treatment.

Quantitative estimation of hair growth using hair weight and number was recorded for 120 weeks in 4 groups of 9 men with androgenetic alopecia. Three double-blind groups applied either 2% or 5% minoxidil solution, or vehicle. The fourth group, unblinded, received no treatment. Measurements of hair weight and number were continued for 96 weeks, when treatment (if any) was stopped, though measurements were continued for another 24 weeks. Although not compared statistically, the placebo and untreated groups behaved in a similar fashion. In contrast, the 5% and 2% minoxidil treatment groups showed a statistically significant increase in mean percentage change in interval weight from baseline compared with placebo; results for number counts were usually less significant. Over 96 weeks, topical minoxidil induced and maintained an increase in interval weight over baseline of about 30%. After treatment was stopped, hair weight and number counts for the minoxidil groups returned to about the same levels as placebo in 24 weeks.

Clinical dose ranging studies with finasteride, a type 2 5alpha-reductase inhibitor, in men with male pattern hair loss.

BACKGROUND: Androgenetic alopecia is a common condition of adult men. Finasteride, a type 2 5alpha-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.

Recalcitrant scarring follicular disorders treated by laser-assisted hair removal: a preliminary report.

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.

The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis.

Many diseases, notably those having a strong autoimmune component, have been shown to have an association with specific human leukocyte antigens (HLA). The molecular basis for this genetic association with disease is the fact that HLA bind and present peptides derived from self and foreign protein antigens to the immune system for recognition and activation of the immune response. Previous studies with heterogeneous groups of alopecia areata (AA) patients have suggested associations with some HLA class I and class II antigens. For this study we selected only patients with long-standing disease and stratified them into two groups by strict definitions of duration and extent of disease: those with patchy AA and those with either alopecia totalis (AT) or alopecia universalis (AU). The patients were tissue typed for HLA class II antigens by biomolecular methods that provided antigen discrimination at an allele level. More than 80% of all of the AA patients typed were positive for the antigen DQB1*03 (DQ3), suggesting that this antigen is a marker for general susceptibility to AA. In addition, two other antigens were found significantly increased in frequency only in the group of AT/AU patients, DRB1*0401 (DR4) and DQB1*0301(DQ7). This strongly suggests that the two clinical types of AA, namely patchy AA versus AT/AU, can be distinguished by a genetically based predisposition to extent of disease.

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.

Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group.

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 5alpha-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 < .001 vs placebo, all comparisons). Clinically significant increases in hair count (baseline = 876 hairs), measured in a 1-inch diameter circular area (5.1 cm2) of balding vertex scalp, were observed with finasteride treatment (107 and 138 hairs vs placebo at 1 and 2 years, respectively; P < .001). Treatment with placebo resulted in progressive hair loss. Patients' self-assessment demonstrated that finasteride treatment slowed hair loss, increased hair growth, and improved appearance of hair. These improvements were corroborated by investigator assessments and assessments of photographs. Adverse effects were minimal. 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.

Hair regrowth. Therapeutic agents.

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.

Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia.

In this study, 12 women and 12 men, ages 18-33 y, with androgenetic alopecia were selected for biopsies from frontal and occipital scalp sites. The androgen receptor, type I and II 5alpha-reductase, cytochrome P-450-aromatase enzyme were measured and analyzed in hair follicles from these scalp biopsies. Findings revealed that both women and men have higher levels of receptors and 5alpha-reductase type I and II in frontal hair follices than in occipital follicles, whereas higher levels of aromatase were found in their occipital follicles. There are marked quantitative differences in levels of androgen receptors and the three enzymes, which we find to be primarily in the outer root sheath of the hair follicles in the two genders. Androgen receptor content in female frontal hair follicles was approximately 40% lower than in male frontal hair follicle. Cytochrome P-450-aromatase content in women's frontal hair follicles was six times greater than in frontal hair follicles in men. Frontal hair follicles in women had 3 and 3.5 times less 5alpha-reductase type I and II, respectively, than frontal hair follicles in men. These differences in levels of androgen receptor and steroid-converting enzymes may account for the different clinical presentations of androgenetic alopecia in women and men.

Cuticle cell defects in lamellar ichthyosis hair and anomalous hair shaft syndromes visualized after detergent extraction.

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.

Heritable factors distinguish two types of alopecia areata.

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, longterm 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.