Gender differences in scalp hair growth rates are maintained but reduced in pattern hair loss compared to controls.

BACKGROUND: Hair loss is related to follicular density, programmed regrowth and hair productivity. OBJECTIVE: The dissatisfaction with hair growth in patients experiencing hair loss might be due to slower linear hair growth rate (LHGR). METHODS: LHGR and hair diameter was evaluated in Caucasian controls and patients with patterned hair loss employing the validated non-invasive, contrast-enhanced-phototrichogram with exogen collection. RESULTS: We evaluated 59,765 anagen hairs (controls 24,609, patients 35,156) and found thinner hairs grew slower than thicker hairs. LHGR in normal women was generally higher than in normal men. LHGR correlates with hair diameter (P < 0.006) and global thinning is associated with slower growth rates. Compared with hair of equal thickness in controls, subjects affected with patterned hair loss showed reduced hair growth rates, an observation found in both male and female patients. Males with pattern hair loss showed further reduction in growth rates as clinical severity worsened. However, sample size limitations prevented statistical evaluation of LHGR in severely affected females. LIMITATIONS: Caucasian ethnicity. CONCLUSION: In pattern hair loss, LHGR significantly contributes to the apparent decrease in hair volume in affected areas. In early onset, LHRG might have a prognostic value in females but not in males.

Body hair counts during hair length reduction procedures: a comparative study between Computer Assisted Image Analysis after Manual Processing (CAIAMP) and Trichoscan(™).

PURPOSE: To compare two measurement methods for body hair. METHODS: Calibration of computer assisted image analysis after manual processing (CAIAMP) showed variation <4% for thickness and <2.3% for densities. Images from 6 body sites with 'good natural contrast between hair and skin' were taken before hair dye, after hair dye or after hair length reduction without hair extraction or destruction. Data in the same targets were compared with Trichoscan(™) quoted for 'unambiguous evaluation of the hair growth after shaving'. RESULTS: CAIAMP detected a total of 337 hair and showed no statistically significant differences with the three procedures confirming 'good natural contrast between hair and skin' and that reduction methods did not affect hair counts. While CAIAMP found a mean number of 19 thick hair (≥30 µm) before dye, 18 after dye and 20 after hair reduction, Trichoscan(™) found in the same sites respectively 44, 73 and 61. Trichoscan(™) generated counts differed statistically significantly from CAIAMP-data. Automated analyses were considered un-specifically influenced by hair medulla and natural or artificial skin background. CONCLUSION: Quality control including all steps of human intervention and measurement technology are mandatory for body hair measurements during experimental or clinical trials on body hair grooming, shaving or removal.

Critical study of hair growth analysis with computer-assisted methods.

BACKGROUND: Computer-assisted image analysis has been proposed for human hair growth studies. METHODS: The performances of Trichoscan, a commercially available automated system combining epiluminiscence microscopy with digital image analysis, developed for office-based hair growth measurements, have been evaluated comparatively on the same skin sites using standardized photographic equipment and calibrated processing for contrast-enhanced phototrichogram (CE-PTG) analysis. This reference method has been validated with scalp biopsies and histological examination of serial sectioning. RESULTS: Besides edge effects, hair fibres escaped the Trichoscan analysis for various reasons including, but not limited to, thickness, pigmentation, closeness and crossing. CONCLUSION: Most of these problems have been identified in the late 1980s and remain largely unsolved by the processing software that was evaluated in 2004. Therefore claims promoting the Trichoscan method for accurate hair measurements in clinical trials on scalp and body hair are not supported by the present investigation. The speed at which the analysis is performed is outweighed by the errors in signal detection. Therefore we suggest that improvements must be clearly documented before Trichoscan is established for quantified diagnostic purposes and detailed hair cycle monitoring during hair trials.

Natural scalp hair regression in preclinical stages of male androgenetic alopecia and its reversal by finasteride.

Using contrast-enhanced phototrichogram (CE-PTG) at monthly intervals during 48 months, we measured the duration of the hair cycle, i.e. anagen, catagen and telogen at the exclusion of exogen. Exogen, a recently identified phase of the hair cycle, is characterized by weakening of anchorage of the club hair to the surrounding epithelium. The processing of the club hair terminates at the time of exogen hair release, i.e. hair shedding. We combined a noninvasive exogen sampling before each CE-PTG so that the area contained only anagen, catagen and telogen hair or empty follicular openings. During the first 24 months of this study, natural regression of hair cycling in early i.e. preclinical stages of androgenetic alopecia (AGA) in androgen sensitive areas was documented. Shortening of the hair cycle of thicker hair characterized progression of AGA. During the next 24 months, finasteride (1 mg/day) was introduced into the system. Shortening of the hair cycle was reversed by finasteride in androgen sensitive sites as long as the affected follicle was able to produce a thick hair fiber at the time of treatment initiation. Compared to the baseline period, responding follicles did not produce thicker hair. On average, they initiated active growth more rapidly by reducing the duration of the lag phase by 40%. The duration of the anagen phase of thick hair showed an average 23% increase. In this particular experiment, the already miniaturized follicles producing thinner hair (<40 microm thickness) at the time of finasteride introduction regressed further on treatment. Our results seem to indicate that reversal of 'hair loss' by finasteride probably means that the terminal type follicles that are functionally deficient--a stage of reversible hypotrophy--will be reactivated by two non-mutually exclusive mechanisms: faster regrowth followed by extension of the duration of anagen. In our study, there was no clear evidence in favour of reversal of miniaturized hair into terminal hair. This new interpretation indicates that miniaturized hair follicles may be an important diagnostic marker of AGA in males but also that it might be less contributive to the therapeutic response to finasteride. Our results highlight that precise measurement of terminal type hair follicle functionalities opens up avenues for the selection of 'drug-responsive organs' in the human scalp in vivo and these may possibly serve to predict 'quality of response to treatment'.

Validation of scalp coverage scoring methods for scalp hair loss in male pattern hair loss (androgenetic alopecia).

BACKGROUND: Global evaluation of hair loss in male subjects affected by androgenetic alopecia has been proposed as a means for monitoring changes over time, including placebo-controlled drug efficacy studies. Because of the potential impact of subjectivity (e.g. placebo effect) of clinical investigators, global photographs (GPs) have been introduced as a more objective record. Examination of paired before and after pictures and rating on a seven-point scale (from greatly decreased -3 to greatly increased +3) have been historically introduced by United States of America (US) experts. METHODS: Based on published GPs and original GPs obtained at our clinical research facility, we developed a training set in order to allow European Union (EU) observers to practice and compare with ratings by the US experts. RESULTS: After training with the seven-point scale, there was a positive correlation between three US and three EU ratings (n=52 paired images from 35 different subjects, r=0.795). The results of a test-retest evaluation was performed on 18 paired images from the initial image collection by the three EU experts. Correlation r=0.806 and identical scores in 78% of cases documents a reproducibility similar to the single one US expert published data (119 subjects, retest correlation 0.76 with 75% identical duplicate ratings). Seventeen subjects taken from a placebo-controlled trial had GPs at 6 and 12 months. The average difference between an efficacious drug treatment and the placebo were almost similar in the US (0.833) as in the EU (0.689) expert panels. We also trained the EU experts in performing the scalp coverage scoring (SCS), a novel system for the global evaluation of scalp hair in vivo and on GP. SCS was performed on single images (randomised as to time and treatment) taken from the same set of 17 paired GPs. This showed a between-group difference of 0.055 at 6 months and 0.201 at 12 months, i.e. 5% improved coverage in favour of the active group. CONCLUSION: After completion of our study, US and trained - calibrated EU experts seem equally valuable in comparing before-after GPs. SCS can also be used on GPs and may support the clinical investigator during inclusion of test subjects and for real-time efficacy evaluation during the trial.

Dermal objective pharmacodynamic profile of cetirizine and epinastine: two controlled, randomised, double-blind, crossover studies.

Two double-blind clinical pharmacology studies were performed in healthy volunteers to compare the dermal pharmacodynamic profile of epinastine with cetirizine, a well-documented anti-H1 antagonist, after oral administration at the usual recommended dosage, i.e. 10 mg cetirizine and 20 mg epinastine (versus placebo). Histamine skin challenges (prick test) were evaluated before and at 1, 2, 4, 8 and 24 hr after drug intake by measuring the wheal and flare area (studies 1 and 2) along with laser Doppler monitoring of the microvascular responses (study 2). A decrease in wheal and flare areas was observed following intake of both drugs compared with placebo controls. With the notable exception of 1 hr post dose wheal values, which were consistently smaller after epinastine, cetirizine was superior to epinastine for both wheal and flare at all other times. At the prick test site, treatment with epinastine and cetirizine accentuated the increase in blood flow induced by histamine. This reflects the decrease of the whealing but there was no significant difference between the two active test compounds. At 1 cm from the prick test site, the administration of both active treatments inhibited the increase of blood flow, and cetirizine showed a more potent inhibitory effect from 8 hr post dose. This reflects the reduction of the flare induced after histamine-receptor activation of the axon reflex. In conclusion, epinastine shows a rapidly greater (within 1 hr post dose on the wheal only) but vanishing effect than cetirizine. At all other time points, cetirizine was generally more effective than epinastine.

Contrast enhanced phototrichogram (CE-PTG): an improved non-invasive technique for measurement of scalp hair dynamics in androgenetic alopecia--validation study with histology after transverse sectioning of scalp biopsies.

Global changes of scalp hair represent the cumulative end result of discrete changes of individual hair follicle structure and/or function. Monitoring of such changes requires an accurate non-invasive method. The phototrichogram (PTG) appears to be an appropriate choice to do so. However, a known weakness of the method is the lack of detection of less pigmented or thinning hair. Balding scalp of male subjects with androgenetic alopecia (AGA) was analysed with our previously published PTG method and with contrast enhanced (CE-)PTG followed by biopsy and transverse section examination with the light microscope. As compared with PTG, the CE-PTG method significantly improved detection not only of thin but also of thick hair. Equal numbers of thick (diameter > 40 mm) hair were detected with CE-PTG and with histology. CE-PTG was also able to detect the severely miniaturised hair fiber (down to 8 mm diameter) and was comparable to scalp biopsy analysis. The latter could identify hair fibres, which did not reach the scalp surface, a measure that is considered as not clinically significant. All growth stages - anagen, catagen and telogen - as well as the empty follicle stage could clearly be observed with CE-PTG. Staging of the more severely affected hair follicles was not always possible neither with CE-PTG nor histology - even with serial sectioning. The finding of such technological advantages makes the CE-PTG a first choice method for detailed analysis of hair cycling in androgenetic alopecia - a scalp disorder characterised by extreme hair follicle miniaturisation, decreased hair pigmentation and hair thinning.

Telogen effluvium after allergic contact dermatitis of the scalp.

OBJECTIVE: After observing 2 cases of acute telogen effluvium induced by allergic contact dermatitis to hair dyes, we decided to evaluate the effects of acute contact dermatitis of the scalp on the hair cycle. DESIGN: Single-center, 6-month study of consecutive patients affected by acute scalp dermatitis. SETTING: Department of Dermatology, University of Bologna, Bologna, Italy. PATIENTS: Diagnosis of allergic contact dermatitis of the scalp was confirmed by patch testing. Eight women presenting with acute contact dermatitis of the scalp entered the study. Hair shedding was evaluated monthly for 6 months by pull test and wash test. Increased hair loss was detected in 4 of the 7 patients who completed the study. Hair loss was mild to moderate and appeared 2 to 4 months after the episode of scalp dermatitis. A scalp biopsy specimen from 2 patients confirmed the diagnosis of telogen effluvium. CONCLUSIONS: Allergic contact dermatitis of the scalp should be included among the possible causes of telogen effluvium. The pathogenesis of telogen effluvium caused by contact dermatitis is unknown but may be related to cytokine release during the inflammatory process.

[Loose anagen hair syndrome: a familial case with fetal hair in meconium]. / Syndrome des cheveux anagènes caducs. Une observation familiale avec emission de cheveux foetaux dans le meconium.

INTRODUCTION: Loose anagen hair syndrome is a recently described hair disorder. We report a familial case. CASE REPORT: Two sisters were examined, 4 years-old and 8 months old, from a consanguineous marriage. At birth, they presented diffuse alopecia of the scalp; the meconium contained black and silky hair. Clinical examination noted the short, fine hair with easy and painless uprooting. No clinical associated symptoms were observed. The trichogram showed 70 p. 100 of anagen hair and 30 p. 100 of telogen hairs. DISCUSSION: Our familial case is original by this clinical symptom: discharge of probably dystrophic foetal hair in the meconium. Loose anagen hair is characterised by easily pluckable hair. The trichogram confirms the diagnostic. It is composed of anagen hairs (80 to 100 p. 100) devoid of sheaths. The loose anagen hair is usually isolated, but associations have been reported. It may occur in families. The precise pathogenesis and treatment of this hair disorder are not known.

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.

Androgenetic alopecia: in vivo models.

Androgenetic alopecia is the most common form of balding in humans. There is great interest in finding a reliable animal model to study the pathogenesis and treatment of this abnormality. The sump-tailed macaque (Macaca artoides) has been the standard model and appears to be useful homologue. These primates are reasonably good predictors of compound efficacy. Due to reduced size and expense, rodent models have been sought. Testosterone inducible models require more development but offer potential. Xenografts of human skin to immunodeficient mice, notably nude or severe combined immunodeficiency, are small, relatively inexpensive, and easy to work with if a source of human tissue is available. Xenografts to double mutant mice for severe combined immunodeficiency and a number of hormone receptor null mutations offer new refinements to these xenograft models.

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.

Comparison of the effects of cetirizine and ebastine on the skin response to histamine iontophoresis monitored with laser Doppler flowmetry.

BACKGROUND: The administration of histamine with iontophoresis is an alternative method to skin prick tests or intradermal injections. Skin reactions obtained with this method can be recorded with laser Doppler flowmetry (LDF) and previous studies with this method have shown histamine-induced laser Doppler changes in the wheal area. OBJECTIVE: In order to compare the influence of two H1 receptor antagonists (cetirizine 10 mg vs. ebastine 10 mg) on the skin vascular responses to histamine introduced by iontophoresis, we designed a double-blind, randomized, two-period crossover trial in which 18 volunteers were randomized. METHODS: Before and 2, 5 and 7 h after drug administration, iontophoresis (30 s, 1.4 mA/cm2) of histamine 10% was performed and followed by (1) monitoring of skin vascular responses with LDF at the administration site and at 1 cm from it, and (2) wheal and flare area measurements. RESULTS: 2, 5 and 7 h after intake of the antihistaminic drug, there were significant differences between both drugs. Concerning LDF recordings, we noted at the histamine administration site an increase in perfusion unit (PU) values which is an effect known to be in proportion to the degree of inhibition of wheal reaction, and at 1 cm distal to the histamine administration site, there was a decrease in PU values. These changes were more marked under cetirizine. A greater suppressive effect of cetirizine on the wheal and flare reaction was consistently observed at all time points during the study, demonstrating its superior efficacy. CONCLUSION: We conclude that (1) cetirizine demonstrated a stronger antihistaminic effect compared to ebastine at all time points; (2) iontophoresis appears to be an appropriate method to study specific microvascular changes at the delivery site of histamine and hence to detect the earliest changes occurring at the site of agonist-antagonist competition in the skin.

Skin signs in the diagnosis of thallium poisoning.

A 45-year-old man developed a painful and rapidly progressive sensory-motor polyneuropathy associated with confusion and convulsions. This resulted in hypoventilation and led to respiratory failure and coma. A rapid and diffuse alopecia occurred after 3 weeks in the intensive care unit. Examination of hair roots under polarized light detected dystrophic anagen hairs with dark bands caused by empty spaces in the disorganized cortex. These dark zones were originally reported in patients with thallium poisoning and a toxicological investigation confirmed thallium exposure. The classical systemic symptoms and the various dermatological signs are reviewed, and the origins of contamination and physiopathology discussed.

Peeling skin syndrome with hair changes.

A 13-year-old boy with typical peeling skin syndrome (PSS) is described. The clinical picture corresponded to the inflammatory variant of PSS (type B). In addition, the patient had gross and microscopic hair anomalies such as trichorrhexis invaginata-like changes, irregular hair shaft torsions and moniliform hair shaft diameter reductions. The observed dysmorphic hair changes are discussed and interpreted as being an integral component of the dermatosis in this case. To the best of our knowledge, such hair anomalies have not yet been described in PSS.

A controlled study of the effects of RU58841, a non-steroidal antiandrogen, on human hair production by balding scalp grafts maintained on testosterone-conditioned nude mice.

Human hair growth can be monitored for several months after the transplantation of scalp samples from men with androgen-dependent alopecia on to female nude mice. Hair production from balding sites has been shown to be inhibited in testosterone-conditioned nude mice. We used this recently reported model to study the effect of a new non-steroidal antiandrogen-RU58841-on human hair growth. Twenty productive scalp grafts from balding men were maintained for 8 months after grafting on to nude mice, and hair production was monitored monthly for 6 months. All mice were conditioned by the topical application of testosterone (testosterone propionate, 300 micrograms in 10 microL; 5 days/week) on the non-grafted flank. The scalp samples were divided equally according to the estimated hair production potential, which was based on the amount of hair present on the scalp samples before grafting. Each of the two equal groups of grafts was further allocated at random to be treated topically (5 days/week) with blinded solutions of either RU58841 1% in ethanol, or ethanol as a control. Twenty-eight active follicles appeared on the 10 control grafts. Among them only two follicles (7%) initiated a second hair cycle. However, the 10 RU58841-treated grafts bore a total of 29 active follicles, and eight of them (28%) showed a second cycle. The values for the linear hair growth rates (LHGR) were significantly (P < 0.04) higher in the RU58841-treated group. Recycling and increased LHGR indicate a positive action for RU58841 on human hair growth from balding samples grafted on to testosterone-conditioned nude mice, and encourage a clinical trial to evaluate its potential in the treatment of androgen-dependent alopecia.