Measuring Reversal of Hair Miniaturization in Androgenetic Alopecia, Chronic Telogen Effluvium, and Diagnostic and Predictive Value of Horizontal Sections of Scalp Biopsy

Kathryn

Measuring Reversal of Hair Miniaturization in Androgenetic Alopecia by Follicular Founts in Horizontal Sections of Serial Scalp Biopsies: Results of Finasteride 1 mg Treatment of Men and Postmenopausal Women

Androgenetic alopecia (AGA) is due to changes of terminal hairs into vellus-like hairs and shortening of the anagen growth phase. Based on Phase 3 studies, finasteride clinically demonstrated a positive effect on hair growth in men with AGA. Whiting et al1 evaluated the effect of finasteride on AGA with horizontal sectioning of scalp biopsies, in both men and postmenopausal women. In the male study, 26 men, 14 on 1 mg of finasteride and 12 controls were biopsied at the start of the study and 12 months later. In the female study, 137 post-menopausal women were included, 94 randomized to 1 mg of finasteride and 50 on placebo, and also were biopsied at the start and 12 months following treatment. The biopsies were read by 1 observer, blinded to patient, treatment, and time of biopsy. Terminal hair bulbs, terminal hairs (including anagen, catagen, and telogen hairs), vellus and vellus-like hairs, stelae, and follicular units were counted. Terminal-to-vellus ratio, percentage of anagen hairs, and percentage of telogen hairs (categorized as both catagen and telogen) were calculated. In the group of men that received treatment, there was a mean increase of 5.4 total terminal hairs, compared to a nonsignificant mean increase of 1.0 in the placebo group. There also was a reciprocal decrease in the mean number of vellus hairs in the finasteride group compared to the placebo group, 3.1 and 1.1 respectively. Terminal-to-vellus ratio increased to 1.5 in the treatment group, compared to 1.1 in the placebo group, although this was not statistically significant, possibly due to the small sample size. In the female study, there was no significant difference between the treatment and placebo groups. This study suggests, by histologic findings, finasteride at a dose of 1 mg can improve AGA in men, but not in postmenopausal women.

Reference

1. Whiting DA, Waldstreicher J, Sanchez M, Kaufman KD. Measuring reversal of hair miniaturization in androgenetic alopecia by follicular founts in horizontal sections of serial scalp biopsies: results of finasteride 1 mg treatment of men and postmenopausal women. J Invest Dermatol Symp Proc. 1999;4(3):282-4.  

Chronic Telogen Effluvium: Increased Scalp Hair Shedding in Middle-Aged Women

Chronic telogen effluvium (CTE) is an idiopathic form of generalized diffuse scalp thinning lasting greater than 6 months and lacking the frontoparietal pattern seen in female androgenetic alopecia (AGA). This study1 aimed to establish clinical and pathologic criteria for the diagnosis of CTE. Diagnoses of CTE versus AGA were made based on clinical evaluation and laboratory work-up to rule out other causes. A total of 355 patients were included in the CTE group and 412 in the AGA group. A control group of 22 patients was also included. Paired scalp biopsies, 1 for horizontal and 1 for vertical sectioning, were performed in all patients. Terminal, vellus-like hairs, follicular stelae, and perifollicular inflammation and fibrosis were evaluated in vertical sections. Follicular structures (hair bulbs, terminal hairs (anagen, catagen, and telogen), telogen germinal units, and vellus-like hairs) and perifollicular inflammation and fibrosis were evaluated in horizontal sections. Peak concentration of follicular structures per mm2, anagen-to-telogen ratios, and terminal-to-vellus-like ratios were calculated by counts in horizontal sections. The mean telogen count seen in patients with CTE was an average of 11%, compared with an average of 6.5% in control patients. The range for telogen count in patients with CTE was 0 to 50% suggesting a fluctuating course of disease. Average follicular units were 13 across all 3 groups. The terminal-to-vellus-like hair ratio was similar between controls and patients with CTE, 7:1 and 9:1, respectively, compared to 1.9:1 in patients with AGA. Inflammation was characterized as mild or moderate. Inflammation or fibrosis was similar between controls and patients with CTE, 40.9% and 40.3% respectively, compared to 71.4% in patients with AGA. Compared to patients with CTE, patients with AGA have an even lower anagen-to-telogen ratio due to a shorter hair cycle. Clinical findings that suggest CTE include a woman in 4th to 6th decade with abrupt onset of hair shedding that persists for longer than 6 months. Histologic findings that suggest CTE is a terminal hair count and terminal-to-vellus-like hair ratio comparable to a normal control, with a low anagen-to-telogen ratio.

Reference

1. Whiting DA. Chronic telogen effluvium: Increased scalp hair shedding in middle-aged women. J Am Acad Dermatol. 1996;35(6):899-906.

Diagnostic and Predictive Value of Horizontal Sections of Scalp Biopsy Specimens in Male Pattern Androgenetic Alopecia

Horizontal sectioning of scalp punch biopsies allows for assessment of hair bulbs, terminal hairs (anagen, catagen, and telogen stage), telogen germinal units, vellus hairs, follicular units, and stelae. Whiting1 compared horizontal sectioning to vertical sectioning for evaluation of male pattern androgenetic alopecia (MPAA). Paired punch biopsies, 1 sectioned vertical and 1 horizontal, from the scalps of 106 men with MPAA were compared to those from 22 control subjects. Vertical sections were examined for terminal hairs, vellus hairs, follicular stelae, and perifollicular inflammation and fibrosis. Horizontal sections were examined for follicular structures (hair bulbs, terminal hairs in any stage, telogen germinal units, and vellus hairs). Horizontal sections provided data for calculation of peak concentration of follicular structures per square millimeter, terminal-to-vellus hair ratios, and anagen-to-telogen ratios. In the control patients, the average number of hairs in a specimen was 40, with an average terminal-to-vellus ratio of  7:1, 93.5% of terminal hairs in anagen and 6.5% in telogen. For the MPAA, the average number of hairs in a specimen was 35, with an average terminal-to-vellus ratio of 1.7:1, with 84% of terminal hairs in anagen and 16% in telogen. Inflammation was divided into “no or mild” and “moderate or severe” perifollicular inflammation/fibrosis. Seventy percent of MPAA specimens contained inflammation and/or fibrosis, compared to 40.9% of control subjects.

A subset of 44 patients with MPAA in the study were treated with topical 2% minoxidil twice daily and followed for at least 1 year and degree of hair growth was correlated with follicular structure density and intensity of inflammatory changes in pretreatment biopsies. Hair regrowth was measured by clinical evaluation. Regrowth and concentration of follicular structures were directly relational, with 86% of patients with more than 4 follicular structures/mm2 having a regrowth, compared to 73% in patients with 2 to 4 follicular structures/mm2 and 11% of patients with less than 2 follicular structures/mm2.

Horizontal sectioning of scalp biopsies allows for analysis of follicular structures, aiding in the diagnosis of MPAA and may aid in predicting response to treatment by assessing viable follicular structures. Diagnostic features of MPAA include (1) moderate increase in follicular stelae, (2) near normal total number of hairs with a reduced terminal:vellus ratio of approximately 2:1, and (3) increase in telogen hairs.

 Reference

1. Whiting DA. Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia. J Am Acad Dermatol. 1993 May;28(5 Pt 1):755-63.