In our research at the Gillette Company Research Institute, we conducted a series of Phase I, Phase II, and Phase III studies between 1988 and 2000, evaluating the efficacy of eflornithine HCl in facial-hair retardation. In the first study ever conducted, the use of Eflornithine in the treatment of unwanted facial hair in women established the efficacy of its use as a topical hair retardant. In that pilot study, Shander et al. [11] found that there was a remarkable benefit of the topical eflornithine (10% eflornithine HCl delivered in an aqueous hydro-alcoholic vehicle) on improving PFB in women with facial hair. Dermatological observations were recorded by a dermatologist who noted skin conditions prior to treatment, at 12 and 24 weeks of treatment, and at 12 weeks after the withdrawal of treatment. Nine women suffering from pseudofolliculitis treated themselves twice daily over a 6-month period with an aqueous-based vehicle (68% water, 16% ethanol, 5% propylene glycol, 5% dipropylene glycol, 4% benzoyl alcohol, and 2% propylene carbonate) containing 10% eflornithine. At the end of the treatment, 5 subjects exhibited complete clearance, 4 of whom cleared within 12 weeks. Four additional women showed progressive improvements during the 24 weeks of treatment.
A study was proposed to evaluate if eflornithine could reduce ingrown hair and lesions in men with PFB. The open-label study in men with PFB reported by Shander et al. [12] was designed to evaluate the mechanism of action of 13.9 % eflornithine cream applied twice daily in men with PFB including:
(1) reduction of ingrown hair
(2) changes in hair shaft histology specifically related to the ratio of paracortical and orthocortical cells
(3) quantification of the angle of emergence of hair from the skin which was not ingrown since changing the angle of emergence could enhance the ability of blade to contact the low-lying hair and increase the shave efficiency.
The results of this research indicate that Ingrown low lying hair ( IGLLHs) are embedded in the grooves and rugosities of the skin, and are predisposed to enter the skin and provoke inflammatory lesions. A reduction in the IGLLHs in hair has significant clinical relevance as these hair have the propensity to become ingrown and cause a papule. Often these hair are not readily visible and can only be observed using high magnification lenses or by the use of facial silicone replicas portraying the facial landscape. We employed the use of facial replicas to identify the ingrown hair, as well as measure the angle of emergence of noningrown hair from the screen.
Facial surface replicas of 48-hour beard growth were obtained at the beginning and end of the 16-week eflornithine-HCL treatment period, and processed to characterize the changes in the number and percentage of IGLLHs, as well as the changes in the angle of emergence. At the start of the study facial replicas from four [4] facial sites exhibiting PFB including the cheek and neck areas on the left – and right-side were prepared in subjects who had refrained from shaving for 48 hours. The sites included four circular areas (0.7 cm diameter) with PFB lesions in the left and right chin and cheek for a total area of 6.22 cm2. Using photographs at the beginning of the study to pinpoint specific facial features, combined with triangulation techniques measuring distance of the site from fixed facial
landmarks, we were able to accurately return to the same sites at the end of the study for making end-of-study replicas.
In addition to quantifying the number of ingrown hair, the angle of emergence of hair that were not ingrown was measured using an automated image analysis technique, in order to provide objective evidence that the treatment altered the shape of hair and their angle of emergence from the skin. Of the 11 men completing topical treatments, 9 were available for facial replica evaluation. One subject was hospitalized for a condition unrelated to topical treatment, one subject shaved on the morning that his final replica was to be obtained. One subject had severe lesions at the start of the study, and his ingrown hair on his face were so dramatically obscured by lesions that pretreatment hair counts could not be accurately obtained as the decrease in his lesion intensity and clinical severity was actually accompanied by an increase in hair.
In eight subjects, the total number of hair in the pretreatment period did not differ from the number in posttreatment. The results from the facial replicas on eight subjects demonstrated a significant (44%) reduction in IGLLHs at the end of the treatment (Fig. 18.3), as well as a significant increase (36%) in the average angle of emergence (AOE) of beard hair measured by image analysis, which is consistent with the reduced tendency to become ingrown.
Clinical evaluations by the Alexander and Delph method [5] were completed in all men at baseline and end of treatment. These reductions in ingrown hair were clinically significant, as 9 of the 11 men demonstrated clinically significant improvements in PFB, including 5 men with marked reductions in lesions and almost total clearance of inflammation, and 4 men with significant improvements in PFB. Figure 18.4 demonstrates a typical
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Before treatment End of treatment Figure 18.4 Marked improvement in PFB after topical Vaniqa treatment. |
marked improvement response in which severity is improved from score of 3 to 1 on the PFB severity scale of Alexander and Delph.
Beard-hair samples were also collected at the beginning and end of treatment, and cross-sections were prepared at a thickness of 2 p, and stained with methylene blue to identify paracortical cells and eosin for the identification of orthocortical cells. The stained sections were then magnified with an Olympus microscope and photographed to provide images for measurements. The cuticle stained an intense dark blue, paracortical cells stained a less intense blue, and orthocortical cells stained a bright red. After the end of treatment, the percentage of eosin-stained orthocortical cells increased, resulting in a striking visual change in cortical staining pattern at the end of treatment. The medulla, when present, stained red as well. The results of this histological analysis are depicted in Fig. 18.5.
For an accurate quantitative image analysis of the paracortical cells, the red staining orthocortical cells and the medulla was subtracted. After extracting out the red level the methylene blue stained areas of paracortical cells area was selected at the best intensity threshold to quantify the area. There was a significant decrease in the percentage of methylene blue-stained paracortical cells from 90 to 76% (P < 0.001). Measurements of the cross-sectional area showed that the area of the beard hair sections increased significantly (p < 0.001) after treatment with DFMO, while the hair parameters, medulla, cortex, and cuticle, calculated as a percentage of the total cross-section, remained unchanged. Moreover, the average width of the cuticle statistically increased 8% (p = 0.0022) from pre – to post-treatment.
We hypothesize that the mechanism of action of Vaniqa in improving PFB involves changes in the ratio of orthocortex to paracortex after administration of eflornithine which modifies the biophysical properties of beard hair. This changes their shape, and the angle of emergence after exiting the follicle orifice thereby reducing the IGLLHs. In addition, the changes in the ratio of orthoccortex to paracortex reflect a morphological modification resulting from decreased cell proliferation, which alters the characteristic asymmetrical pattern of cell differentiation in African American hair follicles (Fig. 18.6).
Pretreatment