|
160
Inhibition of Ornithine Decarboxylase: Effects on the Hair
Follicle Cytoskeleton and Epidermis of Patients with Pseudofolliculitis
Barbae (PFB)
M. Ericson, C. Boeck and M. Hordinsky Dept.
of Dermatology, University of Minnesota Academic Health Center,
Minneapolis, Minnesota, USA
The purpose of this study was to obtain information
on the mechanism of action of eflornithine hydrochloride cream
13.9%, an irreversible inhibitor of the enzyme ornithine decarboxylase,
in the treatment of Grade 3 PFB in adult males of African-American
descent. We hypothesized b.i.d. application of the cream for
16 weeks to the beard region of 10 men with PFB would alter
epidermal thickness, the hair fiber, and hair follicle structure
through disruption of actin bundles. Photographs and 4-mm
skin biopsies were obtained from PFB lesions at Treatment
Days 2 and 114. At the end of the treatment course, clinical
severity of PFB improved in the majority of patients. Formalinfixed
biopsy samples were stained with hematoxylin and eosin and
Ki67 antibody, a marker for cell proliferation. Zamboni’s-fixed
biopsy samples were processed and stained for laser scanning
confocal microscopic (LSCM) analysis. In post-treatment samples;
(1) the number of miniaturized follicles increased and the
number of large curved follicles decreased, (2) epidermal
thickness remained the same in all samples, (3) epidermal
differentiation appeared more organized, and (4) Ki-67 staining
revealed a decrease in epidermal staining in all but 2 patients.
LSCM analysis revealed changes in actin filament architecture
in the keratogenous zone of the outer root sheath of anagen
beard hair follicles. Actin filament bundles also appeared
very disorganized and parallel orientation was lost. We conclude
that eflornithine hydrochloride cream 13.9% may be an effective
drug in the management of PFB and possibly other skin diseases
characterized by abnormal cell proliferation. Our data also
suggest that eflornithine hydrochloride cream 13.9% disrupts
the actin cytoskeleton of the actively growing beard hair
follicle. Disruption of this scaffolding could lead to subsequent
loss of follicle integrity and alteration of growth characteristics
of the beard hair follicle.
|