Gene array profiling and immunomodulation studies define a cell-mediated immune response underlying the pathogenesis of alopecia areata in a mouse model and humans.

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J Invest Dermatol 2002 Aug;119(2):392-402

Gene array profiling and immunomodulation studies define a cell-mediated immune response underlying the pathogenesis of alopecia areata in a mouse model and humans.

Alopecia areata is a suspected autoimmune hair loss disease. In a rodent model, alopecia areata can be induced in normal haired C3H/HeJ mice by transfer of skin grafts from mice with spontaneous alopecia areata. At weeks 2, 4, 6, and 10 after surgery, grafted mice were euthanized, skin collected and processed for histology, and RNA extracted. Age-matched sham-grafted mice, and mice with and without spontaneous alopecia areata, were similarly processed. For comparison, skin biopsies from alopecia areata and androgenetic alopecia affected humans were also collected. Skin mRNA processed to cDNA was analyzed using Affymetrix mouse 11K and human 6800 gene chip(R) array technology. Microarray results indicated 42 known genes upregulated or downregulated during onset of mouse alopecia areata consistent with an inflammatory cell-mediated disease pathogenesis involving antigen presentation, costimulation, and a T helper 1 lymphocyte response. In contrast, 114 genes, many regulating immunoglobulin response, were altered late in disease development. In alopecia areata affected humans, 95 genes were significantly modulated. As confirmation of microarray analysis results, lymph node and spleen cells from alopecia areata affected mice injected into normal haired littermates transferred the alopecia areata phenotype. Alopecia areata onset could be inhibited in skin-grafted mice by modulation with B7.1- and B7.2-specific monoclonal antibodies. In addition, depletion of CD4+ CD8+ expressing cells in chronic alopecia areata affected mice using monoclonal antibodies permitted hair regrowth. The results consistently demonstrated the importance of an immune cell-mediated disease mechanism in alopecia areata pathogenesis and suggested targeting antigen-presenting cells and reactive lymphocytes may be effective in alopecia areata treatment.

Br J Dermatol 2002 Jun;146(6):992-9

Effects of minoxidil 2% vs. cyproterone acetate treatment on female androgenetic alopecia: a controlled, 12-month randomized trial.

BACKGROUND: Hormone studies have demonstrated the androgen-dependent character of female androgenetic alopecia, but there have been few controlled studies of therapies for alopecia in women. OBJECTIVES: To compare topical minoxidil 2% and cyproterone acetate in the treatment of female alopecia. METHODS: Sixty-six women with female-pattern alopecia were randomly assigned for 12 cycles into two groups, 33 received two local applications (2 mL day-1) of topical minoxidil 2% plus combined oral contraceptive and 33 received cyproterone acetate 52 mg day-1 plus ethinyl oestradiol 35 microg for 20 of every 28 days. RESULTS: A mean reduction of 2.4 +/- 6.2 per 0.36 cm2 in hairs of diameter > 40 microm was observed in the cyproterone acetate group (P = 0.05) and a mean increase of 6.5 +/- 9 per 0.36 cm2 in the minoxidil group (P < 0.001). Comparison of the total number of hairs at 12 months and the body mass index (BMI) revealed a borderline positive correlation in the cyproterone acetate group (r = 0.39, P = 0.06) and a negative correlation in the minoxidil group (r = -0.42, P < 0.05). No significant difference was observed in the total number of hairs among cyproterone acetate patients according to the presence or absence of other symptoms of hyperandrogenism, whereas in the minoxidil group, the total number of new hairs was higher in patients with isolated alopecia (Delta = 8.1; P < 0.05). Variations in scalp seborrhoea were significant in both groups, but the result was better (for acne and hirsutism as well) in the cyproterone acetate group than in the minoxidil group (P < 0.001). CONCLUSIONS: Minoxidil treatment was more effective in the absence of other signs of hyperandrogenism, hyperseborrhoea, and menstrual cycle modifications when the BMI was low, and when nothing argued in favour of biochemical hyperandrogenism. Cyproterone acetate treatment was more effective when other signs were present and when the BMI was elevated, factors that favoured a diagnosis of biochemical hyperandrogenism.

Dermatol Surg 2002 Jan;28(1):66-74

Prevention of temporal alopecia following rhytidectomy: the prophylactic use of minoxidil. A study of 60 patients.

BACKGROUND: Temporal hair loss that results from traumatized hair follicles following rhytidectomy is an unsightly complication that can distress both the patient and the operating surgeon. Topical minoxidil is a proven therapy for androgenic alopecia and female senile alopecia. It has also been found to be useful in preventing the hair loss that commonly follows hair transplantation. OBJECTIVE: To analyze through a retrospective study the effect of topical minoxidil on the incidence of temporal hair loss following facelift procedures. To our knowledge this is the first study to investigate the role of minoxidil in preventing post-rhytidectomy temporal alopecia. METHODS: The charts of 60 women with a mean age of 58 years who underwent primary cervicofacial rhytidectomy were studied. Either a standard SMAS/flap technique or pliation was done in all cases. Each patient received either 2% or 5% topical minoxidil for 2 weeks before surgery and for 4 weeks after surgery, with a 5-day break period beginning on the day of surgery. Patients were monitored for complications immediately postoperatively and in 3-6 months of follow-up. RESULTS: Almost 80% of the patients underwent SMAS/flap procedures. Transient temporal alopecia was noted in only one patient, 6 weeks after discontinuing minoxidil. This resolved within 4 weeks of its reintroduction. The only other complications noted included minor hematomas (3.3%), skin slough/infection (1.7%), minor transient and localized edema (8.3%), minor ecchymosis (1.7%), a unilateral neuropraxia of the buccal nerve lasting 3 months (1.7%), and a minor temporary unilateral skin depression (1.7%). Side effects of minoxidil were not observed. CONCLUSION: On comparing our findings to results of larger rhytidectomy series in which minoxidil was not used prophylactically, and our experience before using minoxidil, we conclude that minoxidil plays a role in effectively preventing the temporal hair loss that occurs following primary cervicofacial rhytidectomies. We also found that minoxidil did not negatively impact on the risk of hematoma formation, skin necrosis, edema, or ecchymosis. Side effects of minoxidil did not present a problem.

J Am Acad Dermatol 2001 Sep;45(3 Suppl):S81-6

Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss.

In androgenetic alopecia, or pattern hair loss, follicles undergo miniaturization, shrinking from terminal to vellus-like hairs. Traditionally, this process is thought to progress gradually over a number of follicular cycles. However, it is unlikely that miniaturization can be explained only by a series of progressively shorter anagen cycles. Simple calculations show that this process would take too long for significant miniaturization to occur secondary to shorter anagen cycles alone, especially in view of the latent lag period seen in pattern hair loss that occurs between the loss of a telogen hair and the appearance of an anagen hair. Evidence is presented to support a new concept that miniaturization is an abrupt, large-step process that also can be reversed in 1 hair cycle, as has been shown clinically, with confirmatory histologic evidence, in patients with pattern hair loss responding to finasteride treatment. It is hypothesized that the miniaturization seen with pattern hair loss may be the direct result of reduction in the cell number and, hence, size of the dermal papilla.

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