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.

Eur J Dermatol 2002 Jan-Feb;12(1):38-49

Long-term (5-year) multinational experience with finasteride 1 mg in the treatment of men with androgenetic alopecia.

BACKGROUND: Finasteride 1 mg (Propecia) is indicated for the treatment of men with androgenetic alopecia (male pattern hair loss, MPHL). However, the long-term (> 2 years) efficacy and safety of finasteride in this population has not been previously reported. Objectives. To assess the efficacy and safety of finasteride in men with MPHL compared to treatment with placebo over five years. METHODS: In two 1-year, Phase III trials, 1,553 men with MPHL were randomized to receive finasteride 1 mg/day or placebo, and 1,215 men continued in up to four 1-year, placebo-controlled extension studies. Efficacy was evaluated by hair counts, patient and investigator assessments, and panel review of clinical photographs. RESULTS: Treatment with finasteride led to durable improvements in scalp hair over five years (p 3/4 0.001 versus placebo, all endpoints), while treatment with placebo led to progressive hair loss. Finasteride was generally well tolerated and no new safety concerns were identified during long-term use. CONCLUSIONS: In men with MPHL, long-term treatment with finasteride 1 mg/day over five years was well tolerated, led to durable improvements in scalp hair growth, and slowed the further progression of hair loss that occurred without treatment.

Br J Dermatol. 2003 Jun;148(6):1205-11.

Female alopecia: the mediating effect of attachment patterns on changes in subjective health indicators.

Background The interrelationship between female alopecia and psychological disorders is complex, with a range of psychosocial consequences, but also antecedents. Psychosocial antecedents are to a large extent interpersonal and can be assumed to have a mediating effect on health care utilization and subjective health. Objectives To analyse whether changes in health-related quality of life (QoL) are mediated by relational or attachment styles and whether these styles are associated with a particular, dysmorphophobic type of alopecia. Methods Seventy-four women with androgenetic and diffuse alopecia underwent psychological assessment at the first consultation at a university clinic and at 2 months' follow-up. Attachment styles were evaluated by an observer rating scale. As a primary endpoint a disease-specific QoL instrument was employed. Results Findings indicated an association between patients with nonvisible hair loss and the ambivalent attachment style. Global clinical impressions and attachment indicators, e.g. attachment security and coping strategies, showed significant contributions in predicting changes in the QoL scales 'self-esteem' and 'emotions'. Conclusions These findings suggest that attachment security may be one of the underlying mechanisms mediating subjective health and that a specific attachment vulnerability can be identified in a subgroup of patients with female alopecia. Future studies will have to focus on the relevance of attachment patterns in the doctor-patient relationship and on psychotherapeutic interventions.

Support Care Cancer. 2003 Jun;11(6):371-7. Epub 2003 Mar 21.

Scalp hypothermia to prevent chemotherapy-induced alopecia is effective and safe: A pilot study of a new digitized scalp-cooling system used in 74 patients.

GOALS. The aim of this study was to examine the efficacy and safety of a new digitized, controlled, scalp-cooling system to prevent chemotherapy-induced alopecia. METHOD. Seventy-four female cancer patients who received 13 varying chemotherapy regimens were included in a nonrandomized pilot study. The Digni 2-3 with Dignicap system consists of a refrigerator unit and a control unit integrated into a mobile cabinet and connected to a tight-fitting cooling cap. This system maintains a constant scalp temperature of +5 degrees C for many hours. In this study, 60 patients were treated for ovarian cancer with either taxane or epirubicin combination chemotherapy. Eight patients with Hodgkin's lymphoma, three with breast cancer, two with endometrial cancer, and one with sarcoma were also included. Photo documentation and patient assessment of hair loss and discomfort were performed. RESULTS. In anthracycline-treated patients, total prevention of hair loss was observed, whereas hair loss in paclitaxel/docetaxel-treated patients was minimal to none. The combination of anthracycline and taxane resulted in more hair loss, but only three of six patients used a wig. Scalp cooling was generally very well tolerated; only two of 74 patients discontinued use of the cold cap due to discomfort. No scalp metastases occurred over a median follow-up period of 15 months. CONCLUSIONS. The digitized, controlled, scalp-cooling system represents an effective and safe device that should be clinically evaluated in a randomized trial and in studies using other chemotherapy regimens to determine optimal temperatures and durations of cooling for maximal efficacy.

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DHEA has been suggested to provide numerous potential benefits. DHEA (or dehydroepiandrosterone) is converted into androgens (male hormones) or estrogens (female hormones) in the cells.

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