tretinoin and Alopecia-Areata

Alopecia areata (AA) is a cell-mediated autoimmune disease that targets actively growing hair follicles in mammals, including humans and mice. Development of the C3H/HeJ spontaneous mouse model AA nearly 20 years ago provided a much needed tool to test the hypotheses and ultimately serve as a preclinical model for drug testing. Discoveries in both human AA patients and the mouse model supported each other and lead to discoveries on the incredibly complex genetic basis of this disease. The discovery that A/J, MRL/MpJ, SJL/J, and SWR/J strains also develop AA now allows genome-wide association mapping studies to expand the list of genes underlying this disease. Potential new targets for unraveling the pathogenesis of AA include the role of retinoic acid metabolism in the severity of disease and hair shaft proteins that may be either the inciting antigen or ultimate target of the immune reaction leading to breakage of the shaft causing clinical alopecia. Comparing these model systems with human and mouse clinical disease, for both discovery and validation of the discoveries, continues to resolve the complex questions surrounding AA.

Topics: Alopecia Areata; Animals; Disease Models, Animal; Genetic Predisposition to Disease; Genome-Wide Association Study; Mice; Mice, Inbred C3H; Tretinoin

Topical minoxidil is a trichogenic agent that stimulates the hair follicle via the vasoactive metabolite minoxidil sulfate without any evidence of antiandrogen activity or an effect on the immune system. Less than 5% of the applied dose is absorbed. The therapeutic effect on hair regrowth is demonstrated for androgenetic alopecia in males and females, by a computer-assisted image analysis counting technique of nonvellus hairs from a photographic print. Patients with severe alopecia areata respond poorly to topical minoxidil treatment. The most common adverse reactions are limited to irritant and allergic contact dermatitis on the scalp. The use of retinoic acid with topical minoxidil has been disappointing relative to the increase in systemic exposure. The value of topical minoxidil as an adjunct for the hair transplant procedure and its effect on hair loss from chemotherapy are being evaluated.

Topics: Administration, Cutaneous; Alopecia Areata; Drug Therapy, Combination; Female; Humans; Male; Minoxidil; Tretinoin

Fluconazole-induced alopecia is a significant problem for patients receiving long-term therapy. We evaluated the hair cycle changes of fluconazole in a rat model and investigated potential molecular mechanisms. Plasma and tissue levels of retinoic acid were not found to be causal. Human patients with alopecia attributed to fluconazole also underwent detailed assessment and in both our murine model and human cohort fluconazole induced telogen effluvium. Future work further examining the mechanism of fluconazole-induced alopecia should be undertaken.

Topics: Alopecia Areata; Animals; Antifungal Agents; Disease Models, Animal; Fluconazole; Humans; Male; Mice; Rats; Rats, Wistar; Tretinoin

Mild but efficient treatments of autoimmune diseases are urgently required. One such therapy, long-term maintenance of chronic delayed type hypersensitivity, has been described for alopecia areata (AA), a hair follicle-affecting autoimmune disease. The molecular mechanisms underlying the therapeutic efficacy are unknown, but may involve myeloid-derived suppressor cells (MDSCs). AA-affected mice were treated with squaric acid dibutyl ester (SADBE). The immunoreactivity of SADBE-treated AA lymphocytes and of AA lymphocytes co-cultured with SADBE-induced MDSCs was analyzed. The curative effect of SADBE was abolished by all-transretinoic acid, which drives MDSCs into differentiation, confirming a central role for MDSCs in therapeutic SADBE treatment. SADBE and SADBE-induced MDSCs strongly interfered with sustained autoreactive T-cell proliferation in response to AA skin lysate (autoantigen), which was accompanied by weak ζ-chain down-regulation and strongly impaired Lck activation. In contrast, activation of the mitochondrial apoptosis pathway and blockade of the anti-apoptotic PI3K/Akt pathway by SADBE-induced MDSCs did not require T-cell receptor engagement. Apoptosis induction correlated with high TNF-α expression in SADBE-induced MDSCs and elevated TNFRI levels in AA lymphocytes. SADBE-induced MDSCs interfere with persisting autoreactive T-cell proliferation and promote apoptosis of these T cells, which qualifies MDSCs induced and maintained by chronic delayed type hypersensitivity reactions as promising therapeutics in organ-related autoimmune diseases.

Topics: Adaptor Proteins, Signal Transducing; Alopecia Areata; Animals; Apoptosis; Autoimmune Diseases; Autoimmunity; CD4-CD8 Ratio; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cyclobutanes; Hypersensitivity, Delayed; Lymphocyte Activation; Mice; Mice, Inbred C3H; Mitochondria; Myeloid Cells; Phosphoinositide-3 Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Receptors, Antigen, T-Cell; Receptors, Tumor Necrosis Factor; Signal Transduction; T-Lymphocytes; Tretinoin; Tumor Necrosis Factor-alpha

Kerion Celsi is a parasitic fungal skin infection that tends to occur mainly on the back of the neck, scalp or beard. It is caused by animal fungi. Sometimes the condition resolves itself in a matter of weeks but hair loss in the affected area may be permanent. We report a case of a young woman with Kerion Celsi favored by the use of a tretinoin+minoxidil+betametasone valerate lotion.

Topics: Adult; Alopecia Areata; Betamethasone; Drug Therapy, Combination; Female; Humans; Minoxidil; Tinea Capitis; Tretinoin

Topics: Administration, Topical; Adult; Alopecia Areata; Case-Control Studies; Female; Glucocorticoids; Humans; Injections, Intralesional; Keratolytic Agents; Male; Tretinoin; Triamcinolone Acetonide

Acitretin (etretin [Ro-10-1670]) is the major metabolite of etretinate with a much shorter elimination half-life. The drug was used in the treatment of 20 patients who had cutaneous lupus erythematosus. All patients responded to treatment, but in five, the result was unsatisfactory. In 15 patients, an excellent (total clearing) or good response (marked reduction of all lesions) was seen. In seven of them, acitretin was superior to previous therapy with antimalarials and/or systemic corticosteroids. In particular, five of six patients with subacute cutaneous lupus erythematosus showed complete clearing of their lesions, usually within two to four weeks. Side effects were the same as with etretinate. It is concluded that acitretin is a highly effective and well-tolerated drug in the treatment of cutaneous lupus erythematosus.

Topics: Acitretin; Adult; Aged; Alopecia Areata; Antibodies, Antinuclear; Cholesterol; Drug Administration Schedule; Drug Evaluation; Female; Humans; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid; Male; Middle Aged; Pilot Projects; Tretinoin; Triglycerides

Topics: Administration, Topical; Adrenal Cortex Hormones; Alopecia Areata; Female; Humans; Male; Tretinoin; Vitamin A