Response to minoxidil in severe alopecia areata correlates with T lymphocyte stimulation.

Mitogen-induced T cell blastogenesis was determined in 47 patients with severe alopecia areata, before and after treatment with topical 5% minoxidil, and compared with control values. The group of 36 responders, who demonstrated terminal hair regrowth, showed significantly increased lymphocyte stimulation with concanavalin A and PHA before treatment, which decreased towards control values following hair regrowth. Lymphocytes from non-responders showed no significant differences from controls either before or after treatment. The results suggest that enhanced T cell blastogenesis may predict the response of severe alopecia areata to topical 5% minoxidil therapy.

Evaluation of oral minoxidil in the treatment of alopecia areata.

A dose-response effect has previously been demonstrated in topical minoxidil treatment of alopecia areata. Limitations in minoxidil solubility and percutaneous absorption have impaired the development of more effective topical therapy. Oral minoxidil (5 mg every 12 hours), a dose demonstrated to be relatively well tolerated if a 2-g sodium diet is strictly followed, was given to 65 patients with severe, treatment-resistant alopecia areata in an attempt to bypass the limitations of topical treatment and increase efficacy. Although hair regrowth progressed more rapidly and was more extensive with oral than topical 5% minoxidil, cosmetic response was seen only in 18% of the patients. Neither serum nor tissue levels of minoxidil correlated with response. These findings suggest that improved preparations of topical minoxidil, when used as a single therapeutic agent, are unlikely to be cosmetically effective in the majority of patients with severe alopecia areata.

Evaluation of anthralin in the treatment of alopecia areata.

Anthralin cream 0.5% to 1.0% was used to treat 68 patients with severe alopecia areata. Therapy was relatively well tolerated, although all patients experienced pruritus and local erythema and scaling. Cosmetic response was seen in 17 (25%) of the patients, and was maintained during therapy in 12 (71%) of the 17 cosmetic responders. For the patients treated with 0.5% anthralin, the mean time to response (44 of 66 patients) was 11 weeks; the mean time to cosmetic response (13 of 66 patients) was 23 weeks. Duration of the current episode of hair loss did not correlate with cosmetic response. Compared with other currently available topical treatments, anthralin appears to be a reasonable therapeutic option for severe alopecia areata.

Minoxidil.

Topical minoxidil has shown some promise for the treatment of male-pattern alopecia and alopecia areata. Clinical trials suggest that careful patient selection and appropriate drug formulation are both important factors to maximize efficacy. Side effects attributable to topical minoxidil appear to consist almost entirely of cutaneous reactions in patients who have been studied thus far, i.e., patients without hypertension or cardiovascular disease. The mechanism of minoxidil-induced hair regrowth is not fully understood, but it may involve a synergistic effect of minoxidil on a variety of cell types.

Topical minoxidil therapy for hair regrowth.

The pathogenesis of hair loss, the postulated mechanisms of minoxidil action on hair growth, and clinical trials, adverse reactions, experimental formulations, and percutaneous absorption of topical minoxidil preparations are reviewed. Topical minoxidil seems to normalize hair follicles and increase blood flow to the scalp. In clinical trials of various formulations, results have varied. Improved hair growth occurred after four to six months of therapy; twice-daily application seems to be indicated. The most frequently reported adverse reactions are mild scalp dryness and irritation and, rarely, allergic contact dermatitis. Current recommendations are to reserve topical minoxidil for patients with normal cardiovascular status and to routinely monitor blood pressure, heart rate, and electrocardiographic changes. A new drug application is pending with FDA for use of topical minoxidil in androgenetic alopecia (male-pattern baldness), which is genetically determined and apparently stimulated by androgens. For alopecia areata, which involves hair loss on the body or scalp, usually patchy and of sudden onset, no reliable treatment has been found, although minoxidil may be efficacious in some patients. Minoxidil has generated new interest in hair-loss research. The etiology of hair loss must be better understood before more effective treatment regimens can be designed.

Topical minoxidil solution (1% and 5%) in the treatment of alopecia areata.

Topical minoxidil solution can induce hair regrowth in alopecia areata. A dose-response effect was demonstrated when 48 patients treated with topical 1% minoxidil were compared with 47 patients treated with topical 5% minoxidil. A total of 66 patients were enrolled, 26 of them participating in both study groups. Patients with extensive (75% or greater) scalp hair loss showed a response rate of 38%, defined as terminal hair regrowth, with 1% minoxidil versus an 81% response rate with 5% minoxidil. The current 2% formulation is most likely to elicit cosmetically acceptable regrowth in those with patchy alopecia areata. Occlusion of the treated area appears to be necessary to achieve and maintain maximum results. Nonresponders are most likely to be found among those with the most extensive scalp hair loss. No other clinical features correlate with response to treatment. However, a finding of increased T cell blastogenesis before treatment may predict response. In patients with severe alopecia areata, hair loss generally recurs after treatment is stopped and may recur during treatment. Systemic absorption of topically applied and occluded minoxidil solutions (1% and 5%) was minimal; no clinically significant changes in blood pressure, weight, cardiovascular status, electrocardiogram, electrolytes, complete blood count, or urinalysis were seen. Mild local irritation occurred, and two of the 66 patients developed allergic contact dermatitis to minoxidil, as confirmed by patch tests.

Potential mechanisms of minoxidil-induced hair growth in alopecia areata.

In vivo, topical minoxidil therapy is associated with changes in the follicular epithelium, tissue and blood lymphocyte populations, lymphocyte blastogenic response to mitogens, and perifollicular vasculature. Biopsy specimens taken from areas of terminal hair regrowth show a dose-dependent increase in hair follicle length, a decrease in tissue lymphocyte populations associated with a simultaneous increase in peripheral blood lymphocyte counts, and reopening of previously closed lumina of perifollicular vessels. Responder lymphocytes show pretreatment-increased concanavalin A and phytohemagglutinin-induced blastogenesis, which decrease toward control values after treatment. In vitro, at concentrations approximating the range of tissue levels in patients treated topically with the 5% solution, minoxidil affects both epithelial cells and lymphocytes in tissue culture. Cultured murine epithelial cells show increased cell proliferation and delayed senescence. Cultured human lymphocytes show suppression of mitogen-induced blast transformation. Differential effects on responder, nonresponder, and control lymphocytes are seen. Minoxidil may induce hair regrowth in alopecia areata by a synergistic stimulatory effect on follicular epithelium and a suppressive effect on lymphocyte-mediated immunologic phenomena. A contributing role for its vasodilatory properties must also be considered.

Computer-aided quantification of scalp hair.

In this article we present a statistical model that, when applied in conjunction with existing image analysis technology, allows for a precise quantification of two-component visual fields. Application of this methodology to the problem of quantification of hair density in patients with hair loss disorders yields excellent results. Under photographically controlled conditions this method should yield completely consistent and valid results. The complete absence of subjective bias in the application of this method makes it an extremely attractive alternative to existing procedures. Limitations to the use of this methodology are detailed, and an alternative approach is suggested.

Topical minoxidil dose-response effect in alopecia areata.

Topical 5% minoxidil solution was used to treat 47 patients with severe alopecia areata. Forty patients (85%) had terminal hair regrowth after 48 to 60 weeks of treatment. In the majority of patients, hair regrowth was not cosmetically acceptable. Data were compared with those from a previous study with topical 1% minoxidil solution. Both the percentage of responders and the quality of their hair regrowth were significantly greater with 5% than with 1% topical minoxidil solution. One patient developed an allergic contact dermatitis to minoxidil, but no systemic side effects were detected. The results strongly suggest a dose-response effect for topical minoxidil treatment of alopecia areata and the importance of exploring modifications in dosing and delivery systems to enhance therapeutic efficacy.

Quantification of scalp hair--a computer-aided methodology.

A method for obtaining a quantitative assessment of hair density is described. First, a photographic image of the scalp is digitized onto a high-resolution computer graphics screen. Second, the frequency of each of 256 gray levels (one for each of 500 vertical X 500 horizontal = 250,000 locations on the screen) is obtained and the frequency histogram of gray levels is displayed. Third, a statistical procedure, gaussian mixture analysis, is used to resolve the frequency distribution into two normally distributed component distributions. The first component distribution describes the range of gray levels that are typically associated with hair. The second component distribution describes shades of gray that are typically associated with scalp. The statistical model provides a precise measure of the proportion of the head that exhibits gray levels in each of the two component distributions (hair or scalp). The proportion of the first component distribution is a scale-independent measure of hair density. The difference in this quantity before and after treatment provides an accurate quantitative determination of the change in hair density and hence of the efficacy of treatment.

Chronic active hepatitis associated with etretinate therapy.

Acute hepatitis developed in a patient taking etretinate for severe psoriasis. Discontinuation of therapy was followed by progression of the histological changes to chronic active hepatitis, despite improvement of his clinical and laboratory status. This is the third reported case of chronic active hepatitis associated with etretinate therapy, and the second patient in our group of twenty-two etretinate-treated patients with severe psoriasis to develop clinically significant hepatic disease. Immunological evaluation revealed a marked increase in the patient's OKMI-staining population of peripheral mononuclear cells and augmentation of Con A-induced lymphocyte blastogenesis in the presence of etretinate.

Alopecia areata treated with topical minoxidil.

A 1% minoxidil topical solution was used to treat 48 patients with alopecia areata, ie, 24 patients with patchy disease and 24 patients with alopecia totalis or alopecia universalis. Twenty-five patients had terminal hair regrowth; in 11 of the 25 patients, it was cosmetically acceptable. No clinical features of the disease seemed to indicate the likelihood of hair regrowth. Hair regrowth began approximately two months after the initiation of treatment and was not uniformly well maintained after the treatment was terminated. One patient had an allergic contact dermatitis reaction to the minoxidil solution; no systemic side effects were seen. No notable systemic absorption was found in 18 adult patients. Effects on cutaneous blood flow or the immune system or some direct effect on hair follicles are possible mechanisms by which minoxidil therapy might stimulate hair growth.

Cutaneous T-lymphocyte lymphoma in association with multiple myeloma.

We report a case of cutaneous T-lymphocyte lymphoma in which multiple myeloma, a B-lymphocyte neoplasm, developed. We also review the emerging evidence on the immunoregulatory capacity of neoplastic T lymphocytes. Our case clinically supports the notion that neoplastic T lymphocytes may sometimes express helper activity for a specific B-lymphocyte clone (idiotype-specific helper function).

Direct effects of minoxidil on epidermal cells in culture.

Minoxidil, a potent antihypertensive agent, induces generalized hypertrichosis when administered systemically, or localized hair regrowth when applied topically to sites of severe alopecia areata. The pharmacologic mechanisms by which minoxidil stimulates hair growth are unknown. This study was designed to examine whether minoxidil has direct effects on neonatal murine epidermal cells in culture. In the presence of minoxidil, cultures showed a marked dose-dependent second peak of DNA synthesis 8-10 days after culture initiation. In addition, two morphologically distinct cell types appeared. Indirect immunofluorescence staining with keratin-specific antibody revealed cytoplasmic keratin fibers, suggesting the epidermal origin of these cells. Our experiments demonstrate that minoxidil can affect epidermal cells in culture by altering their growth pattern and phenotypic appearance.

Hepatotoxic reactions in a patient treated with etretinate.

Hepatotoxic reactions and eosinophilia developed in a 74-year-old woman who had been treated with an aromatic retinoid compound, etretinate, for severe psoriasis palmaris et plantaris. Rapid improvement in her condition followed discontinuation of the drug therapy. Liver enzyme elevations recurred after reinstitution of etretinate therapy; these levels quickly returned to normal after the drug therapy was again discontinued. Our patient's reaction to etretinate may have been a hypersensitivity reaction.

Altered erythrocyte membrane phosphorylation in psoriasis.

Autophosphorylation by [gamma-32P]ATP of erythrocyte membranes from controls, psoriatic patients and patients with skin disorders other than psoriasis was compared by polyacrylamide gel electrophoresis. Compared with controls, membranes from psoriatic patients showed significantly less 32P incorporation in the band 2 region (nomenclature of Fairbanks et al., 1971). In addition, psoriasis and some of the other skin diseases examined displayed decreased phosphorylation in the region of bands 2.9-3 and 4.5-4.8. A new polypeptide band in the 18-20,000 dalton region was also observed in the diseases examined. Altered epidermal plasma membranes have been implicated in the pathogenesis of psoriasis, and our findings suggest the defective plasma membranes may be a generalized phenomenon in this disorder.

Erythrocyte membrane phosphorylation in untreated and in etretinate-treated psoriatic patients.

Levels of phosphorylation were decreased in bands 2 to 2.1, 2.9 to 3 and 4.5 to 4.8 of erythrocyte membranes from psoriatic patients compared with control values. In addition, higher than control levels of 32P were incorporated into a new polypeptide band (mol.wt. 18-20,000 daltons) of red cell membranes from patients. Uptake of 32P by these bands returned towards normal after the patients received oral etretinate treatment. These results suggest there is a generalized plasma membrane defect in psoriasis and that etretinate may affect the metabolism of red cell membrane proteins.