Thioredoxin reductase. Role in free radical reduction in different hypopigmentation disorders.

Membrane-associated thioredoxin reductase (TR) has been discovered to reduce free radicals at the surface of the skin. An accurate bioassay for this enzyme has been developed by using a spin-labeled quaternary ammonium salt as a free radical substrate. Enzyme activity has been correlated with the surface area, and units of specific activity have been determined as the sequential decrease in nitroxide radical reduction per 3-mm punch biopsy per ten minutes. The TR activity in a random population of 30 healthy volunteers with different skin types (Fitzpatrick classification I through VI) could be correlated to the skin type. Ten patients with untreated vitiligo, two with piebaldism, three with albinism, and two with postinflammatory leukoderma were examined and the findings were compared with the expected rates for the individuals' skin types. The results from this survey on the human population support our previous molecular experiments on the control of melanin biosynthesis by TR in the epidermis.

Alopecia areata. Autoreactive T cells are variably enriched in scalp lesions relative to peripheral blood.

BACKGROUND AND DESIGN: Alopecia areata is a condition characterized by hair loss in association with perifollicular infiltration of T cells and antigen-presenting cells. Autoreactive T cells are postulated to amplify this abnormality by interacting with DR+ follicular epithelium. These cells may recognize either autologous major histocompatibility complex class II antigen or an autoantigen restricted by major histocompatibility complex class II. Limiting dilution analysis was used to determine the frequency of autoreactive lymphocytes in scalp biopsy specimens and peripheral blood from seven adult patients with alopecia areata. Autoreactive T cells are defined for this study as those that proliferate in response to autologous irradiated peripheral blood mononuclear cells. RESULTS: Autoreactive lymphocytes were enriched in scalp biopsy specimens relative to peripheral blood in five of seven patients. This enrichment was statistically significant in four of five patients. Five autoreactive T-cell clones derived from lesional scalp were characterized. Four of these clones were CD3+CD4+CD8- and one clone was CD3+CD4-CD8+. CONCLUSIONS: Enrichment of autoreactive cells in lesions of alopecia areata supports a role for these cells in the pathogenesis of this condition. Enrichment of autoreactive lymphocytes is also found in allergic contact dermatitis. Thus, these autoreactive lymphocytes may have a general role in inflammation.

Suppressor cell number and function in alopecia areata.

Several values of immunologic function were studied and correlated with disease activity and extent in 14 patients with alopecia areata, alopecia totalis, or alopecia universalis and in a concurrently studied age- and sex-matched control group. As compared with the control group, the patients showed a significantly increased incidence of autoantibody formation, increased concanavalin A-induced suppression of the normal lymphocyte response to mitogens, an increased proportion of suppressor-cytotoxic cells in the peripheral blood, and a decrease in the absolute B-cell count. Absolute total T-cell counts, quantitative serum immunoglobulin determinations, and lymphocyte proliferation after exposure to the mitogens--concanavalin A, phytohemagglutinin, and pokeweed--and to tetanus antigen were comparable for both groups. Neither the percentage of concanavalin A-induced suppression of the normal lymphocyte response to mitogens nor the helper-suppressor ratio correlated significantly with the extent of hair loss. However, patients, particularly those who demonstrated spontaneous regrowth of hair, had increased concanavalin A-induced suppression in conjunction with an increase in the proportion of peripheral suppressor cells.

Familial alopecia areata. HLA antigens and autoantibody formation in an American family.

Ten members of a white American family, spanning three generations, were studied. Three family members from two different generations were affected with hair loss. Two had alopecia universalis; one had alopecia areata. All subjects were HLA-typed using 131 antiserum samples obtained from multiparous female donors defining 41 HLA-A and HLA-B antigen specificities. Six haplotypes were identified. The affected persons and four other family members shared a common haplotype, HLA-A2,B40. The OKT4 (helper), OKT8 (suppressor-cytotoxic) cells, OKT4-OKT8 (helper-suppressor-cytotoxic) ratios and the percentage of B cells found were comparable for both the 12 control subjects and the family members studied. However, family members showed increased autoantibody formation, decreased T-cell percentages, and concanavalin A-induced suppression of the normal lymphocyte response to mitogens.

HLA-D locus associations in alopecia areata. DRw52a may confer disease resistance.

Because predisposition to autoimmunity has been associated with HLA-D alleles and alopecia areata is hypothesized to be a T-cell mediated autoimmune hair loss, we determined DR and DQ alleles in 88 white and 10 American black patients with alopecia areata as well as controls with the use of restriction fragment length polymorphism typing with cDNA probes. White patients with alopecia areata have an increase in the phenotype frequencies of DR4 and DQw8 and an increase in genotype frequencies of DR4 and DR5 (now DRw11[5]). These associations are in agreement with those reported in two other studies but are not significant when corrected by the number of HLA antigens tested. Sixty-one percent of all patients with AA have DR4 and/or DRw11(5) specificities vs 40% of controls, with more DR4,DRw11(5) and DQw7(w3), DQw8(w3) heterozygotes among patients. DQw6(w1) phenotype frequencies and DRw52a phenotype and genotype frequencies are significantly decreased in patients with alopecia areata relative to controls. This highly significant negative association with the HLA DRB3 allele DRw52a in whites persisted even when DR4- or DRw11(5)-positive individuals were excluded from the patient and control groups. These data suggest that HLA-DR4 and DRw11(5) with their associated DQw7(w3) and DQw8(w3) specificities may confer susceptibility to alopecia areata, while DRw52a may confer resistance.

General evaluation of the patient with alopecia.

The evaluation of the patient with alopecia is a multistep process that comprises obtaining a good medical history, performing the clinical examination with a special emphasis on the examination of cut and plucked hair, doing a scalp biopsy, and ordering appropriate laboratory studies. Genetic counseling may be given if it is requested.

Relationship between follicular nerve supply and alopecia.

The emergence of new technologies such as the combination of immunohistochemical techniques with laser scanning confocal microscopy allows one to observe and project the three-dimensional perifollicular innervation in tissue sections measuring up to 200 microns. This technology opens the door to making new discoveries about the innervation of the hair follicle. As new information is generated about the cutaneous sensory nervous system, neuropeptide expression, and the modulation of inflammatory and proliferative processes by the nervous system in the skin, it is likely this knowledge will be applied to enhance our understanding of the biology of the hair follicle in both the normal and diseased state.

The antiandrogens. When and how they should be used.

This article is a useful guide for treating androgen-related skin disorders such as androgenetic alopecia, acne, and hirsutism. All available antiandrogens are discussed, as well as treatment doses, efficacy, and mode of action.

Skin diseases of the external genitalia. Recognition and treatment.

Dermatologic diseases of the genitalia are of several types: congenital diseases, acquired diseases (those caused by viruses, bacteria, fungi, or physical or chemical toxins), tumors, and atrophic dermatoses. The methods available to diagnose these diseases vary. Some conditions may be recognized by appearance alone, whereas others require histopathologic examination of involved skin for correct diagnosis. Some do not need treatment, while others call for an aggressive approach. Some types of genital dermatologic diseases, such as herpes infections and condylomata acuminata, appear to be associated with genital carcinogenesis. Patients with these diseases should be carefully examined.

Inheritance of melanocytic tumors in Duroc swine.

Phenotypes, with respect to cutaneous melanocytic lesions, of 37 Duroc swine from five matings were analyzed prospectively. No evidence for a recessive or X-linked trait was found. Larger numbers of animals will have to be studied to determine whether the presence of these tumors is a multifactorial or autosomal dominantly transmitted trait.