A novel X-linked combined immunodeficiency disease.

A novel X-linked combined immunodeficiency disease was found in five living males in an extended family in the United States. The age of the affected males ranged from 2.5 to 34 yr. The most prominent clinical abnormalities were a paucity of lymphoid tissue; recurrent sinusitis, otitis media, bronchitis, and pneumonia; severe varicella; and chronic papillomavirus infections. The principal immunologic features of the disorder were normal concentrations of serum immunoglobulins but restricted formation of IgG antibodies to immunogens; normal numbers of B cells and NK cells but decreased numbers of CD4+ and CD8+ T lymphocytes, particularly the CD45RA+ subpopulations; diminished proliferative responses of blood T cells to allogeneic cells, mitogens and antigens; and decreased production of IL-2 by mitogen stimulated blood lymphocytes. Thus, affected males in this family carry an abnormal gene on their X chromosome that results in a combined immunodeficiency that is distinct from previously reported disorders.

Correlation of serum 3 alpha-androstanediol glucuronide with acne and chest hair density in men.

Serum 3 alpha-androstanediol glucuronide (3 alpha-Adiol-G) is considered to be an indicator of peripheral tissue androgen metabolism. Precursor circulating androgens are converted in peripheral tissue to dihydrotestosterone (DHT), which is ultimately metabolized to 3 alpha-Adiol-G and secreted from the cell. Elevated serum 3 alpha-Adiol-G concentrations have been reported in women in hyperandrogenic states. We studied 44 consecutive male medical students for chest hair density, acne, and serum dehydroepiandrosterone sulfate (DHEA-S), total testosterone (total T), free and albumin-bound (bioavailable) T (bio T), and 3 alpha-Adiol-G concentrations. Although there was considerable overlap of serum 3 alpha-Adiol-G values among the groups defined by hair density or acne scores, we found statistically significant correlations between serum 3 alpha-Adiol-G and chest hairiness (P = 0.0034), acne (P = 0.0005), and a combined chest hairiness and acne score (P = 0.0018). There was no significant correlation between these clinical parameters and the levels of precursor androgens. There was, however, a strong correlation between serum 3 alpha-Adiol-G and bio T (P = 0.0005), suggesting that in men serum 3 alpha-Adiol-G levels may be dependent upon available free and albumin-bound T. The correlations in men of serum 3 alpha-Adiol-G with chest hair density, acne, and the hairiness and acne index supports the hypothesis that the serum levels of 3 alpha-Adiol-G reflect the extent of androgen action in peripheral tissues.

Clinical and biochemical parameters of androgen action in normal healthy Caucasian versus Chinese subjects.

Stimulation of androgen-sensitive hair follicles is mediated by dihydrotestosterone (DHT), which is formed in these tissues by 5 alpha-reduction of testosterone. A possible mechanism for increased body hair in some human populations might, therefore, be an increase in 5 alpha-reductase activity, resulting in elevated tissue levels of DHT. If present, this finding could have other important clinical implications, since the 5 alpha-reductase enzyme is pivotal in the pathophysiology of prostatic disease. To explore differences in clinical and biochemical parameters of androgen action, we conducted a study of 184 caucasian and Chinese subjects in whom we evaluated chest hair density and serum levels of androgen precursors and 5 alpha-reduced androgen metabolites. Differences in chest hair density were most notable in the men, in whom comparative mean chest hair scores (using a scale of 0-4) were 3.0 vs. 0.8 (P less than 0.0001), caucasian vs. Chinese. Levels of 5 alpha-reduced androgen products were also strikingly higher in the caucasian vs. Chinese subjects. Serum 3 alpha-androstanediol glucuronide levels (nanomoles per L) were 34.7 +/- 2.4 vs. 19.7 +/- 0.9 (P less than 0.001) for the men and 21.5 +/- 3.2 vs. 9.4 +/- 0.6 (P less than 0.001) for the women, and serum levels of androsterone glucuronide (nanomoles per L) were 179 +/- 26 vs. 107 +/- 7 (P less than 0.01) for the caucasian vs. Chinese men and 173 +/- 23 vs. 81 +/- 9 (P less than 0.001) for the women. Serum levels of total and bioavailable testosterone did not differ between the racial groups, but serum levels of the precursor androgens, dehydroepiandrosterone sulfate and androstenedione, were significantly higher in the caucasian vs. Chinese men, but not in the women. We conclude that increased serum levels of 5 alpha-reduced androgen metabolites in caucasians vs. Chinese subjects provide circumstantial evidence for a racial difference in 5 alpha-reductase activity and suggest a mechanism for the increased body hair observed in the caucasian men. Increased levels of precursor androgens may also play a role.

Captopril-induced skin eruptions.

Seven of 23 hypertensive patients treated with captopril (SQ 14,225), an orally active converting enzyme inhibitor, developed a pruritic, erythematous, macular, and papular eruption of the trunk, face, and proximal extremities. The eruption appeared one to 31 weeks after initiation of captopril therapy and was associated with diarrhea (three patients), fever (two patients), and generalized arthralgias (one patient). Six patients had an increased percentage of band cells (5 to 34 per cent) on peripheral smear without an associated leukocytosis. In one patient, the skin rash was associated with a peripheral eosinophilia (20 per cent). Coombs-positive hemolytic anemia, and acute renal failure with eosinophiluria. There were no changes in BUN, creatinine, or urinalyses in the remaining patients. Four patients showed a transient rise in plasma PGE without concomitant changes in plasma PFG2 alpha or 6-keto PGF1 alpha, and three patients had slight elevations in the erythrocyte sedimentation rate. Skin biopsies revealed a perivascular and perifollicular lymphocytic and histiocytic infiltrate with negative immunofluorescence to IgG, IgM, IgA, and beta 1 C. The skin eruption and associated symptoms resolved in all patients, even though captopril administration was continued in six of the seven patients.

Sunscreen use and sun exposure. Trends in a white population.

Four hundred eighty-nine patients were surveyed during the summer months to evaluate their sun-exposure habits and beliefs, and their use of sunscreens. Seventy-one percent had one or more hours of sun exposure on at least one day per week. Men had more sun exposure than women. Subjects 30 years old and younger spent more time in the sun than those older than 30 years. Subjects with skin types 1 and 2 were least frequently sun exposed and tended to use sunscreens most often. Overall, sunscreens were used by 41% of the subjects, one third of whom used them with the belief that tanning would be promoted. In a four-week follow-up evaluation, 342 patients were contacted by telephone. Knowledge of the sun protection factor and sun-exposure risks was improved, presumably by reading an informational pamphlet provided; but sunscreen use improved very little.

Effects of relaxation therapy and hypnotizability in chronic urticaria.

The therapeutic results of hypnosis with relaxation therapy were evaluated in 15 patients with chronic urticaria of 7.8 years' average duration. Compared with baseline and control session values, the hypnosis session provided relief of pruritus as measured by three self-report parameters. There was no change in the number of hives. All subjects were given a standard test for hypnotizability. Assuming that the results were not biased by their preceding relaxation sessions, we determined that six subjects were hypnotizable and nine were nonhypnotizable. Subjects in both groups improved symptomatically, but hypnotizable subjects had fewer hives and became more symptomatic during the control (testing and history taking) session. Hypnotizable subjects also more frequently related stress as a causative factor. At a follow-up examination five to 14 months after the completion of the experimental sessions, six patients were free of hives and an additional seven reported improvement.

Plasmapheresis in a patient with scleromyxedema.

We describe a patient with progressive scleromyxedema who failed to respond to previously described treatment modalities. A trial of plasmapheresis was initiated, but after an initial promising response, his disease continued to progress. The skin involvement appeared to progress even more rapidly after the plasmapheresis was discontinued.

Generalized epidermolytic hyperkeratosis in the child of a parent with nevus comedonicus.

Nevus comedonicus (NC) is rarely associated with the histopathologic changes of epidermolytic hyperkeratosis (EH). A parent with mild focal NC had a child with severe generalized EH. The histopathologic findings of skin biopsy specimens from parent and child showed the distinctive granular and spinous layer vacuoles and coarse keratohyaline granules of EH. This parent and child may be examples of the extremes in expression of an autosomal dominant trait.

Skin infiltration in Hodgkin's disease.

Hodgkin's disease involving the skin is an unusual occurrence and often portends a poor prognosis. We present a case of Hodgkin's disease and extensive skin infiltration with a favorable outcome. A variety of therapeutic modalities, including a mixture of mechlorethamine hydrochloride, vincristine sulfate, prednisone, and procarbazine; electron-beam radiation; topical mechlorethamine hydrochloride; and intravenous vinblastine sulfate were employed with moderate success.

Bacteriology of chronic leg ulcers.

The quantitative bacteriology of 13 chronic leg ulcers was sequentially assessed by both swab and biopsy culture techniques, and the effect of either a 10% benzoyl peroxide lotion or placebo lotion was evaluated. There was good correlation between the swab and biopsy culture techniques in 12 of the 17 instances where simultaneous swabs and biopsies were done. Though the benzoyl peroxide did not favorably affect the bacterial flora, ulcer healing did appear to correlate with quantitative bacterial counts. THREE of five ulcers containing fewer than 10(5) organisms per gram of tissue or per centimeter of ulcer surface area healed, while none of eight ulcers containing more than 10(5) organisms healed. Quantitative bacteriological measurements can serve as useful tools in evaluating healing of leg ulcers.

Cutaneous manifestations of multiple myeloma.

We report the cutaneous manifestations of multiple myeloma, using a retrospective review of 115 patients' records obtained from tumor registry files. Five patients were found to have biopsy-proved extramedullary plasmacytomas without extension from an underlying bony focus. Twelve patients had ecchymoses without thrombocytopenia; two of them had biopsy-proved amyloidosis. One patient presented with pyoderma gangrenosum and was subsequently diagnosed with multiple myeloma. The last patient initially presented with what clinically appeared to be leukocytoclastic vasculitis, and, in the course of a standard workup, he was diagnosed with multiple myeloma. These findings are discussed with regard to the current literature on the cutaneous manifestations of multiple myeloma.

Effect of isotretinoin on serum levels of precursor and peripherally derived androgens in patients with acne.

Sebaceous glands are stimulated by androgens and can convert them to more active forms. Isotretinoin, however, has a profound inhibitory effect on sebaceous gland size and function. This study evaluated the effect of isotretinoin on serum levels of precursor and tissue-derived androgens. Twenty-four subjects (15 men and nine women) were treated for 20 weeks with 1 mg/kg/d of isotretinoin. Serum samples were obtained at baseline, 8, 16, and 24 weeks, and assayed for precursor androgens--total testosterone (TT), free testosterone (free T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S); and tissue androgens--dihydrotestosterone (DHT), and its metabolite, 3 alpha-androstanediol glucuronide (3 alpha-diol G). Isotretinoin had no meaningful effects on precursor androgens, except for producing an elevation of free T in women. In contrast, isotretinoin produced depressions in the serum levels of DHT and 3 alpha-diol G in women and in 3 alpha-diol G in men. These decreases are believed to be the result, rather than the cause, of a reduction in the size of the sebaceous glands: The magnitude of the observed decreases may represent the amount of tissue-derived androgens that sebaceous glands normally contribute to the circulating pool.

Immunosuppression in men with bowenoid papulosis.

The immune status of four men with bowenoid papulosis was evaluated. Each case had been refractory to multiple methods of treatment. Three of the men had other infections and demonstrated a depletion of T4-helper cells. Two of these patients were anergic on skin testing, and the third showed weak reactivity. The fourth patient, who had no evidence of additional infections, had a normal T4 value and T4/T8 ratio, but was anergic on skin testing. All the men were serologically negative for human immunodeficiency virus antibodies. One of the immunosuppressed patients developed squamous cell carcinoma of the tongue, which, along with his bowenoid papulosis, contained human papillomavirus 16 DNA. We suggest that patients with persistent bowenoid papulosis be investigated for altered immune status and followed up as potential candidates for the development of epithelial malignant neoplasms.

Human papillomavirus type 16 in bowenoid papulosis, intraoral papillomas, and squamous cell carcinoma of the tongue.

A 33-year-old immunosuppressed man developed bowenoid papulosis on his genitalia, velvety papules and plaques in his mouth, and invasive squamous cell carcinoma of his tongue. All three lesions were positive for human papillomavirus type 16 (HPV-16). The case provides further circumstantial evidence for a role of HPV-16 in epithelial neoplasia. The possible roles of a second HPV infection and of immunosuppression are also discussed.

Inocoterone and acne. The effect of a topical antiandrogen: results of a multicenter clinical trial.

BACKGROUND AND METHODS: Because acne is androgen dependent, antiandrogen therapy might improve the condition. Inocoterone acetate (RU 882) is a nonsteroidal antiandrogen that binds to the androgen receptor and has antiandrogenic activity in animal models. To test its topical effect on acne, 126 male subjects with facial acne completed a 16-week, multi-center, double-blind study in which the twice-daily application of a 10% solution of inocoterone was compared with vehicle solution. Baseline and monthly examinations included acne lesion counts and general and endocrine laboratory tests. RESULTS: Inflammatory papules and pustules showed greater reduction in the inocoterone-treated subjects than in the subjects treated with vehicle. This difference achieved statistical significance by week 12 (24% reduction vs 10%) and week 16 (26% reduction vs 13%) and, with longitudinal analysis, throughout the course of the study. Global assessments and changes in comedo counts and sebum excretion rates were not significantly different between the groups. No serious adverse reactions were encountered. CONCLUSIONS: In this double-blind study of 126 male subjects with acne, a topical solution of the antiandrogen inocoterone, compared with vehicle, produced a modest but statistically significant reduction in the number of inflammatory acne lesions.

Histologically proven leukemia cutis carries a poor prognosis in acute nonlymphocytic leukemia.

A retrospective study of fifty-eight patients with acute nonlymphocytic leukemia was undertaken to determine the incidence of leukemia cutis and whether skin involvement serves as a prognostic indicator. A clinical diagnosis of leukemia cutis was made in eleven patients (19 percent), and five patients (8.6 percent) had biopsy-confirmed skin involvement. Patients with biopsy-proven leukemia cutis had a median postdiagnosis survival of only 12.5 weeks compared with fifty weeks for the group without skin involvement. We conclude that leukemia cutis is a biopsy diagnosis that occurs in a minimum of 8.6 percent of patients with acute nonlymphocytic leukemia in whom survival appears to be shortened.