A promising new treatment for solar lentigines.

The purpose of this open-label study was to determine the adverse event rate of topical 4HA/tretinoin when used twice daily for up to 24 weeks with concomitant sunscreen in the treatment of solar lentigines and related hyperpigmented lesions. There were two treatment areas: bilateral dorsal forearms, including the back of the hands; and the face, including the forehead and cheek areas. Each treatment area had a target lesion at least 5 mm in diameter and was moderately darker than the surrounding skin. A nine-point bipolar scale was used for evaluation of Target Lesion Pigmentation (0 = extremely lighter than pigment of the surrounding skin, 4 = equal with pigment of surrounding skin, 8 = extremely darker than pigment of surrounding skin). The other solar lentigines present in the treatment areas also had to have an overall pigmentation grade of at least Grade 6. Twice daily applications to individual lesions in each treatment area were made for up to 24 weeks followed by a 4-week follow-up phase. Sunscreen applications (sunscreen with sun protection factor (SPF) 25 or greater) were made every morning and reapplied after six hours if additional sun exposure was expected. Clinical evaluations were performed at weeks 0, 4, 8, 16, 24 and 28. The clinical signs of Target Lesion Pigmentation and Overall Lesion Pigmentation were evaluated at each visit. A total of 96 subjects were enrolled at four study centers; 77 (80%) subjects completed the study. Treatment-related adverse events (AEs) for 4HA/tretinoin included erythema, burning/stinging/tingling, desquamation, pruritus, skin irritation, halo hypopigmentation and hypopigmentation. Five (5%) subjects discontinued from the study due to adverse events considered to be related to study medication. When used with sunscreen of SPF 25 or greater, 4HA/tretinoin was safe and well tolerated and did not produce any unexpected or unusual adverse events.

Evaluating the safety of calcipotriene 30 g per day in patients with psoriasis: a parallel group, vehicle-controlled study.

Elevated blood and urine calcium levels have been reported with the use of high doses of calcipotriene ointment in patients with psoriasis. The objective of this study was to evaluate key measures of calcium metabolism in patients with psoriasis under supervised dosing conditions in a vehicle-controlled study. Of the 24 patients enrolled, 12 each were administered 15 g of ointment containing calcipotriene or vehicle twice a day for 14 days. Blood and urine samples and 24-hour urine collections were obtained at selected time points. All 24 patients completed the study with no significant differences between treatments in any of the laboratory parameters. Trend analysis failed to show any significant differences over time with the exception of calcium, which showed significant changes common to both the calcipotriene and vehicle groups, suggesting that these changes were unrelated to treatment. The results of this study show that the use of calcipotriene ointment at a dose of 30 g per day for 14 days did not produce any significant alterations in blood or urine calcium concentrations and was well tolerated.

Comparative study of calcipotriene (MC 903) ointment and fluocinonide ointment in the treatment of psoriasis.

BACKGROUND: The topical vitamin D analogue calcipotriene has been reported to be an effective treatment for patients with psoriasis. Comparative studies with topical steroids are informative in judging this new therapy. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of calcipotriene ointment 0.005% versus fluocinonide ointment 0.05% in the treatment of plaque psoriasis. METHODS: This study was a randomized, double-blind, parallel-group, active-controlled trial in adults who had at least mild overall disease severity and plaque elevation of at least moderate severity. Treatments were applied twice daily for 6 weeks, and subjects were evaluated at weeks 0, 2, 4, and 6. Subjects were graded on a 9-point scale (0 to 8) for scaling, erythema, plaque elevation, and for overall disease severity. A physician's global assessment of improvement/worsening was performed at every visit. RESULTS: A total of 114 subjects were enrolled at six study sites. Ninety-nine subjects completed the trial. Mean scores for signs of scaling and plaque elevation in calcipotriene-treated subjects were significantly lower by week 2 than in the fluocinonide-treated subjects. These scores continued to be significantly lower than fluocinonide through week 6 (p < 0.05). Mean scores for erythema in calcipotriene-treated subjects were significantly lower than those in fluocinonide-treated subjects at weeks 4 and 6 (p < 0.05). Both the physician's global assessment and overall disease severity showed statistically significant treatment differences in favor of calcipotriene at week 4 (p < 0.05). This superior efficacy continued through week 6. Treatment-related adverse events were observed in 12 calcipotriene-treated subjects and 5 fluocinonide-treated subjects; all were considered minor. CONCLUSION: Calcipotriene was superior to fluocinonide in the treatment of plaque psoriasis.

Primary leiomyosarcoma of the skin. Case report and review of the literature.

Leiomyosarcoma is a rare tumor usually treated by wide local excision. We present a case of primary leiomyosarcoma of the skin on the anterior aspect of the chest wall treated by Mohs micrographic surgery. This is only the second reported case so treated. The patient has remained recurrence-free for 30 months.

Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) in association with a monoclonal IgA gammopathy: a report and review of the literature.

Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) may be associated with a monoclonal gammopathy, most commonly an IgA paraproteinemia. This review looks at the available immunofluorescence staining data in the hope of finding a better characterization of this subset of patients and speculation as to the underlying pathophysiology.

Mycophenolic acid for psoriasis. A review of pharmacology, long-term efficacy, and safety.

In previous studies of up to 2 years' duration, mycophenolic acid has been shown to be an effective psoriasis suppressant. As the result of questions raised regarding the possible immunosuppressive and carcinogenic potentials of the drug, in addition to its apparent acute gastrointestinal side effects, widespread clinical trials were discontinued in 1977. We were given the unique opportunity of continuing to administer the drug on a compassionate-use basis to 85 patients for up to 13 years. In this review we report continued efficacy without dose escalation. Gastrointestinal side effects, prominent in the early years of the study, became infrequent. Although 11.6% of the patients developed uncomplicated zoster, no clinical evidence of immunosuppression was noted. The seven malignant neoplasms that arose in six of the patients were not unusual considering the age of the study population. Six patients died of conditions believed to be unrelated to drug therapy. We continue to believe that mycophenolic acid is an effective drug for the treatment of moderate to severe psoriasis and that the risks of its long-term administration are acceptable. With appropriate clinical and laboratory monitoring it can be given safely to patients who cannot take methotrexate and who may not be candidates for PUVA, retinoids, or other systemic chemotherapy.

Serum angiotensin converting enzyme activity in patients with psoriasis.

Serum angiotensin converting enzyme activity is frequently increased in patients with active sarcoidosis. In spite of a reported association between sarcoidosis and psoriasis, serum angiotensin converting enzyme activities have not been reported for patients with psoriasis. We found the mean (SD) angiotensin-converting enzyme activity for 51 healthy subjects was 18.6 (5.8) kU/l, but for 52 patients with psoriasis without coexisting sarcoidosis, it was 28.3 (6.7) kU/l. There is a significant difference between these means (p less than 0.01). Forty-two percent (22/52) of the psoriasis patients had an increased serum angiotensin converting activity. Other diseases sometimes associated with an increased serum angiotensin converting enzyme activity were excluded as possible causes of a elevated activity in our patients with psoriasis. We conclude that almost half of the patients with psoriasis will have an elevated serum angiotensin converting enzyme activity, even when coexisting sarcoidosis is absent.

Giant melanosomes in the dysplastic nevus syndrome. Electron microscopic observations.

Multiple pigmented lesions including benign lentigines, typical nevi, and dysplastic nevi from 3 patients with the dysplastic nevus syndrome contained giant melanosomes (GM). Ultrastructurally the GM were composed of microvesicles, but lacked limiting membrane and filamentous internal structure. As such, they resembled the GM found in 4 other patients with dysplastic nevus syndrome, leopard syndrome and ocular albinism, but differed from those found in the café-au-lait spots of neurofibromatosis, nevus spilus, vitiliginous achromia, and certain animals.

Correlation of in vivo and in vitro expression of cell-mediated immunity to mumps skin test antigen.

The simplest functional assay of cell mediated immunity, skin testing, is not always possible to do in every patient. A variety of in vitro assays, including lymphocyte transformation (LT), have been developed as possible alternatives to skin testing. In this report studies were undertaken to determine whether LT induced by mumps skin test antigen (MSTA) correlated with skin test sensitivity. LT stimulated by MSTA was performed with cells obtained from 43 normal subjects. Each subject was subsequently skin-tested with up to four concentrations of MSTA. LT results correlated well with skin test reactions. Lymphocytes from all subjects were responsive in LT assays. A less pronounced correlation was observed between the concentration of MSTA used for skin testing and LT. The results of these experiments suggest that LT assays with MSTA provide an adequate substitute for MSTA skin tests.

Delayed hypersensitivity to mumps antigen in humans.

Sixty-one subjects, preselected for mumps sensitivity, were entered into a double-blind protocol to standardize Mumps Skin Test Antigen. Four lots of mumps antigen selected on the basis of in vitro potency tests were used. Four other antigens, Histoplasmin, Dermatophytin-O, Dermatophytin, and fluid tetanus toxoid were also tested; positive reactions for these four antigens occurred in 48, 68, 25, and 43% of individuals, respectively. The mumps lots exhibited delayed hypersensitivity with positivity ranging from 63 to 67% at 20 CFU/ml and 77 to 84% at 80 CFU/ml in the acceptable lots. Side effects were primarily local and minor in nature. Mumps Skin Test Antigen is a useful measure of the integrity of the immune system, but lacks complete specificity because of local dermal factors.

The role of cosmetics in postadolescent acne.

The role of cosmetics in the induction and perpetuation of adult acne has been debated. This study reports the effects of a cosmetic regimen consisting of six formulations of low predicted acnegenic potential on the course of mild postadolescent acne in ten young women. No increase in activity of disease as measured by comedo and inflammatory papule counts was noted in these subjects; on the contrary, a decreasing trend in the total number of comedones and papules was noted throughout the cosmetic use period of the study. The premarketing "in-use" testing of cosmetic formulations intended for use by the postadolescent consumer with mild acne is suggested.

Cimetidine-induced xerosis and asteatotic dermatitis.

Cimetidine, a histamine H2-receptor antagonist, has previously been shown to have antiandrogenic activity in animals and to decrease the sebum excretion rate in humans. Two patients had generalized xerosis and asteatotic dermatitis that developed while they were receiving cimetidine therapy and resolved when cimetidine therapy was discontinued. We postulate that this skin change is related to the antiandrogenic properties of the drug and its effect on the sebum secretion rate.

Treatment of psoriasis with oral mycophenolic acid.

Mycophenolic acid (MPA), an inhibitor of purine synthesis, was evaluated for its therapeutic and adverse effects in 29 patients with psoriasis. MPA was administered orally for at least 12 weeks, during which time the daily dose was increased from 1600 to 4800 mg depending on occurrence of adverse reactions. Complete clearing occurred in 1 of the patients, almost complete clearing in 14, definite improvement in 13, slight or doubtful improvement in 1. The full effect of MPA required a median time of 8 weeks (range 5-14). After discontinuing MPA, relapses began at a median time of 4 weeks (range 3-8). The severity of psoriasis was scored on a 0 to 108 scale using a newly devised system. The mean severity and range before treatment was 47 (21-88); after 12 weeks, 15 (0-50). Adjustment of dose on the basis of side effects resulted in a median daily dose of 3600 mg (range 2400-4800 mg; 30-96 mg/kg ideal weight). Characteristic dose-limiting side effects were soft or frequent bowel movements, diarrhea, nausea, and anorexia. One instance of reversible, dose-related leukopenia was identified.

Vitiligo and dysgammaglobulinemia. A case report and family study.

This report concerns an 8 year old female with vitiligo and dysgammaglobulinemia characterized by absent IgA, very low IgG, and normal IgM. The t-cell immune system was intact but other family members had low levels or absence of IgA. The possible relationship of dysgammaglobulinemia and vitiligo is discussed along with the classification and inheritance of the immune cell defects.