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Biomedical subjects

R S Stern

Publications and source records attributed to R S Stern.

At least 19 recordsLinked to original sources

Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.

BACKGROUND: Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare, life-threatening, drug-induced cutaneous reactions. We conducted a case-control study to quantify the risks associated with the use of specific drugs. METHODS: Data were obtained through surveillance networks in France, Germany, Italy, and Portugal. Drug use before the onset of disease was compared in 245 people who were hospitalized because of toxic epidermal necrolysis or Stevens-Johnson syndrome and 1147 patients hospitalized for other reasons (controls). Crude relative risks were calculated and adjusted for confounding by multivariate methods when numbers were large enough. RESULTS: Among drugs usually used for short periods, the risks were increased for trimethoprim-sulfamethoxazole and other sulfonamide antibiotics (crude relative risk, 172; 95 percent confidence interval, 75 to 396), chlormezanone (crude relative risk, 62; 21 to 188), aminopenicillins (multivariate relative risk, 6.7; 2.5 to 18), quinolones (multivariate relative risk, 10; 2.6 to 38), and cephalosporins (multivariate relative risk, 14; 3.2 to 59). For acetaminophen, the multivariate relative risk was 0.6 (95 percent confidence interval, 0.2 to 1.3) in France but 9.3 (3.9 to 22) in the other countries. Among drugs usually used for months or years, the increased risk was confined largely to the first two months of treatment, when crude relative risks were as follows: carbamazepine, 90 (95 percent confidence interval, 19 to infinity); phenobarbital, 45 (19 to 108); phenytoin, 53 (11 to infinity); valproic acid, 25 (4.3 to infinity); oxicam nonsteroidal antiinflammatory drugs (NSAIDs), 72 (25 to 209); allopurinol, 52 (16 to 167); and corticosteroids, 54 (23 to 124). For many drugs, including thiazide diuretics and oral hypoglycemic agents, there was no significant increase in risk. CONCLUSIONS: The use of antibacterial sulfonamides, anticonvulsant agents, oxicam NSAIDs, allopurinol, chlormezanone, and corticosteroids is associated with large increases in the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. But for none of the drugs does the excess risk exceed five cases per million users per week.

Adrenal Cortex Hormones

The safety of etretinate as long-term therapy for psoriasis: results of the etretinate follow-up study.

BACKGROUND: Etretinate is an aromatic retinoid given orally to treat severe psoriasis, a chronic disease that often requires long-term therapy. OBJECTIVE: We assessed the safety of long-term therapy with etretinate for psoriasis. METHODS: This 5-year prospective study of a cohort of 956 patients with psoriasis treated with etretinate assessed the frequency of adverse events in relation to total use and in relation to the frequency of these events in control populations. RESULTS: Our data do not provide evidence for an increased risk of cardiovascular disease, cancer, diabetes, or inflammatory bowel disease in association with long-term etretinate use. Although some patients reported that joint problems improved with the use of etretinate, a greater number associated the use of etretinate with joint problems. CONCLUSION: With proper patient selection and monitoring, long-term etretinate therapy (up to 4 years) does not appear to be accompanied by a substantial increased risk of major adverse effects.

Adult

Photosensitivity associated with combined UV-B and calcipotriene therapy.

BACKGROUND: Ultraviolet B phototherapy is an effective agent for the treatment of psoriasis; its most frequent acute side effect is burning of the skin. It has been combined with various other topical or systemic agents to augment therapeutic effect. Recently, UV-B therapy has been used with calcipotriene ointment (Dovonex, Westwood-Squibb, Buffalo, NY), a new vitamin D analogue. OBSERVATIONS: We report four cases of chronic plaque psoriasis that developed in patients who used UV-B phototherapy for a substantial period without ill effects and in whom photosensitivity reactions within psoriatic plaques developed after calcipotriene ointment was added, without changes in their UV-B dosage or frequency of treatment. The time from starting calcipotriene therapy to the development of photosensitivity ranged from 4 to 28 days, and the number of UV-B exposures during this period varied between one and 12 treatments. The mean UV-B dose at burning was 1114mJ/cm2. Twenty-two patients had used calcipotriene in combination with UV-B therapy of a total of 103 UV-B-treated patients during the period when the adverse events occurred. Half these patients started calcipotriene therapy prior to starting treatment with UV-B. However, cases of photosensitivity occurred only in the remaining half of the patients in whom calcipotriene therapy was added during UV-B therapy. Combined therapy was able to be continued or resumed in two patients by reduction of the UV-B dose. In three cases, phototesting, confirmed greater photosensitivity to calcipotriene-treated skin than to skin to which hydrated petrolatum was applied. CONCLUSIONS: Calcipotriene ointment should be introduced with caution in patients already receiving UV-B phototherapy, particularly those receiving high doses of UV-B. The mechanism of this photosensitivity reaction is unknown. This increased sensitivity to UV-B may be a result of the effect of calcipotriene on stratum corneum thickness, epidermal melanization, a result of its effect on the inflammatory reaction to UV-B irradiation, or, possibly, because it is a phototoxic agent.

Adult

Epidemiology of adverse cutaneous reactions to drugs.

Adverse cutaneous reactions to drugs are among the most frequent adverse reactions to many systemically administered therapeutic agents. In addition to these reactions resulting in discontinuation of drugs important to a patient's treatment, some adverse cutaneous reactions to drugs may result in substantial morbidity or even death. The early recognition of these clinically important reactions is made on clinical grounds. Epidemiologic data do suggest, however, that a relatively small number of drugs are responsible most often for these most serious reactions.

Drug Eruptions

Lack of efficacy of phenytoin in recessive dystrophic epidermolysis bullosa. Epidermolysis Bullosa Study Group.

BACKGROUND: Recessive dystrophic epidermolysis bullosa is an uncommon, severely disabling, heritable disorder characterized by abnormal fragility of the skin. Open trials have suggested that phenytoin is an effective treatment, and this therapy is now widely used. METHODS: To determine the efficacy of phenytoin in the treatment of recessive dystrophic epidermolysis bullosa, we performed a randomized, double-blind, placebo-controlled, crossover trial in 36 patients. Each treatment was given for five to seven months, separated by a two-month period. We measured the total number of blisters and erosions on the entire body, the size of three plaques containing blisters and erosions, and the number of blisters and erosions in the three plaques at the beginning and end of each treatment period in each patient. RESULTS: Twenty-two patients completed both courses of therapy, seven patients completed one course, and seven patients withdrew before completing a single course. There was no significant difference in disease activity between phenytoin treatment and placebo treatment, as measured by changes in the number of blisters and erosions on the entire body (7 percent decrease vs. 6 percent increase), in the area of three designated plaques (0.4 percent decrease vs. 0.2 percent increase), or in the number of blisters and erosions in the designated plaques (12 percent decrease vs. 31 percent increase). CONCLUSIONS: Phenytoin is not an effective treatment for patients with recessive dystrophic epidermolysis bullosa.

Adolescent

Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. Skin Cancer Prevention Study Group.

OBJECTIVE: The primary aims of this study were to assess risk of subsequent basal and squamous cell skin cancer among patients with a prior history of these tumors and to examine these risks in relation to patient characteristics and life-style factors. DESIGN: Follow-up of participants in a randomized trial of betacarotene as a possible skin cancer preventive agent. SETTING: Clinical centers in Los Angeles, Calif, San Francisco, Calif, Minneapolis, Minn, and Hanover, NH. PARTICIPANTS: Patients (n = 1805) who were diagnosed as having a basal or squamous cell skin cancer between January 1980 and February 1986 and were free of skin cancer at study entry. MAIN OUTCOME MEASURE: Time from study entry to first new occurrence of basal and squamous cell skin cancer. RESULTS: The estimated risk of developing one or more new skin cancers was 35% at 3 years and 50% at 5 years. New skin cancers tended to be of the same cell type as the previous skin cancers. For both basal and squamous cell skin cancer, risk was higher among patients who were male, were over the age of 60 years, had more prior skin cancers, had severe actinic skin damage, or who burned easily with sun exposure. Compared with those who had never smoked, the rate of subsequent squamous cell skin cancer was higher among current smokers (rate ratio, 2.01; 95% confidence interval, 1.21 to 3.34) and former smokers (rate ratio, 1.62; 95% confidence interval, 1.07 to 2.47) and increased with both duration and amount smoked. There was no clear relationship between smoking and basal cell skin cancer; the rate appeared lower among heavy smokers but was unrelated to duration of smoking. CONCLUSIONS: Persons with a prior nonmelanoma skin cancer had a substantial 5-year risk of developing another tumor of the same histologic type. Number of previous skin cancers, solar damage, and skin sensitivity to sun exposure were particularly related to this risk. The increased risk of squamous cell skin cancer associated with cigarette smoking merits further study.

Adult

Epidemiology of isotretinoin exposure during pregnancy.

BACKGROUND: Exposure to isotretinoin during pregnancy is associated with a high risk of major fetal malformations. OBJECTIVE: Our purpose was to determine the reasons for and outcomes of in utero isotretinoin exposure. METHODS: On the basis of 433 spontaneous reports, we describe the likely reasons these exposures occurred and the outcomes of these pregnancies. In our analysis of the outcomes of pregnancy, we separately consider the pregnancies known to us before their outcomes were determined as prospective cases. RESULTS: Timing of conception in relation to initiation of therapy with isotretinoin was known for 396 women. Of these, 130 patients (33%) were already pregnant when they started isotretinoin. An additional 65 patients (16%) became pregnant in the first 3 weeks of isotretinoin use. Pregnancy outcomes were known on 409 pregnancies. Among these, 222 (54%) ended in elective abortion and 29 (7%) in spontaneous or missed abortion. Of 151 births, 72 (48%) were normal, 71 (47%) had congenital malformations, and 8 (5%) had abnormalities other than malformations. Of 94 prospectively ascertained pregnancies that ended in births, 28% had congenital malformations (95% confidence interval 19% to 37%). Exposure to isotretinoin during any time and for as little as one capsule within the first trimester have been associated with congenital malformations. CONCLUSION: The high proportion of exposures in already or recently pregnant women illustrates the importance of obtaining a negative pregnancy test before the initiation of isotretinoin therapy and of delaying the commencement of isotretinoin therapy until the onset of the next menstrual period. Furthermore, the importance of reliable contraceptive methods should be emphasized to patients when isotretinoin is prescribed. Young women seem to be at an especially high risk of pregnancy exposure to isotretinoin. There is a substantial risk of congenital malformation at all therapeutic doses of isotretinoin, even when the duration of exposure is brief.

Abnormalities, Drug-Induced

The prevalence of acne on the basis of physical examination.

BACKGROUND: It has been suggested that cystic acne is rare in women 15 to 44 years of age and infrequent in men. OBJECTIVE: To determine the prevalence of acne, we analyzed the primary data from the National Health and Nutrition Examination Survey (NHANES) that included a cutaneous examination of a stratified random sample of 20,749 noninstitutionalized U.S. residents. METHODS: We calculated the prevalence of various disease states based on NHANES primary data and the NHANES population weights. Prevalence estimates and male/female ratios of these estimates were calculated. RESULTS: From 1971 to 1974, the projected prevalence of acne conglobata (grade IV acne) for women and men 15 to 44 years of age in the United States was 250,000 and 570,000, respectively. At the time of examination, an additional 582,000 women and 749,000 men were projected to have moderate acne with cysts and scars. Therefore the prevalence of acne conglobata and acne of at least a moderate degree with cysts and scars was 832,000 for women and 1,319,000 for men 15 to 44 years of age. The male/female ratio for acne with cysts and scars is approximately 1.6:1. CONCLUSION: The NHANES examination data demonstrate that acne with cysts and scars is common in both men and women.

Acne Vulgaris

Risks of cancer associated with long-term exposure to PUVA in humans: current status--1991.

Since 1975 oral 8-methoxypsoralen administered in association with ultraviolet-A radiation (UVA), (PUVA) has been widely used to treat psoriasis and other cutaneous diseases. PUVA is mutagenic, and in animals carcinogenic. Prospective study of a cohort of patients with psoriasis who were first treated with PUVA in 1975-1976 has provided data on the carcinogenic risk of this treatment. There is a dose-dependent increase in the risk of squamous cell cancer of the skin associated with exposure to PUVA. A recent large-scale Swedish study confirmed this association. The risk of squamous cell cancer of the genitals of males exposed to high doses of PUVA is especially high. A consistent, confirmed, and significant relationship of exposure to PUVA to other types of malignancies in man has not been established. Although highly effective in the treatment of psoriasis, the risk of squamous cell cancer associated with long-term therapy with PUVA must be considered in determining when this therapy is appropriate for an individual patient. Additional study of PUVA-treated patients will better define the full spectrum of the carcinogenic risk of PUVA therapy and the clinical behavior of tumors that arise in association with this treatment.

Carcinoma in Situ

Diagnostic accuracy and appropriateness of care for seborrheic keratoses. A pilot study of an approach to quality assurance for cutaneous surgery.

In 1985 there were more than 40 million visits for ambulatory surgical procedures in the United States. Although benign cutaneous lesions are among the most frequent conditions to receive surgical treatment in ambulatory settings, their treatment is seldom subject to peer review. In this pilot study we assessed diagnostic accuracy and appropriateness of care using information available from the surgical pathology laboratory. We assessed these two measures of physician performance for 527 seborrheic keratoses removed by 133 clinicians affiliated with four different institutions. Overall, a correct preoperative diagnosis was provided in only 49% of cases. Dermatologists had the highest diagnostic accuracy (61% vs 35% for all other physicians). An appropriate procedure for the actual pathological diagnosis was performed in only 50% of cases. Lesions with a correct preoperative diagnosis were more than eight times more likely to receive appropriate care. Our data suggest that many clinicians fail to note a correct diagnosis of common cutaneous lesions before surgical removal, and many patients are treated with procedures that are more invasive than necessary for the final pathological diagnosis. Because the approach used in this pilot study relies on data already available, it has promise as a low-cost method of monitoring the quality of care of ambulatory surgery.

Adult

Psychological aspects of 211 female patients attending a urodynamic unit.

Psychological aspects of 211 female patients attending a Urodynamic Unit were assessed by means of standardized questionnaires. Patients with genuine stress incontinence (GSI) showed changes comparable to other patients with longstanding physical complaints. Patients with sensory urgency (SU) lacked self esteem and were more anxious than those with GSI. Patients with detrusor instability (DI) were as anxious and lacking in self esteem as patients with sensory urgency and additionally had morbid thoughts and worries and higher scores on the hysteria sub-scale of the Crown-Crisp Experiential Index. Roughly a quarter of all the patients reported that their urinary symptoms rendered life intolerable and they were as anxious, depressed and phobic as psychiatric inpatients.

Adolescent

Outcomes of pregnancies among women and partners of men with a history of exposure to methoxsalen photochemotherapy (PUVA) for the treatment of psoriasis.

Because oral methoxsalen and UV-A radiation (PUVA) therapy is mutagenic, concern exists about the potential for teratogenic effects resulting from the use of this therapy at the time of conception and during pregnancy. After 12.8 years of prospective study, we documented the pregnancy outcomes among 1380 patients (892 men and 488 women) who received PUVA treatments. Ninety-four men reported 167 pregnancies in their partners, and 93 women reported 159 pregnancies. For 34% of pregnancies among partners of male patients, the man received PUVA therapy near the time of conception. Nineteen percent of female patients reported exposure to PUVA at the time of conception or during pregnancy. Induced and spontaneous abortions were reported as the outcome of pregnancy more often by female than by male patients (12% vs 30%). Two congenital malformations and two stillbirths occurred, an incidence not significantly different from that expected for the general population. Although the power of our study to detect an increase in the risk of specific defects is limited, our data show no evidence to suggest that PUVA is a potent teratogen. Still, because PUVA is mutagenic, we believe it prudent for patients to avoid PUVA treatment during pregnancy whenever practical.

Abortion, Induced

Magnitude and duration of UV-B-induced tolerance.

Using repeated minimal erythema dose (MED) testing, we investigated the magnitude and duration of tolerance to short-wave UV radiation in the B range (UV-B) in 37 patients with psoriasis who received at least 12 UV-B phototherapy treatments. Without substantial erythema developing, half of the patients received UV-B doses in excess of 13 times their pretreatment MED dose and a fourth received UV-B doses in excess of 28 times their pretreatment MED dose. On average, tolerance faded to about half that present at the last UV-B treatment in 3 weeks. Six weeks after therapy was stopped, most posttreatment MEDs were less than twice the pretreatment MED. The magnitude of tolerance achieved and the rate of decay did not vary with skin type. Our findings indicate that repeated exposures to suberythemal or mildly erythematous doses of UV-B can induce exceptional degrees of tolerance to UV-B radiation. The duration of this increase in tolerance is, however, short.

Adult

Genital tumors among men with psoriasis exposed to psoralens and ultraviolet A radiation (PUVA) and ultraviolet B radiation. The Photochemotherapy Follow-up Study.

Squamous-cell cancer occurs only rarely on the male genitalia. In a 12.3-year prospective study of 892 men in a cohort of patients with psoriasis who had been treated with oral methoxsalen (8-methoxypsoralen) and ultraviolet A photochemotherapy (PUVA), we identified 14 patients (1.6 percent) with 30 genital neoplasms. The standard morbidity ratio (which was used as a measure of the risk of a genital neoplasm) comparing morbidity among patients treated with PUVA with that expected on the basis of population incidence data was 95.7 (95 percent confidence interval, 43.8 to 181.8) for invasive squamous-cell carcinoma of the penis and scrotum, and 58.8 (26.9 to 111.7) for invasive and in situ penile tumors. In patients exposed to high levels of PUVA, the incidence of invasive squamous-cell carcinoma was 286 times that in the general population and 16.3 times that in patients exposed to low levels (P less than 0.001 for both comparisons). After controlling for the level of exposure to PUVA, we found that patients exposed to high levels of ultraviolet B radiation had a risk of genital tumors 4.6 times higher than that in other patients (95 percent confidence interval, 1.4 to 15.1). The strongly dose-dependent increase in the risk of genital tumors associated with exposure to PUVA and ultraviolet B radiation that we observed makes it prudent for men to use genital protection whenever they are exposed to PUVA or other forms of ultraviolet radiation for therapeutic, recreational, or cosmetic reasons.

Adult