Studies on the epidemiology of common adverse cutaneous drug reactions have rarely been reported, since they can only be successfully conducted in clinics of internal medicine employing consultant dermatologists and having a comprehensive or intensive system of monitoring. Between 1974 and 1993, the adverse skin reactions occurring in divisions of general internal medicine of three different hospitals were monitored by a computerized comprehensive system. The "drug-monitoring patient" was defined as the recipient of at least one drug during hospitalization. The relationship of the skin reactions to drug causality in these patients had to be either definite (proven by re-exposure) or probable (drug relation greater than that of nondrug causality). The skin reactions were classified into four diagnostic groups. Maculopapular exanthema, urticaria, and vasculitis were the three main groups. The fourth group comprised cases of nonhomogeneous but clinically well-defined special exanthema. For selected drugs and years of observation, special emphasis was placed on the study of time patterns (reaction time, exposure time). A total of 1317 definite or probable drug-induced skin reactions occurred during the hospitalization of 48,005 consecutively admitted "drug-monitoring patients": 1201 cases of maculopapular exanthema, 78 cases of urticaria, 18 cases of cutaneous vasculitis, and 20 cases of special exanthema (five of erythema multiforme minor, six of fixed eruption, one of photosensitivity reaction, and eight of acneiform eruption). The main drugs involved did not differ for the three main types of skin reactions, penicillins ranking in the first place, followed by sulfonamides--most often combined with trimethoprim--and in the third place nonsteroidal anti-inflammatory drugs. The reaction time (time from last drug exposure to first skin manifestation) for urticaria showed a relevant proportion of the acute type (within 1 h) and most of the subacute type (1-24 h). For maculopapular exanthema, the subacute or, rarely, the latent type (1-8 days, exceptionally more than 8 days) predominated. For aminopenicillins, the rate of occurrence of skin reactions increased with increasing exposure time up to 12 days, and then markedly diminished. Possibly due to the tendency to withdraw suspected drugs even in the case of minor (e.g., maculopapular) skin reactions, no severe events such as erythema multiforme major/Stevens-Johnson syndrome or toxic epidermal necrolysis occurred.

All 5,047 consecutive inpatients admitted to the Internal Medicine Division of a teaching hospital (Zieglerspital, Berne) between 1982 and 1985 were registered in accordance with the CHDM (Comprehensive Hospital Drug Monitoring) questionnaire of adverse drug reactions (ADRs). Of them, 2,439 were treated with at least one potassium losing diuretic. The hospital records of the patients were reviewed with particular regard to serum potassium levels, and on the basis of this evaluation, the patients were assigned to four different diuretic treatment groups, and the incidence of hypokalaemia related to diuretic treatment was estimated. The overall rate of occurrence of hypokalaemia was 21.1% at a serum potassium level < 3.5 mmol.l-1, and 3.8% < 3.0 mmol.l-1. Hypokalaemia of less than 3.5 mml.l-1 developed 24.9% (217/870) of patients treated with potassium losing diuretics alone; in 19.7% (101/513) treated with potassium losing diuretics in conjunction with potassium substitution, in 15.1% (66/438) treated with a combination of diuretics (potassium losing with potassium sparing), and in 20.0% (12/60) treated with combined diuretics and potassium substitution. Only the differences between the first and the two subsequent groups were statistically significant. The overall incidence of hypokalaemia below 3.0 + mmol.l-1 was significantly lower in the patients on combined diuretics without potassium substitution than in the patients on potassium losing diuretics with potassium substitution. Oral or parenteral administration of glucocorticoids (prednisone 5 to 2,000 mg/d) was a significant risk factor for hypokalaemic events. beta 2-Adrenoceptor agonists had not effect. The patient's age, sex, renal function and numbers of drugs received were evaluated in a multivariate analysis, in order to take into account their influence on the risk of developing hypokalaemia. The number of drugs above 12 (and, less importantly, female sex) was the main risk factor for this ADR. The comparison between hypokalaemia and hyperkalaemia in this group of inpatients showed the significance of reduced renal function in the occurrence of hyperkalaemia.

The hospital prevalence rate for upper gastrointestinal ulcerative disease in 28,531 inpatients consecutively admitted in two teaching hospitals in the Comprehensive Hospital Drug Monitoring (CHDM) in Berne, from 1974 to 1985, was 2.2% (1.8% for gastric or duodenal ulcer, and 0.4% for erosive gastritis). This was based on the evaluation of 634 patients after exclusion of the subgroup of patients with hepatic cirrhosis or upper gastrointestinal neoplasia. After exclusion of patients on anticoagulant therapy (n = 73), 561 (= 100%) patients could be further studied. Of them, 33.3% (n = 187) were found to have been exposed to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, within 21 days prior to confirmation of the diagnosis. The observed relative risk (RR) of developing a substantial acute upper gastrointestinal bleeding (Hb less than 10 g/100 ml for men, and less than 9 g/100 ml for women, or a decrease in Hb of more than 25%) was 1.61 when patients exposed to NSAIDs (n = 187) were compared to patients not exposed to those drugs (n = 374). Although there was no significant sex difference overall, the RR for gastrointestinal bleeding differed considerably in the various age-groups; it was elevated in men under 40 years (RR = 2.86) and in women over 60 years of age (RR = 1.89), as compared to the mean RR of 1.61.