Drug-related lupus.

All physicians should be alerted to the many drugs and other agents that are associated with drug-related lupus, as there is an increasing number of such drugs. A wide range of immune responses and antibodies are being reported with this syndrome. A new concern is the perceived ability of new biologic treatments to induce these autoimmune phenomena. More in-depth studies of various environmental factors are providing new insights into possible mechanisms. These include the immune responses to the drugs, their metabolites, and drug-altered conjugates; bioactivation mechanisms of drug protein conjugation; the role of macrophages in antigen recognition and processing; and lastly, the important role of the acetylation of various drugs and the relationship to immunogenetic factors. Continued study of this human experimental model of lupus will help to clarify the etiology and mechanisms of systemic lupus erythematosus itself.     

Drug-related lupus. Clinical and etiologic considerations

Drug-related lupus (DRL) was first described in 1945 in association with sulfadiazine. Since that time, more than 50 medications have been implicated in this syndrome and its associated laboratory abnormalities. Several mechanisms for these findings have been postulated, but no one mechanism has been established as pre-eminent. The clinical spectrum, when it does occur, is characterized by polyserositis: arthritis, pleuritis, pericarditis, and peritonitis. Many of the well-known features of SLE are rarely, if ever, seen in DRL.     

Drug-related lupus in a patient with rheumatoid arthritis under sulfasalazine treatment

Summary The induction of lupus-like syndromes with the appearance of single-stranded DNA antibodies is a well-known complication of drug therapy. In this report we present a patient with an erosive seropositive rheumatoid arthritis developing the clinical and serological features of systemic lupus erythematosus including the occurrence of double-stranded DNA antibodies under sulfasalazine treatment.     

Drug-related syncope

The records of 483 patients admitted to the emergency room because of syncope were reviewed. Forty-one patients were found to have drug-related syncope. Thirty-nine experienced syncope related to drugs administered for cardiovascular disease. The most frequently associated diseases were anginal syndrome (22 patients), hypertension (13 patients), and a history of myocardial infarction (6 patients). Thirty-eight patients experienced symptomatic orthostatic hypotension following drug taking (nitrates in 19 patients, beta blockers in 10 patients, nifedipine in 3 patients, prazosin and quinidine in 2 patients each, methyldopa and verapamil in 1 patient each). One patient developed complete heart block as a result of digoxin intoxication. Two patients developed the characteristic picture of anaphylactic reaction (1 with ampicillin, 1 with dipyrone). During one-year follow-up, without the offending medications, no further syncopal episodes were reported by these patients. We conclude that drug-related syncope was more common among our patients with syncope than had been reported previously. It is suggested that drug-related syncope should be taken into consideration in any patient with syncope who is treated by any of the above-mentioned drugs.     

Drug-related suicide: a DAWN profile.

Drug-related suicides and suicide attempts/gestures account for a relatively large percentage of the drug-involved cases seen by hospital emergency rooms and medical examiners. While tranquilizer involvement characterizes the largest subgroup of suicide cases in the emergency room, barbiturate involvement is most frequently true of suicide cases seen by medical examiners. However, in both settings the suicides tend to be older and to include relatively more females and fewer Blacks than the nonsuicides.     

Drug-related recurrent meningitis

A 56-year-old man presented with recurrent smear and culture-negative meningitis having ingested Ibuprofen before each episode. The association between Ibuprofen and meningitis has been well established in systemic lupus erythematosus but has been reported only rarely in previously healthy patients.     

Drug-related pleural and mediastinal disorders

The full range of mediastinal and pleural toxic effects of various drugs is reviewed. The importance of clinical information in suggesting the diagnosis of drug-induced disorders is emphasized. A separate section on the pleural and mediastinal toxic effects of illicit drugs is included.     

Drug-related disorders of water and electrolyte metabolism

Pharmacologic treatment may lead to diverse disturbances of water and electrolyte metabolism as adverse drug events. Diuretics are particularly likely to cause these complications typically including volume depletion, metabolic alkalosis, hyponatremia, and hypokalemia. Salt and water retention with edema formation is most frequently elicited by antihypertensives, steroid hormones, and nonsteroidal anti-inflammatory drugs. Drug-induced disorders of Na+ concentration may usually be attributed to altered antidiuretic hormone (ADH) effects, either as diabetes insipidus or as the syndrome of inappropriate ADH secretion. With hyper- and hypokalemia, redistribution between intra- and extracellular fluid as well as renal excretion play a role. Strategies to prevent these adverse drug reactions include careful consideration of risk factors and clinical and laboratory controls in the course of treatment.     

Drug-related arrhythmias during therapy of congestive heart failure

Summary It is now recognized that ventricular and supraventricular arrhythmias are serious complications of congestive heart failure. There are four possible drug-related mechanisms: diuretic-induced electrolyte imbalance; digitalis-induced arrhythmias; use of sympathomimetic agents; and drug interactions with digoxin. In selecting optimal therapy for congestive heart failure all these drug interactions need to be borne in mind.