Serologic Evaluation of Patients Receiving Procainamide

Abstract

This controlled study examined the characteristics of serologic abnormalities in 52 patients receiving procainamide for cardiac arrhythmias, who had no symptoms of a connective tissue disease. Antinuclear antibodies occurred in 43 patients (83%). Significant elevation of antibody binding to single-stranded DNA (mean f SEM 30 f 2.6%), double-stranded DNA (13 f l.l%), Z-DNA (optical density 0.54 f 0.06), and p l y A (7.2 2 0.6%) was seen (P < 0.001). Thirty-four patients (65.4%) had antibodies to total histones, most frequently, the J42A/2B dmer. IgG antibodies to H2A/2B correlated with the cumulative procainamide dose. One patient subsequently developed drug-related lupus. Procainamide (PA) is the agent most commonly implicated in drug-related lupus (DRL), with DRL occurring in 30% of patients positive for fluorescent antinuclear antibody (FANA) who take PA. Many of the features of DRL are nonspecific, thus making diagnosis difficult. Autoantibodies have been proposed to be of value in the diagnosis of DRL and, possibly, in the identification of people at risk for the development of DRL (1). Antinuclear and antihistone antibodies (AHA) have been reported to be highly sensitive for DRL (1,2). However, there is little information regarding the prevalence, and type of serologic abnormalities in patients without symptoms of a connective tissue disease. We report here the results of our serologic evaluation of 52 such patients receiving long-term therapy with procainamide. PATIENTS AND METHODSPatients. Fifty-two patients receiving PA who were attending the outpatient departments of the Veterans Administration (VA) or University of Cincinnati (UC) hospitals were included. There were 50 males (39 Caucasian and 11 black) and 2 females (1 black and 1 Caucasian). Their mean age was 65.8 years (range 47-82). The average daily dose of PA was 3.0 gm (range 0.75-5 gm), and the mean duration of therapy was 40 months (range 1 month to 8 years). Patients with evidence of systemic lupus erythematosus (SLE) at the time of study entry were excluded. Reevaluation of all patients was attempted to determine if evidence of lupus subsequently developed. DRL was diagnosed if patients developed musculoskeletal or pleuropericardial features which resolved upon discontinuation of PA. All 52 of these patients are part of a prospective study (3).Controls. Three groups of control subjects were assessed. One was a group of elderly subjects who were preselected based on age. These were 33 Caucasian individuals who were taking no medications; 28 were men and 5

Drugs and autoimmunity – A contemporary review and mechanistic approach

“…Since then, this has been the prototype drug for drug-induced autoimmunity. Procainamide treatment for cardiac arrhythmias in 52 patients, who had no previous evidence of lupus or connective tissue disease, was associated with the formation of anti-nuclear antibodies in 43/52 of these patients [6]. Autoantibodies to histones were present in 34/ 52 patients, with the most commonly detected target being the H2A.…”

Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor α: Findings in open-label and randomized placebo-controlled trials

“…Drugs such as hydralazine, procainamide, penicillamine, and sulfasalazine have been implicated in the induction of a syndrome that resembles systemic lupus erythematosus (SLE), as well as the induction of lupusrelated autoantibodies without clinical symptoms (1)(2)(3). Since the advent of biologic therapy, there has also been a report of patients developing a lupus-like syndrome or lupus-associated antibodies following treatment with interferon-␥ (IFN␥) and IFN␣ (4)(5)(6).…”

Are There Environmental Forms of Systemic Autoimmune Diseases?

“…With different drugs, there appears to be a broad array of autoantigenic epitopes to the individual histone and histone complexes. Recent work suggests that a switch from IgM to IgG isotype may precede the development of lupuslike syndromes, particularly in patients taking procainamide (5 It is appropriate to make some specific comments relative to some drugs and biologic agents. Minocycline hydrochloride, a (6) and to the present time, an additional 76 cases have been published.…”