Procainamide lupus erythematosus

Procainamide Systemic lupus erythematosus, diarrhea, nausea, vomiting, TdP, aggravation of underlying HF, conduction disturbances or ventricular arrhythmias, agranulocytosis... 

The prolonged administration often leads to the development of a positive antinuclear antibody (ANA) test, with or without symptoms of a lupus erythematosus-like syndrome. If a positive ANA titer develops, assess the benefit/risk ratio related to continued procainamide therapy. 

Long-term drug use leads to increased antinuclear antibody titers in more than 80% of patients more than 30% of patients receiving long-term procainamide therapy develop a clinical lupus erythematosus-like syndrome. The symptoms may disappear within a few days of cessation of procainamide therapy, although the tests for antinuclear factor and lupus erythematosus cells may remain positive for several months. 

Certain autoimmune syndromes can be induced by drugs. Examples include systemic lupus erythematosus following hydralazine or procainamide therapy, "lupoid hepatitis" due to cathartic sensitivity, autoimmune hemolytic anemia resulting from methyldopa administration, thrombocytopenic purpura due to quinidine, and agranulocytosis due to a variety of drugs. As indicated in other... 

Certain collagen-like diseases are caused by hypersensitivity reactions to drugs. Hydralazine, and particularly procainamide, may produce a clinical picture similar to systemic lupus erythematosus (43). A number of cases of polyarteritis nodosa have developed during treatment with guanethidine and after repeated exposure to the sulfonamides, penicillin, and iodides (44). Nephropathy has been reported following high doses of methicillin and benzylpenicillin (45). 

Hydralazine has been in use since the 1950s and is usually used in combination with other drugs such as diuretics and P-blockers. In a significant number of patients, and typically after 18 months, adverse effects started to appear. These included joint and muscle pain (arthralgia and myalgia), a rash on the face and inflamed blood vessels (vasculitis). The rash on the face made afflicted patients look wolf-like, which gave rise to the name for the syndrome. Lupus erythematosus (Lupus is Latin for wolf). This disease can be caused by other drugs, such as isoniazid very occasionally and procainamide more frequently. It may also have other, unknown, causes and has some similarities with rheumatoid arthritis. 

More than 80 drugs have been associated with drug-induced lupus erythematosus, including procainamide, hydralazine, isoniazid, and minocycline (Box 35-7). 

Collagen diseases (type II) and syndromes resembling them, e.g. systemic lupus erythematosus are sometimes caused by drugs, e.g. hydralazine, procainamide, isoniazid, sulphonamides. Adrenal steroid is useful. 

T e III reactions are mimicked by nitrofurantoin (pneumonitis) and penicillamine (nephropathy). Lupus erythematosus due to drugs (procainamide, isoniazid, phenytoin) may be pseudoallergic. 

Lupus erythematosus e.g. hydralazine, isoniazid, procainamide, phenytoin, oral contraceptives, sulfazaline. 

Drug-induced lupus erythematosus, caused by hydralazine, procainamide, sulfasalazine. 

Acetyl transferease NAT2 Slow, rapid acetylators Isoniazid Sulfamethazine Procainamide Sufasalazine Paraminosalicylic acid Hydralazine Toxic neuritis, lupus erythematosus. (Slow acetylators)... 

Kushner W, Jones C, Schmid FR, Askenazi J. Remission of procainamide-induced lupus erythematosus with N-acetylprocainamide therapy. Ann Intern Med 1979 90(5) 799-801. 

Procainamide is one of the common causes of drug-induced lupus-like sjmdrome (41), which is contrasted with idiopathic lupus erythematosus in Table 1. 

Agudelo CA, Wise CM, Lyles MF. Pure red cell aplasia in procainamide induced systemic lupus erythematosus. Report and review of the literature. J Rheumatol 1988 15(9) 1431-2. 

Sherertz EF. Lichen planus following procainamide-induced lupus erythematosus. Cutis 1988 42(l) 51-3. 

Quinidine may be associated with a syndrome called cinchonism, which is characterized by headache, vertigo, and tinnitus. Procainamide may result in hypotension or a reversible syndrome similar to lupus erythematosus. Patients may develop positive antinuclear antibody (ANA) titers and complain of rash, arthralgia, and arthritis. Disopyramide is poorly tolerated due to its anticholinergic effects (urinary retention, dry mouth, blurred vision), and its use should be avoided in patients with congestive heart failure (CHF) due to negative inotropic effects. 

Procainamide is used in veterinary practice as an antiarrhythmic. Clinical effects seen in animals are similar to those seen in humans and include arrythmias, gastrointestinal complaints, and systemic lupus erythematosus-like syndrome. 

Procainamide may induce a syndrome similar to systemic lupus erythematosus. This syndrome consists of arthralgias, myalgias, pleurisy, rash, fever, and elevated nuclear antibodies. Patients who are slow acetylators are at increased risk for developing this syndrome. While some studies have reported that less than one in 500 on chronic procainamide therapy developed this syndrome, others have reported this syndrome in up to 30% of patients on long-term therapy. Other side effects with chronic use include development of neutropenia, thrombocytopenia, hemolytic anemia, agranulocytosis, liver failure, a myasthenia-like syndrome, and psychosis with hallucinations. 

Symptoms of intoxication include (1) bradycardia, (2) prolongation of the QRS interval, (3) atrioventricular block, and (4) induced arrhythmias. These symptoms occur at blood concentrations of procainamide and NAPA exceeding 30[ig/mL. Hypotension sometimes encountered in procainamide therapy is not related to excessive plasma concentration. The development of systemic lupus erythematosus associated with procainamide therapy is not related to plasma concentration but is associated with the acetyla-tor status of the patient slow acetylators predominate in the group in whom the syndrome develops. 

Glomerulonephritis is one of the most serious complications of systemic lupus erythematosus (SLE) and accounts for much of the morbidity and mortality of patients afflicted with the disease. The renal manifestations of lupus nephritis are variable and encompass a wide spectrum of histopathologic lesions. ° ° The underlying histopathology is associated with different prognoses and responses to therapy, which cannot be predicted solely based on clinical manifestations. A renal biopsy is therefore required to assess the severity of the disease and to predict the short-term and long-term outcomes associated with therapy. Drugs, such as hydralazine and procainamide, are known to precipitate a lupus syndrome however, they are unlikely to cause disease that affects the kidney. 

Acetylation genotypic variations (fast and slow). Drug-induced systemic lupus erythematosus (SLE) by slow acetylators with hydralazine > procainamide > isoniazid (INH). 

Certain drugs, such as hydralazine, procainamide, isoniazid, chlorpromazine, and minocycline, can provoke lupus-like manifestations (D Cruz, 2000). Clear differences between systemic lupus erythematosus and lupus syndrome can be identified — hence the recommended different terminology. Typical clinical features of the drug-induced lupus syndrome include arthralgias, arthritis, rash, and... 

A recently suggested mode of action of the induction of immune responsiveness as a result of drug exposure also involves interference with central tolerance induction in the thymus. It has been demonstrated that intrathymic injection of procainamide-hydroxyl-amine, a metabolite of procainamide, alters positive selection and results in systemic lupus erythematosus-like changes (appearance of antibodies to a histone [H2A-H2BJ-DNA complex) in C57BL/6 mice (Kretz-Rommel et al., 1997 Rubin Kretz-Rommel, 2001). 

Dubois EL Strain L (1972) Failure of procainamide to induce a systemic lupus erythematosus-like disease in animals. Toxicol Appl Pharmacol, 21(2) 253-259. 

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