Lupus syndrome, hydralazine-induced

The rate of drug metabolism, which is in part under genetic control, may be of importance. The population with low levels of hepatic acetyltransferase activity seems at greater risk of developing the hydralazine-induced lupus syndrome (Perry et al. 1970), but this does not hold for procainamide-induced lupus. Genetic factors have also been implied in pseudoallergic reactions, such as aspirin intolerance (Lockey et al. 1963). 

There is an increase in the incidence of hydralazine-induced lupus erythematosus (LE) in the exposed population with increasing dose as can be seen in Table 7.9. However, patients who develop LE do not have a significantly different cumulative intake of hydralazine from those patients who do not develop the syndrome. This latter observation is consistent with the absence of a clear dose-response relationship in many cases of toxicity with an immunological basis. 

A particularly good example of a drug inducing SLE is the vasodilator hydralazine, sometimes used for the treatment of hypertension. The drug-induced lupus syndrome... 

C4b2b bound to immune complexes prevents their precipitation and promotes immune complex clearance by the CRa receptor, especially if the C4 is the C4B isotype (see discussion later in this chapter). The binding of C4A to drugs such as procainamide and hydralazine interferes with clearance of immune complexes this may be important in the etiology of drug-induced lupus syndromes. 

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... 

Other adverse effects are caused by immunological reactions, of which the drug-induced lupus syndrome is the most common. Hydralazine also can result in an illness that resembles serum sickness, hemolytic anemia, vasculitis, and rapidly progressive glomerulonephritis the mechanism of these autoimmune reactions is unknown. The drug-induced lupus syndrome usually occurs after at least 6 months of continuous treatment with hydralazine, and its incidence is related to dose, sex,... 

Differences in acetylation rates have also been shown to occur with procainamide, but unlike hydralazine, the conclusion is less clear. Henningsen et al. (1975) carried out a prospective study of 42 patients on long-term procainamide treatment they were able to show that 12 patients (29%) developed a classic drug-induced lupus syndrome. The acetylation status was determined on 11 of these 12 patients, 8 proved to be slow and 3 fast acetylation. The authors concluded that... 

Cameron HA, Ramsay LE. The lupus syndrome induced by hydralazine a common complication with low dose therapy. Brit Med J 1984 289 410-412. 

One side effect unique to hydralazine is a dose-dependent drug-induced lupus-like syndrome. Hydralazine is eliminated by hepatic A-acetyltransferase. This enzyme displays genetic polymorphism, and slow acetylators are especially prone to develop drug-induced lupus with hydralazine. This syndrome is more common in women and is reversible on discontinuation. Drug-induced lupus may be avoided by using less than 200 mg hydralazine daily. Other side effects of hydralazine include dermatitis, drug fever, peripheral neuropathy, hepatitis, and vascular headaches. For these reasons, hydralazine has limited usefulness in the treatment of hypertension. However, it is still used with isosorbide dinitrate in patients with heart failure (especially African-Americans) and is useful in patients with severe chronic kidney disease and kidney failure. 

Since the original reports by Perry and Schroder (1954) and Dunstan et al. (1954) describing a lupus-like syndrome inducible with hydralazine, and by Ladd (1962) with procainamide, much attention has been paid to the relationship of drug-induced lupus with the established clinical entity - systemic lupus erythematosus. 

Hahn et al. (1972) examined four patients with hydralazine lupus and found drug-specific antibodies in them all. Moreover, demonstration of the antibody correlated with the lupus syndrome, as patients treated with hydralazine, but with no clinical signs of lupus, did not have detectable hydralazine antibodies. The finding that hydralazine induces drug-specific antibodies only in association with the active lupus syndrome may not be a true reflection of its immunogenic potential. 

Urinary tract Hydralazine has been associated with ANCA positive pauci-immune glomerulonephritis and pulmonary alveolar hemorrhage [105 ]. In this case anti-double-stranded DNA and antihistone antibodies were present in the absence of full classification criteria for drug-induced lupus-like syndrome. The symptoms and renal function improved after withdrawal of hydralazine and a short course of cyclophosphamide and prednisone. 

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... 

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