Systemic lupus erythematosus hydralazine

This leaves hydralazine as the only drug of this kind available to date on the U.S. market for chronic use. The total picture of the mechanism of action of hydralazine is still not clearly defined but there is general agreement that direct relaxation of the vasculature leading to reduced peripheral resistance is the principal component of its mechanism of action. This drug has stood the test of time despite such side effects as headache, tachycardia and a syndrome which resembles acute systemic lupus erythematosus, often called "hydralazine syndrome" (1). 

Lupus erythematosus Hydralazine may produce a clinical picture simulating systemic lupus erythematosus including glomerulonephritis. Symptoms usually regress when the drug is discontinued, but residual effects have been detected years later. Long-term treatment with steroids may be necessary. 

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... 

The drug hydralazine is a vasodilator used for the treatment of hypertension. In a significant proportion of individuals, it causes a serious adverse effect, drug-induced systemic lupus erythematosus (SLE). This is a systemic kind of toxic effect, as there is no particular target organ or tissue. It is an example of immune-media ted toxicity that involves autoimmunity and shows a number of interesting features. 

Table 7.9 Incidence of Hydralazine-Induced Systemic Lupus Erythematosus...

Perry HM. Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis. 

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). 

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. 

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... 

Speirs C, Fielder AH, Chapel H, Davey NJ, Batchelor JR (1989) Complement system protein C4 and susceptibility to hydralazine-induced systemic lupus erythematosus. Lancet, 1(8644) 922-924. 

TABLE 7.7 Incidence of hydralazine-induced systemic lupus erythematosus... 

Hydralazine. Vasodilator drug which causes systemic lupus erythematosus in a significant proportion of patients. Several predisposing factors have been identified dose (>25 mg) duration of therapy (mean 18 months) acetylator phenotype (slow) HLA type (DR4) gender (females males, 4 1). Antinuclear antibodies and antihydralazine antibodies detected in serum. Causes a Type III immune reaction. Mechanism is unclear but may involve reaction of parent drug or metabolite with protein. Interference with the complement system and interaction with nucleic acids also occur. Metabolism also may be mediated by myeloperoxidase in activated neutrophils. 

PERRY, H.M. (1973) Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis. Am. J.Med., 54, 58. 

First-pass acetylation in the Gl mucosa and liver is related to genetic acetylator phenotype (8). Acetylation phenotype is an important determinant of the plasma concentrations of hydralazine when the same dose of hydralazine is administered orally. Slow acetylators have an autosomal recessive trait that results in a relative deficiency of the hepatic enzyme N-acetyl transferase, thus prolonging the elimination half-life of hydralazine (see Chapter 10). This population of hypertensive patients will require an adjustment in dose to reduce the increased overactive response. Approximately 50% of African Americans and Caucasians, and the majority of American Indians, Eskimos, and Orientals are rapid acetylators of hydralazine. This population of patients will have subtherapeutic plasma concentrations of hydralazine because of its rapid metabolism to inactive metabolites and shorter elimination times. Patients with hydralazine-induced systemic lupus erythematosus frequently are slow acetylators. 

Pepys J, Davies RJ (1978) Occupational asthma. In Middleton E Jr, Reed CE, Ellis EF (eds) Allergy principles and practice. Mosby, St. Louis, p 812 Perry HM (1973) Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis. Am J Med 54 58... 

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. 

Alarcon-Segoria D, Wakins KG, Worthington JW (1967) Clinical and experimental studies on the hydralazine syndrome and its relationship to systemic lupus erythematosus. Medicine (Baltimore) 46 1-33... 

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