Hydralazine lupus erythematosus

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. 

When administered chronically in high doses, hydralazine may produce a rheumatoidlike state that when fully developed, resembles disseminated lupus erythematosus. 

V-Acetylation /V-acetyl transferase Hydralazine (antihypertensive) Lupus erythematosus-like syndrome... 

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...

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. 

What are the predisposing factors identified in human patients that are important in the immune-media ted adverse effect lupus erythematosus caused by the drug hydralazine ... 

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). 

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. 

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

Hydralazine (see also Ch. 23) relaxes arterial smooth muscle and reduces peripheral vascular resistance. Reflex tachycardia limits its usefulness and lupus erythematosus may be induced when the dose exceeds 100 mg per day. 

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)... 

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. 

A. Hydralazine and Minoxidil These older vasodilators have more effect on arterioles than on veins. They are orally active and suitable for chronic therapy. Hydralazine apparently acts through the release of nitric oxide. However, it is rarely used at high dosage because of its toxicity therefore, its efficacy is limited, fts toxicities include compensatory responses (tachycardia, salt and water retention Table 11-2) and drug-induced lupus erythematosus, which is reversible upon stopping the drug. However, this effect is uncommon at dosages below 200 mg/d. 

---