Original Article

Hydralazine-induced Lupus: Maintaining Vigilance with Increased Use in Patients with Heart Failure

Authors: Shannon W. Finks, PHARMD, BCPS, A Lloyd Finks, MD, Timothy H. Self, PHARMD

Abstract

Objective: To review data concerning the incidence and danger of hydralazine-induced systemic lupus erythematosus (SLE) and review how best to monitor patients placed on chronic hydralazine therapy.


Data Sources: Literature was sought utilizing PUBMED (1960 to present) and MEDLINE (1966 to present). Search terms included hydralazine, drug-induced systemic lupus erythematosus, congestive heart failure, and antinuclear antibody.


Data Synthesis: A major adverse effect of hydralazine therapy is drug-induced SLE. An evaluation of case reports and review of the literature was undertaken to determine the significance of this major adverse effect and stress the importance of close monitoring of patients placed on chronic hydralazine therapy for heart failure. Risk factors are discussed including high daily doses, slow acetylator and HLA-DRw4 phenotypes, therapy longer than 3 months, and female gender.


Conclusions: Following the publication of A-HeFT, an increase in the amount of hydralazine prescribed in patients with heart failure has been noted. Patients should be closely monitored when initiating hydralazine and during chronic therapy. Although dose limitation of hydralazine reduces risk, low doses are well documented to be associated with SLE. A baseline antinuclear antibody level should be determined on initiation of hydralazine, but it is not recommended to regularly check antinuclear antibody levels because a positive result does not necessarily indicate SLE is present. Patients should be monitored at each visit for signs and symptoms of SLE, and, if any signs and symptoms of the syndrome develop while the patient is on hydralazine therapy, the drug should be discontinued immediately because complications from the syndrome can be potentially fatal.


Key Points


* Patients should be closely monitored when initiating hydralazine and in chronic therapy.


* For systemic lupus erythematosus (SLE) induced by hydralazine, musculoskeletal symptoms are the most common clinical manifestation.


* Laboratory results that lead to the diagnosis of drug-induced lupus include antinuclear antibody (ANA), lupus erythematosus cells, rheumatoid factor, and antihistone antibodies.


* Although dose limitation of hydralazine reduces risk, low doses are well documented to be associated with SLE. A baseline antinuclear antibody (ANA) level should be determined on initiation of hydralazine, but it is not recommended to regularly check ANA levels.


* Antihistone antibody, although 50% sensitive to idiopathic SLE, has sensitivity of up to 90% in drug-induced lupus.


* Patients should be monitored at each visit, and, if any signs and symptoms of SLE develop while the patient is on hydralazine therapy, the drug should be discontinued immediately because complications from the syndrome can be potentially fatal.

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