Personalized Medicine for HLA-associated Drug-hypersensitivity Reactions

Mandvi Bharadwaj; Patricia Illing; Lyudmila Kostenko


Personalized Medicine. 2010;7(5):495-516. 

In This Article

Hydralazine-induced Systemic Lupus Erythematosus & HLA-DRw4

Hydralazine is a smooth muscle relaxant used in the treatment of hypertension. Since its introduction in the early 1950s there have been numerous reports of a hydralazine-induced systemic lupus erythematosus (SLE)-like syndrome. SLE is a multisystem autoimmune disease involving a tableau of symptoms, including arthritis, arthralgia, anorexia, fever, joint pain and swelling and the presence of antinuclear antibodies.[76] When associated with hydralazine use, symptoms resolve on cessation of hydralazine treatment. A British study estimated incidence at 6.7% of individuals undergoing up to 3 years hydralazine treatment of less than or equal to 200 mg/day. Furthermore, they saw that incidence was sex biased appearing in 11.6% of women and 2.8% of men, and that increased dose increased the incidence of disease.[77] Hydralazine–SLE has also been associated with what has been coined the 'slow acetylator phenotype', which results in slower drug elimination.[78,79]

In 1980 an association was noted with HLA-DRw4 that appeared in 73% of patients experiencing hydralazine–SLE, compared with 33% of healthy subjects, 25% of slow acetylators undergoing hydralazine treatment but not experiencing SLE, and 25% of individuals experiencing idiopathic SLE.[80] A sex bias was once again seen in this study, with fewer males than females suffering from hydralazine–SLE; however, it appears that owing to the absence of the risk factor of being female, HLA-DRw4 and the slow acetylator phenotype may be more crucial to disease development in men.[80] The authors of this study suggested that females possessing the slow acetylator phenoytpe in conjunction with HLA-DRw4 should be precluded from hydralazine use; however, as this study was of limited size (26 hypersensitive individuals) and a later study failed to observe a similar association,[81] preclusion on this basis seems premature.