Clinical Characteristics of Hydralazine-induced Lupus

Abstract

Introduction The use of hydralazine has been associated with the development of lupus erythematosus and lupus-like syndromes. We performed this retrospective study to identify clinical characteristics of individuals who developed hydralazine-induced lupus. Material and methods We performed a single-center retrospective review of seven individuals who had a diagnosis of hydralazine-induced lupus by International Classification of Diseases, Ninth Revision (ICD9) code and were on hydralazine prior to their diagnosis. Clinical and laboratory data were obtained from a review of the medical record up to 12-month follow-up. Results Of the seven individuals with hydralazine-induced lupus, five were Caucasian (71%) and two were African-American. The mean age at the time of diagnosis was 62 years. Four (57%) were male. The majority of individuals were exposed to hydralazine for more than 12 months (83%). Four individuals had biopsy-proven lupus nephritis and four individuals had cardiopulmonary and skin involvement. Six patients were positive for antinuclear antibody (ANA) with a homogenous pattern, and five of those were positive for anti-histone antibody. Additionally, positive anti-double-stranded DNA (anti-dsDNA) antibody, anti-cardiolipin antibodies, low complements, positive lupus anticoagulant, and leukopenia were seen in 42% of our cohort. Of the five individuals in whom anti-myeloperoxidase (MPO) antibody was strongly positive, all had renal involvement defined by an elevated creatinine with three having biopsy-proven lupus nephritis. Three other individuals with MPO positivity had concurrent cardiopulmonary and skin involvement. Four individuals were positive for anti-proteinase 3 (PR3) antibody, three of whom were strongly positive with renal involvement defined by an elevated creatinine with two having biopsy-proven lupus nephritis. The level of anti-dsDNA antibody and anti-PR3 antibody normalized at three months while anti-MPO antibody took 12 months to normalize following cessation of hydralazine. When checked, low complement component 3 (C3) and anti-histone antibody persisted past 12 months. In addition to the withdrawal of hydralazine, six individuals were treated with hydroxychloroquine and five with mycophenolate mofetil. Three of four individuals with renal involvement received plasmapheresis and two received cyclophosphamide and hemodialysis. Conclusion Hydralazine can aggravate and unmask incipient lupus. Since the presentation can be varied, early recognition of symptoms is critical. Precautions should be taken before initiating this medication in individuals with certain risk factors. Once diagnosed, potential serological findings such as a positive anti-MPO/anti-PR3 antibody could predict more severe manifestations such as pulmonary-renal complications.

Keywords: drug induce lupus; drug-induced lupus; hydralazine; hydralazine induced lupus; lupus; systemic lupus erythematosus (sle).