Case Presentation: A 74-year-old African-American woman presented to our Emergency Department with hemoptysis and severe respiratory distress. Two weeks prior to presentation, she was admitted with persistent cough and blood streaked sputum of 1-month duration and was treated with antibiotics for a presumptive diagnosis of pnemonia after a negative bronchoscopy and bronchoalveolar lavage (BAL). Her medical history included hypertension managed with carvedilol and hydralazine at stable doses for several years. Examination was significant for pallor, labored breathing and coarse crackles on bilateral lung fields. She was stabilized on high flow oxygen and following lab tests revealed moderate anemia (Hb-6.7gm/dl). Serology demonstrated a positive p-ANCA with high MPO(Myeloperoxidase) titers (1:80) and a negative ANA, Anti-ds DNA, anti-histone antibody, Proteinase-3 and anti-glomerular basement membrane antibody. Computed Tomography scan of the chest without contrast revealed bilateral airspace opacities. A repeat bronchoscopy with BAL was performed which revealed grossly bloody mucosal secretions that failed to clear despite instillation and aspiration of sterile saline solution, confirming diffuse alveolar hemorrhage (DAH).
A diagnosis of drug induced vasculitis (DIV) was considered, and hydralazine was discontinued. Because of her increased oxygen requirements, steroid pulse was started to halt worsening of hypoxia. While her respiratory status improved, her creatinine worsened and urinalysis showed 85 RBCs per high power field and an estimated daily protein excretion of 1.05 g/gm of creatinine. A kidney biopsy was recommended for evaluation of glomerulonephritis, but the patient declined.
Subsequently, she was started on plasmapheresis and immunosuppressive therapy with rituximab for worsening renal function. Her respiratory status and creatinine level improved after 3 weeks and eventually got discharged to a rehabilitation facility. She was seen in our clinic for her subsequent rituximab infusions and remained asymptomatic.
Discussion: Drug induced vasculitis is a diagnostic challenge because there is no unique clinical, laboratory or pathological diagnostic marker. Therefore, a careful drug history and high index of suspicion is critical in making the correct diagnosis. The positive p-ANCA and MPO with high titers, a long history of hydralazine use, absence of any evidence of SLE or primary vasculitis and clinical improvement after discontinuation of hydralazine and initiation of immunosuppressive therapy supports the diagnosis of DIV in our patient. We present this case to highlight that DIV should be considered in patients on hydralazine presenting with pulmonary renal syndrome and prompt discontinuation of the drug is essential to avoid long term sequelae.
Conclusions: Hydralazine is a widely used antihypertensive, known to cause drug-induced lupus erythematosus but has rarely been reported to cause Antineutrophil Cytoplasmic Antibody (ANCA) positive vasculitis. Although rare, hydralazine-associated ANCA vasculitis is rapidly progressive and can lead to adverse and even a fatal outcome. Hence, the differential diagnosis of pulmonary renal syndrome should include hydralazine-associated small vessel vasculitis in patients treated with this medication. High index of clinical suspicion with prompt withdrawal of the drug is of utmost importance.