The Journal of the Arkansas Medical Society Med Journal May 2019 Final 2 - Page 9

CASE REPORT Hydralazine-induced Rheumatologic Disease: Back to the Future Sruthi Kanu ru, MD; 1 Neriman Gokden, MD; 2 Shirin Trisha, MD; 3 Seth Mark Berney, MD 4 1 Assistant Professor of Medicine, Central Arkansas Veterans Healthcare System, UAMS 2 Professor of Pathology and Urology, Director of Anatomic Pathology, Vice-Chair for Faculty Affairs, UAMS 3 rd 3 year Medicine-Pediatrics Resident, UAMS 4 Professor of Medicine, Chief, Division of Rheumatology, Director, Rheumatology Fellowship Program, UAMS ABSTRACT W e present a patient who devel- oped both drug-induced lupus and vasculitis after taking hy- dralazine. Additionally, we review the literature about these disorders. An 81-year-old hypertensive female developed serositis, leukopenia, thrombo- cytopenia, positive ANA (Antinuclear antibody) and antihistone antibodies, hypocomplementemia, a pauci immune glomerulonephritis, and positive ANCA (Anti-Neutrophilic Cytoplasmic Autoantibody) after six months of hydralazine. Although lupus and vasculitis are known side effects of hydralazine, their frequency decreased significantly 25 years ago, as angiotensin-converting enzyme inhibitors replaced hydralazine. However, use of hydralazine increased recently after heart-failure patient sur- vival improved with the combination of hydralazine and nitrates. It is important to recognize the auto- immune complications of hydralazine, especially in the setting of its increased clinical use. INTRODUCTION Hydralazine is an arterial vasodilator to treat hypertension and heart failure since 1953. 1 Al- though lupus and vasculitis are well described side effects of hydralazine, 2 their frequency has decreased significantly because angiotensin- converting enzyme inhibitors replaced hydralazine, resulting in several generations of physicians who are unfamiliar with its complications. In 2004, the recognition that heart-failure patients treated with hydralazine and nitrates survive longer has caused increased use of hydralazine and the possibility of a resurgence of its adverse effects. We present a patient with hypertension who developed both lupus and ANCA positive pauci- immune glomerulonephritis after six months of hydralazine therapy. CASE PRESENTATION An 81-year-old female with renal insufficiency (baseline creatinine= 1.5 mg/dl), hypertension (treated with hydralazine for the prior six months), hypothyroidism, and hyperlipidemia was admitted to an outside hospital with four months of intermittent, subjective fever; malaise; fatigue; weakness; nau- sea; diarrhea; vomiting; 40 pounds of unintentional weight loss; and two weeks of decreased urination and leg swelling. Her physical exam and diagnostic laboratory test results on admission to the outside hospital: Temp: 98.1; BP: 137/71; HR: 75; RR: 20 Skin: morbilliform eruption of the neck and upper chest, arms and forearms bilaterally Lung exam: rales at left lower base Heart sounds: normal Muscle strength: 4/5 in proximal upper and lower extremities WBC: 1000/mm3  (nl= 3-12,000) Hemoglobin: 9.1 g/dL (nl= 11.5-16) Platelet: 76000/mm3 (nl= 150,000-500,000) Potassium: 6.6 mmol/L (nl= 3.5-5.1) Bun: 44 mg/dl (nl= 6-20) Cr: 2.6 mg/dl (nl= 0.4-1.0) UA: 40-50 RBCs/hpf (nl= 0-2/) LDH: 986 IU/L (nl= 100-248) Blood and urine cultures: sterile daily, megestrol acetate 400 mg daily, calcium/ vitamin D 600mg/400 IU daily, simvastatin 40 mg nightly. Her physical exam and diagnostic laboratory test results on arrival: Vitals: Temp 98.2; RR 14; BP 135/75; P 75 General: patient appeared sick but in no acute distress Lungs: clear to auscultation bilaterally Skin: morbilliform eruption of the neck, upper chest and bilateral upper extremities, sparing the hands; Ecchymoses on her forearms Cardiac: regular rate of S1 S2 without S3, S4, mur- murs. Abdomen: bowel sounds present, soft, nontender, without hepatosplenomegaly Extremities: diffuse 4+ pitting edema Neurologic: 3/5 proximal muscle strength; 4+/5 distal muscle strength WBC 8840/mm 3 (nl= 3-12,000) Hemoglobin 9.3 mg/dL  (nl= 11.5-16 g) Platelet count 37000/mm 3  (nl= 150,000-500,000) Peripheral smear: rare schistocytes Haptoglobin: 165 mg/dl (nl= 30-200) Sodium 134 mmol/L (nl= 135-145) Potassium 6.6 mmol/L (nl= 3.5- 5.1) She underwent dialysis to treat her hyperka- lemia, received filgrastim for the leukopenia with improvement (5000/mm 3 ) but a worsened throm- bocytopenia (35000/mm 3 ). Because of her acute kidney injury, thrombocytopenia, and elevated LDH, her doctors transferred her to our hospital to undergo plasmapheresis for atypical hemolytic uremic syn- drome (HUS). Her medications on transfer included: aspirin 81 mg daily, levothyroxine 75 mcg daily, hydralazine 25 mg TID, triamterene/hydrochlorothiazide 75/50 mg Figure 1. Partial-cellular crescent present in a normocellular glomerulus, PAS stain, 400X NUMBER 11 > Continued on page 250. MAY 2019 • 249