Case Presentation:
An 82-year-old female with a medical history including breast cancer treated with lumpectomy, moderate aortic stenosis, heart failure with preserved ejection fraction, chronic kidney disease stage IV with associated anemia of chronic disease, type 2 diabetes mellitus (diet-controlled), essential hypertension, hyperlipidemia, and a prior hemorrhagic stroke in the right basal ganglia in February 2021 presented with progressive shortness of breath, productive cough, low-grade fever, and lethargy persisting for two weeks. She was diagnosed with left lower lobe community-acquired pneumonia complicated by left-sided parapneumonic effusion. Initial management included azithromycin for three days and intravenous ceftriaxone for five days. A left-sided thoracocentesis was performed, yielding approximately 500 mL of transudative fluid.
On the fifth day of hospitalization, the patient developed severe lethargy, arthralgia, and painful cutaneous lesions affecting her hands, forehead, and back. She also reported blurred vision with serosanguinous tearing.
Clinical Findings:
Upon examination, vital signs were as follows: blood pressure of 138/80 mmHg, heart rate of 105 beats per minute, respiratory rate of 18 breaths per minute, oxygen saturation of 95% on room air, and temperature of 36.7°C. The patient appeared lethargic. The head, eyes, ears, nose, and throat examination revealed crusting over the nostrils and tender cervical lymphadenopathy. Ophthalmologic assessment demonstrated bilateral palpebral edema, subconjunctival hemorrhage, conjunctivitis, and chemosis. Skin examination identified a maculopapular rash on the forehead, nonblanching palpable purpura on the back, and bilaterally hemorrhagic bullae on the digits. Cardiac examination revealed a grade 4/6 systolic murmur at the aortic area without additional heart sounds. Pulmonary auscultation detected rhonchi localized to the left lower lobe. The patient or her family had no history of autoimmune or inflammatory disorders. She denied smoking, alcohol consumption, or substance use. Home medications included hydralazine, aspirin, atorvastatin, anastrozole, furosemide, gabapentin, and metoprolol.
Diagnostic Assessment:
Laboratory tests revealed hemoglobin of 9.6 g/dL, platelet count of 405,000/µL, white blood cell count of 3,650/µL, and eosinophil count of 0.16 K/µL. Renal function tests showed creatinine of 2.69 mg/dL and an estimated glomerular filtration rate of 16.9 mL/min/1.73 m², worsening from values recorded three months earlier. Inflammatory markers were significantly elevated, with an erythrocyte sedimentation rate of 68 mm/h and C-reactive protein of 219.1 mg/L. Additional findings included high aldolase levels (8.8 U/L) and elevated brain natriuretic peptide (482 pg/mL). Serological testing identified a positive antinuclear antibody (ANA) at a titer of 1:1280 with a homogeneous pattern. Additionally, perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) was positive, while cytoplasmic ANCA (c-ANCA) was negative. Myeloperoxidase (MPO) antibody was elevated at 2.6 U, and proteinase 3 (PR3) antibody was 4.4 U. Rheumatoid factor (RF) was mildly elevated, while anti-cyclic citrullinated peptide, antihistone antibody, cryoglobulin, and anti-double-stranded DNA antibody levels were within normal ranges. Infectious disease screening, including hepatitis B and C serology, respiratory viral panel, and tuberculosis testing, was negative.
Thoracocentesis fluid analysis revealed a transudative effusion based on Light’s criteria, with lactate dehydrogenase (LDH) of 115 U/L and total protein of 3 g/dL. Urinalysis detected microscopic hematuria and proteinuria, but 24-hour urine protein remained within normal limits. Electrocardiography showed sinus tachycardia with nonspecific ST-T wave changes, without significant changes compared to a previous electrocardiogram.
Imaging studies, including chest radiography and computed tomography, confirmed left lower lobe pneumonia with an adjacent pleural effusion. Additionally, a moderate to large pericardial effusion was noted. Given the clinical presentation and laboratory findings, the differential diagnosis included hydralazine-induced lupus, hydralazine-induced vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and mixed cryoglobulinemia.
Diagnosis:
The patient had been on hydralazine 50 mg three times daily for over two years, a medication associated with drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Given the chronic use of hydralazine, the presence of p-ANCA positivity, elevated MPO antibody, and clinical features, including pulmonary, renal, and dermatologic involvement, a diagnosis of hydralazine-induced AAV was established after excluding infectious, malignant, and alternative autoimmune causes. A kidney biopsy was not pursued as renal function improved with fluid resuscitation, suggesting a prerenal etiology. A skin biopsy was also not obtained as the patient declined the procedure.
Treatment:
Hydralazine was discontinued, and the patient was initiated on high-dose corticosteroid therapy with methylprednisolone 60 mg daily for seven days, followed by a taper at discharge. An attempt at pericardiocentesis for symptomatic relief was unsuccessful. Throughout hospitalization, her symptoms improved significantly after discontinuing hydralazine, further supporting the diagnosis.
Outcome and Follow-Up:
At a follow-up visit two months later, echocardiography demonstrated complete resolution of the pericardial effusion. The patient remained on low-dose prednisone (5 mg daily).
Over the following year, she developed a nontraumatic ulcer on her left heel, which required surgical debridement. Given the suspected association with her vasculitis, she was started on avacopan. Despite initial renal improvement, kidney function progressively declined, necessitating the initiation of peritoneal dialysis. At the time of reporting, she was in the process of obtaining vascular access for hemodialysis.
