Double ANCA-positive vasculitis in a patient with infective endocarditis
A 45-year-old male consulted a general practitioner for his pedal edema of 1 week duration. He was detected to have renal dysfunction and was referred to us. The patient was unwell, 2 months after a tooth extraction and had consulted three doctors for his clubbing and generalized feeling of lassitude. He never had any medical illness in the past and was told to be normal after evaluation. The details of those evaluations were not available. The patients also had dyspnea on doing more than ordinary work for 6 months and had paroxysmal nocturnal dyspnea (PND) of 1 month duration. The clinical examination showed pallor, pan-digital clubbing and pedal edema. The blood pressure was 110/70 mm Hg, pulse rate 98/min, and respiratory rate 26/min. The kidneys were 9.5 cm long on both sides with increased cortical echogenicity, hemoglobin was 6.5 g/dl, serum urea 107 mg/dl, serum creatinine 4.5 mg/dl, Modified Diet in Renal Disease estimated glomerular filtration rate (MDRD e-GFR) 23 ml/min/1.73 m2), and normal WBC count (total count 5600/mm3). The urine showed microscopic hematuria (RBC > 100/hpf), hyaline, granular casts, and 24-h proteinuria was 650 mg/day. The chest X-ray film showed normal findings. The dyspnea and PND improved with blood transfusion and diuretics. The renal biopsy showed pauci-immune fibro-cellular crescentic vasculitis [Figures and ] with vessel necrosis and inflammation [].\nThe c-ANCA and p-ANCA were elevated, and the C3 complement was repeatedly low and C4 was low normal. Three doses of 0.5 g of injectable methylprednisolone were given followed by oral steroid (0.5 mg/kg/day) along with oral cyclophosphamide (1 mg/kg/day). The renal functions improved and the serum creatinine stabilized at 1.8 mg/dl. Echocardiography showed small vegetations in the mitral leaflets with severe mitral regurgitation, moderate severe mitral stenosis, and severe pulmonary arterial hypertension. The patient was characterized as “possible infective endocarditis” as per the modified Duke's criteria for infective endocarditis with one major criteria – positive echocardiogram for infective endocarditis with an oscillating intra-cardiac mass on the mitral valve, and two minor criteria: (1) predisposing rheumatic mitral valve disease with a recent history of tooth extraction and (2) immunological renal involvement in the form of dual ANCA-positive vasculitis. The cyclophosphamide was stopped and steroids were rapidly tapered and stopped. The vegetations grew in size over the next 4 weeks despite empirical antibiotics for culture-negative endocarditis. Due to absence of history of fever or leukocytosis and as all the blood cultures were negative, it was not clear if the patient had infective endocarditis or the small vegetations were secondary to vasculitis. The vegetation continued to grow despite vancomycin, cefaperazone/sulbactum therapy, and hence the valve was replaced with a bioprosthetic valve. The abnormal valve with the vegetation is shown in . The C3 normalized within a month after valve replacement, c-ANCA was negative after 2 months, and p-ANCA normalized when it was tested after 4 months. The immunosuppression was stopped within 2 weeks after diagnosis and the patient continues to be stable over the 4 months follow-up now.