ANCA Negative Vasculitis Manifesting as Pulmonary-Renal Syndrome in a Patient with Chronic Osteomyelitis

A man in his early 60s, with a history of obstructive airway disease and hypertension, had a fall from a height 1 year ago. He developed a fracture of the left distal tibia and fibula, for which open reduction and internal fixation (ORIF) was done. Since then, he has had persistent pain and discharge from the implant site, for which multiple antibiotics were given and debridement was done numerous times. Three months ago, he was admitted to an outside hospital with similar complaints, and a pus culture grew methicillin-resistant Staphylococcus aureus. The patient gave a history of sudden onset right upper and lower limb weakness associated with slurring of speech, which recovered in <24 hours. A magnetic resonance imaging (MRI) of the brain revealed multiple thromboembolic acute infarcts. The patient now presented with high-grade fever, cough with expectoration, and shortness of breath (grade 3 mMRC) for 5 days. On examination, he was febrile, tachycardic, with a saturation of 92% on room air. Systemic examination revealed bilateral infrascapular crepitations and a mid-ejection systolic murmur in the aortic area. Laboratory investigations revealed leukocytosis, raised creatinine, and inflammatory markers. A chest X-ray done on day 1 revealed cardiomegaly. An X-ray of the left lower limb revealed changes of chronic osteomyelitis (Fig. 1). Blood, urine, and sputum cultures were sterile. An ultrasonography (USG) of the whole abdomen showed a splenic infarct with 190cc liquefaction. A 2D echocardiography revealed severe aortic stenosis. A plain computed tomography (CT) of the chest/abdomen showed moderate pleural effusion bilaterally with collapse/consolidation in both lungs. There was evidence of hypodense fluid density with internal hyperdense content and lobulated margins seen in the spleen. An USG-guided splenic infarct aspiration was done, which was sterile. Sequestration and debridement of the lower limb wound were done, and the culture revealed Acinetobacter baumannii. On day 12, the patient had an episode of macroscopic hematuria, which resolved spontaneously. The coagulation profile was normal. On day 14, a similar episode reoccurred. In view of hematuria, resistant hypertension, worsening fluid overload, rising 24-hour urinary protein, and creatinine, a differential of nephrotic vs nephritic syndrome was made. The patient was stabilized with antibiotics, blood transfusion, and dialysis, and we proceeded with a kidney biopsy. The kidney biopsy revealed crescentic glomerulonephritis (Figs 2A and (B). Mild tubular atrophy and inflammation, as well as fibrosis of the interstitium, were also seen. Immunofluorescence revealed IgM positivity, and the rest (mesangial, IgG, IgA, C3, C1q, Kappa, and Lambda) were negative. ANA (IF), ANA profile, c-ANCA, p-ANCA were negative, and ASO titers were normal. The patient then developed massive hemoptysis. The coagulation profile and platelet counts were repeated, which were normal. A chest X-ray, done immediately, revealed diffuse bilateral infiltrates (right > left) (Fig. 3A). An urgent high-resolution computed tomography (HRCT) chest was done, which showed alveolar opacities in the medial aspects of both lungs with interlobular septal thickening and pleural and pericardial effusion, with a high possibility of alveolar hemorrhage (Fig. 3B). Hemoglobin showed a significant fall from 8.8 to 6.2 gm/dL. A diagnosis of pulmonary renal syndrome with the following possible etiologies was made.