A  65 year old male with recently diagnosed P-ANCA (MPO+) vasculitis presented to his primary care physician with mild dyspnea for the preceding 3-4 weeks, productive cough, and low-grade fever. At initial presentation six months prior, he complained of rash, leg swelling, sinus pressure, hearing loss, and tingling sesations in his extremities. Due to concern for an antibody-associated vasculitis, both kidney and skin biopsies were obtained. Renal biopsy showed a necrotizing glomerulonephritis with glomerular fibrinoid necrosis, cellular glomerular crescents, and scattered mesangial IgA and C3 deposition. Skin pathology was interpreted as leukocytoclastic vasculitis, with direct immunofluorescence demonstrating perivascular complement C3 deposition without immunoreactivity for IgG, IgA, and IgM. Concordantly, ANCA titers showed positive P-ANCA and negative C-ANCA, and the patient was discharged with diagnosis of P-ANCA vasculitis with overlapping IgA nephropathy. Patient was started on cyclophophamide, pulse dosed prednisone followed by taper from 60 mg to 30mg at presentation, and monthly inhaled pentamidine for Pneumocystic Jiroveci Pneumonia (PJP) prophylaxis. Because an array of etiologies could be responsible for his current symptomatology, his primary care physician orderd a chest x-ray, which showed non-specific reticular opacities (Figure 1). These radiologic findings in combination with his clinical presentation led to direct admission for further evaluation.

Once admitted to the general medicine service, the patient’s O₂ saturation was noted at 91%, and he had 3+ pitting lower extremity edema despite a stable dose of torsemide. Arterial blood gas revealed a PaO2 of 59 mm Hg. A chest CT without contrast showed ground glass attenuation with interlobular septal thickening (Figure 2).

Differential diagnosis included infection in the setting of immunosuppression, vasculitis flare presenting with pulmonary changes, cyclophosphamide-induced pneumonitis, and cyclophosphamide-induced cardiotoxicity. Infectious workup including blood and urine cultures were negative. Cardiotoxicity was ruled out by lack of jugular venous distention on exam, normal NT Pro-BNP, and unremarkable echocardiogram.

A bronchoscopic evaluation was then performed. Bronchoalveolar lavage ruled out unusual infectious etiologies and diffuse alveolar hemorrhage, while biopsy ultimately showed organizing pneumonia (Figure 3). Based on the chronology of events, the diagnosis of cyclophosphamide-induced pneumonitis was favored. The patient was discharged with oxygen on a slow taper of 60 mg prednisone daily with plans to alter his immunosuppression regimen. Over the next 3 months, his symptoms improved significantly. He was ultimately transitioned to azathioprine and rituximab for management of his underlying vasculitis.  By 6 months following his initial presentation for pulmonary symptoms, the patient was using only 10 mg of prednisone daily.