CMV Positivity in an Immunocompetent Patient: A Case of Granulomatous with Polyangiitis with CMV Co-Infection

Summary: Cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) part of the ANCA-associated vasculitis (AAV) is a group of systemic small vessel vasculitides with multiple potential factors contributing to pathogenesis. Infection-induced AAV has been described, while certain infections themselves may also cause a limited vasculitis that improves with clearance of the infectious process. Our case presents a rare presentation of an immunocompetent patient with CMV positivity in the pre-treatment phase of AAV, which presented a diagnostic challenge as inflammatory changes were attributed initially to CMV infection. We present a 71-year-old female with a past medical history of recently treated uncomplicated UTI, chronic rhino-sinusitis and hypertension who presented with 1 month history of generalized weakness and oral ulcers. Laboratory examination was remarkable for leukocytosis, thrombocytosis, elevated ESR of 120 mm/hr and elevated CRP of 24 mg/dL. Hospital course was complicated by upper gastrointestinal bleed with severe anemia and hypovolemic shock. Endoscopy revealed multiple ulcers in the mouth, ischemic ulcers in the transverse colon, and active esophagitis. CMV immuno-positive cells were present on biopsy, for which treatment with Ganciclovir was started. Additional labs demonstrated positive c-ANCA and anti-PR3 antibody, for which rheumatology was consulted. On physical exam, the patient had oral ulcers and synovitis of the bilateral metacarpophalangeal, proximal interphalangeal, and wrist joints. She also had multiple purpuric lesions and hemorrhagic papules on the dorsal palm and fingers; and dry gangrene noted. Her muscle strength was 3/5 in the upper extremities and 2/5 in the hips and thighs during flexion. Her labs demonstrated a c-ANCA of 1:80, anti-proteinase-3 antibody of 52.3 IU/mL, and proteinuria on urinalysis. An electromyography showed evidence of mononeuritis multiplex and a CT- chest showed multiple pulmonary nodules. At this time she was diagnosed with Granulomatous with polyangiitis (GPA). Other differentials were explored and excluded, including antiphospholipid syndrome and cryoglobulinemia. Due to proteinuria a kidney biopsy was recommended, but the patient declined. She was treated for active CMV with Galciclovir and started on an induction regimen of Rituximab and high-dose steroids. A 6-month follow-up appointment showed significant improvement. The case remains complex, as CMV could itself cause vasculitis or may induce onset of her underlying GPA. We believe the latter to be the case, given her serologies, and the fact that she had no prior known immunosuppressive state, making her CMV infection potentially due to her untreated GPA. Providers should keep a broad differential for immunocompetent patients with atypical infection, being careful to consider an underlying autoimmune disease.