TOPIC: Pulmonary Manifestations of Systemic Disease
      TYPE: Medical Student/Resident Case Reports
      INTRODUCTION: The antineutrophil cytoplasmic associated (ANCA)-associated vasculitides (AAV) are a group of rare vasculitis syndromes characterized by systemic inflammation and necrosis of vessel walls. Granulomatosis with polyangiitis (GPA) is a type of AAV that most commonly presents with renal and pulmonary involvement. We present a case of GPA in a healthy patient with no identifiable triggers.
      CASE PRESENTATION: A 60-year-old man with no smoking history presented with weakness, fatigue, diffuse arthralgias, and dyspnea on exertion of 2 months' duration. He reported progression to conversational dyspnea, oliguria, epistaxis, severe abdominal pain, and melena in the days prior to presentation. Physical exam was notable for bibasilar rales. Labs showed acute renal failure with elevated creatinine and BUN, normocytic anemia, microscopic hematuria, proteinuria, and elevated inflammatory markers. CT thorax demonstrated bilateral spiculated pulmonary nodules and bilateral pleural effusions. Further labs demonstrated high c-ANCA titer and an elevated anti-proteinase 3 antibody. Pulmonary nodule biopsy showed necrotizing granulomas, and renal biopsy demonstrated pauci-immune necrotizing, crescenteric glomerulonephritis consistent with GPA. Steroids and rituximab were begun with clinical improvement.
      DISCUSSION: GPA is a rare AAV that classically affects the small-to-medium renal and pulmonary vessels. The incidence is reported to be 4.9-10.6 cases/million/year, most commonly occurring in caucasians in northern latitudes. The etiology of GPA is unclear, but is likely due to complex interactions between genetic predispositions to immune self-intolerance being triggered by various environmental factors including infection, medications, and silica exposure. Genetic associations include HLA-DP, SERPINA1, and PRTN3 genes. Clinical presentation varies from limited disease to multisystem organ involvement. Although there is overlap between GPA and other AAVs, GPA can be distinguished by upper respiratory tract involvement and is most commonly associated with c-ANCA reactive against proteinase 3 (PR3-ANCA). Diagnosis requires prompt treatment with steroids and immunosuppressive agents such as cyclophosphamide, azathioprine, rituximab, or abatacept. Although induction therapy is effective at inducing remission, difficulties persist in preventing disease relapse. In addition, patients also require treatment with trimethoprim-sulfamethoxazole to prevent relapse and for Pneumocystis prophylaxis.
      CONCLUSIONS: GPA is a rare type of AAV most commonly affecting renal and pulmonary vessels. It is distinguished from other AAVs by upper respiratory tract involvement and PR3-ANCA. Treatment consists of steroids and immunosuppression followed by maintenance and prophylactic therapy with concern for relapsing disease. GPA is an important, albeit rare condition to consider in the setting of pulmonary-renal involvement.
      REFERENCE #1: Cartin-Ceba R, Peikert T, Specks U. Pathogenesis of ANCA-Associated Vasculitis. Curr Rheumatol Rep. 2012;14(6):481-493. doi:10.1007/s11926-012-0286-y
      REFERENCE #2: Comarmond C, Cacoub P. Granulomatosis with polyangiitis (Wegener): Clinical aspects and treatment. Autoimmun Rev. 2014;13(11):1121-1125. doi:10.1016/j.autrev.2014.08.017
      REFERENCE #3: Muller K, Lin JH. Orbital Granulomatosis With Polyangiitis (Wegener Granulomatosis): Clinical and Pathologic Findings. Arch Pathol Lab Med. 2014;138(8):1110-1114. doi:10.5858/arpa.2013-0006-RS
      DISCLOSURES: No relevant relationships by Mohammad Ahmed, source=Web Response
      No relevant relationships by Bilal Bangash, source=Web Response
      No relevant relationships by Matthew Juarez, source=Web Response