June 2018 Case

Laura Stephens, MD (Fellow), Mary Wong, MD (Resident), Chelsea Hayes, MD (Faculty), Ellen Klapper, MD (Faculty)

A 64-year-old man with a history of hypersensitivity pneumonitis, chronic sinusitis refractory to multiple therapies, and recent migratory polyarthralgia presented to an outside hospital with a cough, fever, and bilateral lower extremity edema. He was treated with antibiotics for pneumonia. His clinical status deteriorated and he developed massive hemoptysis (with resultant drop in hemoglobin from 11 g/dL to 6 g/dL); acute kidney injury with gross hematuria (serum creatinine rose from 0.9 to 2.6 mg/dL); and hypoxemic respiratory failure, requiring intubation.

The patient was treated with high-dose corticosteroids, azathioprine, and hydroxychloroquine and then transferred to Cedars-Sinai Medical Center for higher level of care. Radiographic imaging revealed extensive bilateral consolidation of the lungs, and bronchoscopy with bronchial alveolar lavage was compatible with diffuse alveolar hemorrhage (Image 1).

Concern for antibody-mediated vasculitis as the underlying cause of diffuse alveolar hemorrhage and acute kidney injury led to the prompt initiation of therapeutic plasma exchange. The patient was treated with seven plasma exchange procedures (Table 1), as well as cyclophosphamide immunosuppression therapy. Laboratory test results eventually revealed c-ANCA and anti-PR-3 antibodies, consistent with a diagnosis of granulomatosis with polyangiitis (Table 2).

The patient’s pulmonary and renal function responded to treatment. He was extubated with minimal oxygen requirements, and his serum creatinine and urine output normalized. Further management included gentle steroid taper to prevent relapse, sulfamethoxazole/trimethoprim, and additional cyclophosphamide administration.

Granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis) is a rare, systemic disease characterized by necrotizing vasculitis, extravascular granulomatous inflammation primarily involving the respiratory tract, and serum positivity for anti-neutrophil cytoplasmic antibodies (ANCAs). Clinical presentation is variable and can range from insidious fatigue and sinusitis, to acute pulmonary-renal syndrome with rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage.

Diagnosis of GPA is established by clinical findings and laboratory testing and/or tissue biopsy. Specifically, demonstration of c-ANCA/PR-3 antibodies, as c-ANCA positivity is present in up to 95% of GPA patients with generalized disease, and autoantibodies directed against PR-3 (an elastinolytic serine protease in azurophil granules) are detectable in up to 95% of histologically-proven cases.

Diffuse alveolar hemorrhage (DAH) is a severe complication of GPA, carrying a significant mortality risk. Early recognition and treatment are critical. In addition to aggressive immunosuppressive therapy, prompt initiation of therapeutic plasma exchange has been shown to be effective in the management of DAH. For this reason, current American Society for Apheresis guidelines recognize ANCA-associated DAH as a category I indication for apheresis. That is, therapeutic plasma exchange is recommended as first-line therapy in conjunction with other modes of treatment for this catastrophic clinical condition, and it can be lifesaving—as it was in the patient presented above.