Case Presentation: Our patient is a 77-year-old female with no past medical history who presented with two weeks of dyspnea on exertion, scant hemoptysis, and rhinorrhea with occasional blood. Vitals showed tachycardia, tachypnea, and hypoxia with saturations 95% on 15 L/min via heated high flow nasal cannula. Exam revealed accessory muscle use, faint bibasilar rales, and trace peripheral edema. Urine was positive for blood and protein. Hemoglobin was 7.8 g/dL, serum creatinine was 2.21 mg/dl, and an arterial pO2 of 57 mmHg. Chest CT revealed diffuse patchy airspace opacities. She was admitted to the intensive care unit and intubated. A diagnostic bronchoscopy revealed diffuse alveolar hemorrhage. High dose steroids and plasma exchange were empirically started. Later investigations would support granulomatosis with polyangiitis.
Discussion: The initial first choice therapy for GPA remission induction is glucocorticoids with a combination of either rituximab or cyclophosphamide as described in the RAVE (2010) and RITUXVAS (2010) trials. The role of plasma exchange, however, has only been evaluated in patients with severe disease. Its effectiveness, as shown in the MEPEX trial (2007) was limited to reducing hemodialysis (HD) dependence at 3 months, but it was never evaluated for reducing the need for intubation. Patients enrolled in MEPEX had a serum creatinine >5.8 mg/dl or required HD and were randomly assigned to either oral cyclophosphamide and plasma exchange or oral cyclophosphamide and IV methylprednisolone (MeP) with a primary end point of recovery at 3 months. MEPEX showed increased rate of renal recovery with plasma exchange. No pulmonary outcomes were evaluated. Our patient presented with diffuse alveolar hemorrhage (DAH) requiring intubation, but without indications for HD and with a peak creatinine of 2.59. Despite severe disease, she would have been excluded from both the RAVE trial and the MEPEX trial. We initiated MeP and plasma exchange over immunomodulation due to the severity of respiratory failure from DAH. Despite limited evidence, a small retrospective study in the American Journal of Kidney Disease (Klemmer et al, 2003) lends support to our decision. This retrospective review of ANCA-associated DAH treated with plasma exchange resulted in resolution of DAH all patients without complication. Another publication in the Journal of Clinical Apheresis (Anoek et al, 2014) that reviewed patients with progressive ANCA-associated vasculitis despite appropriate therapy with cyclophosphamide and glucocorticoids found that plasmapheresis added significant improvement in renal function and survival.
Our patient tolerated plasma exchange well and was extubated after three days of mechanical ventilation. Rituximab was started shortly thereafter for remission induction, and ultimately she never required dialysis. She continues to follow up with rheumatology and nephrology and her disease is currently in remission at four months.
Conclusions: DAH requiring intubation in patients with relatively preserved renal function presents a unique opportunity for early initiation of plasma exchange. We chose to initiate plasma exchange immediately in addition to immunosuppression with high dose MeP and had a favorable outcome. Further study, including the yet to be published PEXIVAS trial evaluating early plasma exchange, would be required to better elucidate the role of plasma exchange in DAH requiring intubation.