Case Presentation: 49-year-old male patient with history of hypertension was sent by his nephrologist to the ER for unexplained worsening renal function and likely renal biopsy. Vital signs were stable, exam was unremarkable, however BUN was 85 mg/dL with creatinine of 10.1 mg/dL (baseline of 1.5 mg/dL). 24-hour urine protein excretion was 5.2 grams. The patient was started on pulse dose methylprednisolone for a total of 3 days. CT scan of chest showed ground-glass opacities and interstitial thickening more pronounced at the bases. Rheumatologic workup was significant for p-ANCA with Myeloperoxidase antibody (MPO) of 134 AU/mL (normal< 26), negative Anti-PR3 and Anti-GBM and normal C3 and C4 levels. Renal biopsy revealed active pauci-immune crescentic and necrotizing glomerulonephritis with fibrinoid necrosis involving an artery consistent with rapidly progressive glomerulonephritis (RPGN). A diagnosis of microscopic polyangiitis (MPA) was made. Patient progressively became encephalopathic and had an episode of massive hemoptysis of 400 cc frank blood. Subsequently, the patient was intubated and started on hemodialysis. Nebulized tranexamic acid (TXA) and protamine sulfate were used to stop hemoptysis. Bronchoscopy with bronchoalveolar lavage (BAL) revealed blood with increasingly hemorrhagic appearance of consecutive BAL aliquots consistent with Diffuse Alveolar Hemorrhage (DAH). The patient was then tapered to methylprednisolone 60 mg IV every 6 hours, and rituximab, cyclophosphamide, and plasmapheresis were initiated. On day 15, the patient was extubated and eventually did not require further dialysis. On day 18, the patient was transferred to medical floors in stable condition.

Discussion: AAV (ANCA-Associated Vasculitis) are a heterogeneous group of systemic autoimmune diseases characterized by small-vessel necrotizing vasculitis with multisystem involvement. Pulmonary Renal Syndrome (PRS) is defined as concurrent autoimmune-induced DAH and RPGN. The commonest causes include AAV and anti-GBM disease. Pathophysiology involves predominantly neutrophilic inflammation leading to fibrinoid necrosis of the capillary walls with the loss of the integrity of the alveolar-capillary membrane. Patients can present within a spectrum ranging from asymptomatic radiographic abnormalities to severe life-threatening respiratory failure. Signs of alveolar hemorrhage are bilateral opacities, ground-glass pattern and/or consolidation because of alveolar filling. Bronchoscopy with BAL confirms the presence of intra-alveolar blood and results in an increasingly hemorrhagic appearance of consecutive BAL aliquots in DAH. Remission induction is commonly achieved with high dose IV methylprednisolone (0.5-1 g/day) for 3-5 days. Plasmapheresis has also been used in severe cases; other agents include mycophenolate mofetil, cyclophosphamide, and rituximab. Low-dose glucocorticoids for at least 18 months along with a steroid-sparing agent such as azathioprine are the mainstay for maintaining remission. In our patient, inhaled TXA was used for pulmonary hemorrhage; however, more data is needed to conclusively comment on its efficacy in the setting of PRS.

Conclusions: PRS often presents with non-specific symptoms requiring high index of suspicion and multidisciplinary input. Once suspected, appropriate autoimmune workup should be undertaken, usually followed by renal biopsy. Prompt initiation of potent immunosuppressants and supportive care form the foundation of treatment.

IMAGE 1: Figure 1 – Renal biopsy showing glomeruli with active cellular crescents and necrotizing lesions. Fibrinoid necrosis in a vessel wall pointed by the arrow

IMAGE 2: Figure 2 – Immunofluorescence fibrinogen staining in crescents