Pulmonary renal syndrome (PRS) confers a high mortality in the critical care setting. Prompt diagnosis and appropriate treatment are keys to preventing long term morbidity. However, there may be considerable overlap both symptomatically and serologically between the various etiologies of PRS, making initial treatment decisions difficult. We present a case of a patient with the antineutrophil cytoplasmic autoantibodies (ANCA)-positive Goodpasture’s Overlap Syndrome, defined as PRS seropositive for both ANCA and anti-glomerular basement membrane autoantibodies (anti-GBM).
A 41 year-old white male, previously healthy smoker, presented with two weeks of increasing dyspnea, diffuse myalgias, and hemoptysis. On presentation the patient was profoundly hypoxemic with respiratory distress requiring intubation in the emergency room. On exam, he was afebrile, tachycardic, and hypotensive. Lungs had diminished breath sounds at bases and bilateral rhonchi. Laboratory studies were significant for elevated creatinine and blood urea nitrogen, leukocytosis and eosinophilia. Chest x-ray revealed bilateral pulmonary infiltrates. The patient developed progressive renal failure needing dialysis, shock requiring pressor support, and persistent hypoxemia. A bronchoscopy was preformed with bronchoaveolar lavage demonstrating alveolar hemorrhage with 23% macrophages, 30% neutrophils, and 46% eosinophils. Serum quantitative immunoglobulins were significant for IgE of 1043 mg/dl. A sinus CT showed right maxillary and ethmoid sinusitis. Based on the clinical picture, elevated IgE, and peripheral / BAL eosinophilia a diagnosis of Churg-Strauss was made and the patient initiated on prednisone therapy without improvement for five days. Subsequent serologic evaluation was positive for rheumatoid factor (1:80), C-ANCA (1:512), and anti-GBM at 106 EU/ml. The patient was then initiated on plasmapheresis for presumed Goodpasture’s disease. A renal biopsy displayed anti-glomerular basement membrane antibody and C-ANCA positive focal crescentric and necrotizing glomerulonephritis consistent with ANCA-positive Goodpasture’s Overlap Syndrome. He was continued on plasma exchange until his anti-GBM titers normalized, and treated with high dose prednisone and cyclophosphamide. The patient was successfully liberated from mechanical ventilation and hemodialysis. He was discharged home on prednisone and mycophenolate mofetil. He continues to be dialysis independent at one year follow-up.
Pulmonary renal syndrome, initially described by Goodpasture in 1919, is usually associated with either ANCA (60-70%) or anti-GBM (20%) antibodies. It has recently been recognized that patients may present as both ANCA and anti-GBM antibody positive. Approximately 5% of ANCA positive sera is also anti-GBM positive and 32% of anti-GBM positive sera is ANCA positive. However there are only a few case series that correlate these serological findings with the clinical progression of these patients. There is still debate on the prognosis of these patients, in part due to a lack of clear diagnostic criteria and differences in treatment modalities. Some studies suggest these dually positive patients have a similar clinical course to ANCA vasculitis with many (75%) recovering renal function. Others suggest near universal renal failure in these patients similar to those with Goodpasture’s syndrome.
It is vital to differentiate ANCA-positive anti-GBM patients from other causes of PRS in order to deliver appropriate treatment in a timely fashion. Plasma exchange, while a mainstay of therapy in Goodpasture’s syndrome, is not thought to be beneficial for ANCA positive vasculitis and may not be routinely offered unless an diagnosis of Overlap Syndrome is considered. Prompt and aggressive plasmapheresis for ANCA positive anti-GBM positive patients may portend a greater likelihood of renal recovery as in our patient.
Matthew Exline, None.