A rare presentation of pulmonary hemorrhage with hepatitis C-associated cryoglobulinemia and membranoproliferative glomerulonephritis

Cryoglobulinemia (CG)-associated pulmonary hemorrhage is an unusual entity. An even rarer occurrence is that of membranoproliferative glomerulonephritis (MPGN) in a patient with CG and alveolar hemorrhage. As far as we can tell, there has been no more than a total of four such cases that have been formally published, and this would be the fifth case [1,2]. A 46-year-old Caucasian woman presented to the emergency department with acute respiratory failure, petechiae, pulmonary hemorrhage, azotemia, proteinuria, and hematuria for 10 days. A ventilation/perfusion lung scan was read as low probability for a pulmonary embolism. Additional serologic examinations included negative ANA, anti-GBM, pANCA, cANCA, hepatitis B and HIV antibody. SPEP (serum protein electrophoresis) was also unremarkable. Hepatitis C antibody was positive, and quantitative testing for CG revealed type II (mixed CG, 0.2 g/dL). C3 and C4 complement levels were low. Renal biopsy revealed MPGN. Bronchoscopy did not demonstrate any endobronchial abnormality. The patient was treated with intravenous methylprednisolone, and both hemoptysis and renal function improved. She did not return for follow-up care. CG associated with HCV has been recognized to cause pulmonary complications which are usually mild and without any significant signs or symptoms. Alveolar hemorrhage in CG is rare; there have been only 10 case reports in English medical literature [1]. Patients with the cryoglobulinemic pulmonary hemorrhage have an extremely poor prognosis and high mortality at presentation and even a poorer prognosis in survivors having further hemorrhagic episodes [1]. Diagnosis of pulmonary hemorrhage associated with HCV-associated CG requires a high index of suspicion; in this case, the patient presented to the emergency services with severe respiratory insufficiency and bilateral alveolar infiltrates on chest radiograph. Her acute respiratory decompensation with diffuse alveolar infiltrates and hemoptysis is indicative of alveolar hemorrhage syndrome [3]. The diagnosis can also be confirmed with the demonstration of hemosiderophages in alveolar lavage obtained by bronchoscopy. It has been established that patients with CG with chronic infection by HCV are sometimes linked to membranoproliferative glomerulonephritis with a survival rate of 33–49% after a mean follow-up of 10 years. Managing an autoimmune manifestation of an infectious disease is complex. Although immunosuppressive agents may be needed to control potentially life-threatening autoimmune complications, there is a risk that the infection might get worse. A reasonable approach is first to control the acute autoimmune manifestations of disease with immunosuppressive therapy and then to deal with the underlying infection to prevent relapse [3]. We conclude that both alveolar hemorrhage and renal involvement associated with HCV-related type CG are exceptional entities. This poses problems regarding treatment as each patient may need a tailored treatment [1]. Conflict of interest statement. None declared.