A 30 year old Hispanic female with no past medical history presented with a one week history of progressive dyspnea and lower extremity edema. Her dyspnea was present at rest, and she also reported orthopnea and nocturnal cough. She denied any associated chest pain, nausea, or diaphoresis.
Upon presentation, vital signs were stable other than elevated blood pressure. Bibasilar crackles were present, and lower extremity pitting edema was present up to her knees. Chest radiograph revealed bilateral pleural effusions. CT angiography was negative for pulmonary embolism. Echocardiography and abdominal ultrasound were unremarkable.
Laboratory data revealed a creatinine of 1.3mg/dL, as well as nephrotic range proteinuria (4.7 grams of protein over a 24 hour period). The patient was started on intravenous furosemide in an unsuccessful attempt to overcome her volume overload, and her renal function continued to worsen. Autoimmune workup revealed positive anti-SSA antibody and rheumatoid factor. Serum levels of complement component C4 were undetectable. Kidney biopsy confirmed the diagnosis of Sjogren’s syndrome-associated mixed cryoglobulinemic membranoproliferative glomerulonephritis. The patient completed a course of plasmapheresis, and was started on therapy with rituximab and steroids. While she initially went into remission following treatment, she has since had one relapse that was successfully treated with a course of cyclophosphamide.
Discussion:
Cryoglobulinemia is characterized by the presence of immunoglobulins that reversibly precipitate at low temperatures. This may result in a clinical syndrome of systemic inflammation and tissue damage (commonly affecting the kidneys and skin) caused by cryoglobulin-containing immune complex deposition and complement activation. Patients with type II (mixed) cryoglobulinemia contain rheumatoid factors associated with chronic inflammatory states such as SLE, Sjogren Syndrome, and viral infections. Hospitalists must be able to recognize when acute kidney injury may be a manifestation of a rare underlying disease process, especially in young patients with no known contributing factors.
Conclusions:
Cryoglobulinemia is a rare disease entity that can result in devastating organ damage, including membranoproliferative glomerulonephritis. Diagnosis requires a high degree of suspicion in patients with acute kidney injury and findings suggestive of rheumatologic disease. Patients with cryoglobulinemia are usually diagnosed in the inpatient setting, and often respond to immunosuppressive regimens.