A 58-Year-Old Man With a Rash and Elevated Creatinine Levels

Discussion

Extrahepatic manifestations of HCV infection are common and increase morbidity and mortality among HCV-infected patients, even in the absence of cirrhosis.^[1,2] In addition to the healthcare costs of HCV-associated liver disease, the economic burden of extrahepatic manifestations of HCV was $1.5 billion in 2014.^[3] Extrahepatic manifestations of HCV include mixed cryoglobulinemia, Sjögren syndrome, type 2 diabetes, porphyria cutanea tarda, hypothyroidism, lymphoproliferative disorders, and cardiovascular disease, among others.^{[4,5,6,7,8,9]}

Chronic HCV infection is highly prevalent in liver and kidney transplant recipients, with an increased incidence of clinically significant extrahepatic manifestations due to concurrent immunosuppression.^[10,11,12] Lymphoproliferative disorders and HCV-related kidney disease are serious consequences of untreated HCV posttransplant.^[13] Clinically aggressive cases of mixed cryoglobulinemia can lead to rapidly progressive posttransplant renal failure due to immune-complex deposition that damages the glomerulus. HCV infection also further increases the risk for diabetes mellitus in transplant recipients, which can also contribute to progressive renal dysfunction.^[10,14]

Cryoglobulinemia is most strongly associated with HCV but also occurs less often from hepatitis B virus (HBV), HIV, monoclonal gammopathies, and some autoimmune disorders.^{[15,16,17,18]} Mixed cryoglobulinemia is caused by an immune complex reaction to HCV virion with HCV immunoglobulin G, rheumatoid factor, and complement to form polyclonal cryoglobulins. Immune complex deposition in small-vessel walls and cryoprotein precipitation in vessel lumens lead to cryoglobulinemia syndrome.^[19]

Patients with HCV commonly have circulating cryoglobulins, with symptomatic disease occurring in about 20% of patients with cryoglobulins in the serum.^[16,20] Rates are similar in liver transplant recipients.^[21] HCV-associated mixed cryoglobulinemia most often leads to subclinical or mild disease and can present with the Meltzer triad of purpura, arthralgia, and weakness.^[22] Aggressive disease course is seen in 15%-20% of patients with HCV who have cryoglobulinemia. Cryoglobulinemia vasculitis syndromes can cause renal disease, digital ischemia, neuropathy, pulmonary disease, gastrointestinal hemorrhage and ischemia, and liver disease.^[15] Among such patients, renal failure is the most common cause of death.

HCV-cryoglobulinemic renal disease typically presents with microscopic hematuria and mild proteinuria without significant renal dysfunction.^[20] Approximately 30% of patients with HCV-associated mixed cryoglobulinemia develop some degree of renal dysfunction, with a small percentage developing fulminant renal failure. Overall mortality is high in patients with mixed cryoglobulinemia and renal insufficiency.^[19] Thus, early diagnosis and treatment of HCV in patients with cryoglobulin-related renal disease is important to curb progression of renal dysfunction.^[23,24] Patients with HCV who have proteinuria and microscopic hematuria should have renal biopsy to evaluate for cryoglobulinemia or other HCV-related glomerular diseases.^[25]

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Cite this: F. Gerald Wade, Elie Ghoulam, Thomas Fay, et. al. A 58-Year-Old Man With a Rash and Elevated Creatinine Levels - Medscape - Oct 02, 2019.