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

F. Gerald Wade, MD; Elie Ghoulam, MD; Thomas Fay, MD; George Vasquez Rios, MD; Kamran Qureshi, MD

Disclosures

October 02, 2019

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]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....