A Unique Symptomatic Presentation of Type II Cryoglobulinemia Syndrome With Chronic Hepatitis C Virus Infection

Abstract

Introduction: Cryoglobulinemia refers to the presence of blood protein precipitates, known as cryoglobulins, in an individual’s serum and plasma. The prevalence of clinically significant cryoglobulinemia is estimated to be 1 in 100,000 individuals. The disease can be classified into 3 types with the Brouet classification scheme, which is based on the immunological analysis of cryoglobulins. Type I consists of an isolated monoclonal immunoglobulin. Type II or mixed cryoglobulinemia is a combination of polyclonal immunoglobulins with a monoclonal immunoglobulin and rheumatoid factor activity. Type II is associated with chronic viral infections as well, such as hepatitis C infection. Type III contains multiple polyclonal immunoglobulins. A 59-year-old female patient with a medical history of chronic hepatitis C virus infection, hepatic cirrhosis, gastroesophageal reflux disease, and hypertension presented with the complaint of generalized abdominal pain and constipation. The pain was dull, non-radiating, and severe in intensity. Physicial examination was remarkable for abdominal distention, tenderness to palpation, guarding, rebound tenderness, and mild global jaundice. Laboratory values demonstrated elevated bilirubin and C-reactive protein levels, transaminitis, thrombocytopenia, and hepatitis C virus antibodies. Laxatives were given due to her constipation, and within 24 hours, she passed a large bowel movement, which relieved her abdominal pain. A new-onset rash then developed the following morning. It was a pruritic, burning rash present primarily on her abdomen and lower extremities. Non-palpable, non-blanching petechiae and ecchymoses were appreciated. Punch biopsies confirmed the presence of a superficial leukocytoclastic vasculitis with intravascular microthrombi. Direct immunofluorescence confirmed the presence of colloid bodies positive for IgG, IgM, and IgA. Per pathology, these findings were pathognomonic for mixed cryoglobulinemia. Methyl-prednisolone was given every 8 hours for treatment, which abated the patient’s rash within 24 hours. This presentation of mixed cryoglobulinemia syndrome is not typical. The non-palpable, non-inflammatory petechiae and ecchymoses found on our patient are normally present in type I cryoglobulinemia on mucous membranes and not in mixed cryoglobulinemia. Despite this atypical presentation, the medical team was confident in the diagnosis due to biopsy results and the immunological analysis of cryoglobulins. Therefore, the common belief that mixed cryoglobulinemia is associated with palpable purpura may not always be true, and it is important to recognize that the clinical presentation of cryoglobulinemia can be a combination of the multiple types.