Review Question - QID 221284

This patient with palpable purpura, peripheral neuropathy, arthralgias, low complement levels, and elevated liver enzymes, most likely has mixed cryoglobulinemia syndrome. Hepatitis C viral load should be performed because many of these cases are related to hepatitis infection.

Mixed cryoglobulinemia syndrome is a condition that is typically characterized by purpura, arthralgias, and weakness. This syndrome is commonly associated with chronic inflammatory disorders such as HIV infection, chronic HCV infection, and systemic lupus erythematosus. Cryoglobulins are antibodies that can be either monoclonal IgM or polyclonal IgG and can form immune complexes that activate the complement pathway. Therefore, almost all cases of this syndrome have increased rheumatoid factor and hypocomplementemia. While severe cases with renal and neurologic involvement may require immunosuppression and plasmapheresis, the primary treatment approach focuses on managing the underlying disease.

Anis et al. review the evidence regarding vasculitis with renal involvement in patients with essential mixed cryoglobulinemia. They found that essential mixed cryoglobulinemia requires extensive laboratory investigation for proper diagnosis. They recommend establishing new consensus guidelines to detect cryoglobulinemic syndromes and reduce variability in inter-laboratory reporting.

Figure/Illustration A is a clinical photograph demonstrating purpuric lesions with ulceration (blue circles). These skin findings are consistent with a diagnosis of mixed cryoglobulinemia.

Incorrect Answers:
Answer 1: Anti-cardiolipin antibody assays can be used to screen for antiphospholipid syndrome, an autoimmune disease that increases coagulability. This patient has no history of cardioembolic events and no indications of pro-coagulability on physical exam.

Answer 2: Bone marrow biopsy is the test of choice to screen for type 1 cryoglobulinemia, which is often associated with hematologic conditions like multiple myeloma, Waldenström macroglobulinemia, or chronic lymphocytic leukemia. It is often asymptomatic but can present with hyper-viscosity symptoms like blurry vision and dizziness.

Answer 3: A chest radiograph is useful in evaluating for sarcoidosis, which can present with skin findings and pulmonary symptoms. Patients with sarcoidosis have erythema nodosum (painful nodules usually on the anterior tibia) and do not have symptoms of peripheral neuropathy. Furthermore, sarcoidosis does not cause hypocomplementemia or explain the positive rheumatoid factor in this patient.

Answer 5: Parvovirus B19 IgM antibody levels can help identify a parvovirus B19 infection, which can present acutely with arthritis of the hands, knees, and ankles as well as a reticular, maculopapular rash involving the trunk and limbs. This diagnosis would not explain the laboratory findings of hypocomplementemia, positive rheumatoid factor, and increased creatinine.

Bullet Summary:
Mixed cryoglobulinemia associated with hepatitis C should be suspected in patients who present with rash, arthralgia, peripheral neuropathy, and hypocomplementemia.