How I treat cryoglobulinemia

Abstract

Cryoglobulinemia is a distinct entity characterized by the presence of cryoglobulins in the serum. Cryoglobulins differ in their composition, which has an impact on the clinical presentation and the underlying disease that triggers cryoglobulin formation. Cryoglobulinemia is categorized into two main subgroups: type I, which is seen exclusively in clonal hematologic diseases, and type II/III, which is called mixed cryoglobulinemia and is seen in hepatitis C virus infection and systemic diseases such as B-cell lineage hematologic malignancies and connective tissue disorders. Clinical presentation is broad and varies between types but includes arthralgia, purpura, skin ulcers, glomerulonephritis, and peripheral neuropathy. Life-threatening manifestations can develop in a small proportion of patients. A full evaluation for the underlying cause is required, because each type requires a different kind of treatment, which should be tailored on the basis of disease severity, underlying disease, and prior therapies. Relapses can be frequent and can result in significant morbidity and cumulative organ impairment. We explore the spectrum of this heterogeneous disease by discussing the disease characteristics of 5 different patients.

Peripheral nervous system involvement in lymphomas

“…In the occurrence of cryoglobulinemia, both type I (monoclonal IgMs or IgGs, rarely IgAs) and type II (mixed forms, usually associated with HCV infections or connective tissue diseases) can be associated with MGUS or B‐cell malignancies (WM, CLL), with a predominance of type II cryoglobulins in WM. Type III cryoglobulinemia caused by polyclonal IgM with rheumatoid factor activity and polyclonal IgG is seen predominantly in connective tissue diseases or in chronic infections (mainly HCV) . Monoclonal IgMs behaving as cryoglobulins cause severe painful neuropathy that may present with multifocal distribution also involving cranial nerves.…”

“…Cryoglobulins‐associated neuropathy also benefit from rituximab, as well as from steroids and plasma‐exchange in case of life‐threatening manifestations . IgM AL neuropathy may respond to bortezomib‐ or bendamustine‐based chemotherapy and may be ibrutinib …”

Non-Anti-Neutrophil Anti-Cytoplasmic Antibodies Associated Methimazole-Induced Nephritis: Case and Review of Literature

“…SSA/SSB and positive cryoglobulinemia were both characteristics described in Day et al's carbimazole-induced vasculitis. In our patient, however, cryoglobulin quantity was negative and there was no other clear supporting evidence for cryoglobulinemia such as skin lesions including palpable purpura, ulcers, and areas of necrosis that occur in 69-89% of mixed cryoglobulinemic disease [12]. There was no evidence of cryoglobulin-associated glomerulonephritis.…”

Peripheral Ulcerative Keratitis Associated with HCV-Related Cryoglobulinemia

“…If more than one immunoglobulin component is present, they are termed mixed cryoglobulins. Their prevalence, however, is far more common in HCV patient [4] and can lead to mixed cryoglobulinemia syndrome, a small to medium vessel vasculitis, resulting from production of polyclonal IgG and monoclonal (type II) or polyclonal (type III) IgM with rheumatoid factor activity [5]. This condition is associated with HCV infection in the large majority of patients, where a viral induced clonal B-cell expansion results in production of IgM that interacts with anti-HCV IgG and forms immune complexes [5].…”

“…A report by Johnson and Ohlstein, 2011 [3], describes a case of PUK and necrotizing scleritis induced by trauma in a patient with HCV-related cryoglobulinemia, without systemic involvement. It is known that the vast majority of patients with circulating cryoglobulins remain asymptomatic [4], although probably with higher sensitivity to trigger events. Also, PUK with associated scleritis may be the first clinical sign of MC [6].…”