Cryoglobulinemic vasculitis
From Wikipedia, the free encyclopedia
| Cryoglobulinemic vasculitis | |
|---|---|
| Specialty | Hematology |
Cryoglobulinemic vasculitis is a form of inflammation affecting the blood vessels (vasculitis) caused by the deposition of abnormal proteins called cryoglobulins. These immunoglobulin proteins are soluble at normal body temperatures, but become insoluble below 37 °C (98.6 °F) and subsequently may aggregate within smaller blood vessels. Inflammation within these obstructed blood vessels is due to the deposition of complement proteins which activate inflammatory pathways.[1]
Cryoglobulinemic vasculitis most commonly affect the skin, causing a raised, pinpoint rash on the lower extremities known as purpura. The kidneys may additionally be affected by this form of vasculitis, resulting in membranoproliferative glomerulonephritis. Fevers, painful muscles and joints, and peripheral nerve damage are other common manifestations of cryoglobulinemic vasculitis.[2]
The incidence of cryoglobulinemic vasculitis is low and highly corresponds to the presence of hepatitis C virus infection, with increased prevalence in Southern Europe. Only about 30% of individuals with cryoglobulinemia develop vasculitis and associated symptoms.[3] In a review of 279 patients, the average age of patients with symptomatic disease associated with hepatitis C virus was 54 years old, with an equal distribution between men and women.[4]
Pathophysiology
Cryoglobulinemia is currently classified by the type of immunoglobulin, IgM or IgG, present in blood as well as whether the immunoglobulin is monoclonal or polyclonal. Type II cryoglobulinemia, is defined as a mix of monoclonal IgM or polyclonal IgG, whereas type III cryoglobulinemia is classified as IgM and IgG that are both polyclonal only. The immunoglobulins in either cryoglobulinemia type have rheumatoid factor activity, allowing binding of the Fc subunit of IgM to IgG which has the capacity to activate complement proteins and deposit in the endothelium of small and medium-sized blood vessels.
In contrast, type I cryoglobulinemia causes damage solely due to hyperviscosity syndrome, which refers to the aggregation and resulting obstructing nature of cryoglobulins in blood vessels resulting in reduced perfusion of tissues and possibly necrosis if prolonged. Therefore, vasculitis generally occurs only in patients affected by mixed (type 2 and 3) cryoglobulinemia, as simple (type 1) cryoglobulinemia causes a hyperviscosity syndrome without complement activation.[5]
The large majority of cases of cryoglobulinemic vasculitis are associated with underlying medical conditions which contribute to or exacerbate the pathophysiology, the most common being hepatitis C virus infection. There are a number of other rheumatologic, oncologic, inflammatory, and infectious associations including Sjogren's syndrome, B-cell lymphoma, rheumatoid arthritis, systemic lupus erythematous, and other hepatitis viral infections. Type III cryoglobulinemia is most associated with autoimmune conditions.[6]
Manifestations
At least 50% of patients with cryoglobulinemic vasculitis have only mild symptoms. More severe symptoms involve renal, gastrointestinal, and neurological damage with cardiovascular and respiratory complications presenting more rarely in a population of 279 patients with cryoglobulins and hepatitis C infection.[4] Prevalence of these symptoms may vary depending on the underlying etiology contributing to the cryoglobulinemia.[7]
Only about 5–10% of patients with cryoglobulins found in the bloodstream due to Hepatitis C virus develop symptoms.[4] Approximately 20-40% of individuals with symptomatic cryoglobulinemic vasculitis eventually develop renal damage, usually years following initial diagnosis.[6]
Relapse in vasculitis refers to the recurrence or reactivation of disease symptoms and inflammation after a period of improvement or remission.A systematic review was conducted to investigate the identifiable risk factors for relapse in non-infectious cryoglobulinemic vasculitis with an underlying immunopathological cause, specifically in relation to the type of immunoglobulin involved.[8]