Etiology and pathogenesis of rheumatoid vasculitis
- Patrick Whelan, MD, PhD
Patrick Whelan, MD, PhD
- Clinical Assistant Professor of Microbiology and Immunology, University of Southern California
Rheumatoid vasculitis (RV) refers to a destructive, inflammatory process that is centered on the blood vessel wall itself. The condition occurs in patients with longstanding, severe rheumatoid arthritis (RA). RV is often associated with substantial potential morbidity, requires intensive immunosuppressive therapy, and leads to a significantly higher mortality than RA itself. Within a given patient with RV, clinical features of both medium- and small-vessel disease may be found. RV leads to necrosis, blood vessel occlusion, and tissue ischemia in a manner that resembles other forms of systemic vasculitis, particularly polyarteritis nodosa (medium-vessel disease) and cutaneous small-vessel vasculitis. (See "Overview of and approach to the vasculitides in adults" and "Clinical manifestations and diagnosis of polyarteritis nodosa in adults" and "Overview of cutaneous small vessel vasculitis".)
Understanding of the precipitating factors for these extremes of blood vessel inflammation in RA is limited. Although the decreased life expectancy and early cardiovascular mortality in RA are well-recognized, any relationship between atherosclerotic vascular disease leading to thrombosis and RV is dubious, despite many common risk factors for these two RA complications. Atherosclerotic coronary heart disease and its relationship to RA are discussed in detail separately. (See "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management".)
The etiology and pathogenesis of RV are reviewed in this topic. The epidemiology, clinical manifestations, diagnosis, and treatment of this disorder are discussed separately. (See "Clinical manifestations and diagnosis of rheumatoid vasculitis" and "Treatment of rheumatoid vasculitis".)
HISTOPATHOLOGY AND CLASSIFICATION
Rheumatoid vasculitis (RV) has been classified among the forms of vasculitis associated with systemic disease, rather than as a small-, medium-, or variable-vessel form of vasculitis (see "Overview of and approach to the vasculitides in adults"). The first series of patients with RV was published in 1951, describing transmural inflammation of large arterioles and small arteries in 5 of 55 patients (9 percent) who underwent skeletal muscle biopsy . A classification of vasculitis published in 1978 focused on the skin manifestations of RV and placed it as a subcategory of hypersensitivity angiitis associated with immune complex deposition primarily in small venules . Although this type of blood vessel involvement occurs in RV, the most devastating clinical features of the condition stem from vasculitis affecting medium-sized arteries in a manner resembling polyarteritis nodosa. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults".)
Placing RV in any classification of vasculitis is difficult because of the variability both in the size of the vessel involved and in the histologic findings. Three major vasculitis classifications published in the 1990s chose not to address “secondary” forms of vasculitis that occur in patients with known “connective tissue disorders” (systemic autoimmune rheumatic diseases) [3-5]. However, a group of vasculitis experts convened in 2011 for the second International Chapel Hill Consensus Conference updated the previous classification and chose to include four new categories of vasculitis, one of which was “vasculitis associated with systemic disease” . The conference participants were reluctant to broadly divide all the different vasculitic diseases into “primary” and “secondary” forms of vasculitis, due to the expectation that ongoing research might be expected to eventually move certain conditions from the primary into the secondary category as the pathogenesis of these diseases becomes better understood. (See "Overview of and approach to the vasculitides in adults".)
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- HISTOPATHOLOGY AND CLASSIFICATION
- ETIOLOGY AND RISK
- Genetic risk factors
- Cigarette smoking
- Mechanisms of vascular injury
- - Endothelial cell antibodies
- - Immune complex deposition
- - Cell-mediated immunity
- - Cytokine- and free radical-mediated endothelial injury
- Other factors