Clinical manifestations and diagnosis of rheumatoid vasculitis
- Patrick Whelan, MD, PhD
Patrick Whelan, MD, PhD
- Associate in Rheumatology (Pediatrics)
- Massachusetts General Hospital for Children
Blood vessel inflammation is a central feature of rheumatoid arthritis (RA). Synovial membrane inflammation is characterized histologically by mononuclear cell cuffing of postcapillary venules. In addition, vascular inflammation is considered the primary event in the formation of rheumatoid nodules . In nodule formation, small-vessel vasculitis leads to fibrinoid necrosis that forms the core of the lesion, surrounded by fibroblastic proliferation.
In contrast to this type of blood vessel inflammation, however, the term “rheumatoid vasculitis” (RV) refers specifically to a protean, destructive inflammatory process that is centered on the blood vessel wall itself and that is associated with substantial morbidity. RV may affect a wide range of blood vessel types, from medium-sized muscular arteries to somewhat smaller arterioles to post-capillary venules. Within a given patient, clinical features of both medium- and small-vessel disease may be found. RV leads to necrosis, to blood vessel occlusion, and to tissue ischemia in a manner that resembles other forms of systemic vasculitis, particularly polyarteritis nodosa. (See "Clinical manifestations and diagnosis of polyarteritis nodosa in adults".)
This topic will review the clinical features of RV and the ways in which the diagnosis is established. The epidemiology, pathophysiology, and treatment of RV are presented separately. (See "Epidemiology and pathogenesis of rheumatoid vasculitis" and "Treatment of rheumatoid vasculitis".)
Rheumatoid vasculitis (RV) typically occurs in patients with longstanding, joint-destructive rheumatoid arthritis (RA). In one study, the mean duration between the diagnosis of RA and the onset of vasculitic symptoms was 13.6 years . Presentations of RV within five years of the RA diagnosis are very unusual. In a study of patients with RV diagnosed between 1980 and 1993, many (68 percent) had rheumatoid nodules (picture 1) and patients were typically strongly positive for rheumatoid factor . In a study of patients between 2000 and 2010, rheumatoid nodules were seen in only 44 percent of patients . RV usually develops at a time when the inflammatory arthritis is “burned out” (ie, when the erosive process that led to joint destruction has become less active). At such times, unfortunately, patients who have already incurred considerable morbidity from RA and its therapies require intensive, potentially toxic treatments more than ever.
In a cohort of 86 patients with RV diagnosed between 2000 and 2010, risk factors associated with the development of RV, after adjusting for age and disease duration, included current smoking at time of RA diagnosis, coexistent vascular disease (both peripheral vascular disease and cerebrovascular disease), and severe RA (defined by the presence of radiographic erosions, rheumatoid nodules, or a requirement for joint surgery) . Patients who had used biologic agents were at increased risk, while those who had received hydroxychloroquine or low-dose aspirin were at reduced risk.
- SOKOLOFF L, MCCLUSKEY RT, BUNIM JJ. Vascularity of the early subcutaneous nodule of rheumatoid arthritis. AMA Arch Pathol 1953; 55:475.
- Scott DG, Bacon PA, Tribe CR. Systemic rheumatoid vasculitis: a clinical and laboratory study of 50 cases. Medicine (Baltimore) 1981; 60:288.
- Voskuyl AE, Zwinderman AH, Westedt ML, et al. Factors associated with the development of vasculitis in rheumatoid arthritis: results of a case-control study. Ann Rheum Dis 1996; 55:190.
- Makol A, Crowson CS, Wetter DA, et al. Vasculitis associated with rheumatoid arthritis: a case-control study. Rheumatology (Oxford) 2014; 53:890.
- Myasoedova E, Crowson CS, Turesson C, et al. Incidence of extraarticular rheumatoid arthritis in Olmsted County, Minnesota, in 1995-2007 versus 1985-1994: a population-based study. J Rheumatol 2011; 38:983.
- Bartels C, Bell C, Rosenthal A, et al. Decline in rheumatoid vasculitis prevalence among US veterans: a retrospective cross-sectional study. Arthritis Rheum 2009; 60:2553.
- Ward MM. Decreases in rates of hospitalizations for manifestations of severe rheumatoid arthritis, 1983-2001. Arthritis Rheum 2004; 50:1122.
- Ntatsaki E, Mooney J, Scott DG, Watts RA. Systemic rheumatoid vasculitis in the era of modern immunosuppressive therapy. Rheumatology (Oxford) 2014; 53:145.
- Vollertsen RS, Conn DL, Ballard DJ, et al. Rheumatoid vasculitis: survival and associated risk factors. Medicine (Baltimore) 1986; 65:365.
- Geirsson AJ, Sturfelt G, Truedsson L. Clinical and serological features of severe vasculitis in rheumatoid arthritis: prognostic implications. Ann Rheum Dis 1987; 46:727.
- Sayah A, English JC 3rd. Rheumatoid arthritis: a review of the cutaneous manifestations. J Am Acad Dermatol 2005; 53:191.
- Bywaters EG. A Variant of Rheumatoid Arthritis resembling Palindromic Rheumatism. Ann Rheum Dis 1949; 8:1.
- Watts RA, Carruthers DM, Scott DG. Isolated nail fold vasculitis in rheumatoid arthritis. Ann Rheum Dis 1995; 54:927.
- BYWATERS EG. Peripheral vascular obstruction in rheumatoid arthritis and its relationship to other vascular lesions. Ann Rheum Dis 1957; 16:84.
- Puéchal X, Said G, Hilliquin P, et al. Peripheral neuropathy with necrotizing vasculitis in rheumatoid arthritis. A clinicopathologic and prognostic study of thirty-two patients. Arthritis Rheum 1995; 38:1618.
- Said G, Lacroix C. Primary and secondary vasculitic neuropathy. J Neurol 2005; 252:633.
- SCHMID FR, COOPER NS, ZIFF M, McEWEN C. Arteritis in rheumatoid arthritis. Am J Med 1961; 30:56.
- Okhravi N, Odufuwa B, McCluskey P, Lightman S. Scleritis. Surv Ophthalmol 2005; 50:351.
- Squirrell DM, Winfield J, Amos RS. Peripheral ulcerative keratitis 'corneal melt' and rheumatoid arthritis: a case series. Rheumatology (Oxford) 1999; 38:1245.
- Horo S, Sudharshan S, Biswas J. Recurrent posterior scleritis--report of a case. Ocul Immunol Inflamm 2006; 14:51.
- Fong LP, Sainz de la Maza M, Rice BA, et al. Immunopathology of scleritis. Ophthalmology 1991; 98:472.
- McCluskey PJ, Watson PG, Lightman S, et al. Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients. Ophthalmology 1999; 106:2380.
- SOKOLOFF L. The heart in rheumatoid arthritis. Am Heart J 1953; 45:635.
- CRUICKSHANK B. The arteritis of rheumatoid arthritis. Ann Rheum Dis 1954; 13:136.
- van Albada-Kuipers GA, Bruijn JA, Westedt ML, et al. Coronary arteritis complicating rheumatoid arthritis. Ann Rheum Dis 1986; 45:963.
- JOHNSON RL, SMYTH CJ, HOLT GW, et al. Steroid therapy and vascular lesions in rheumatoid arthritis. Arthritis Rheum 1959; 2:224.
- Takayanagi M, Haraoka H, Kikuchi H, Hirohata S. Myocardial infarction caused by rheumatoid vasculitis: histological evidence of the involvement of T lymphocytes. Rheumatol Int 2003; 23:315.
- Wållberg-Jonsson S, Cvetkovic JT, Sundqvist KG, et al. Activation of the immune system and inflammatory activity in relation to markers of atherothrombotic disease and atherosclerosis in rheumatoid arthritis. J Rheumatol 2002; 29:875.
- Park YB, Ahn CW, Choi HK, et al. Atherosclerosis in rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound. Arthritis Rheum 2002; 46:1714.
- Kumeda Y, Inaba M, Goto H, et al. Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis. Arthritis Rheum 2002; 46:1489.
- Kaneko S, Yamashita H, Sugimori Y, et al. Rheumatoid arthritis-associated aortitis: a case report and literature review. Springerplus 2014; 3:509.
- Gravallese EM, Corson JM, Coblyn JS, et al. Rheumatoid aortitis: a rarely recognized but clinically significant entity. Medicine (Baltimore) 1989; 68:95.
- Loricera J, Blanco R, Hernández JL, et al. Non-infectious aortitis: a report of 32 cases from a single tertiary centre in a 4-year period and literature review. Clin Exp Rheumatol 2014.
- Slobodin G, Naschitz JE, Zuckerman E, et al. Aortic involvement in rheumatic diseases. Clin Exp Rheumatol 2006; 24:S41.
- Yousem SA, Colby TV, Carrington CB. Lung biopsy in rheumatoid arthritis. Am Rev Respir Dis 1985; 131:770.
- Boers M, Croonen AM, Dijkmans BA, et al. Renal findings in rheumatoid arthritis: clinical aspects of 132 necropsies. Ann Rheum Dis 1987; 46:658.
- Harper L, Cockwell P, Howie AJ, et al. Focal segmental necrotizing glomerulonephritis in rheumatoid arthritis. QJM 1997; 90:125.
- Qarni MU, Kohan DE. Pauci-immune necrotizing glomerulonephritis complicating rheumatoid arthritis. Clin Nephrol 2000; 54:54.
- Pagnoux C, Mahr A, Cohen P, Guillevin L. Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss syndrome, or rheumatoid arthritis-associated vasculitis. Medicine (Baltimore) 2005; 84:115.
- Achkar AA, Stanson AW, Johnson CM, et al. Rheumatoid vasculitis manifesting as intra-abdominal hemorrhage. Mayo Clin Proc 1995; 70:565.
- Babian M, Nasef S, Soloway G. Gastrointestinal infarction as a manifestation of rheumatoid vasculitis. Am J Gastroenterol 1998; 93:119.
- Mizuno K, Ikeda K, Saida Y, et al. Hepatic hemorrhage in malignant rheumatoid arthritis. Am J Gastroenterol 1996; 91:2624.
- Mongan ES, Cass RM, Jacox RF, Vaughen JH. A study of the relation of seronegative and seropositive rheumatoid arthritis to each other and to necrotizing vasculitis. Am J Med 1969; 47:23.
- van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, et al. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum 2004; 50:709.
- Sihvonen S, Korpela M, Mustila A, Mustonen J. The predictive value of rheumatoid factor isotypes, anti-cyclic citrullinated peptide antibodies, and antineutrophil cytoplasmic antibodies for mortality in patients with rheumatoid arthritis. J Rheumatol 2005; 32:2089.
- Laskari K, Ahmadi-Simab K, Lamken M, et al. Are anti-cyclic citrullinated peptide autoantibodies seromarkers for rheumatoid vasculitis in a cohort of patients with systemic vasculitis? Ann Rheum Dis 2010; 69:469.
- Tervaert JW, Damoiseaux J, Boomsma MM, Stegeman CA. Absence of anti-cyclic citrullinated peptide antibodies in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2002; 46:849.
- Belizna C, Duijvestijn A, Hamidou M, Tervaert JW. Antiendothelial cell antibodies in vasculitis and connective tissue disease. Ann Rheum Dis 2006; 65:1545.
- Matsumoto I, Staub A, Benoist C, Mathis D. Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme. Science 1999; 286:1732.
- van Gaalen FA, Toes RE, Ditzel HJ, et al. Association of autoantibodies to glucose-6-phosphate isomerase with extraarticular complications in rheumatoid arthritis. Arthritis Rheum 2004; 50:395.
- Franco AE, Schur PH. Hypocomplementemia in rheumatoid arthritis. Arthritis Rheum 1971; 14:231.
- Glass D, Soter NA, Schur PH. Rheumatoid vasculitis. Arthritis Rheum 1976; 19:950.
- Schneider HA, Yonker RA, Katz P, et al. Rheumatoid vasculitis: experience with 13 patients and review of the literature. Semin Arthritis Rheum 1985; 14:280.
- Conn DL, McDuffie FC, Dyck PJ. Immunopathologic study of sural nerves in rheumatoid arthritis. Arthritis Rheum 1972; 15:135.
- EPSTEIN WV, ENGLEMAN EP. The relation of the rheumatoid factor content of serum to clinical neurovascular manifestations of rheumatoid arthritis. Arthritis Rheum 1959; 2:250.
- CLINICAL PRESENTATION
- Constitutional symptoms
- Cutaneous vasculitis
- Neurologic disease
- Ocular disease
- Cardiac disease
- Pulmonary disease
- Renal disease
- Gastrointestinal, pancreatic, and hepatic disease
- LABORATORY FINDINGS
- - Rheumatoid factor
- - Anti-CCP antibodies
- - Antinuclear antibodies
- - Antineutrophil cytoplasmic antibodies
- - Anti-endothelial cell antibodies
- - Antibodies to glucose-6-phosphate isomerase
- Confirming the diagnosis
- - Angiography
- DIFFERENTIAL DIAGNOSIS
- Mimics of vasculitis
- Other vasculitides
- SUMMARY AND RECOMMENDATIONS