Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases
- Robert D Inman, MD, FRCPC, FACP, FRCP Edin
Robert D Inman, MD, FRCPC, FACP, FRCP Edin
- Professor of Medicine and Immunology
- University of Toronto
Arthritis is a recognized extraintestinal manifestation of several illnesses and conditions, including inflammatory bowel disease (IBD), bacterial infections of the gut, gluten-sensitive enteropathy (celiac disease), various parasitic infections, pseudomembranous colitis, and Whipple’s disease, as well as following intestinal bypass surgery. Other illnesses also have a propensity for causing inflammation of joints and the gut.
The clinical manifestations, and diagnosis of arthritis associated with IBD are presented here. Other disorders associated with both gastrointestinal disease and joint involvement are discussed here briefly, particularly in the context of the differential diagnosis of patients with these symptoms and findings. The treatment of IBD-associated arthritis; and the pathogenesis, other clinical manifestations, diagnosis, and management of inflammatory bowel disease, including Crohn disease and ulcerative colitis, are reviewed in detail separately. (See "Treatment of arthritis associated with inflammatory bowel disease" and "Immune and microbial mechanisms in the pathogenesis of inflammatory bowel disease" and "Clinical manifestations, diagnosis and prognosis of Crohn disease in adults" and "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults" and "Management of severe ulcerative colitis in adults" and "Overview of the medical management of mild to moderate Crohn disease in adults".)
There are several mechanisms which may underlie concurrent inflammation in the gut and the joint, but the precise pathogenic pathways remain to be defined. A disturbance of the gut barrier is postulated as the first and primary process for most of these proposed mechanisms. An alternative suggestion is that shared genetic or environmental factors predispose individuals to various organ manifestations of these inflammatory conditions, such as gut or joint involvement . In addition, there may be a role for translocation of pathogens, as occurs in parasitic rheumatism, in which case effective antihelminthic treatment resolves the arthritis. There may also be circulating microbial elements, as proposed for post-Yersinia reactive arthritis, in which case the pathogen cannot be cultured from the synovial fluid.
Both human leukocyte antigen (HLA) and non-HLA genes have been associated with different articular phenotypes, with an increase in HLA-B27 in patients with spondylitis/sacroiliitis (see 'Laboratory findings' below). Molecular mimicry, in which an immune response to a gut-derived antigen cross-reacts with normal host protein, has been invoked to explain the role of human leukocyte antigen (HLA)-B27 in post-dysenteric reactive arthritis, but this mechanism has proved difficult to confirm definitively in either the clinical setting or in experimental models of colitis. Circulating immune complexes, initiated by an immune response to gut microbes, have been implicated in the arthritis following intestinal bypass surgery.
The concept of distinctive trafficking of gut-derived immunocompetent cells has been supported by studies of the integrins which direct the homing patterns of circulating lymphocytes. Cells such as mucosa-associated invariant T cells (MAITS) can be recovered from the synovial fluid of patients with ankylosing spondylitis . Integrins, such as alpha4-beta7 integrin, are thought to have a role in mediating trafficking of lymphocytes to gut and joint tissues.
- Said-Nahal R, Miceli-Richard C, Berthelot JM, et al. The familial form of spondylarthropathy: a clinical study of 115 multiplex families. Groupe Français d'Etude Génétique des Spondylarthropathies. Arthritis Rheum 2000; 43:1356.
- Gracey E, Yao Y, Green B, et al. Sexual Dimorphism in the Th17 Signature of Ankylosing Spondylitis. Arthritis Rheumatol 2016; 68:679.
- De Keyser F, Elewaut D, De Vos M, et al. Bowel inflammation and the spondyloarthropathies. Rheum Dis Clin North Am 1998; 24:785.
- Van Praet L, Van den Bosch FE, Jacques P, et al. Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model. Ann Rheum Dis 2013; 72:414.
- Karreman MC, Luime JJ, Hazes JM, Weel AE. The Prevalence and Incidence of Axial and Peripheral Spondyloarthritis in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis 2016.
- Rudwaleit M, Baeten D. Ankylosing spondylitis and bowel disease. Best Pract Res Clin Rheumatol 2006; 20:451.
- Scarpa R, del Puente A, D'Arienzo A, et al. The arthritis of ulcerative colitis: clinical and genetic aspects. J Rheumatol 1992; 19:373.
- Leirisalo-Repo M, Turunen U, Stenman S, et al. High frequency of silent inflammatory bowel disease in spondylarthropathy. Arthritis Rheum 1994; 37:23.
- de Vlam K, Mielants H, Cuvelier C, et al. Spondyloarthropathy is underestimated in inflammatory bowel disease: prevalence and HLA association. J Rheumatol 2000; 27:2860.
- Tromm A, May D, Almus E, et al. Cutaneous manifestations in inflammatory bowel disease. Z Gastroenterol 2001; 39:137.
- Atzeni F, Defendenti C, Ditto MC, et al. Rheumatic manifestations in inflammatory bowel disease. Autoimmun Rev 2014; 13:20.
- Inman RD. Arthritis and enteritis--an interface of protean manifestations. J Rheumatol 1987; 14:406.
- Lubrano E, Ciacci C, Ames PR, et al. The arthritis of coeliac disease: prevalence and pattern in 200 adult patients. Br J Rheumatol 1996; 35:1314.
- Weiner SR, Clarke J, Taggart N, Utsinger PD. Rheumatic manifestations of inflammatory bowel disease. Semin Arthritis Rheum 1991; 20:353.
- Gravallese EM, Kantrowitz FG. Arthritic manifestations of inflammatory bowel disease. Am J Gastroenterol 1988; 83:703.
- Stolwijk C, Pierik M, Landewé R, et al. Prevalence of self-reported spondyloarthritis features in a cohort of patients with inflammatory bowel disease. Can J Gastroenterol 2013; 27:199.
- Wordsworth P. Arthritis and inflammatory bowel disease. Curr Rheumatol Rep 2000; 2:87.
- Fomberstein B, Yerra N, Pitchumoni CS. Rheumatological complications of GI disorders. Am J Gastroenterol 1996; 91:1090.
- Orchard TR, Holt H, Bradbury L, et al. The prevalence, clinical features and association of HLA-B27 in sacroiliitis associated with established Crohn's disease. Aliment Pharmacol Ther 2009; 29:193.
- Peeters H, Vander Cruyssen B, Laukens D, et al. Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn's disease. Ann Rheum Dis 2004; 63:1131.
- McEniff N, Eustace S, McCarthy C, et al. Asymptomatic sacroiliitis in inflammatory bowel disease. Assessment by computed tomography. Clin Imaging 1995; 19:258.
- van Tubergen A, Heuft-Dorenbosch L, Schulpen G, et al. Radiographic assessment of sacroiliitis by radiologists and rheumatologists: does training improve quality? Ann Rheum Dis 2003; 62:519.
- Kitis G, Thompson H, Allan RN. Finger clubbing in inflammatory bowel disease: its prevalence and pathogenesis. Br Med J 1979; 2:825.
- Schiellerup P, Krogfelt KA, Locht H. A comparison of self-reported joint symptoms following infection with different enteric pathogens: effect of HLA-B27. J Rheumatol 2008; 35:480.
- Carubbi F, Ruscitti P, Pantano I, et al. Jejunoileal bypass as the main procedure in the onset of immune-related conditions: the model of BADAS. Expert Rev Clin Immunol 2013; 9:441.
- McGill PE. Rheumatic syndromes associated with parasites. Baillieres Clin Rheumatol 1995; 9:201.
- Peng SL. Rheumatic manifestations of parasitic diseases. Semin Arthritis Rheum 2002; 31:228.
- McGill PE. Geographically specific infections and arthritis, including rheumatic syndromes associated with certain fungi and parasites, Brucella species and Mycobacterium leprae. Best Pract Res Clin Rheumatol 2003; 17:289.
- Baloch HM, Armstrong DT, Pulling TM, Miller LM. Hookworm-associated reactive spondyloarthritis. Arthritis Rheumatol 2014; 66:578.
- CLINICAL MANIFESTATIONS
- Peripheral arthritis
- - Type I arthropathy
- - Type II arthropathy
- Spondylitis and sacroiliitis
- Enthesitis and dactylitis
- Laboratory findings
- Radiographic findings
- DIFFERENTIAL DIAGNOSIS
- Joint disease and IBD
- Other diseases with bowel and joint involvement
- - Reactive arthritis
- - Whipple's disease
- - Behçet's syndrome
- - Celiac disease
- - Intestinal bypass arthritis
- - Parasitic rheumatism
- - Pseudomembranous colitis
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS