BOWEL INFLAMMATION AND THE SPONDYLOARTHROPATHIES

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The concept of spondyloarthropathies (SpA) gathers together a group of chronic diseases with common clinical, biological, genetic and therapeutic characteristics. The concept forms a distinct entity, different from other rheumatic diseases. The target organs are not only the joint, but also the axial skeleton, the enthesis, the eye, the gut, the urogenital tract, the skin and sometimes the heart. The prevalence of this entity in the general population is estimated 1%, equal to the prevalence of rheumatoid arthritis. Diseases included within this concept are ankylosing spondylitis (AS), reactive arthritis (ReA) and Reiter's disease, undifferentiated spondyloarthropathies (Undiff SpA), some forms of psoriatic arthritis (PsA), of juvenile chronic arthritis (JCA), of acute anterior uveitis (AAU), and the idiopathic inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Clinical characteristics of these diseases are the absence of rheumatoid factor and rheumatoid nodules, the presence of a typical pattern of inflammatory arthritis (pauci-articular, asymmetrical, involving large and small joints mostly of the lower limbs), the presence of inflammatory enthesiopathies (mostly of the feet), the presence of sacroiliitis and sometimes spondylitis, the clinical overlap between different diseases of the concept, the familial aggregation of these diseases, and the strong genetic relationship to human leukocyte antigen (HLA) B27.

The axis between the gut and the joints is suggested by several clinical situations as the arthritis occurring in Whipple's disease 70 and in celiac disease. 9, 74 Inflammatory polyarthritis has been reported after intestinal bypass surgery for morbid obesity. 20, 144 Enterogenic ReA induced by Salmonella typhimurium, Shigella enteritidis, Yersinia enterocolitica, and Campylobacter enteritidis and the peripheral arthritides occurring in UC and CD are other evidence of the relation between the locomotor system and the gastrointestinal tract.

In animal models, peripheral arthritis was described in pigs by feeding them a protein-rich diet, and an intestinal overgrowth of Clostridium perfringens was observed. 81 A mouse model of peripheral arthritis was reported by oral challenge with bovine serum albumin. 68 More recently, in transgenic HLA-B27 rats and mice, inflammatory bowel lesions, especially located in the colon, were found in all diseased animals. 51, 59 The gut lesions and the joint abnormalities did not occur in animals developed in germ-free conditions, and these phenomena appear once the animals are put in normal conditions. 139

All these findings suggest that the gut can play an important role in the pathogenesis of many rheumatic conditions even if the clinical gut manifestations are minimal or absent or when they follow inflammatory joint features.

Section snippets

Prevalence of Gut Abnormalities in Spondyloarthropathies

Since the first report on subclinical gut inflammation in SpA patients, 88 revealed by ileocolonoscopy, exploring the whole colon, cecum, and terminal ileum, several authors have confirmed these findings in different forms of spondyloarthropathy (SpA). 3, 29, 32, 49, 66, 67, 95, 137 The prevalence of macroscopic and microscopic signs of gut inflammation reported by the respective authors is listed in Table 1. In enterogenic ReA, macroscopic lesions were found in approximately 50% of patients,

RHEUMATIC MANIFESTATIONS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Rheumatic symptoms are the most common extraintestinal manifestations in patients with IBD. In some cases, the occurrence of arthritis is related to the presence of other extraintestinal manifestations, such as uveitis and erythema nodosum. The peripheral arthritis and the spondylitis occurring in patients with IBD are considered as enteropathic arthritides. Other locomotor extraintestinal manifestations include granulomatous joint and bone involvement, periostitis, clubbing, and osteoporosis.

The Gut in Animal Models of Spondyloarthropathy

The challenging link between gut inflammation and arthropathies in humans has also been documented in some animal models of SpA. HLA-B27 transgenic rats provide the first and most convincing model in which a relationship between gut and synovial inflammation was observed. Several lines of rats transgenic for various class 1 HLA heavy chains and human β2m-microglobulin (hβ2m) genes have been established. 51 Half of the lines expressing HLA-B27 and hβ2m develop a spontaneous, multisystem,

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    Address reprint requests to Dr. Eric Veys University Hospital Ghent Department of Rheumatology De Pintelaan 185 B-9000 Gent Belgium

    Supported by NFWO grant 3.0028.95 and 3.0022.96 and by a concerted action grant GOA96001 of the University of Belgium. Dr. Elewaut is a NFWO Research Assistant.

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