CiteULike: zubin_ars arthritis

Gut inflammation and spondyloarthropathies.

F De Keyser — 2008-02-12T22:11:32-00:00

Curr Rheumatol Rep, Vol. 4, No. 6. (December 2002), pp. 525-532.

Spondyloarthropathies (SpA) are a group of related disorders with common clinical and genetic characteristics. The prototype disease in this group is ankylosing spondylitis; other entities include reactive arthritis, psoriatic arthritis, and arthritis in patients with inflammatory bowel disease. Over recent years, there has been a special interest in the relation between spondylitis/synovitis and gut inflammation in patients with SpA. Two thirds of patients with undifferentiated SpA show histologic signs of gut inflammation, and a fraction of these patients go on to develop clinically overt Crohn's disease. In this review, the authors will focus on 1) the growing evidence that has been provided that gut inflammation in SpA is immunologically related to Crohn's disease, based on the molecular characterization of the inflammation (lymphocyte homing markers and ligands, T cell cytokines, macrophage markers, and serology); and 2) on the therapeutic implications resulting from this concept. The recent introduction and positioning of anti-tumor necrosis factor-alpha therapy in patients with ankylosing spondylitis and other types of SpA is, in large part, based on this concept.

Immune linkages between inflammatory bowel disease and spondyloarthropathies.

D Baeten — 2008-02-12T22:11:01-00:00

Curr Opin Rheumatol, Vol. 14, No. 4. (July 2002), pp. 342-347.

Gut involvement is a prominent feature of spondyloarthropathy (SpA). Analysis of immune alterations of the gut in SpA have shown two distinct aspects. On the one hand, gut inflammation in SpA seems closely related with gut inflammation seen in Crohn disease. On the other hand, gut inflammation in SpA is associated with peripheral joint inflammation. Recent studies have provided new insights into this gut-synovium axis. First, there is little new evidence to support the concept of viable microbial pathogens recirculating to the joint. In contrast, it seems likely that both bacterial antigens and reactive T cell clones home to the joint, and that adhesion molecules such as the beta7 integrins and VAP1 play an important role in this process. Second, there is increasing evidence that the different disease localizations in SpA are characterized by alterations of the innate immune system, which contribute to a breakdown of the immune tolerance and the creation of an inflammation-prone environment. Mediators of the innate immune system, such as scavenger receptors, interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-alpha), may therefore be interesting targets for therapeutic intervention, as illustrated by the effect of TNF-alpha blockade in SpA.

Therapy of spondylarthropathy in inflammatory bowel disease.

S Generini — 2008-02-12T22:09:37-00:00

Clin Exp Rheumatol, Vol. 20, No. 6 Suppl 28. (c 2002)

Musculoskeletal manifestations represent the most common extra-intestinal complication of inflammatory bowel diseases (IBD) and are usually included in the clinical spectrum of the spondyloarthropathies (SpA). Although control of intestinal inflammation often ameliorates articular symptoms, sometimes arthropathy is independent of the gut disease course and may require the same therapeutic options which apply to primary SpA diseases, but with caution so as not aggravate the IBD. At the moment, salicylates (sulphasalazine and mesalazine) and selective COX-2 inhibitors (which are preferable to traditional NSAIDs although they cannot be assumed to be safe for the gastrointestinal tract) are the first choice treatment. Several immunosuppressive and biological agents including methotrexate, thalidomide and TNFalpha antagonists have efficacy for both articular and intestinal inflammation and are currently in use for the induction of remission and for maintenance in more severe cases. New combination therapies and novel biologically-driven treatments, targeted to specific pathophysiological processes, might offer less toxicity and the potential for better treatment outcomes.

The role of gut inflammation in the pathogenesis of spondyloarthropathies.

H Mielants — 2008-02-12T22:08:10-00:00

Acta Clin Belg, Vol. 51, No. 5. (1996), pp. 340-349.

The concept of spondyloarthropathy (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, 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. Genetical predisposition (HLA-B27) is one of the clues to the pathogenesis of the disease. Since reactive arthritis is induced by specific urogenital or enterogenic bacteriae, and since the gut is implicated in different forms of spondyloarthropathies, especially in IBD, it was clear that the gut could play an important role by permitting exogenous factors to enter the body. This hypothesis was the rationale for investigating the gut in the spondyloarthropathies by performing ileocolonoscopies. In the first ileocolonoscopic studies of SpA patients, histological signs of gut inflammation were found in a relatively great number of patients, mostly without any clinical intestinal manifestations. These lesions were not seen in other inflammatory joint diseases. Further ileocolonoscopic studies confirmed the strong relationship between gut and joint inflammation. In patients in whom a second ileocolonoscopy was performed, remission of the joint inflammation was always connected with a disappearance of the gut inflammation, whereas persistence of locomotor inflammation was mostly associated to the persistence of gut inflammation. The hypothesis was proposed that some patients with a spondyloarthropathy had a form of subclinical Crohn's disease in which the locomotor inflammation was the only clinical expression. This hypothesis was confirmed in prospective long-term studies in which the ileocolonoscoped patients were reviewed 2 to 9 years later: about 6% of SpA patients not presenting any sign of Crohn's disease at first investigation but demonstrating gut inflammation on biopsy, developed full-blown Crohn's disease. The discovery of subclinical gut inflammation in the SpA had therapeutic consequences. Sulphasalazine (SASP) has been proven to be an active drug in the treatment of IBD. Since the gut could play a crucial role in SpA, it was logic to use this drug in the treatment of this disease. Multiple open and double-blind studies have proven the effectiveness of this drug in SpA; recent studies concluded that the beneficial effect of the drug in this disease entity is more prominent on the peripheral arthritis than on the axial disease.

Therapy insight: how the gut talks to the joints--inflammatory bowel disease and the spondyloarthropathies.

C Meier — 2008-02-12T21:58:04-00:00

Nat Clin Pract Rheumatol, Vol. 3, No. 11. (November 2007), pp. 667-674.

Axial and peripheral arthritis can occur in up to 30% of patients with inflammatory bowel disease. Likewise, the presence of gut inflammation in primary spondyloarthropathies is underappreciated, with subclinical gut inflammation documented in up to two-thirds of patients with this group of inflammatory disorders. Common genetic and immunologic mechanisms underlie the coincidence of inflammation in the joints and the intestine. New research highlights the critical role of innate and adaptive immune responses directed against components of the enteric microbial flora in driving gut and articular inflammation. Indeed, elucidation of genetic and serological immune markers will define clinically important subgroups of patients with these heterogeneous diseases. The treatment of inflammatory articular manifestations of inflammatory bowel disease is similar to the treatment of primary spondyloarthropathies. A notable exception is the use of NSAIDs, which can precipitate flares of inflammatory bowel disease and should be used with caution. Agents that target tumor necrosis factor have been a major advance in the treatment of both gut and joint inflammation in inflammatory bowel disease.

Gut inflammation in the spondyloarthropathies.

H Mielants — 2008-02-12T21:56:57-00:00

Curr Rheumatol Rep, Vol. 7, No. 3. (June 2005), pp. 188-194.

In this paper, the ample experimental, clinical, genetic, histopathologic, and immunologic evidence for an important role of the gut in the pathogenesis of spondylarthropathy (SpA) and for an overlap between SpA and Crohn's disease is reviewed. These data suggest that SpA and Crohn's disease should be scientifically and clinically considered as distinct phenotypes of common immune-mediated inflammatory disease pathways rather than as separate disease entities. Classification, diagnosis, and therapy based on pathophysiologic insights is likely to become superior to an approach based exclusively on signs and symptoms, as evidenced by the recent evolution in treatment of SpA by tumor necrosis factor-a blockade.

The therapeutic potential of anti-cytokine antibodies in the treatment of chronic inflammatory disease

Natalie Davidson — 2008-02-12T21:12:31-00:00

Expert Opinion on Investigational Drugs, Vol. 7, No. 7. (July 1998), pp. 1115-1120.