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Mechanisms for the induction of rheumatic symptoms by gastrointestinal disease

Ann L Parke, MD
Section Editor
Joachim Sieper, MD
Deputy Editor
Paul L Romain, MD


Certain gastrointestinal diseases can produce extraintestinal manifestations. A common example of this phenomenon occurs in patients with inflammatory bowel disease (IBD) who may develop arthritis, iritis, skin disease (eg, erythema nodosum), vasculitis, and hemolytic anaemia [1-4]. In one series, 36 percent of patients with ulcerative colitis or Crohn's disease had one or more of these manifestations [1]. These manifestations were more frequent with colitis than with inflammation limited to the small bowel (42 versus 23 percent).

The observation that the extraintestinal symptoms generally improve or disappear when the gastrointestinal disease is effectively treated suggests that the association is causal [1,5-7]. The precise mechanisms by which this occurs are not fully understood.

The mechanisms by which gastrointestinal disease may induce rheumatic symptoms are reviewed here. The clinical manifestations, diagnosis, and treatment of arthritis associated with gastrointestinal disease are presented separately. (See "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases".)


The adult human gastrointestinal tract is not a complete barrier, being permeable to some macromolecules [8]. Permeability is increased in certain disease states, including inflammatory bowel disease (IBD), celiac disease, and stress [9-11]. Environmental factors can also influence gastrointestinal permeability, including the administration of nonsteroidal antiinflammatory drugs (NSAIDs), excessive chronic alcohol intake, and gastrointestinal pathogens [12-19]. Thus, the adult gastrointestinal tract is a potential source for exposure to both bacterial and dietary antigens, particularly when permeability is increased.

The epithelial lining of the gastrointestinal tract is one cell thick and includes specialized cells (M cells) that permit transepithelial transport of foreign material from the lumen to mucosal lymphoid tissues. The intraepithelial pocket of the M cell contains many T and B lymphocytes and occasional macrophages. These cells are closely associated with the plasma membrane of the pocket; studies have suggested that, within the M cell pocket, there is interaction of T cells with antigen presenting B-cells [13].

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Literature review current through: Nov 2017. | This topic last updated: Feb 12, 2016.
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