The gut and the inflammatory bowel diseases inside-out: extra-intestinal manifestations

An increasing deal of attention is being conveyed on the extra-intestinal manifestations (EIM) of inflammatory bowel diseases (IBD). We compiled the present review in an attempt to upgrade the accuracy of the classification of such polymorphic entities. We focused on three patterns. First, the conventional EIM localized to bone and joints, to the eye, to the biliary tree and to the skin. Second, the so-called IBD-like syndromes accompanied by bone marrow-derived anomalies of innate or acquired immunity. Third, specific disorders of the skin and of the lungs. EIM are thought to derive from an altered gut permeability, the release of cross-reacting antigens, and subsequent peripheral inflammation; T helper 17 cells boosted by a polymorphic interleukin 23 circuitry would be the main effectors of this chain. Inflammatory bowel disease-like pictures would derive from inborn errors of the immune response causing undue inflammation home to the gut. Monogenic IBD belong to this subset, and are of specific pediatric interest. Psoriasis, chronic obstructive pulmonary disease, and IBD are all inflammatory disorders of the barrier organs: skin, lungs, and gut. The demonstration that specific antigen hyper- or hyporesponsiveness raised at any of the three districts can modulate the response of the other two sites, has led to the innovative concept of a system-wide mucosal immunological organ. An improved knowledge of these entities has not only a speculative importance, but can also bear a clinical impact, insofar as EIM prove often more disabling than the underlying IBD itself.