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

Abstract

An increasing deal of attention is being conveyed on the extra-intestinal manifestations 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 extra-intestinal manifestations 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. The extra-intestinal manifestations 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 the extra-intestinal manifestations prove often more disabling than the underlying IBD itself.

Oral Manifestations of Inflammatory Bowel Disease and the Role of Non-Invasive Surrogate Markers of Disease Activity

“…While UC affects the rectum and a variable extent of the colon, CD can involve any location of the gastrointestinal (GI) tract, from the oral cavity to the anus. Furthermore, up to 36% of patients with IBD may have extra-intestinal manifestations (EIM) [3][4][5] which can affect almost any organ of the body (eyes, joints, liver, pancreas, skin, blood, and mouth) [6,7].…”

<p>Identification of Novel Therapeutic Molecular Targets in Inflammatory Bowel Disease by Using Genetic Databases</p>

“…1,2 While the disease is predominantly described as a gastrointestinal disease, symptoms involving other organ systems are increasingly recognized. 3,4 In the past decade, studies conducted in both animals and human models have suggested that several genetic factors are involved in the pathogenesis of IBD. [5][6][7][8][9][10] Animal studies have argued for an immune mediated role for IBD.…”

Incidence of Prostate Cancer in Inflammatory Bowel Disease: A Meta-Analysis

“…Although it is reported that the pathogenesis of IBD originates from a dysregulated interaction between genetic and environmental factors, the precise etiology is still unknown [2,3]. Patients may also present extra-intestinal manifestations, such as arthritis, erythema nodosum, uveitis, or primary sclerosing cholangitis [4]. It is estimated that 1.5 million Americans and 2.2 million people in Europe are affected by IBD, and several studies have identified an increase in incidence, particularly in newly industrialized countries [5,6].…”