[Crohn's disease: a still tourbillon of etiopathogenetic theories and therapeutic strategies. Some implications in the field of urology].
Despite of scientific efforts over seven decades, the etiopathogenesis of Crohn's disease (CD) remains still unknown. Some conflicting hypotheses are to be settled about etiologic factors as well as on pathogenetic mechanisms. According to some authors, the disease appears to be caused by a congenital lack of patency of mesenteric lymphatic collectors giving rise to lymph-seepage in the corresponding bowel segment with following development of lymphocytic lymphangitis and transparietal phlogosis. Considering this etiopathogenetic philosophy, the surgical therapy has to be performed prompty and has to take the form of segmentary intestinal resection, depending on disease-related intestinal involvement (ileum, ileum plus right colon, ileum plus right and left colon). Other proposed pathogenetic hypotheses for CD refer, instead, to immune-mediated mechanisms, leading to identify this pathology with an abnormal immune inflammatory response in the intestinal wall to one or more undefined antigens, in genetically predisposed person (genetic background). Whereas the prevalent viewpoint is that CD lesions are induced by a dysregulated adaptive-acquired immune system, current studies lead to form the hypothesis that the disease might be initiated by a defective innate immune response. The CD acquired immune profile focuses on T-helper-l (Th1) type, with increasing production of TNF-a, IL-12, Interferon-g and other specific cytokines. In the field of diagnostic imaging, MR findings, 99mTc or 111In labelled autologous leucocyte scintigraphy or 18FDG/PET images strongly correlate with "active" phase of inflammation and contribute to differentiate this condition from established intestinal wall fibrosis, The Montreal classification of inflammatory bowel disease (2005) provides a useful framework for describing CD phenotype and for identifying different serological and genetic markers that may predict the disease course. Urological complications such as renal stones, obstructive uropathy, entero-vescical fistulas, kidney parenchymal disease, are not uncommon. According to immune-mediated pathogenesis-related theories, the basic therapy consist of medical strategies. In the last decades many inflammatory cytokines (TNF-a, IL-12, IL-1, etc.) have been targeted for therapy, particularly in patients with steroid-immunomodulator refractory or fistulizing disease, by achieving a cytokine blockade with monoclonal antibodies. Even regulatory antinflammatory cytokines, such as IL-10 and IL-11, are undergoing trials. In the clinical ground, a better assessment of etiopathogenesis of CD and of the individual case-related evolutive phase, is likely to warrant the selective drug therapies, the avoidance of untimely surgery and the prophylaxis of recurrences.
Alberti
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Libero Docente di Semeiotica Chirurgica, Università degli Studi di Parma, Italy.
D015415:Biomarkers / Q000097:blood; D003113:Colonoscopy; D003424:Crohn Disease / Q000150:complications / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D017370:Interleukin-11 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D007674:Kidney Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015415:Biomarkers; D016207:Cytokines; D007375:Interleukin-1; D017370:Interleukin-11; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma