THE ROLE OF BIOLOGIC THERAPY IN THE TREATMENT OF EXTRAINTESTINAL MANIFESTATIONS AND COMPLICATIONS OF INFLAMMATORY BOWEL DISEASE

Abstract

Ekstraintestinalne manifestacije javljaju se u oko 35 % bolesnika s upalnim bolestima crijeva. Najčešće su zahvaćeni koštanozglobni sustav, koža, oči te jetra i žučni sustav. Zahvaćenost koštano-zglobnog sustava se javlja u 5-10 % bolesnika s ulceroznim kolitisom (UC) i u 10-20 % bolesnika s Crohnovom bolešću (CB). Simptomi variraju od blage artralgije do teškog akutnog artritisa. Primarni sklerozirajući kolangitis (PSC), autoimuni hepatitis, bolesti gušterače, kolestaza, kolelitijaza i porast aminotransferaza smatraju se hepatobilijarnim manifestacijama. Najčešće se prepoznaje PSC, osobito kod bolesnika s UC (oko 7,5 %). Biološka terapija neučinkovita je u liječenju te nema utjecaja na prirodni tijek bolesti. Od kožnih manifestacija najčešće se javljaju nodozni eritem (3-20 %) i gangrenozna pioderma (0,5-20 %). Oftalmološki poremećaji javljaju se u 2-5 % bolesnika s upalnim bolestima crijeva. Tegobe variraju od blagog konjunktivitisa do teških upala očnih ovojnica. Infliksimab je u CB indiciran u liječenju spondiloartropatija, artritisa/artralgija, gangrenozne pioderme, nodoznog eritema te oftalmoloških manifestacija, osim optičkog neuritisa. Slične su indikacije za upotrebu adalimumaba, osim što nema indikacije u liječenju nodoznog eritema. Kod bolesnika s UC, infliksimab je indiciran u liječenju spondiloartropatija i gangrenozne pioderme. Komplikacije upalnih bolesti crijeva su fistule, stenoze I strikture crijeva, apscesi, perforacije, krvarenja iz probavnog sustava te nastanak karcinoma crijeva i drugih maligniteta. Liječenje anti-TNF lijekovima dokazano je učinkovito jedino u liječenju perianalnih fistula u bolesnika s CB.Extraintestinal manifestations occur in about 35% of patients with inflammatory bowel diseases (IBD). Most frequently affected are bones and joints, skin, eyes, liver and biliary ducts. Extraintestinal manifestations of IBD are divided in two groups: reactive manifestations which depend on activity of IBD – peripheral arthritis, erythema nodosum, aphthous stomatitis, episcleritis and other manifestations which are independent on activity of IBD – pyoderma gangrenosum, uveitis, axial arthropathy, primary sclerosing cholangitis (PSC). Most affected are bones and joints. Symptoms vary from mild arthralgia to severe arthritis with painful swallowing of joints. They occur in about 5-10% of patients with ulcerative colitis (UC) and in 10-20% of patients with Crohn’s disease (CD). Both peripheral and axial joints can be affected. According to available data, most patients with active IBD and concomitant arthritis have benefit from infliximab therapy. Infliximab is also effective in maintenance of remission in group of patients with spondyloarthropathy. Adalimumab showed similar efficacy in treatment of ankylosing spondylitis, but there are still no data about efficacy of adalimumab in treatment of patients with IBD and concomitant arthritis. Primary sclerosing cholangitis, autoimmune hepatitis, cholestasis, cholelithiasis and elevation of aminotransferase are also considered to be extraintestinal manifestations of IBD. Most frequent is PSC which affects usually patients with UC (7.5% of patients). Course of liver disease is completely independent on activity of IBD, and destruction of biliary ducts is usually irreversible and refractory on treatment and most of the patients need liver transplantation. Anti-TNF therapy is also ineffective in treatment of PSC and has no impact on disease course and outcome. However, there is no contraindication for anti-TNF therapy of concomitant active IBD in this group of patients. Erythema nodosum (EN) and pyoderma gangrenosum (PG) are usual skin manifestations of IBD. Erythema nodosum occurs in about 3-20%, and pyoderma gangrenosum in about 0.5-20% of patients with IBD. Infliximab is proven to be effective in treatment of PG,but there is still not enough evidence on efficacy of anti-TNF drugs in treatment of EN and other rare skin manifestations of IBD. About 2-5% of patients with IBD have also some ophthalmological disorder. Symptoms vary from mild conjunctivitis to severe inflammation of eye membranes – iritis, episcleritis, scleritis and uveitis. It seems that infliximab and adalimumab can diminish uveitis and scleritis in patients with different autoimmune disorders and IBD. According to guidelines of American Gastroenterology Association (AGA), in group of patients with CD, infliximab is indicated in treatment of spondyloarthropathies, arthritis, arthralgia, pyoderma gangrenosum, erythema nodosum, uveitis and other ophthalmological manifestations of IBD except optical neuritis which can worse or be consequence of anti-TNF treatment. Similar indications exist for use of adalimumab except in case of erythema nodosum. In group of patients with extraintestinal manifestations of UC, infliximab is indicated in treatment of spondyloarthropathies and pyoderma gangrenosum. Complications of IBD are fistulas (perianal and non-perianal), stenosis and strictures, abscesses, bowel perforations, gastrointestinal bleeding and development of different malignomas. Anti-TNF drugs are proven to be effective and indicated only for treatment of perianal fistulas in patients with Crohn’s disease. In group of patients with UC, there are only few case reports on beneficial effect of infliximab in treating chronic pouchitis and infliximab in treatment of these patients still cannot be recommended

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