[The role of biologic therapy in the treatment of extraintestinal manifestations and complications of inflammatory bowel disease]

Milan Kujundzić
Acta Medica Croatica: C̆asopis Hravatske Akademije Medicinskih Znanosti 2013, 67 (2): 195-201
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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