Extraintestinal Manifestations of Inflammatory Bowel Disease: Focus on the Musculoskeletal, Dermatologic, and Ocular Manifestations

Paul E. Evans, MD; Darrell S. Pardi, MD

Disclosures

March 19, 2007

Musculoskeletal Manifestations

The peripheral and axial musculoskeletal syndromes associated with IBD are considered part of the seronegative spondyloarthropathies, and are seen in approximately 30% of patients with IBD.[6] Peripheral arthritis associated with IBD is typically classified into types 1 and 2.[7] Type 1 disease affects fewer than 5 large joints, is acute and is self-limited, and is usually associated with active disease in the bowel. Type 2 disease typically chronic, affects 5 or more small joints, is symmetrical, and is not associated with the activity of the bowel disease. Axial arthropathies, including sacroiliitis and ankylosing spondylitis, are also associated with IBD but are usually independent of disease activity. Ankylosing spondylitis and sacroiliitis involve inflammation of the spine and sacroiliac joints, respectively. They present as pain and stiffness in the low back that is worse in the morning and relieved with exercise.

Prevalence and Risk

In a large, retrospective review of IBD patients, joint complications were found in 16% and 33% of those with ulcerative colitis and Crohn's disease, respectively.[8] Type 1 peripheral arthritis was found in 4% of ulcerative colitis and 6% of Crohn's disease patients. Type 2 disease was found in 3% of patients with ulcerative colitis and 4% of patients with Crohn's disease. Ankylosing spondylitis was found in 1% of both ulcerative colitis and Crohn's disease patients. The remainder of the patients were categorized as nonspecific arthralgias.[8] Many other studies have also found a higher risk of joint manifestations in Crohn's disease compared with ulcerative colitis.[2,3,6,9] Disease location also appears to influence risk. Patients with more extensive ulcerative colitis and colonic involvement in Crohn's disease are more likely to have joint complications.[3] There may also be subsets of IBD patients at increased risk for joint problems. For example, cigarette smoking and appendectomy were found to increase the risk of spondyloarthropathies in patients with ulcerative colitis.[10]

Issues in Diagnosis

The diagnosis of joint-related complications in IBD is based largely on the overall clinical picture and the exclusion of other disease processes. It is important to consider osteonecrosis, particularly in patients previously treated with corticosteroids. Septic arthritis should always be considered in the differential diagnosis. In addition, other intestinal disorders are associated with joint manifestations, including: Whipple's disease, Behcet's syndrome, and gluten-sensitive enteropathy.[11] Radiographs of the spine and sacroiliac joints can show the chronic changes associated with ankylosing spondylitis and sacroiliitis, such as syndesmophytes and sacroiliac erosions. In a study[12] in which Crohn's disease patients underwent computed tomography (CT) evaluation, 29% showed changes consistent with sacroiliitis whereas only 3% of those patients had symptoms of low back pain, suggesting that radiologic changes appear before symptoms.

Treatment

There are multiple therapeutic options for the management of seronegative spondyloarthropathy associated with IBD. Nonsteroidal anti-inflammatory drugs have traditionally been used to treat both axial and peripheral arthropathies. A small, open-label study[13] of a cyclooxygenase-2 inhibitor conducted in IBD patients with peripheral arthritis showed improvement in 41% of patients, with minimal side effects. These drugs are not optimal for treating IBD patients, as they may be associated with disease exacerbation.[14] In patients with spondyloarthropathies, sulfasalazine administered at doses of 3 g per day has been shown to significantly improve patients' overall assessment of their symptoms, and is therefore an option for patients taking aminosalicylates.[15] Methotrexate also has some effect in patients with ankylosing spondylitis and peripheral arthritis.[16] Multiple studies have also examined the effect of antitumor necrosis factor-alpha antibodies in the treatment of ankylosing spondylitis.[16,17,18,19,20,21] Infliximab, adalimumab, and etanercept have demonstrated rapid improvement in symptoms in the majority of patients with ankylosing spondylitis. On the basis of these studies, these medications should be considered in patients with IBD and significant axial arthropathies.

Osteoporosis

Patients with IBD are at increased risk for developing osteoporosis, secondary to the disease process itself, as well as secondary to the medications commonly used for treatment (such as corticosteroids). The fracture risk in IBD patients is 40% greater than that of the general population.[22] All IBD patients older than age 65, with a history of glucocorticoid use for more than 3 months' duration, should undergo bone mineral density scan.[23] Plain radiographs of the peripheral joints can show effusions and changes of osteoporosis, but typically demonstrate no evidence of erosion. Regular exercise and adequate calcium and vitamin D intake should be ensured with supplementation as necessary. Avoidance of tobacco, excess alcohol, and minimizing corticosteroid use are essential.[23] Bisphosphonates are effective in increasing bone mineral density in patients with osteoporosis and should be used in those with known osteoporosis, atraumatic fractures, and in patients who cannot withdraw from corticosteroids after 3 months.[24]

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