Some patients with inflammatory bowel disease have significant symptoms outside of the gastrointestinal tract. These extra-intestinal symptoms can at times be even more significant than the intestinal symptoms. Arthritis, skin conditions, inflammation of the eye and liver are the most common. While the cause is unknown, it is believed that all of these complications represent an abnormal response of the immune system. Activation of the immune system ignites inflammation in the intestine as well as other parts of the body.

Arthritis is the most common extraintestinal complication of inflammatory bowel disease. It affects one-quarter of patients. There are three types of arthritis that occurs; peripheral arthritis, spondylitis and ankylosing spondylitis. Peripheral arthritis usually affects the large joints of the arms and legs, including the elbows, wrists, knees, and ankles. It is more common in patients whose inflammatory bowel disease involves the colon. Joint disease correlates with activity of colitis. Spondylitis causes pain and stiffness in the lower spine and sacroiliac joints (at the bottom of the back). As opposed to peripheral arthritis, symptoms may come on months or even years before the symptoms of inflammatory bowel disease appear. Unlike peripheral arthritis, spondylitis may cause permanent damage if the bones of the vertebral column fuse together causing decreased range of motion in the back. A more severe form of spinal arthritis, ankylosing spondylitis is a rare complication affecting between 2% and 3% of people with inflammatory bowel disease. It is seen more often in Crohn's disease than in ulcerative colitis. In addition to causing arthritis of the spine and sacroiliac joints, ankylosing spondylitis can cause inflammation of the eyes, lungs, and heart valves. Most affected individuals share a common genetic marker. Symptoms may continue to worsen even after surgical removal of the colon.

After arthritis, skin disorders represent the next most common extraintestinal complication of inflammatory bowel disease. Erythema nodosum consists of tender red nodules, which usually appear over the shins or ankles and sometimes on the arms. It occur more commonly in patients with ulcerative colitis than Crohn's. It tends to improve when the bowel disease is brought under control. Ulcerated lesions containing pus are classic of Pyoderma gangrenosum . It is often found on the shins or ankles but sometimes occurs on the arms, too. It is more common among people with ulcerative colitis (5%) than those with Crohn's disease (1%). Pyoderma gangrenosum often follows a similar course to the pattern of the inflammatory bowel disease itself, and may heal as the symptoms are brought under control.

Approximately 10% of people with inflammatory bowel disease experience eye problems. Most of these are treatable and do not pose any significant threat as far as loss of vision is concerned. The most common eye complication in inflammatory bowel disease is uveitis, a painful inflammation of the middle layer of the eye wall. Patients with uveitis may experience pain, blurred vision, sensitivity to light, and redness of the eye. Uveitis generally improves when the inflammatory bowel disease is brought under control, but the ophthalmologist may prescribe special eye drops containing steroids to help reduce inflammation. If left untreated, uveitis may progress to glaucoma and vision loss.