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Review: What are the Manifestations of Inflammatory Bowel Diseases Beyond the GI Tract?

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Inflammatory bowel diseases (IBD) manifest not only in the gastrointestinal (GI) tract, but also affect joints, skin, eyes, liver, lung, and pancreas. Up to half of patients with IBD have extraintestinal manifestations (EIMs) of IBD. Therapies for intestinal inflammation are not sufficient to treat EIMs such as anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis (PSC), which usually occur independent of disease flares. In the October issue of Gastroenterology, Gerhard Rogler et al review the epidemiology, pathophysiology, clinical presentation, and treatment of EIMs in patients with IBD.

The extra-intestinal symptoms of IBD most commonly involve the musculoskeletal system (peripheral and axial arthritis and enthesitis), skin (pyoderma gangrenosum, erythema nodosum, Sweet syndrome, and aphthous stomatitis), hepatobiliary tract (PSC), and eyes (episcleritis, anterior uveitis, and iritis).

EIMs differ from the extra-intestinal complications of IBD, which are direct or indirect sequela of intestinal inflammation. EIMs are inflammation that develops outside of the GI tract in patients with IBD, caused by disrupted immune regulation and possibly the same environmental or genetic factors that cause gut inflammation. EIMs develop in patients with ulcerative colitis or Crohn’s disease.

Although the EIMs of IBD occur more frequently in areas (see Figure), almost any organ can be affected, and EIMs are not always obvious or easy to detect. For example, acute or chronic pancreatitis associated with IBD (and not with IBD medications such as azathioprine) is rare, whereas asymptomatic exocrine insufficiency, pancreatic duct abnormalities, and hyperamylasaemia occur in up to18% of patients with IBD. Disorders such as pneumonitis or PSC can persist in patients with ulcerative colitis even after proctocolectomy.

In this review article Rogler et al discuss the prevalence and incidence of different types of EIMs. Some patients with IBD develop more than 1 EIM, either before or after the onset (or diagnosis) of IBD. The authors also review the genetic and environmental factors that can lead to development of IBD and its EIMs, as well as the immune system and intestinal microbiome alterations associated with each.

Rogler et al describe the most common EIMs of IBD, such as musculoskeletal disorders (affect up to 46% of patients with IBD) that include arthritis, and spondyloarthropathy. The authors review the different treatment options for these EIMs, including non-steroidal anti-inflammatory drugs, which might be associated with development of intestinal ulcerations and flares in patients with IBD. A COX2 inhibitor (celecoxib, 14 days) was shown to be safe in patients with quiescent ulcerative colitis and nonspecific arthritis or arthralgia.

The skin disorders that are often seen in patients with IBD include erythema nodosum, pyoderma gangrenosum, and Sweet syndrome. Oral pathologies include aphthous stomatitis (in patients with Crohn’s disease) and periodontitis.

EIMS also occur in the eye—up to 7% of patients with IBD have ocular manifestations, including episcleritis, scleritis, and anterior uveitis. Less common ocular EIMs are retinal vasculitis, papillitis, corneal infiltrates, myositis, scleromalacia perforans, and optic neuritis.

Hepatobiliary EIMs include PSC, (found in 5% of patients with ulcerative colitis), autoimmune hepatitis, IgG4-related cholangitis, and granulomatous hepatitis. Patients with IBD also have an increased risk of acute myocardial infarction and heart failure, as well as a 3-fold increase in risk of venous thromboembolic events such as deep vein thrombosis, splanchnic VTE, and lung embolism. The authors propose that endothelial dysfunction, platelet activation, and impaired fibrinolysis are contributing factors. The risk of venous thromboembolic events increases with the severity of inflammation and is highest in hospitalized patients with acute severe colitis.

Rare EIMs of IBD include pancreatitis, bronchiopulmonary disorders (interstitial lung disease and granulomatous lung disease), glomerulonephritis, amyloidosis, nephrolithiasis, and pericarditis/myocarditis.

Fatigue and pain are frequently reported by patients with IBD. The authors explain that more than 50% of patients with IBD have pain for more than 5 years. Up to 60% report abdominal pain, 38% report back pain, 29% report knee pain, and 26% report hip pain (26%). Most patients state that these pain attacks affect their activities of daily living.

Rogler et al explain that, for treatment, it is important to differentiate pain as a symptom of the intestinal disease (inflammation, stricture, abscesses, and fistulae), pain as a symptom of EIMs, and pain as an independent of IBD or its EIMs. Treatment should involve physical therapy, pain medicine and psychiatry, and cognitive behavioral therapy, although there have been few studies of the efficacy of multidisciplinary approaches. The authors conclude that considerations of EIMs of IBD can inform patient management.

 

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Kristine Novak

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About The Author:

Dr. Kristine Novak

Dr. Kristine Novak

Dr. Kristine Novak is a science writer and editor based in San Francisco. She has extensive experience covering gastroenterology, hepatology, immunology, oncology, clinical, and biotechnology research discoveries.

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