Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management

Abstract

Inflammatory bowel diseases (IBDs) are systemic diseases that manifest not only in the gut and gastrointestinal tract, but also in the extraintestinal organs in many patients. The quality of life for patients with IBD can be substantially affected by these extraintestinal manifestations (EIMs). It is important to have knowledge of the prevalence, pathophysiology, and clinical presentation of EIMs in order to adapt therapeutic options to cover all aspects of IBD. EIMs can occur in up to 24% of patients with IBD before the onset of intestinal symptoms, and need to be recognized to initiate appropriate diagnostic procedures. EIMs most frequently affect joints, skin, or eyes, but can also affect other organs, such as the liver, lung, and pancreas. It is a frequent misconception that a successful therapy of the intestinal inflammation will be sufficient to treat EIMs satisfactorily in most patients with IBD. In general, peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum can be associated with active intestinal inflammation and can improve on standard treatment of the intestinal inflammation. However, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis usually occur independent of disease flares. This review provides a comprehensive overview of epidemiology, pathophysiology, clinical presentation, and treatment of EIMs in IBD.

Keywords: Arthralgias; Arthritis; Crohn’s Disease; Erythema Nodosum; Extraintestinal Manifestations; Inflammatory Bowel Disease; Primary Sclerosing Cholangitis; Psoriasis; Pyoderma Gangrenosum; Spondyloarthropathy; Ulcerative Colitis; Uveitis.

Figure 1:

Epidemiology of extraintestinal manifestations in IBD patients A) Dependent on the definition the prevalence of EIMs is reported to be between 6% and 47% of all patients. B) Patients may be affected by more than one EIM. More than 20% of all IBD patients report 2 EIMs. More than 10% of patients report 3 or more different EIMs. C) EIMs may occur before or after the diagnosis of IBD:; 26% of all patients with EIMs report occurrence of EIMs up to 25 months (median 5 months) before IBD diagnosis.

Figure 2:

Shared genetic risk factors between IBD and extraintestinal manifestations

Figure 3:

EIMS of IBD affect many organs; green = frequent EIMs; blue = rare EIMs

Figure 4:

Rare extraintestinal manifestations of IBD that should be recognized: A) 50-year-old patient with indeterminate colitis, presenting with a febrile diffuse papulo-pustular and necrotizing skin eruption that healed with significant scarring and appeared 14 days after onset of treatment with azathioprine (1). B) 17-year-old male patients with CD presented with a symmetrical nontender swelling of the lower lip. The swelling had been present for the previous 5 years. The clinical and histological changes were consistent with the diagnosis of orofacial granulomatosis. Further diagnostic tests confirmed the presence of intestinal CD. (2) C) 48 year old female patient with CD and ileocecal resection presenting with “metastatic CD” of the genital skin with histologically visible granuloma. D) 34 year old female CD patient presenting with a nodular form of skin manifestation in the genital area E) Retroauricular atypical pyoderma in a 35 years of female patient with ulcerative colitis. The patient later on developed a colitis associated rectum carcinoma. F) Pulmonary involvement in a 62 year old patient with ulcerative colitis. The pulmonary changes (bronchiectasis and relapsing infection) developed rapidly after colectomy.^,