What are the extra-intestinal manifestations of ulcerative colitis and how are they managed?

Extra-Intestinal Manifestations of Ulcerative Colitis

Up to 50% of patients with ulcerative colitis will develop at least one extra-intestinal manifestation during their disease course, with musculoskeletal involvement being the most common, affecting approximately 20% of patients. 1

Clinical Significance and Timing

• Extra-intestinal manifestations (EIMs) can present before UC is even diagnosed, making recognition critical for early detection of the underlying disease 1
• The probability of developing EIMs increases with disease duration, and patients who already have one EIM are at heightened risk for developing additional manifestations 1
• Some EIMs (peripheral arthritis, erythema nodosum) parallel intestinal disease activity and improve when the UC flare is treated, while others (ankylosing spondylitis, uveitis, primary sclerosing cholangitis, pyoderma gangrenosum) run an independent course requiring specific therapy 2, 1
• Complex EIMs require multidisciplinary management involving specialists in the affected organ systems 1

Major Categories of Extra-Intestinal Manifestations

Musculoskeletal Manifestations (Most Common - 20% of patients)

Peripheral Arthropathy:

• Type I (pauci-articular): Affects less than five large joints asymmetrically, typically weight-bearing joints, occurs in 4-17% of UC patients, is acute and self-limiting, and directly parallels intestinal disease activity 1, 3
• Type II (polyarticular): Affects more than five small joints symmetrically, occurs in approximately 2.5% of UC patients, runs independent of UC activity, and can persist for months to years 1, 3
• Diagnosis is clinical, based on painful swollen joints (synovitis) with exclusion of rheumatoid arthritis, osteoarthritis, and connective tissue diseases 1

Axial Arthropathy:

• Radiological sacroiliitis occurs in 20-50% of UC patients, but progressive ankylosing spondylitis develops in only 1-10% 1
• MRI is the gold standard for early detection, as it identifies inflammation before bone lesions appear on plain radiography 1, 3
• HLA-B27 is found in 25-75% of UC patients with ankylosing spondylitis but only 7-15% with isolated sacroiliitis, making it unreliable as a diagnostic test in IBD 1, 3

Dermatologic Manifestations

• Erythema nodosum: Affects extensor surfaces of lower extremities, closely parallels disease activity, and treatment follows that of the underlying UC 1
• Pyoderma gangrenosum: Runs an independent course from intestinal disease activity and requires specific therapy beyond UC treatment 1

Ophthalmologic Manifestations

• Iritis/uveitis: More common in women, run an independent course from intestinal disease activity 1

Hepatobiliary Manifestations

• Primary sclerosing cholangitis (PSC): Life-threatening complication that runs independent of intestinal disease activity, more common in males, and associated with increased risk of pouchitis in patients undergoing ileal pouch-anal anastomosis 1

Hematologic Manifestations

• Anemia: Found in 21% of all UC patients, most commonly iron deficiency anemia, anemia of chronic disease, or combination of both 1
• Iron deficiency is diagnosed when serum ferritin is <30 μg/L without active disease, or up to 100 μg/L may still indicate deficiency with inflammation 1
• Venous thromboembolism: Life-threatening complication requiring vigilance 1

Management Algorithm

For EIMs That Parallel Intestinal Disease Activity

Type I Peripheral Arthropathy:

1. First-line: Treat the underlying UC flare, which typically resolves joint symptoms within weeks 1, 3
2. Add NSAIDs or systemic corticosteroids if needed for symptom control 1, 3

Erythema Nodosum:

• Treatment parallels that of underlying UC 1

For EIMs That Run Independent of Intestinal Disease Activity

Type II Peripheral Arthropathy:

1. First-line: NSAIDs or systemic corticosteroids 1, 3
2. Consider immunomodulators or anti-TNF therapy for refractory cases 1

Axial Arthropathy:

1. First-line: NSAIDs for symptom control 1, 3
2. For patients refractory to or intolerant of NSAIDs: Anti-TNF agents (infliximab, adalimumab, golimumab have well-established efficacy and safety in ankylosing spondylitis) 1, 3
3. Treatment decisions should be shared with a rheumatologist 1, 3

Pyoderma Gangrenosum:

• Requires specific therapy beyond UC treatment, often anti-TNF agents 4

Anemia:

• Iron supplementation is recommended in all UC patients when iron deficiency anemia is present 1
• Total iron requirement should be estimated based on hemoglobin levels and body weight 1

Critical Clinical Pitfalls to Avoid

• Do not assume all arthropathy will improve with UC treatment alone: Type II peripheral arthropathy and axial arthropathy require specific management independent of intestinal disease control 1, 3
• Do not rely on HLA-B27 testing for diagnosis of axial arthropathy in UC patients: Due to lower prevalence than in idiopathic AS, it is unreliable as a diagnostic test in IBD 1
• Do not use plain radiography alone for early axial arthropathy diagnosis: MRI can identify non-radiographic sacroiliitis before bone changes are visible on plain films 1, 3
• Do not underdiagnose anemia: All UC patients should be screened with full blood count, serum ferritin, and CRP levels 1
• Do not fail to recognize that patients with one EIM are at increased risk for developing additional EIMs, requiring heightened surveillance 1

Risk Factors for Developing EIMs

• Extensive UC (pancolitis) 1
• Longer disease duration 1
• Presence of one EIM increases risk for others 1
• Non-smoking status 1
• NSAID use 1
• Primary sclerosing cholangitis increases risk of pouchitis post-surgery 1