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

Extra-Intestinal Manifestations of Ulcerative Colitis

Up to 50% of UC patients 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 Risk Factors

Extra-intestinal manifestations (EIMs) can present before UC diagnosis is established, making early recognition critical. 1 The probability of developing EIMs increases with:

• Disease duration 1
• Extensive colitis (pancolitis) 1
• Presence of one existing EIM (increases risk for additional manifestations) 1
• Non-smoking status 1

Approximately 27% of UC patients develop EIMs, which significantly impact quality of life and can be life-threatening in cases like primary sclerosing cholangitis and venous thromboembolism. 1, 2

Major Categories of Extra-Intestinal Manifestations

1. Musculoskeletal Manifestations (Most Common - 20% of patients)

Type I Peripheral Arthropathy:

• Affects fewer than 5 large joints asymmetrically 1
• Typically involves weight-bearing joints (knees, ankles, hips) 1
• Parallels intestinal disease activity - resolves when UC is treated 1
• Occurs in 4-17% of UC patients 1
• Acute and self-limiting course 1

Type II Peripheral Arthropathy:

• Affects more than 5 small joints symmetrically 1
• Runs independent of UC activity 1
• Can persist for months to years 1
• Occurs in approximately 2.5% of UC patients 1
• Requires specific therapy beyond UC treatment 1

Axial Arthropathy (Sacroiliitis/Ankylosing Spondylitis):

• Radiological sacroiliitis occurs in 20-50% of UC patients 1
• Progressive ankylosing spondylitis occurs in only 1-10% 1
• Runs completely independent of intestinal disease activity 1
• HLA-B27 found in 25-75% of UC patients with ankylosing spondylitis, but only 7-15% with isolated sacroiliitis 1
• MRI is the gold standard for early detection - identifies inflammation before bone lesions appear on plain radiography 1

2. Dermatologic Manifestations

Erythema Nodosum:

• Affects extensor surfaces of lower extremities 1
• Closely parallels intestinal disease activity 1
• Treatment follows that of underlying UC 1

Pyoderma Gangrenosum:

• Runs independent of intestinal disease activity 1
• Requires specific therapy beyond UC treatment 1

3. Ophthalmologic Manifestations

Iritis/Uveitis:

• More common in women 1
• Runs independent of intestinal disease activity 1
• Requires urgent ophthalmology referral to prevent vision loss 3

4. Hepatobiliary Manifestations

Primary Sclerosing Cholangitis (PSC):

• Life-threatening complication 1
• Runs completely independent of intestinal disease activity 1
• More common in males 1
• Associated with increased risk of pouchitis in patients undergoing ileal pouch-anal anastomosis 1

5. Hematologic Manifestations

Anemia:

• Found in 21% of all UC patients 1
• Most common forms: iron deficiency anemia, anemia of chronic disease, or combination 1
• Diagnostic criteria for iron deficiency: serum ferritin < 30 μg/L without active disease; ferritin up to 100 μg/L may still indicate deficiency with inflammation 1

Venous Thromboembolism:

• Life-threatening complication requiring vigilance 1

Management Approach

General Treatment Algorithm

The fundamental principle: EIMs that parallel intestinal disease activity respond to UC treatment, while those running an independent course require specific targeted therapy. 1

Specific Treatment Protocols

Type I Peripheral Arthropathy:

1. First-line: Treat the underlying UC flare - typically resolves joint symptoms within weeks 1, 4
2. Add NSAIDs or systemic corticosteroids if needed for symptom control 1

Type II Peripheral Arthropathy:

1. First-line: NSAIDs or systemic corticosteroids 1, 4
2. Consider immunomodulators or anti-TNF therapy for refractory cases 1

Axial Arthropathy:

1. First-line: NSAIDs for symptom control 1, 4
2. For patients refractory to or intolerant of NSAIDs: anti-TNF agents (infliximab, adalimumab, golimumab) 1, 4
3. Treatment decisions should be shared with a rheumatologist 1, 4

Anemia:

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

Erythema Nodosum:

• Treat the underlying UC flare 1

Pyoderma Gangrenosum:

• Requires specific treatment including corticosteroids and cyclosporine 3
• May require anti-TNF therapy 5

Uveitis/Iritis:

• Urgent ophthalmology referral 3
• Specific therapy independent of UC treatment 1

Primary Sclerosing Cholangitis:

• Monitoring for complications 3
• Eventual liver transplantation consideration 3

Multidisciplinary Management

Complex EIMs should be managed through multidisciplinary team meetings involving specialists in the affected organ systems. 1 This includes rheumatologists for arthropathy, dermatologists for skin manifestations, ophthalmologists for eye involvement, and hepatologists for PSC. 1, 5

Critical Clinical Pitfalls to Avoid

Never 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 ankylosing spondylitis, 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, 4

Do not underdiagnose anemia - all UC patients should be screened with full blood count, serum ferritin, and CRP levels. 1

Recognize that patients with one EIM are at increased risk for developing additional EIMs - requiring heightened surveillance. 1

Avoid NSAIDs in active UC when possible - NSAID use is a risk factor for EIMs. 1