How are extraintestinal manifestations of Crohn's disease managed?

Management of Extraintestinal Manifestations of Crohn's Disease

The management of extraintestinal manifestations (EIMs) in Crohn's disease fundamentally depends on whether the manifestation parallels intestinal disease activity or runs an independent course—manifestations that parallel bowel inflammation (Type I peripheral arthropathy, erythema nodosum) respond to treatment of the underlying Crohn's flare, while independent manifestations (axial arthropathy, pyoderma gangrenosum, uveitis, primary sclerosing cholangitis) require specific targeted therapy beyond treating gut inflammation. 1

Classification Framework

EIMs occur in 25-50% of Crohn's disease patients and significantly impact morbidity, mortality, and quality of life. 1 The probability of developing EIMs increases with disease duration, and patients with one EIM face increased risk for additional manifestations, requiring heightened surveillance. 1

Activity-Dependent vs. Activity-Independent EIMs

Activity-Dependent (Parallel Bowel Disease):

• Type I peripheral arthropathy (pauciarticular, <5 large joints asymmetrically) 1
• Erythema nodosum (extensor surfaces of lower extremities) 1

Activity-Independent (Require Specific Therapy):

• Type II peripheral arthropathy (polyarticular, >5 small joints symmetrically) 1
• Axial arthropathy (ankylosing spondylitis/sacroiliitis) 1
• Pyoderma gangrenosum 1
• Uveitis/iritis 1
• Primary sclerosing cholangitis 1

Musculoskeletal Manifestations (Most Common EIM)

Joint involvement affects 20-25% of Crohn's disease patients, representing the most frequent extraintestinal manifestation. 1

Type I Peripheral Arthropathy

• First-line: Treat the underlying Crohn's disease flare, which typically resolves joint symptoms within weeks 1
• Adjunctive: NSAIDs or systemic corticosteroids for symptom control if needed 1
• Affects fewer than five large joints asymmetrically, typically weight-bearing joints 1

Type II Peripheral Arthropathy

• First-line: NSAIDs or systemic corticosteroids 1
• Refractory cases: Immunomodulators or anti-TNF therapy 1
• Runs independent of Crohn's disease activity and can persist for months to years 1

Axial Arthropathy (Ankylosing Spondylitis/Sacroiliitis)

• First-line: NSAIDs for symptom control 1
• Refractory or intolerant to NSAIDs: Anti-TNF agents (infliximab, adalimumab) 1, 2
• Treatment decisions should be shared with a rheumatologist 1
• Diagnostic approach: MRI is the gold standard for early detection, as it identifies non-radiographic sacroiliitis before bone changes appear on plain radiography 1
• Critical pitfall: Do not use HLA-B27 testing as a diagnostic test in IBD patients due to unreliable sensitivity 1

Dermatologic Manifestations

Erythema Nodosum

• Treatment: Address the underlying Crohn's disease flare, as this manifestation closely parallels intestinal disease activity 1
• Affects extensor surfaces of lower extremities 1

Pyoderma Gangrenosum

• Treatment: Requires specific therapy beyond treating gut inflammation 1
• Options: Corticosteroids and cyclosporine 1
• Runs an independent course from intestinal disease activity 1

Ophthalmologic Manifestations

Uveitis/Iritis

• Urgent ophthalmology referral required to prevent vision loss 1
• More common in women and runs independent of intestinal disease activity 1
• Requires specific treatment beyond Crohn's disease management 1

Hepatobiliary Manifestations

Primary Sclerosing Cholangitis (PSC)

• Life-threatening complication requiring monitoring for complications and eventual liver transplantation consideration 1
• Runs completely independent of intestinal disease activity 1
• No specific therapy effectively treats PSC; management focuses on surveillance and complication management 1

Oral Manifestations

Oral Crohn's Disease

• Best managed in conjunction with a specialist in oral medicine 1
• Treatment options: Topical steroids and infliximab 1

Hematologic Manifestations

Anemia

• Found in 21% of all Crohn's disease patients 1
• Most common forms: Iron deficiency anemia and anemia of chronic disease 1
• Management: Screen routinely and provide iron supplementation when iron deficiency is present 1

Venous Thromboembolism

• Life-threatening complication requiring vigilance 1
• Consider thromboprophylaxis during hospitalizations and severe flares 1

Perianal and Fistulating Disease

Simple Perianal Fistulae

• First-line: Metronidazole and ciprofloxacin 1

Complex or Refractory Fistulae

• Treatment: Infliximab and surgery 1, 2
• Infliximab is FDA-approved for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn's disease 2

Anti-TNF Therapy for Multiple EIMs

Infliximab and adalimumab have emerged as important therapeutic options for multiple EIMs that are refractory to conventional therapy or run independent of intestinal disease activity. 1

• Infliximab dosing for Crohn's disease: 5 mg/kg at 0,2, and 6 weeks, then every 8 weeks 2
• Some adult patients who initially respond may benefit from increasing the dose to 10 mg/kg if they later lose their response 2
• FDA-approved indications: Reducing signs and symptoms, inducing and maintaining clinical remission in moderately to severely active Crohn's disease, and treating fistulizing disease 2

Critical Clinical Pitfalls to Avoid

Never assume all arthropathy will improve with Crohn's disease treatment alone—Type II peripheral arthropathy and axial arthropathy require specific management independent of intestinal disease control. 1

Do not rely on plain radiography alone for early axial arthropathy diagnosis—MRI can identify non-radiographic sacroiliitis before bone changes are visible. 1

Do not use HLA-B27 testing as a diagnostic test for axial arthropathy in IBD patients due to unreliable sensitivity. 1

Do not underdiagnose anemia—all Crohn's patients should be screened routinely. 1

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