What is the management plan for extraintestinal manifestations of Crohn's disease?

Management of Extraintestinal Manifestations of Crohn's Disease

The management of extraintestinal manifestations (EIMs) in Crohn's disease depends critically on whether the manifestation parallels intestinal disease activity or runs an independent course—manifestations that parallel activity (peripheral arthritis type I, erythema nodosum) should be treated by addressing the underlying intestinal inflammation, while those running independently (axial arthropathy, uveitis, pyoderma gangrenosum, primary sclerosing cholangitis) require specific targeted therapy beyond treating the gut disease. 1

General Principles

EIMs occur in approximately 25-50% of Crohn's disease patients and significantly impact quality of life, morbidity, and in some cases (primary sclerosing cholangitis, venous thromboembolism) can be life-threatening. 2, 3, 4 The probability of developing EIMs increases with disease duration, and patients who already have one EIM are at increased risk for developing additional manifestations. 2

Complex EIMs should be managed through multidisciplinary team meetings involving specialists in the affected organ systems. 2

Musculoskeletal Manifestations (Most Common EIM)

Joint involvement occurs in approximately 20-25% of Crohn's disease patients and represents the most frequent extraintestinal manifestation. 2, 3

Type I Peripheral Arthropathy (Pauci-articular)

• Affects fewer than five large joints asymmetrically, typically weight-bearing joints 2
• Directly parallels intestinal disease activity and is acute and self-limiting 2
• First-line treatment: Treat the underlying Crohn's disease flare, which typically resolves joint symptoms within weeks 2
• If additional symptom control needed: NSAIDs or systemic corticosteroids 2

Type II Peripheral Arthropathy (Polyarticular)

• Affects more than five small joints symmetrically 2
• Runs independent of Crohn's disease activity and can persist for months to years 2
• First-line treatment: NSAIDs or systemic corticosteroids 2
• For refractory cases: Consider immunomodulators (azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day) or anti-TNF therapy 1, 2

Axial Arthropathy (Ankylosing Spondylitis/Sacroiliitis)

• Radiological sacroiliitis occurs in 20-50% of Crohn's patients, but progressive ankylosing spondylitis occurs in only 1-10% 2
• Runs completely independent of intestinal disease activity 2
• MRI is the gold standard for early detection, as it identifies inflammation before bone lesions become visible on plain radiography 2
• First-line treatment: NSAIDs for symptom control 2
• For patients refractory to or intolerant of NSAIDs: Anti-TNF agents (infliximab, adalimumab) 1, 2, 5
• Treatment decisions should be shared with a rheumatologist 2

Critical pitfall: HLA-B27 testing is unreliable as a diagnostic test in IBD-associated axial arthropathy due to lower prevalence than in idiopathic ankylosing spondylitis. 2

Dermatologic Manifestations

Erythema Nodosum

• Affects extensor surfaces of lower extremities and closely parallels intestinal disease activity 2
• Treatment: Address the underlying Crohn's disease flare 2
• Corticosteroids if needed for symptom control 5, 3

Pyoderma Gangrenosum

• Runs an independent course from intestinal disease activity 2
• Requires specific treatment beyond treating gut inflammation 5
• Treatment options include: Corticosteroids (topical or systemic), cyclosporine, tacrolimus, or infliximab for severe/refractory cases 5

Ophthalmologic Manifestations

Uveitis/Iritis

• More common in women and runs independent of intestinal disease activity 2
• Requires urgent ophthalmology referral to prevent vision loss 3
• Treatment: Topical corticosteroids for anterior uveitis 5
• For refractory cases: Systemic corticosteroids, immunomodulators, or anti-TNF therapy 5, 3
• Screening may be appropriate for eye disease to prevent complications 3

Hepatobiliary Manifestations

Primary Sclerosing Cholangitis (PSC)

• Life-threatening complication that runs completely independent of intestinal disease activity 2
• More common in males 2
• Associated with increased risk of pouchitis in patients who undergo ileal pouch-anal anastomosis 2
• No specific medical therapy has proven effective for PSC itself 5
• Management focuses on monitoring for complications (cholangitis, cirrhosis, cholangiocarcinoma) and eventual liver transplantation consideration 5

Oral Manifestations

Oral Crohn's Disease

• Best managed in conjunction with a specialist in oral medicine 1
• Treatment options include: Topical steroids, topical tacrolimus, intra-lesional steroid injections, enteral nutrition, and infliximab 1
• No randomized controlled trials exist for oral Crohn's disease 1

Hematologic Manifestations

Anemia

• Found in 21% of all Crohn's disease patients 2
• Most common forms: Iron deficiency anemia, anemia of chronic disease, or combination of both 2
• All Crohn's patients should be screened with full blood count, serum ferritin, and CRP levels 2
• Diagnostic criteria for iron deficiency: Serum ferritin <30 μg/L without active disease; serum ferritin up to 100 μg/L may still indicate iron deficiency with inflammation 2
• Iron supplementation is recommended in all Crohn's patients when iron deficiency anemia is present 2

Venous Thromboembolism

• Life-threatening complication requiring vigilance 2
• Consider thromboprophylaxis during hospitalizations and severe flares 2

Perianal and Fistulating Disease

Simple Perianal Fistulae

• Metronidazole 400 mg three times daily (first-line) and/or ciprofloxacin 500 mg twice daily 1
• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day are potentially effective where distal obstruction and abscess have been excluded 1

Complex/Refractory Perianal Fistulae

• MRI and examination under anesthetic are particularly helpful for defining anatomy 1
• Infliximab (three infusions of 5 mg/kg at 0,2, and 6 weeks) should be reserved for refractory cases and used as part of a strategy that includes immunomodulation and surgery 1
• Surgery (Seton drainage, fistulectomy, advancement flaps) is appropriate for persistent or complex fistulae in combination with medical treatment 1
• Elemental diets or parenteral nutrition have a role as adjunctive therapy, but not as sole therapy 1

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, 5, 3 Recent studies show promise for anti-TNF agents in treating most extraintestinal manifestations of Crohn's disease, potentially permitting more steroid-sparing disease control. 3

Key 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 2
• Do not rely on plain radiography alone for early axial arthropathy diagnosis—MRI can identify non-radiographic sacroiliitis before bone changes are visible 2
• Do not underdiagnose anemia—all Crohn's patients should be screened routinely 2
• Recognize that patients with one EIM are at increased risk for developing additional EIMs, requiring heightened surveillance 2
• Do not use HLA-B27 testing as a diagnostic test for axial arthropathy in IBD patients due to unreliable sensitivity 2