Extra-intestinal manifestations in IBD

Extra-intestinal manifestations

  • Extra-intestinal manifestations occur in 35% patients with Crohn's disease (less in those exclusively with small bowel disease)
  • Type 1 peripheral arthritis, erythema nodosum, oral aphthous ulcers and episcleritis are associated with disease activity
  • Pyoderma gangrenosum, uveitis, axial arthropathy and primary sclerosing cholangitis (PSC) are generally independent of disease activity
Manifestations

ECCO Statement 10I (CD 2016)

Antithrombotic prophylaxis should be considered in all hospitalised and outpatients with severe disease [EL4]. Treatment of venous thromboembolism in IBD should follow established antithrombotic therapy options [EL1]

Further information

  • Patients with IBD are at increased risk for venous thromboembolism (VTE), and should be advised how to limit this risk
  • Attempt to reduce other VTE risk factors e.g. OCP use, long distance travel
  • Provide VTE prophylaxis to all hospitalised IBD patients
  • Investigate and treat as per international guidelines
  • There is no significant excess risk of major GI bleeding in UC patients (no data in CD)
Venous thrombo-embolism

 
 

  • Cardiopulmonary disease may be related to IBD, and should be considered in patients with relevant symptoms
  • Rare association, the prevalence is unknown
  • Note sulfasalazine, mesalazine and methotrexate cause pneumonitis
  • Exclude opportunistic infection in patients taking anti-TNF
Cardiopulmonary disease

Metabolic bone disease

  • Risk factors:
    • age of patient and age at diagnosis
    • male gender
    • high body mass index
    • long duration of disease
    • previous surgery
    • previous corticosteroids
Metabolic bone disease

ECCO Statement 10D (CD 2016)

Patients on corticosteroid therapy or those with reduced bone density should receive calcium and vitamin D supplements [EL2]. Isotonic exercise [EL2] and cessation of smoking [EL2] are beneficial. Patients with established fractures should be treated with bisphosphonates [EL2]. The efficacy of primary prevention of fracture with bisphosphonates has not been demonstrated. Routine hormone replacement in postmenopausal women is not warranted due to the risk of side effects. Men with low testosterone may benefit from its therapeutic administration [EL3]

Further information

  • Bisphosphonates indicated if previous fragility fracture; however their use as primary prevention of fractures unproven in Crohn's disease (though established in post-menopausal and steroid induced osteoporosis) but should be considered if other risk factors present
Consider treatment if previous fragility or vertebral fracture

  • Recommended in persistently active disease, prolonged steroid use, prolonged disease duration
  • Risk factors:
    • age of patient and age at diagnosis
    • male gender
    • high body mass index
    • long duration of disease
    • previous surgery
    • previous corticosteroids
Baseline DXA scan

ECCO Statement 10D (CD 2016)

Patients on corticosteroid therapy or those with reduced bone density should receive calcium and vitamin D supplements [EL2]. Isotonic exercise [EL2] and cessation of smoking [EL2] are beneficial. Patients with established fractures should be treated with bisphosphonates [EL2]. The efficacy of primary prevention of fracture with bisphosphonates has not been demonstrated. Routine hormone replacement in postmenopausal women is not warranted due to the risk of side effects. Men with low testosterone may benefit from its therapeutic administration [EL3]

Further information

  • Prescribe >/= 800-1000 i.u. vitamin D & 500-1000 mg Ca++ daily. Encourage exercise, smoking cessation; and treat active Crohn's disease
Prophylactic treatment if steroid therapy

  • Consider 800-1000 i.u. vitamin D daily if serum levels low. Interval for repeat DEXA scanning depends on risk factors
Normal results

T<-2.5 (>50y)

T<-1.0 & >-2.5 (>50y)

Z<2.0 (<50y)

No treatment

ECCO Statement 10D (CD 2016)

Patients on corticosteroid therapy or those with reduced bone density should receive calcium and vitamin D supplements [EL2]. Isotonic exercise [EL2] and cessation of smoking [EL2] are beneficial. Patients with established fractures should be treated with bisphosphonates [EL2]. The efficacy of primary prevention of fracture with bisphosphonates has not been demonstrated. Routine hormone replacement in postmenopausal women is not warranted due to the risk of side effects. Men with low testosterone may benefit from its therapeutic administration [EL3]

Further information

  • Prescribe >/= 800-1000 i.u. vitamin D & 500-1000 mg Ca++ daily. Encourage exercise, smoking cessation; and treat active Crohn's disease
Osteoporosis

ECCO Statement 10D (CD 2016)

Patients on corticosteroid therapy or those with reduced bone density should receive calcium and vitamin D supplements [EL2]. Isotonic exercise [EL2] and cessation of smoking [EL2] are beneficial. Patients with established fractures should be treated with bisphosphonates [EL2]. The efficacy of primary prevention of fracture with bisphosphonates has not been demonstrated. Routine hormone replacement in postmenopausal women is not warranted due to the risk of side effects. Men with low testosterone may benefit from its therapeutic administration [EL3]

Further information

  • Prescribe >/= 800-1000 i.u. vitamin D & 500-1000 mg Ca++ daily. Encourage exercise, smoking cessation; and treat active Crohn's disease
Osteopaenia

ECCO Statement 10D (CD 2016)

Patients on corticosteroid therapy or those with reduced bone density should receive calcium and vitamin D supplements [EL2]. Isotonic exercise [EL2] and cessation of smoking [EL2] are beneficial. Patients with established fractures should be treated with bisphosphonates [EL2]. The efficacy of primary prevention of fracture with bisphosphonates has not been demonstrated. Routine hormone replacement in postmenopausal women is not warranted due to the risk of side effects. Men with low testosterone may benefit from its therapeutic administration [EL3]

Further information

  • Prescribe >/= 800-1000 i.u. vitamin D & 500-1000 mg Ca++ daily. Encourage exercise, smoking cessation; and treat active Crohn's disease
Low bone mass

ECCO Statement 10D (CD 2016)

Patients on corticosteroid therapy or those with reduced bone density should receive calcium and vitamin D supplements [EL2]. Isotonic exercise [EL2] and cessation of smoking [EL2] are beneficial. Patients with established fractures should be treated with bisphosphonates [EL2]. The efficacy of primary prevention of fracture with bisphosphonates has not been demonstrated. Routine hormone replacement in postmenopausal women is not warranted due to the risk of side effects. Men with low testosterone may benefit from its therapeutic administration [EL3]

Further information

  • Bisphosphonates indicated if previous fragility fracture; however their use as primary prevention of fractures unproven in Crohn's disease (though established in post-menopausal and steroid induced osteoporosis) but should be considered if other risk factors present
Consider treatment

Re-check DEXA in 3-5 years

Ocular

Ocular manifestations

  • Uveitis and episcleritis are rare ocular manifestations of IBD, presenting as painful red eyes
Red eye(s)

  • May be painless, with hyperaemic sclera and conjunctiva
  • Itching and burning may occur
  • Usually self-limiting
Episcleritis

Diagnosis uncertain

  • Less common than episcleritis
  • Frequently bilateral, insidious in onset and long-lasting, with eye pain, blurred vision, photophobia and headaches
Uveitis

Topical steroids, analgesics, treat Crohn's disease

 

Urgent referral to opthalmologist

Hepatobiliary disease

Hepatobiliary disease

  • Hepatobiliary disease is rarer in Crohn's disease than UC
  • Primary sclerosing cholangitis (PSC) is the most common condition; peri-cholangitis, steatosis, chronic hepatitis, cirrhosis, and gallstone formation are also over-represented. Drug induced liver injury also occurs
Considerations

  • Serological liver screen comprises Hepatitis A, B, C; iron studies; copper & caeruloplasmin (<40y); alpha-1 antitrypsin; immunoglobulins and auto-antibodies
Serological liver screen, US

Diagnosis established

 

Diagnosis uncertain

Provide treatment

Consider DILI
(Drug Induced Liver Injury)

ECCO Statement 10E (CD 2016)

Magnetic resonance cholangiography is now established as the first-line diagnostic test for primary sclerosing cholangitis [EL2]. Primary sclerosing cholangitis substantially increases the risk of both cholangiocarcinoma and colorectal carcinoma [EL1]

MRCP

 

  • Liver biopsy performed to assess for intra-hepatic PSC. Often delayed until abnormal LFT (at least 2x ULN) present for > 6 months
Consider liver biopsy

  • High risk of CRC in IBD-associated PSC mandates annual colonoscopic surveillance
  • Cholangiocarcinoma and colon cancer rarer in Crohn's associated PSC
  • Refer to hepatologist
PSC

 

  • 13-15mg/kg/d ursodeoxycholic acid is associated with improvements in histology and possibly reduction in colon cancer risk. Use of UDCA is however controversial, and for example not recommended by the American Association for the Study of Liver Diseases
Consider UDCA

ERCP for brushing & dilatation

Liver transplantation

Cutaneous

Cutaneous manifestations

Considerations

ECCO Statement 10H (CD 2016)

Treatment of erythema nodosum is usually based on that of the underlying Crohn’s disease. Systemic steroids are usually required [EL4]. Pyoderma gangrenosum is initially treated with systemic steroids [EL4], infliximab [EL2], adalimumab [EL4] or calcineurin inhibitors [EL4]

Further information

  • 7.5% lifetime risk in Crohn's disease (less in UC)
  • Associated with disease activity
  • Clinical diagnosis, with raised, tender, red or violet subcutaneous nodules, 1-5 cm in diameter, usually on extensor surfaces
  • Treatment based on treating active Crohn's disease
Erythema nodosum

ECCO Statement 10H (CD 2016)

Treatment of erythema nodosum is usually based on that of the underlying Crohn’s disease. Systemic steroids are usually required [EL4]. Pyoderma gangrenosum is initially treated with systemic steroids [EL4], infliximab [EL2], adalimumab [EL4] or calcineurin inhibitors [EL4]

Further information

  • 0.6-2.1% lifetime risk in CD
  • May be associated or independent of disease activity
  • Commonly peri-stomal or pre-tibial, or at sites of prior trauma. Initially single or multiple erythematous papules that coalesce forming deep ulcers. Histology may be required to confirm diagnosis
  • Treat urgently to prevent extensive ulceration. Consider infliximab in absence of rapid response to systemic steroids. Topical tacrolimus, systemic ciclosporin and ileostomy reversal are alternative therapies
Pyoderma gangrenosum

  • Rare. Tender, red inflammatory papules, usually affecting the upper limbs, face or neck. Histology characteristic
  • Associated with disease activity, female gender, colonic disease, and other EIM
  • Steroid responsive
  • In 29 patients with pyoderma gangrenosum treated with IFX, the response rate was over 90% in patients with symptoms <12 weeks, but less than 50% in those with disease present for more than 3 months
Sweet's syndrome

Arthritis

ECCO Statement 10A (CD 2016)

Diagnosis of arthropathy associated with IBD is made on clinical grounds based on characteristic features and exclusion of other specific form of arthritis [EL3]

Further information

  • Inflammatory pain is worse with rest, and improves with exercise
Considerations

ECCO Statement 10B (CD 2016)

In the case of peripheral arthritis there is general support for use of physiotherapy, short term treatment with non-steroidal anti-inflammatory agents, and local steroid injections [EL4]. The emphasis should be on treating the underlying Crohn’s disease [EL2]. Sulfasalazine has a role in persistent peripheral arthritis [EL2]

Peripheral arthritis

 

ECCO Statement 10C (CD 2016)

In axial arthropathy evidence supports the use of intensive physiotherapy [EL2], and NSAIDs, but due to safety concerns long-term treatment with NSAIDs is best avoided if possible [EL2]. Anti-TNF is the preferred treatment of ankylosing spondylitis intolerant or refractory to NSAIDs [EL2]. Sulfasalazine [EL2], methotrexate [EL2] and thiopurines [EL4] are only marginally effective

Further information

  • MRI best imaging modality, and demonstrates inflammation prior to bony abnormalities
  • Radiographic sacro-ilitis is often asymptomatic and may not progress, present in 25-50% of patients with Crohn's disease, of whom only 7-15% are HLA B27 positive
  • Ankylosing spondylitis occurs in 4-10% of CD patients, presents with chronic inflammatory back pain and reduced spinal flexion and subsequently reduced chest expansion. HLA B27 is positive in 25-75% patients, but is not of diagnostic value
  • Treatments comprise short-term NSAIDs (COX2 inhibitors if NSAIDs not tolerated); intensive physiotherapy; local steroid injection; and anti-TNF for treatment resistant arthritis
Axial arthritis

  • In 4-17% of patients with Crohn's disease, related to disease activity and responds to Crohn's disease treatment
  • Affects ankles, knees, hips, wrists and sometimes elbows and shoulders, typically asymmetric
  • Usually self limiting over weeks
  • Symptomatic treatment comprises short-term NSAIDs (COX2 inhibitors if NSAIDs not tolerated); physiotherapy; local steroid injection; sulfasalazine for persistent large joint arthritis; and anti-TNF for treatment resistant arthritis
Pauci-articular (type 1)

  • In 2.5% of patients with Crohn's disease, independent of disease activity, thus requires symptomatic treatments
  • Mainly affects small joints of the hand, which are painful and swollen (synovitis)
  • Treatments comprise short-term NSAIDs (COX2 inhibitors if NSAIDs not tolerated); physiotherapy; local steroid injection; sulfasalazine for persistent large joint arthritis; and anti-TNF for treatment resistant arthritis
Poly-articular (type 2)

 
 

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