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Enteropathic Arthropathies

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

Synonyms: enteropathic arthritis, arthritis associated with inflammatory bowel disease, reactive arthritis

Enteropathic arthropathy is an umbrella term used to describe various patterns of inflammatory arthritis which may be associated with a range of gastrointestinal (GI) pathologies. Its constituent conditions are classified as part of the seronegative spondyloarthropathies. Its various associated diseases are outlined below:1,2

Pathophysiology

This is poorly understood. Abnormal permeability of the bowel to bacterial antigens, which then locate in articular tissues and lead to an inflammatory response, is one possible mechanism. Genetic susceptibility (particularly HLA-B27 positivity) and immunological dysmodulation may also play a role.3 Cross-reactivity between articular tissue self-antigens and bacterial antigens may be the underlying immunological mechanism. HLA-B27 positivity may play its role by allowing bacterial peptide antigens to be presented to CD8+ cells, inducing a cellular immune cascade.2,4 Intestinal bacterial overgrowth is thought to be important where the condition develops after intestinal bypass surgery.

Epidemiology

Figures from the USA indicate that the current annual incidence of ulcerative colitis (UC) is 6-8 cases per 100,000 population with a prevalence of 70-150 cases per 100,000 population. For Crohn's disease (CD), the current annual incidence in the USA is 2 cases per 100,000 population with prevalence around 20-40 cases per 100,000 population. The incidence of both conditions appears to be rising. Roughly 10-20% of those with inflammatory bowel disease (IBD) suffer some form of peripheral arthritis and/or sacroiliitis/spondylitis, the predominant forms of enteropathic arthropathy.

Reactive arthritis is thought to affect around 2-3% of all patients with Salmonella spp., Shigella spp. and Campylobacter spp. infections.5 Arthritis in patients who have undergone intestinal bypass surgery is relatively common with some series showing up to 80% affected in the medium to long term. Chronic arthritis is present in up to 25% of such patients.2

Risk factors

  • HLA-B27 positivity is strongly associated with axial (spondylitic) forms of the disease in IBD, but not the peripheral form; reactive arthritis is also strongly associated with HLA-B27 positivity.
  • The male:female ratio is 1:1 for peripheral forms of arthritis with spondyloarthropathy appearing to be more common in males.
  • The peak age of incidence is 15-35 years of age.2

Presentation

Symptoms

  • Axial arthritis (spondylitis and sacroiliitis) associated with inflammatory bowel disease (IBD):
    • The condition may precede any GI symptoms and be active despite good control of bowel disease.
    • There is a gradual onset of low back pain radiating down the back of the legs.
    • Symptoms tend to be worse in the morning.
    • Prolonged sitting or standing can bring the symptoms on.
    • Moderate movement tends to improve the symptoms.
    • The arthritis tends to be chronic and long-standing.
  • Peripheral arthritis of IBD:
    • The condition is usually associated with GI symptoms, but may take some time to emerge after the onset of bowel problems.
    • It is more likely to affect sufferers of Crohn's disease (CD) rather than ulcerative colitis (UC).
    • There is an asymmetric, oligoarticular arthritis that predominantly affects the lower limbs.
    • The arthritis is usually transient and migratory, but may affect progressively more joints in some cases.
  • Enthesopathy of IBD:
    • This tends to cause severe localised pain in the heel where the insertion of the Achilles tendon is affected; disease of the patellar tendon causes pain on the tibial tuberosity or on the patella itself; the insertion of other tendons or other fascial areas can be inflamed causing, for example, buttock pain or pain in the sole of the foot (plantar fasciitis).
  • Extra-articular manifestations of IBD:
  • Reactive arthritis following intestinal infection:
    • This typically manifests as an acute asymmetrical oligoarthritis with a predilection for the knees and ankles.
    • It may occur several weeks or months after the initial bout of enteritis.
  • Arthritis due to intestinal-bypass surgery performed to correct morbid obesity:
    • Polyarthritis and an associated dermatitis may occur, and are thought to be due to bacterial overgrowth occurring in the bypassed section of bowel, leading to the formation of pathological immune complexes; if the procedure is reversed then the symptoms resolve.
  • Whipple's disease arthritis:
    • This occurs most commonly in middle-aged men.
    • As well as the typical GI symptoms, there is a migratory polyarthritis that can precede GI symptoms by months to years.
  • Coeliac disease arthritis:
    • This is a relatively rare feature of the condition.
    • It tends to present as a symmetrical arthritis of the lumbar spine, hips, knees and shoulders and may be the presenting feature of the illness before typical coeliac symptoms become apparent.
    • The arthritis usually resolves when the gut symptoms respond to a gluten-free diet.
  • Collagenous colitis:
    • This is a rare condition of unknown cause where there is linear deposition of collagen beneath the epithelium of the colon.
    • It causes chronic watery diarrhoea and abdominal pain.
    • About 10% of sufferers have peripheral arthritis of the hands and wrists that is responsive to non-steroidal anti-inflammatory drugs (NSAIDs).
    • The condition appears to be benign and self-limiting in the majority of cases but may cause long-term chronic disease in a minority.6

Signs

  • Check the temperature to look for evidence of fever.
  • Look at the eyes for evidence of anterior uveitis.
  • Look in the mouth to detect any ulceration or other oral manifestations of IBD.
  • Check the skin for rashes, particularly pyoderma gangrenosum and erythema nodosum.
  • The joints should be carefully examined to establish the presence of inflammation and to determine the symmetry and severity of the arthritis.
  • The spine needs careful assessment of its range of motion; palpate for tenderness over the sacroiliac joints.
  • Periarticular structures should be palpated to look for evidence of enthesopathy.
  • Palpate the heel and soles of the feet to detect tenderness and swelling due to Achilles tendonitis or plantar fasciitis.
  • Abdominal examination is necessary to detect any tenderness or suggest an alternative cause for intestinal symptoms.

Differential diagnosis

Investigations

  • Stool microscopy and culture where the aetiology of any bowel disease is undetermined.
  • Sigmoidoscopy/colonoscopy/upper GI endoscopy may be needed.
  • FBC to detect iron deficiency anaemia, leukocytosis or thrombocythaemia associated with inflammatory bowel disease (IBD) or other GI conditions.
  • ESR/CRP are usually elevated.
  • X-ray of affected joints (particularly the spine/sacroiliac joints/calcaneum).
  • Synovial fluid aspiration and analysis (shows mononuclear inflammatory cells and is culture-negative without crystals).
  • Consider autoimmune screen and anti-endomysial antibodies if any other inflammatory condition/coeliac disease suspected.

Associated diseases

See list in description section at head of document.

Management

Nondrug

  • Maintenance of moderate activity and spinal mobility with physiotherapy and exercises is important, particularly for axial forms of the disease.
  • Modification of the diet based on the underlying GI condition may help to alleviate gut-related symptoms.
  • Extra-articular disease, particularly that affecting the eyes, requires early recognition and referral to specialist services for management and monitoring.
  • When ulcerative colitis (UC) requires a colectomy; it has been shown to subsequently resolve peripheral joint disease but not axial arthritis.

Drugs2,7

  • NSAIDs may be used to treat acute joint inflammation but must be given with care as they may worsen GI symptoms.
  • Control of the underlying GI condition may improve the arthritis, but this is often not the case for axial arthritis associated with inflammatory bowel disease (IBD).
  • Intra-articular and systemic corticosteroids are useful for the peripheral arthritis of IBD but have little effect on axial involvement.
  • Sulfasalazine is widely used and is effective in treating both GI and rheumatological symptoms in IBD; it should be given under specialist supervision.
  • Methotrexate, azathioprine, pamidronate and ciclosporin have all been used as disease-modifying drugs with variable success, under specialist supervision.
  • Tumour necrosis factor (TNF) antagonists are increasingly being shown to be effective agents in the management of arthritis and bowel disease in IBD.8 They appear to be very effective against enthesopathy and axial disease, which have traditionally been very hard to treat. They are expensive and can have significant side-effects; their use should be supervised in specialist clinics, preferably as part of a clinical audit and ongoing guideline development programme. National Institute for Health and Clinical Excellence (NICE) guidance on their use in IBD and arthropathies is now available.9,10
  • Treatment or prophylaxis of osteoporosis using bisphosphonates, calcium and vitamin D may be necessary.

Complications

  • Side-effects and toxicity caused by drug therapy.
  • Complications of inflammatory bowel disease (IBD).
  • Ocular complications due to uveitis.
  • Secondary amyloidosis of Crohn's disease (CD).
  • Loss of mobility and increasing disablement in severe cases of axial arthritis (rare).

Prognosis

This is dependent very much on the specific underlying cause. Inflammatory bowel disease (IBD)-related arthritis tends to carry the worse long-term prognosis, particularly where there is severe axial involvement. The use of TNF-alpha antagonists is offering new hope in treating severe cases. The majority of cases are amenable to useful therapy and maintain an active and independent lifestyle.

Prevention

Disability can be circumvented in those who suffer axial arthritis, by the maintenance of an exercise programme to preserve spinal mobility. There are no known strategies to prevent inflammatory bowel disease (IBD) or arthropathy in its sufferers.

Document references

  1. Keat A; ABC of rheumatology. Spondyloarthropathies. BMJ. 1995 May 20;310(6990):1321-4.
  2. Minerva P; Enteropathic Arthropathies, Medscape, Dec 2008
  3. Holden W, Orchard T, Wordsworth P; Enteropathic arthritis. Rheum Dis Clin North Am. 2003 Aug;29(3):513-30, viii. [abstract]
  4. Wollheim FA; Enteropathic arthritis: how do the joints talk with the gut? Curr Opin Rheumatol. 2001 Jul;13(4):305-9. [abstract]
  5. Keat A; Reiter's syndrome and reactive arthritis in perspective. N Engl J Med. 1983 Dec 29;309(26):1606-15.
  6. Madisch A, Miehlke S, Lindner M, et al; Clinical course of collagenous colitis over a period of 10 years. Z Gastroenterol. 2006 Sep;44(9):971-4. [abstract]
  7. Reveille JD, Arnett FC; Spondyloarthritis: update on pathogenesis and management. Am J Med. 2005 Jun;118(6):592-603. [abstract]
  8. Van den Bosch F, Kruithof E, De Vos M, et al; Crohn's disease associated with spondyloarthropathy: effect of TNF-alpha blockade with infliximab on articular symptoms. Lancet. 2000 Nov 25;356(9244):1821-2. [abstract]
  9. Crohn's disease - infliximab (review) and adalimumab (review of TA40), NICE Technology Appraisal (May 2010); Use of tumour necrosis factor alpha (TNF a) inhibitors (adalimumab, and infliximab [review]) for Crohn's disease (review of TA40)
  10. Ulcerative colitis (acute exacerbations) - infliximab, NICE Technology Appraisal Guidance (December 2008); Infliximab for the treatment of acute exacerbations of ulcerative colitis

Internet and further reading

© EMIS 2011Author: Dr Richard DraperReviewer: Dr Cathy Jackson
Document ID: 1644Document Version: 23Last Reviewed: 6 Jul 2011
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