Enteropathic Arthropathies

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 that may be associated with a range of gastrointestinal pathologies. Its constituent conditions are classified as part of the seronegative spondylarthropathies. Its various associated diseases are outlined below:^1,2

• Spondylarthropathy and peripheral arthritis due to inflammatory bowel disease (IBD), i.e. Crohn's disease (CD) and ulcerative colitis (UC)
• Arthritis associated with other gastrointestinal pathologies such as coeliac disease, Whipple's disease, collagenous colitis and following intestinal-bypass surgery.
• Reactive arthritis due to gastrointestinal infection/infestation with:
  • Bacteria such as Shigella spp., Salmonella spp., Yersinia spp. and Campylobacter spp.
  • Parasites such as Strongyloides stercoralis, Entamoeba histolyticum, Taenia spp. (tapeworm), Ascaris lumbricoides, Cryptosporidium spp. and Giardia lamblia

This is poorly understood. Abnormal permeability of the bowel to bacterial antigens that 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 though to be important where the condition develops after intestinal bypass surgery.

US figures indicate that the current annual incidence of UC is 6–8 cases per 100,000 population with a prevalence of 70–150 cases per 100,000 population. For CD, the current US annual incidence 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 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 M:F ratio is 1:1 for peripheral forms of arthritis with spondylarthropathy appearing to be commoner in males.
• The peak age of incidence is 15–35 years of age.²

Symptoms

• Axial arthritis (spondylitis and sacroiliitis) associated with IBD:
  • The condition may precede any gastrointestinal 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 gastrointestinal symptoms, but may take some time to emerge after the onset of bowel problems.
  • It is more likely to affect sufferers of CD rather than 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:
  • Intestinal symptoms can include abdominal pain, diarrhoea, cramping, weight loss and the passage of blood or mucus per rectum.
  • There are dermatological associations with pyoderma gangrenosum affecting UC cases and erythema nodosum being seen with CD.
  • The mouth may be affected by frequent, recurrent, painful aphthous ulcers.
  • The eye may be painful and red with blurred vision due to anterior uveitis.
  • Fever may be associated with IBD; a chronic low-grade fever may be a manifestation of secondary amyloidosis in CD.
• 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 gastrointestinal 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 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 sacro-iliac joints.
• Peri-articular 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.

• Any cause of peripheral polyarthritis
• Any cause of spondylarthropathy
• Rheumatoid arthritis
• Gout
• Sarcoidosis
• Gonococcal arthritis
• Behçet's syndrome
• Lyme disease
• Septic arthritis

• 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, leucocytosis or thrombocythaemia associated with IBD or other GI conditions.
• ESR/CRP usually elevated.
• X-ray of affected joints (particularly spine/S-I 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 other inflammatory condition/coeliac disease is suspected.

See list in description section at head of document.

Non-drug

• 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.
• Colectomy may be used to treat some cases of UC; it has been shown to resolve peripheral joint disease but not axial arthritis.

Drugs^2,7

• NSAIDs may be used to treat acute joint inflammation but must be given with care as they may worsen gastrointestinal symptoms.
• Control of the underlying gastrointestinal condition may improve the arthritis, but this is often not the case for axial arthritis associated with 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 gastrointestinal 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. NICE guidance on their use in inflammatory bowel disease and arthropathies is now available and more is expected.^9,10
• Treatment or prophylaxis of osteoporosis using bisphosphonates, calcium and vitamin D may be necessary.

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

This is dependent very much on the specific underlying cause. IBD-related arthritis tends to carry the worse long-term prognosis, particularly where there is severe axial involvement. The use of TNF-α 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.

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 IBD or arthropathy in its sufferers.