Inflammatory bowel disease (IBD) is a common medical problem in the United States. There may be a genetic predisposition for the development of IBD. Gastrointestinal symptoms of IBD are often accompanied by symptoms in other body systems. Joint complaints are commonly noted in IBD patients, and may be the primary presenting complaint in some.
Inflammatory Bowel Disease
Inflammatory bowel disease is a chronic inflammatory disease primarily affecting the gastrointestinal (GI) tract, though other body systems may be involved (Table 1). The two major forms of IBD encountered in the United States are Crohn's disease (CD) and ulcerative colitis (UC). Arthropathy is not uncommon in patients with IBD and joint pain may be the sole reason for presentation to a sports medicine physician. It is estimated that over one million people in the United States have IBD. The incidence of CD is 3.6 to 8.8 in 100,000 people, and the incidence of UC is three to 15 in 100,000. UC is slightly more common in males, CD slightly more common in females . The estimated annual cost of IBD, considering both direct and indirect cost, is estimated at $1.8 to $2.6 billion .
The etiology is not fully understood, but there appears to be a genetic predisposition for the development of IBD and specific gene mutations may place the IBD patient at greater risk for experiencing extra-intestinal manifestations of their inflammatory disease. Mutations of the CARD15 gene are associated with a higher incidence of CD. CARD15 mutations are noted in 48% patients with spondyloarthropathy and GI inflammation compared with 28% of patients with spondyloarthropathy without GI inflammation . Gene mutations appear to increase the likelihood that antigen exposure, gut bacteria, will create an inflammatory response in the GI tract as well as other tissues.
Common presenting complaints of IBD include abdominal pain and cramping, diarrhea, rectal bleeding, weight loss, and fever. Some patients, however, present only due to the presence of extra-intestinal manifestations, delaying the diagnosis of IBD. Physical examination is often normal although general abdominal tenderness may be present. Oral and perianal ulcers may be noted with CD. Other potential examination and laboratory findings include decreased weight, heme positive stool, and anemia. Diagnostic imaging and endoscopy, with or without biopsy, are needed to make an accurate diagnosis. Barium enema studies may reveal stricture, “string sign,” fistula formation, and skip lesions in CD. The same study in UC patients may reveal more diffuse changes, the appearance of a “lead pipe” colon with loss of haustral markings. Colonoscopy with biopsy is often performed for definitive diagnosis. Differences between CD and UC are outlined in Table 2.
Extra-intestinal manifestations (EIMs) often, but not always, parallel the clinical course of IBD. EIMs are more frequent in patients with IBD of greater than 10 years' duration. They tend to be more commonly seen in patients with CD (36.6% vs 15.0%) but there are exceptions. Primary sclerosing cholangitis and ocular EIMs may be more common in UC. EIMs are generally more common in women but again, there are exceptions. Hepatobiliary EIMs tend to be more common in men. Men with UC are more likely to experience arthropathy than women with UC [4••].
Inflammatory Bowel Disease Arthropathy
Arthropathy is a common EIM of IBD. A patient may have axial arthropathy, peripheral arthropathy, or both. The common axial arthritides include sacroileitis and ankylosing spondylitis. The incidence of axial changes approaches 20 times that seen in the general population. Ankylosing spondylitis (AS) is associated with the presence of the HLA-B27 gene (90% in classic AS, 50% in IBD patients with AS) .
Peripheral arthropathy can be subdivided into two types [5••]. Type I peripheral arthritis tends to be more acute, self-limiting and pauciarticular (< five joints). It typically affects the larger joints of the lower extremities and is often associated with the presence other EIMs. Type I peripheral arthropathy tends to parallel the activity of the bowel disease. In Type II arthropathy, the findings are more chronic, bilateral, symmetrical, and polyarticular (> five joints). It typically affects the smaller joints of the upper extremities and the course tends to run independently of the course of the intestinal disease.
Joint EIMs are generally more prevalent in patients with CD. Axial arthritis is reported in 10.2% of patients with CD compared with 3.2% in UC patients. Type I peripheral arthritis is also more common in CD patients (11.4% vs 2.7%). There appears to be an equal prevalence of Type II peripheral arthritis. Joint findings are more common in women (26.4%) compared with men (18.4%). In those with UC, joint EIMs are three times more common if pancolitis is present [4••].
Patients will usually present due to joint pain and swelling that is not related to any injury or trauma. The clinician must maintain a high index of suspicion for IBD arthropathy as patients presenting with joint complaints may not equate them with GI problems. Therefore, they don't mention the GI trouble and delay accurate diagnosis. On examination, joint effusions are often present and the patient is tender to general palpation of the involved joints. Range of motion deficits may be noted. The affected joints should be ligamentously stable with good strength, though strength may be limited by pain. An accurate diagnosis depends on making an accurate diagnosis of IBD.
If IBD arthropathy is suspected in a patient who has not been diagnosed with IBD, general treatments for the joint pain may be initiated as further work-up of GI disease is undertaken. These treatments may include rest, ice, rehabilitation exercises, and analgesic medications. Nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided in these circumstances as they may exacerbate the GI disease. In a case-controlled study of patients admitted to the hospital for exacerbations or onset of IBD, 31% were found to be on NSAIDs at the time of admission compared with 2% NSAID use in the control group . In another case-controlled study of 200 patients admitted to the hospital for colitis, a high correlation of current (OR 1.77) and recent (OR 1.93) NSAID use was found [7•].
Currently, treatments for IBD include corticosteroids, sulfasalazine, methotrexate and tissue necrosis factor (TNF)-αblockers. Treatment of the underlying IBD usually results in control of joint related complaints. Disease modifying agents, like sulfasalazine, have been shown to be effective in controlling the pain of peripheral arthropathy but don't effect axial flexibility . The effect of methotrexate appears to be similar . Common dosing for these medications is listed in Table 3. The TNF-α blocker infliximab has been shown to be effective in reducing IBD-related joint complaints, causing rapid and sustained relief of pain when given on a regular basis [10,11].
The Effects of Exercise
Exercise in previously sedentary patients with CD, even a modest 12-week walking program, can bring about psychological and physical improvements without exacerbating disease activity . Whether or not exercise improves GI function in IBD patients is an area of debate, most changes are insignificant , but patients may report subjective improvement. It has been suggested that regular exercise (5 years of regular weekly exertion) may prevent IBD . Regular physical exercise may reduce the risk of CD by 50% but the same study did not show a reduced risk of UC.
The sports medicine physician must keep a high index of suspicion for IBD arthropathy in athletes who present with axial arthropathy or peripheral arthropathy that is not related to injury or overuse. Diagnosis may be difficult and relies on accurate diagnosis of the GI disease. Joint symptoms usually respond to treatment of the bowel disease. Other standard treatments of joint pain, including ice, rest, rehabilitation exercises and analgesics can be utilized, though NSAIDs should be avoided as they may lead to a worsening of the GI symptoms. Exercise won't likely worsen IBD symptoms but whether exercise prevents IBD is still an area of debate.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance
1. Loftus EV, Sandborn WJ: Epidemiology of inflammatory bowel disease.Gastroenterol Clin North Am
2. Hay JW, Hay AR: Inflammatory bowel disease: costs-of-illness.J Clin Gastroenterol
3. DeVos M: Review article: joint involvement in inflammatory bowel disease.Aliment Pharmacol Ther
2004, 20(Suppl 4): 36–42.
4.•• Lakatos L, Pandur T, David G, et al.
: Association of extraintestinal manifestations of inflammatory bowel disease in a province of western Hungary with disease phenotype: results of a 25-year follow-up study.World J Gastroenerol
Important long-term study outlining the prevalence of various EIMs associated with IBD.
5.•• Orchard TR, Wordsworth BP, Jewell DP: Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history.Gut
Outlines the various types of arthropathy associated with IBD.
6. Felder JB, Korelitz BI, Rajapakse R, et al.
: Effects on nonsteroidal anti-inflammatory drugs on inflammatory bowel disease: a case-control study.Am J Gastroenterol
7.• Evans JM, McMahon AD, Murray FE, et al.
: Non-steroidal anti-inflammatory drugs are associated with emergency admission to hospital for colitis due to inflammatory bowel disease.Gut
Large case-controlled study that shows the risk of NSAID use in IBD patients.
8. Clegg DO, Reda DJ, Wisman MH, et al.
: Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis.Arthritis Rheum
9. Altan L, Bingol U, Karakoc Y, et al.
: Clinical investigation of methotrexate in the treatment of ankylosing spondylitis.Scand J Rheumatol
10. Generini S, Giacomelli R, Fedi R, et al.
: Infliximab in spondyloarthropathy associated with Crohn's disease: an open study on the efficacy in inducing and maintaining remission of musculoskeletal and gut manifestations.Ann Rheum Dis
11. Van den Bosch F, Kruithof E, De Vos M, et al.
: Crohn's disease associated with spondyloarthropathy: effect of TNFalpha blockade with infliximab on articular symptoms.Lancet
12. Loudon CP, Corroll V, Butcher J, et al.
: The effects of physical exercise on patients with Crohn's disease.Am J Gastroenterol
13. D'Inca R, Varnier M, Mestriner C, et al.
: Effect of moderate exercise on Crohn's disease patients in remission.Ital J Gastroenterol Hepatol
14. Persson P, Leijonmarck C, Bernell O, et al.
: risk indicators for inflammatory bowel disease.Int J Epidemiol