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Arthritis associated with gastrointestinal disease
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2012. | This topic last updated: Jun 11, 2011.

INTRODUCTION — Arthritis is a recognized extraintestinal manifestation of several illnesses and conditions, including inflammatory bowel disease (IBD), bacterial infections of the gut, gluten sensitive enteropathy (celiac disease), various parasitic infections, pseudomembranous colitis, and following intestinal bypass surgery. Other illnesses have a propensity for causing inflammation of joints and the gut. Examples discussed in this review include Behçet’s and Whipple's diseases.

The clinical features of arthritis associated with IBD are discussed in detail here, along with the treatment for synovitis in patients with Crohn's disease and ulcerative colitis. The pathogenesis of these manifestations and the treatment of IBD are discussed separately. (See "Mechanisms for the induction of rheumatic symptoms by gastrointestinal disease" and "Immunologic basis for extraintestinal manifestations in inflammatory bowel disease" and "Overview of the medical management of mild to moderate Crohn's disease in adults" and "Medical management of ulcerative colitis".)

Therapy for reactive arthritis (formerly called Reiter syndrome), Behçet’s and Whipple's diseases are also discussed separately. (See appropriate reviews).

PREVALENCE AND ASSOCIATED DISEASES — Arthritis occurs in 9 to 53 percent of patients with IBD [1-9]. Arthritis is somewhat more likely to occur in patients with large-bowel disease and in those patients with complications such as abscesses, pseudomembranous polyposis, perianal disease, massive hemorrhage, erythema nodosum, stomatitis, uveitis, and pyoderma gangrenosum. Among patients with Crohn's disease, those with colonic involvement are at higher risk of developing synovitis than those with isolated small bowel disease. Males and females are affected equally. Both children and adults are at risk for this complication of IBD. In addition subclinical gut inflammation, documented by endoscopy, has been described in up to two-thirds of patients with spondyloarthropathies [10].

ULCERATIVE COLITIS AND CROHN'S DISEASE — Ulcerative colitis and regional enteritis (Crohn's disease) are the most frequently encountered types of idiopathic IBD that are associated with arthritis or spondylitis and are discussed first. Other disorders associated with joint pain and/or inflammation are discussed later. (See 'Other diseases with bowel and joint involvement' below.)

Clinical manifestations — Arthritis may affect the spine, sacroiliac joints, appendicular joints, or a combination of these articulations. Peripheral arthritis may be acute and remitting (Type I), or be a more chronic problem or have frequent relapses (Type II) [11]. Complications of IBD may also cause joint pain and must be distinguished from sterile inflammation. Bacterial infection of the sacroiliac or peripheral joints may occur due to fistulization or bacteremia. Adverse effects of treatment of IBD may also affect joints. Osteonecrosis (avascular necrosis of bone) due to glucocorticoid use is one example. (See "Osteonecrosis (avascular necrosis of bone)".)

Spondylitis and sacroiliitis — Spondylitis occurs in 1 to 26 percent of patients with IBD [1-4,7,12]. Males are more frequently affected than females. Patients typically complain of prolonged stiffness in the back and/or buttocks in the morning or after rest. Stiffness and associated pain are often relieved by exercise. Back symptoms are unrelated to those of the gastrointestinal disease. Physical examination may reveal limited spinal flexion and reduced chest expansion. Spondylitis may be the only articular manifestation or it may occur in association with type I peripheral arthropathy [11], which is discussed below.

Asymptomatic sacroiliitis, detected by radiography, occurs in 4 to 18 percent of patients with IBD [12]. By contrast, 52 percent of patients with IBD have abnormal technetium pyrophosphate bone scans of the sacroiliac joints [4,12]. No increased frequency of HLA-B27 in the subset of patients with IBD and radiographic sacroiliitis was apparent in this study.

In contrast, sacroiliitis in patients with Crohn's disease is strongly associated with CARD15 gene polymorphisms [13]. In a study of 102 patients with Crohn's disease, 23 were found to have radiological evidence of sacroiliitis. Although only three of these patients were HLA-B27 positive, 78 percent of those with sacroiliitis had a CARD15 variant, compared with only 48 percent of those who did not have sacroiliitis (odds ratio 3.8).

The presence of an abnormal radiograph of the sacroiliac joints does not indicate a higher risk for the development of spondylitis. Magnetic resonance imaging can also reveal changes (picture 1).

Type I arthropathy — In type I arthropathy, the peripheral arthritis tends to be acute, is pauciarticular (affecting six or fewer joints), is often associated with flares of the bowel disease, occurs early in the course of the bowel disease, is self-limiting (90 percent under 6 months), and does not result in joint deformities [11,14]. The knee is most commonly affected. Five percent of IBD patients develop type I arthropathy. Joint symptoms may occur prior to the onset of symptoms suggestive of bowel disease.

Type II arthropathy — In Type II arthropathy, patients have polyarticular disease, with metacarpophalangeal (MCP) joints being particularly involved [11]. Other joints (knees, ankles, elbows, shoulders, wrists, proximal interphalangeal (PIP), and metatarsophalangeal (MTP) joints) are less often affected. Approximately one half of the patients with IBD have migratory arthritis. Active synovitis may persist for months, and may recur repeatedly. Episodes of exacerbations and remissions may continue for years.

Type II arthropathy affects 3 to 4 percent of patients with IBD. Articular involvement rarely precedes the diagnosis of IBD and joint symptoms typically do not parallel the activity of bowel disease [11].

Laboratory findings — The peripheral white blood cell count, hematocrit, erythrocyte sedimentation rate, and serum C-reactive protein concentration usually reflect the activity of the intestinal disease and are therefore of little help in assessing arthritis or spondylitis. Serum levels of rheumatoid factor are not elevated.

HLA-B27 is found in 50 to 75 percent of the patients with axial arthritis [4]. An increase in frequency in HLA-B27, B35, and DRB1*0103 has been described in those with a type I peripheral arthritis; type II arthropathy has been associated with HLA-B44 (and not B27) [11]. While the reported HLA associations are of interest, HLA typing has no role in management of individual patients.

Synovial fluids have yielded from 5000 to 12,000 white blood cells per microliter, predominantly polymorphonuclear leukocytes [4,12]. Synovial membrane biopsies reveal nonspecific abnormalities, including: proliferation of synovial lining cells, increased vascularity, and infiltration of mononuclear cells [4,12].

Radiographic findings — Radiographs of the spine and pelvis may show typical findings of ankylosing spondylitis and sacroiliitis. Plain film radiographs of the peripheral joints demonstrate soft-tissue swelling, juxtaarticular osteoporosis, mild periostitis, and effusions, usually without erosions or destruction. Radiographs frequently have abnormal findings even in asymptomatic patients with IBD. In one study, for example, plain film and computer aided tomography (CT) were used to evaluate the sacroiliac joints of 65 patients with IBD, none of whom had symptoms of sacroiliitis; 18 percent had finding of sacroiliitis by plain film and 32 percent had had abnormal sacroiliac joints noted by CT scanning [15].

Diagnosis — There is no pathognomonic finding to confirm the clinical suspicion of arthritis due to IBD. While the diagnosis may be suspected in the proper clinical setting, it remains largely one of exclusion. (See "Evaluation of the adult with polyarticular pain".) If the arthritis affects a single joint (monoarthritis), or a few joints (oligoarthritis), it is particularly important to perform a joint aspiration to exclude septic arthritis, the presentation of which may be atypical in patients with IBD who are receiving antiinflammatory or immunosuppressive treatment. (See "Evaluation of the adult with monoarticular pain".)

Differential diagnosis — The differential diagnosis of joint pain in a patient with IBD is broad. Disorders causing joint pain that may occur with increased frequency in this setting include, but are not limited to:

In addition to the disorders listed above, there are other diseases and states that have prominent intestinal manifestations and are associated with arthritis. These include reactive arthritis (formerly Reiter syndrome), Whipple's disease, Behçet’s syndrome, intestinal bypass, gluten sensitive enteropathy, and parasitic infestations. Each of these conditions is discussed following the section on treatment of arthritis in IBD. (See 'Other diseases with bowel and joint involvement' below.)

Treatment — Effective treatment of the underlying IBD is often helpful in controlling the peripheral arthritis. Spinal involvement is more problematic and no therapy has been definitively shown to slow the radiographic progression of spondylitis. (See "Assessment and treatment of ankylosing spondylitis in adults".)

Peripheral arthritis — Some agents, notably sulfasalazine, azathioprine, 6-mercaptopurine, methotrexate, glucocorticoids, and tumor necrosis factor (TNF) inhibitors may be helpful for both bowel and joint inflammation [17-22]. NSAIDs may relieve the arthritic symptoms, but may have an adverse effect on the IBD. There is only limited information from randomized trials to guide treatment decisions for arthritis associated with inflammatory bowel disease; most of the available information is from small case series. Our recommendations are based upon the available evidence, inferences from studies of other forms of arthritis, including spondyloarthritis and reactive arthritis, and our clinical experience.

  • NSAIDs — Nonsteroidal antiinflammatory drugs (NSAIDs) relieve pain and inflammation, but should be used with caution because of possible gastrointestinal side effects. Although careful epidemiologic studies investigating the possible link between NSAIDs and the development of IBD have not been performed, a number of reports suggest that NSAIDs increase the risk for the development of IBD and may exacerbate underlying IBD [7,17,23,24]. However, some patients with IBD appear to be able to tolerate NSAIDs. (See "NSAIDs: Adverse effects on the distal small bowel and colon" and "Definition of and risk factors for inflammatory bowel disease".)

    The new onset of symptoms of IBD or worsening of previously diagnosed bowel disease in a patient whose arthritis is being treated with NSAIDs presents a challenging management problem. Agents effective for treatment of idiopathic IBD may improve bowel inflammation due to NSAIDs [23]. Similarly, radiographic studies and even endoscopic findings and biopsies may be unable to differentiate these causes [23]. Thus, improvement in symptoms and the mucosal appearance following withdrawal of the potentially offending NSAID may provide the best support for NSAIDs being the cause. (See "NSAIDs: Adverse effects on the distal small bowel and colon", section on 'Management'.)

    Experience with the cyclooxygenase-2 (COX-2) selective inhibitors, including celecoxib, is limited in patients with IBD. Because COX-2 activity promotes epithelial proliferation and wound healing, COX-2 inhibition could, theoretically, have deleterious effects in patients with IBD [25]. On the other hand, selective COX-2 inhibitors ameliorate the severity of experimental colitis [23]. The only placebo-controlled trial to assess the effect on bowel disease in patients with IBD used celecoxib as the active drug and no significant difference in the rate of relapse of IBD was noted after two weeks [26].

    One of the largest studies included 45 patients with IBD and arthralgias who were treated with rofecoxib, which is no longer available, for from three days to three months [27]. Arthralgia relief was reported by 71 percent of patients (complete relief in 18 percent and partial relief in 53 percent). However, nine patients (20 percent) required discontinuation of therapy due to the development of gastrointestinal symptoms, which subsided after treatment was stopped. This was a higher rate of discontinuation than was observed in a control group of 30 patients with dyspepsia (3 percent). The percentage of patients who required discontinuation was similar for those with Crohn's disease or ulcerative colitis.
  • Sulfasalazine — Sulfasalazine is an azo-bonded combination of 5-aminosalicylic acid and sulfapyridine [28]. Sulfasalazine is poorly absorbed in the small intestine. In the colon, sulfasalazine is split by bacteria into its constituent moieties. The 5-amino compound lowers colonic prostaglandin E and alters gut flora. The sulfapyridine appears to be antiarthritic [28]. (See "Sulfasalazine and 5-aminosalicylates in the treatment of ulcerative colitis".)
  • Immunomodulatory agents — Other immunomodulatory therapies used for IBD, including azathioprine and 6-mercaptopurine, may also have beneficial effects on joint disease. However, aminosalicylates (eg, mesalamine), which are useful for controlling intestinal inflammation, appear to have no direct antiinflammatory effect on the synovium [17].
  • Anticytokine therapies — Anticytokine therapies, particularly those that inhibit tumor necrosis factor alpha (TNF alpha), have been used for treating Crohn's disease (see "Infliximab in Crohn's disease" and "Adalimumab for treatment of Crohn's disease in adults"). These agents have also proven useful for patients with rheumatoid arthritis or reactive arthritis. (See "Overview of biologic agents in the rheumatic diseases" and "Reactive arthritis (formerly Reiter syndrome)".)

    There are as yet only anecdotal reports and small uncontrolled series that address the usefulness of anti-TNF alpha treatment in patients with IBD and peripheral arthritis [18,21,29,30]. Additional clinical experience is needed to assess the efficacy and safety of cytokine inhibitors in the treatment of arthritis in patients with IBD.

Recommendations — Since the peripheral arthritis associated with IBD is generally nondestructive, therapy is primarily directed at symptomatic relief.

  • Despite concern about the potential for NSAIDs and COX-2 selective agents to cause worsening bowel inflammation, we have used agents from both of these classes successfully in patients with IBD. However, if symptoms or signs of IBD develop or worsen during use of NSAIDs or COX-2 selective treatment, it is prudent to temporarily or permanently discontinue their use.
  • If NSAIDs or COX-2 selective agents do not result in acceptable symptomatic relief, we recommend addition of sulfasalazine, if it is not already being used to treat bowel disease. The initial dose is 500 mg twice daily with an increase in daily dose of 1000 mg every two weeks until arthritis symptoms improve or a maximum dose of 1500 mg three times daily is reached. Maintaining the maximum dose for up to 12 weeks is recommended before assessing efficacy.
  • We recommend methotrexate, if sulfasalazine is not effective. However, patient or physician concerns about the potential hepatotoxicity of methotrexate may make azathioprine or 6-mercaptopurine more attractive alternatives. (See "Immunomodulator therapy in Crohn's disease".)

    Orally administered methotrexate is adequately absorbed, even in patients with active IBD [31]. Although subcutaneous injection of methotrexate may reduce portal venous concentrations of the drug, it has not been proven that this reduces the risk of hepatotoxicity. If dose limiting gastrointestinal side effects from methotrexate develop during oral therapy, switching to parenteral administration is recommended.

    The dosage used for subcutaneous administration is the same as for oral methotrexate. A typical beginning dose is 7.5 mg per week. The dose is increased in 2.5 to 5 mg increments, at approximately monthly intervals, until joint inflammation is controlled, or a dose of 25 mg per week is reached. Concomitant use of folic acid, 1 mg per day or weekly folinic acid (racemic leucovorin 2.5 to 5 mg or L-leucovorin 1 to 2 mg weekly) 24 hours following the methotrexate dose, is recommended to avoid nuisance side effects such as oral ulcers. Supplemental folate or leucovorin may also reduce the risk of myelotoxicity. (See "Use of methotrexate in the treatment of rheumatoid arthritis".)
  • If the addition of methotrexate, azathioprine, or 6-mercaptopurine has not successfully controlled the arthritis, glucocorticoids may be useful, and may be administered either systemically or via intraarticular injection. (See "Joint aspiration or injection in adults: Technique and indications".)
  • If polyarticular synovitis persists despite the treatment outlined above, use of a TNF-alpha antagonist, either by intravenous infusion of infliximab or subcutaneous administration of adalimumab or etanercept, is recommended. Dosing regimens developed for patients with rheumatoid arthritis are appropriate. Skin testing for latent tuberculosis is mandatory, since use of anti-TNF alpha therapies may cause reactivation. (See "Overview of biologic agents in the rheumatic diseases".)

    The presence of active infection is an absolute contraindication to the use of either of these cytokine inhibitors. Patients with evidence of latent, previously untreated tuberculosis should begin antituberculous therapy prior to beginning anti-TNF-alpha therapy. (See "Treatment of latent tuberculosis infection in HIV-negative adults".)

Spondylitis and sacroiliitis — The axial disease associated with IBD is treated as is any spondyloarthropathy. The treatment for spinal and sacroiliac involvement is symptomatic, as it is for the peripheral arthritis. (See "Assessment and treatment of ankylosing spondylitis in adults".) However, even if back pain and stiffness are controlled, radiographic progression to bony ankylosis may occur. NSAIDs or COX-2 selective agents are used to treat spinal pain and stiffness. The same concerns and cautions that were noted above for peripheral arthritis apply to their use for spondylitis and sacroiliitis.

As noted earlier, experience with infliximab is limited to small case series in which it has been associated with improvement in symptoms of spondylitis as well as peripheral arthritis during treatment with infliximab [30]. Whether anti-TNF therapy has any long term effect upon the progression of spondylitis remains to be determined.

In selecting among the available anti-TNF therapies, it should be noted that while etanercept may be used safely, and is reported to be effective for arthritis and spinal involvement in Crohn's disease, it is of no benefit for the intestinal manifestations of that disorder, unlike infliximab, which is often used for Crohn's disease and complications such as fistula formation [32,33]. (See "Infliximab in Crohn's disease".)

Recommendations — Nonpharmacologic and pharmacologic treatment are complementary for patients with spinal involvement.

  • The author recommends referral to a physical therapist for instruction in back exercises; these are aimed at prevention of neck and back deformities.
  • Of the available NSAIDs, indomethacin and naproxen have been used successfully, but antiinflammatory doses of any NSAID or COX-2 selective agent may be effective for symptoms of spondylitis or sacroiliitis.
  • For patients refractory to NSAIDs or COX-2 selective agents alone, methotrexate is recommended with dosing as described above for peripheral arthritis. An alternative to methotrexate is sulfasalazine.

Although data are limited, it can be expected that sacroiliac and spinal inflammation associated with IBD will respond to anti-TNF therapy as it does in ankylosing spondylitis.

OTHER DISEASES WITH BOWEL AND JOINT INVOLVEMENT — In addition to ulcerative colitis and Crohn's disease, several other illnesses and conditions have intestinal involvement and arthritis as prominent clinical features. These include, but are not limited to: reactive arthritis (Reiter syndrome), Whipple's disease, Behçet’s disease, celiac disease, parasitic infestation, pseudomembranous colitis, and as a result of intestinal bypass surgery. These disorders are also considerations in the differential diagnosis of patients with suspected IBD and arthritis.

Reactive arthritis — Reactive arthritis may occur after enteric infection due to Salmonella, Shigella, Yersinia, or Campylobacter species [17,34]. The incidence of reactive arthritis following bacterial dysentery has been reported to range from 2 to 33 percent [2]. An increased risk of arthritis is associated with Yersinia infection and presence of HLA-B27 genotype [1]. HLA-B27 has been found in over ninety percent of such cases.

Joint pain following diarrheal illness due to pathogenic E. coli infection has been noted. This group of E. coli includes enterotoxigenic E. coli (ETEC), attaching and effacing E. coli (A/EEC), enteropathogenic E. coli (EPEC), and verocytotoxin (shigatoxin)-producing E. coli (VTEC). (See "Pathogenic Escherichia coli".) Unlike reactive joint pain following Salmonella, Shigella, and Yersinia infection, the risk for developing arthralgia following E. coli infection is not affected by HLA-B27 status [35].

Joint symptoms develop within two to three weeks of developing diarrhea. The knee, ankle, wrist, and sacroiliac joints are commonly involved. Demonstration of a pathogenic organism by stool culture and/or finding a rise in antibody titers to the putative organism is helpful in confirming the clinical suspicion of reactive arthritis. Antibiotic treatment may be effective if begun during the diarrheal phase, but is not effective once arthritis is present. (See "Reactive arthritis (formerly Reiter syndrome)".)

Whipple's disease — Whipple's disease is due to infection with Tropheryma whippelii. Infection can be wide spread and may cause diarrhea, malabsorption, and weight loss. Systemic infection is often associated with joint manifestations. The knee, ankle, and wrist are frequently affected. Some patients may develop spondylitis and or sacroiliac joint involvement. In some patients the articular symptoms develop prior to symptomatic enteric involvement. Small bowel biopsy is usually diagnostic. Whipple's disease requires long-term antibiotic therapy. (See "Whipple's disease".)

Behcet's disease — Behçet’s disease is characterized by oral and genital ulceration, iritis, and occasionally by central nervous system involvement. In addition, oligoarticular, asymmetric arthralgia and/or arthritis may develop in approximately 50 percent of patients. The knee, ankle, wrist, and elbow are common sites of involvement. Mucosal ulceration of the small bowel is a frequent manifestation and may cause nausea, diarrhea, abdominal pain, and distension. Behçet’s disease may be particularly difficult to distinguish from IBD. The presence of pathergy, sterile neutrophilic infiltration of sites of injury, may be one helpful diagnostic clue. (See "Clinical manifestations and diagnosis of Behçet’s disease" and "Treatment of Behçet’s disease".)

Celiac disease — Diet sensitive enteropathy/arthropathy (gluten sensitive enteropathy or celiac disease) may be associated with arthritis in some patients [3]. Articular involvement was peripheral in 10 percent, axial in 8 percent, and combined in 9 percent. The arthritis is typically nonerosive and can be either oligo-or polyarticular. Joint symptoms may precede gastrointestinal manifestations of the disease. Joint symptoms respond to a gluten free diet. (See "Pathogenesis, epidemiology, and clinical manifestations of celiac disease in adults" and "Management of celiac disease in adults".)

A patient has been described who developed arthritis due to milk allergy [36]. The arthritis could be provoked by challenge with milk and alleviated by milk withdrawal. Occasional patients with lactose deficiency have been reported to have arthritis [37].

Intestinal bypass arthritis — Intestinal bypass surgery was developed for the treatment of obesity in 1952; 11 years later arthritis was recognized as a postoperative complication [1,2]. Polyarthralgia and sometimes arthritis has been reported to occur weeks or years following surgery in 8 to 36 percent of patients [1,2]. Because of an unacceptably high incidence of adverse effects, including arthritis, the jejunocolic and jejunoileal bypass operations have been abandoned. (See "Surgical management of severe obesity".)

Joint pain and tenderness exceed objective findings in most cases of intestinal bypass associated arthropathy, but episodes with abrupt onset of pain and inflammation may also develop. Tenosynovitis is common, with episodes possibly lasting for days and even months affecting the knee, wrist, ankle, shoulder, and finger joints. It may also be responsible for pain in the neck and back. This risk of developing this syndrome is higher after jejunocolic than after jejunoileal surgery and higher in females than males. There is often an associated urticarial, vesicular, pustular, macular, or nodular skin eruption. (See "Neutrophilic dermatoses", section on 'Bowel-associated dermatosis-arthritis syndrome'.) The Raynaud phenomenon has been reported in one-third of patients.

Plain radiographs generally show no joint damage, although marginal erosions may develop in patients with persistent arthritis. Synovial fluids generally have white blood cell counts of 500 to 27,000 per microliter with predominantly polymorphonuclear leukocytes. Synovial biopsies show chronic synovitis with lymphocytes but without lymphoid follicles. Tests for rheumatoid factor, antinuclear antibodies, and HLA-B27 are usually negative, while immune complexes (and cryoglobulins) are often present. These complexes contain bacterial antigens (eg, E. coli, B. fragilis), their antibodies, IgA secretory component, and various complement components (eg, C3, C4, C5) [2].

NSAIDs and glucocorticoids are effective in controlling joint symptoms but more lasting results can be achieved by use of tetracycline therapy to decrease bacteria overgrowth. Severe and refractory arthritis may require reanastomosis of the bowel.

Parasitic rheumatism — Parasitic infections of the gut have been associated with arthritis and other rheumatic disease syndromes [2,38-40]. These include Strongyloides stercoralis, Taenia saginata, Endolimax nana, and Dracunculus medinensis. As the parasites are not isolated from the joints it has been postulated that the joint symptoms represent a form of reactive arthritis. (See "Reactive arthritis (formerly Reiter syndrome)".)

Pseudomembranous colitis — Arthritis associated with pseudomembranous colitis has been described following antibiotic therapy in case series. In a report of four patients, arthritis developed 9 to 35 days after the onset of diarrhea [2]. The large joints of the lower extremity are most often affected. Clostridium difficile was isolated from two patients. (See "Clinical manifestations and diagnosis of Clostridium difficile infection in adults".)

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SUMMARY AND RECOMMENDATIONS — Arthritis may occur as an extraintestinal manifestation of several conditions, including inflammatory bowel disease (IBD) and a number of other disorders. Other illnesses, such as Behçet's disease, may cause inflammation of both the joints and the gut. (See 'Introduction' above.)

  • Arthritis occurs in a significant minority of patients with IBD, including both ulcerative colitis and regional enteritis (Crohn’s disease); it is more likely in patients with large-bowel disease and in those patients with gastrointestinal complications and other extraintestinal involvement. (See 'Prevalence and associated diseases' above.)
  • Spondylitis more frequently affects men with IBD. Typical symptoms include prolonged stiffness and pain in the back and/or buttocks in the morning or after rest, which is often relieved by exercise. Back symptoms are unrelated to those of the gastrointestinal disease. Limited spinal flexion and reduced chest expansion may occur. Spondylitis may be the only articular manifestation or it may occur in association with type I peripheral arthropathy. (See 'Spondylitis and sacroiliitis' above.)
  • Type I peripheral arthritis in IBD may be acute, remitting, pauciarticular, and occur early in disease. It commonly involves the knee and is usually nondeforming. Type II peripheral arthritis may be more chronic or have frequent relapses, polyarticular, and frequently involves the metacarpophalangeal joints. (See 'Clinical manifestations' above and 'Type I arthropathy' above and 'Type II arthropathy' above.)
  • Acute phase reactants usually reflect the activity of the intestinal disease and are not useful in assessing arthritis or spondylitis. HLA-B27 is found in 50 to 75 percent of the patients with axial arthritis and may be increased in type I peripheral arthritis, but HLA typing has no role in management of individual patients. Synovial fluids are moderately inflammatory. (See 'Laboratory findings' above.)
  • Radiographs of the spine and pelvis may show typical findings of ankylosing spondylitis and sacroiliitis. Plain radiographs of the peripheral joints may demonstrate soft-tissue swelling, juxtaarticular osteoporosis, mild periostitis, and effusions, usually without erosions or destruction. Radiographs, particularly of the sacroiliac joints, frequently have abnormal findings even in asymptomatic patients with IBD. (See 'Radiographic findings' above.)
  • There is no pathognomonic finding to confirm that arthritis is due to IBD. It thus remains a diagnosis of exclusion, and septic arthritis should be excluded, particularly in patients with monoarthritis or oligoarthritis, given the risk of fistulization or bacteremia. The differential diagnosis also includes hypertrophic osteoarthropathy, osteonecrosis, erythema nodosum (particularly if periarticular), and the other disorders discussed in this topic review. (See 'Diagnosis' above and 'Differential diagnosis' above.)
  • Effective treatment of the underlying IBD is often helpful in controlling the peripheral arthritis of IBD, which is generally nondestructive; therapy is primarily directed at symptomatic relief. In patients with peripheral arthritis we use nonsteroidal antiinflammatory drugs initially, but if these are poorly tolerated use sulfasalazine. If these steps are ineffective we switch to methotrexate, or use azathioprine or 6-mercaptopurine as an alternative. In patients resistant to these therapies we use a tumor necrosis factor (TNF) alpha inhibitor. (See 'Peripheral arthritis' above and 'Recommendations' above.)
  • The axial disease associated with IBD is treated similarly to ankylosing spondylitis. The treatment for spinal and sacroiliac involvement is symptomatic and radiographic progression may occur despite the control of symptoms. In patients unresponsive to or intolerant of NSAIDs, we perform a trial of methotrexate, and if ineffective use a TNF inhibitor. An alternative to methotrexate is sulfasalazine. (See 'Spondylitis and sacroiliitis' above and 'Recommendations' above.)
  • Other conditions with both intestinal involvement and arthritis as prominent clinical features include reactive arthritis (Reiter syndrome), Whipple's disease, Behçet's disease, celiac disease, parasitic infestation, pseudomembranous colitis, and as a result of intestinal bypass surgery. These disorders are also considerations in the differential diagnosis of patients with suspected IBD and arthritis. (See 'Other diseases with bowel and joint involvement' above.)

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