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GI Joint

A Major in the Spondyloarthritis War

By Lianne

GI Joint
This article originally appeared in the Winter 2015 issue of Spondylitis Plus, the quarterly news magazine of Spondylitis Association of America. Members receive every copy of Spondylitis Plus in the mail for free.

Inflammation of the gastrointestinal tract is common in Ankylosing Spondylitis (AS). Up to 60% of AS patients who have no gastrointestinal symptoms will have microscopic (on biopsy) inflammation in the gut when colonoscopy is performed1,2. Most of these patients do not develop overt inflammatory bowel disease (IBD) like Crohn’s disease or Ulcerative colitis. Recent studies show about 3-4% of patients have IBD when they are diagnosed with Ankylosing Spondylitis, but after 20 years, approximately 10% have IBD3,4.

Patients with Ankylosing Spondylitis and IBD share similar important genetics5. The gut and joint inflammation on a shared genetic background highlights the importance of this connection and how these are related diseases. Data shows that patients with AS have first degree relatives with a 3-fold higher risk of Crohn’s disease, and patients with Crohn’s disease have first degree relatives with a 3-fold higher risk of Ankylosing Spondylitis6.

Just as patients with AS can develop IBD, patients with Crohn’s disease and Ulcerative colitis can also develop arthritis7. This can occur in the sacroiliac joints and spine (and is identical to Ankylosing Spondylitis) and/or in the smaller joints of the extremities (knee, ankle, feet, hands etc). The most common joint manifestation is the sacroiliac joint - affecting 10-20% of patients with IBD. Note that some of these patients will not have SI joint pain, and the finding is often noted on imaging done for other reasons (like a CT scan done for IBD). The sacroiliitis (back/buttock and hip involvement) can occur when the IBD is silent or active and can continue even when patients undergo colectomy in Ulcerative colitis.

The small joint arthritis can behave differently. There are two types of small joint arthritis (along with the arthritis in the SI joint) described in Table 1 below.

Table 1. Arthritis types in IBD

 

Type I Arthritis

Type II Arthritis

Spondylitis

What percent of IBD patients are affected?

3-6%

2-4%

~20%

What joints are usually affected?

Large joints in legs – knee, ankle, foot

small joints in hands – wrist, fingers

Sacroiliac & spine

How many joints are typically affected at 1 time

<5

>5

n/a

Can occur when?

As first sign of IBD

After the onset of the IBD

Often in younger patients

Disease course

Acute & remitting

Chronic & relapsing

Typically chronic

With GI activity

Yes

Not necessarily

Not necessarily

Medications for Arthritis associated with IBD

The treatment of the joint disease in IBD depends on which joints are affected and whether the IBD is also active.

If the sacroiliac joints are active, then the appropriate treatment is either a drug class called Non-steroidal anti-inflammatory drugs (NSAIDs) which are sometimes contraindicated in patients with IBD because of the concern for IBD flare in the setting of these agents, or the biologic agents. Examples of NSAIDs are ibuprofen or naproxen over the counter; celecoxib is sometimes preferred as it may be safer in the gastrointestinal system, though the evidence of this in IBD is weak. The American College of Rheumatology recently published guidelines in Axial Spondyloarthritis and did not recommend a preferred NSAID in the setting of IBD because of the weak evidence8. If NSAIDs are not a possibility, then the only other class of drugs with proven efficacy at this time is the biologic agents - Tumor Necrosis Factor Inhibitors (TNFI). For patients with sacroiliitis and IBD, a certain type of TNFI is preferred, called a monoclonal antibody8. See table 2 for specific drugs.

In the setting of small/peripheral joint arthritis (the arthritis affecting the joints of the extremities) the treatment depends on whether the IBD is active. If there is IBD activity, then the recommendation would be to treat the underlying IBD. If the IBD is quiet, then we would use the usual agents for small joint arthritis including sulfasalazine, methotrexate, azathioprine, and/or low doses of prednisone temporarily, or the biologic agents, like the TNFI. Besides the NSAIDs, all the medications listed below in table 2 may also help the IBD.

Table 2. Medications for arthritis in setting of IBD

Medication

Helps back & sacroiliac joints

Helps small & large joints

Taken by mouth or injection

NSAIDs

Yes

Yes

By mouth

Prednisone 20mg or less

No

Usually

By mouth

High dose prednisone

Yes, but not recommended (high risk of side effects)

Yes, but not recommended (high risk of side effects)

Either

Sulfasalazine
(Azulfadine)

Not usually

Yes

By mouth

Methotrexate
(Rheumatrex)

No

Yes

Either

Azathioprine
(Immuran)

No

Yes

By mouth

Adalimumab
(Humira)

Yes

Yes

By injection SQ (subcutaneous)

Certolizumab
(Cimzia)

Yes

Yes

By injection SQ

Golimumab
(Simponi)

Yes

Yes

By injection (approved by SQ but available by IV (intravenous)

Infliximab
(remicaid)

Yes

Yes

By IV injection

Another TNFI, Etanercept (Enbrel) works for the joints, but not the IBD and is generally not preferred if there is IBD in the presence of the arthritis. In this group, the TNFI listed in table 2 are preferred.

For those patients with IBD that is resistant to TNFI, their gastroenterologists might consider a new drug, Vedolizumab. This drug works by staying inside the gut, but as a result will not treat the arthritis, if this is occurring independent of the GI disease activity.

Besides arthritis with inflammation, patients with IBD can have other reasons for joint pain and arthritis. IBD patients can be more hypermobile (very flexible) which may lead to joint injury and pain. Patients with or without IBD can develop osteoarthritis – arthritis as a result of wear and tear. Though this can happen from the arthritis associated with the IBD after long bouts of inflammation, these are more commonly not thought to be inflammatory and are treated conservatively with pain control and physical therapy.  Occasionally, the arthritis is severe enough to require joint replacement – especially in the hips and knees. This procedure can dramatically improve quality of life in patients who have joints with severe damage. Finally, patients with chronic disease may also develop a widespread pain syndrome called Fibromyalgia, which is not immune mediated or associated with inflammation, but can be very disabling and is treated with regular exercise, cognitive behavioral therapy and occasionally pharmacologic therapy.

References

  1. Van Praet, L. et al. Degree of bone marrow oedema in sacroiliac joints of patients with axial spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort. Annals of the Rheumatic Diseases 73, 1186–1189 (2014).
  2. Cypers, H., Van Praet, L., Varkas, G. & Elewaut, D. Relevance of the gut/joint axis for the management of spondyloarthritis in daily clinical practice. Current Opinion in Rheumatology 26, 371–376 (2014).
  3. Stolwijk, C. & Essers, I. The epidemiology of extra-articular manifestations in ankylosing spondylitis: a population-based matched cohort study. Annals of the Rheumatic Diseases 1373–1378 (2015). doi:10.1136/annrheumdis-2014-205253
  4. Stolwijk, C., van Tubergen, A., Castillo-Ortiz, J. D. & Boonen, A. Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Annals of the Rheumatic Diseases 65–73 (2014). doi:10.1136/annrheumdis-2013-203582
  5. Reveille, J. D. Genetics of spondyloarthritis—beyond the MHC. Nature Publishing Group 8, 296–304 (2012).
  6. Geirsson, A. J., Eyjolfsdottir, H., Bjornsdottir, G., Kristjansson, K. & Gudbjornsson, B. Prevalence and clinical characteristics of ankylosing spondylitis in Iceland - a nationwide study. Clin Exp Rheumatol 28, 333–340 (2010).
  7. Orchard, T. R., Wordsworth, B. P. & Jewell, D. P. Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history. Gut 387–391 (1998).
  8. Ward, M. M. et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis & Rheumatology 1–17 (2015). doi:10.1002/ART.39298
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Lianne

Lianne

Dr. Gensler is the Director of the Ankylosing Spondylitis Clinic at University of California San Francisco (UCSF). She is an Assistant Professor of Medicine in the division of Rheumatology and sees patients in addition to teaching and performing research in spondyloarthritis.

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