Co-managing inflammatory diseases: A complex prescription
Inflammatory Bowel Disease
Inflammatory bowel diseases (IBD) include Crohn's disease and ulcerative colitis. Both are idiopathic inflammatory conditions that affect the gastrointestinal tract, and both cause diarrhea, abdominal pain, blood in the stool, and fatigue. Ulcerations cover affected areas of the bowel and, occasionally in Crohn's disease, tracts known as fistulas can lead to open communication between the bowel and other body cavities, such as the bladder, or the skin. The natural history of IBD, particularly Crohn's disease, can be progressive and as it evolves over time, more complicated disease necessitates intensive medical therapy and can lead to surgery. Surgery for difficult-to-treat complications is quite common in IBD, and can lead to loss of significant portions of the bowel. IBD is not rare, with a prevalence of 150-200/100,000 and an incidence of 5-12/100,000.
Spondyloarthropathies are inflammatory disorders characterized by chronic low back pain or inflammation of the joints of the (typically) lower extremities. They are comprised of a group of diseases, including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, arthritis associated with IBD, and undifferentiated spondyloarthritis. These conditions are often associated with the presence of HLA-B27, a histocompatability molecule involved in regulation of the immune system. Commonly, they exhibit other inflammatory manifestations that are not associated with joints (extra-articular), such as inflammation of the eye (uveitis), inflammation of tendons (enthesitis), psoriasis, dactylitis, and IBD. Although spondyloarthropathies share several characteristics, the natural history varies between them from the acute, self-limited joint inflammation of reactive arthritis to the chronic, progressive, and debilitating spinal arthritis of ankylosing spondylitis. The course of IBD-associated spondyloarthropathy differs depending on which joints are affected; if peripheral joints (those further from the spine) are inflamed, arthritis is usually temporary and leads to minimal destruction of the joint. However, IBD-associated ankylosing spondylitis, which involves the vertebrae and their joints, is usually a chronic, progressive illness that can lead to permanent joint destruction, fusion and osteoporosis of the vertebrae. The spondyloarthropathies are among the most common rheumatologic conditions, with a prevalence of 0.9-1.5%, making them collectively at least as common as rheumatoid arthritis.
IBD and ankylosing spondylitis (AS) commonly involve inflammatory manifestations outside the gut and joints, respectively. Uveitis and psoriasis occur frequently in both. Not only that, AS and peripheral arthritis are common in IBD, and IBD frequently accompanies AS. Around 5-10% of people with IBD fulfill the diagnostic criteria for having AS, and close to the same proportion of those with AS will present with IBD. As well, two thirds of those with a spondyloarthropathy show microscopic inflammation on endoscopy that resembles IBD, and up to one third of those with IBD will have some sort of joint symptoms. However, both AS and IBD are complex to diagnose and even more complex to manage. In both, if those with complicated and progressive disease behaviour are not adequately treated and monitored, permanent disability and low quality of life can result.
A Look At Treatments
There are similarities in how physicians care for these patients. In AS and IBD, the goal is to treat symptoms and minimize complications, yet also minimize the adverse effects and costs of treatment. Therefore, in certain circumstances patients begin treatment on agents with lower effectiveness and fewer side effects. If symptoms are not controlled, then therapy steps up to other, more efficacious treatments. In IBD, medical therapy progresses from 5-ASA (5-aminosalicylic acid) derivatives in ulcerative colitis, such as mesalamine (Asacol®, Mesasal®, Pentasa®, Salofalk®, Mezavant®) and olsalazine sodium (Dipentum®) to oral corticosteroids to immunosuppressives, such as azathioprine (Imuran®) and methotrexate (Rheumatrex™), to biologic agents, such as infliximab (Remicade®) and adalimumab (Humira®). Interestingly, one medication, etanercept (Enbrel®), an anti-TNF agent effective in patients with AS, is ineffective in IBD. Medical therapy of AS progresses from NSAIDs (such as ibuprofen), to sulfasalazine and local steroid injections in peripheral disease, to biologics (such as infliximab, adalimumab, or etanercept) in patients with persistent disease.
Recent research has shown exciting new frontiers in the treatment strategies of AS and IBD, especially Crohn’s. Both diseases are chronic and progressive and as inflammation proceeds, irreversible damage can be done to the target organ (intestines in IBD, and joints of the spine in AS). The key is to predict which patients will show this type of unrelenting inflammatory damage before it actually occurs, and to treat these individuals with potent agents earlier in the course of the disease. Evidence from recent trials in AS and Crohn’s disease shows that very high rates of remission can be attained by using biologics to treat patients with early disease. The treatment strategy in this case begins with the proven most effective therapy – biologics, instead of less effective ones. This approach is not yet standard practice, due mostly to difficulties in predicting which people will have an aggressive disease course and the high cost associated with TNF inhibitors. However, this and similar research, has spurred gastroenterologists and rheumatologists to determine earlier if less potent therapy has failed, in order to move on to more effective therapies in a timely manner before permanent damage has occurred. Using more potent therapies early on may be particularly relevant in patients with IBD and AS; several studies show that anti-TNF antibody therapy is effective for treating both joint and bowel symptoms.
Diagnosing Clues for the Rheumatologist
AS and IBD can be challenging to diagnose, since many other conditions can show similar symptoms. Dr. Bressler offered some helpful hints to the rheumatologists to help differentiate between IBD and irritable bowel syndrome (IBS):
- Does diarrhea awaken the patient from sleep? (if yes, then IBD should be considered)
- How much bloating does the patient have? (bloating is a symptom usually of IBS)
- Has there been significant weight loss? (weight loss common in IBD)
- Does the patient have drenching night sweats? (a symptom consistent with IBD)
- How urgent are the patient’s bowel movements? (more urgent usually in IBD)
Diagnosing Clues for the Gastroenterologist
Dr. Shojania had questions that a gastroenterologist could use to differentiate between mechanical back pain and AS-associated inflammatory back pain:
- Does morning back stiffness last more than 30 minutes? (if yes, more likely the inflammatory back pain of AS, in contrast to mechanical back pain)
- Is there pain in the bottom of the feet or heels? (if yes, this might indicate enthesitis, which is associated with AS)
- Is there a history of eye inflammation requiring eye drops? (typical for AS, especially when only one eye is involved)
- Is there a history of swollen joints? (peripheral arthritis is common in AS)
- Is there a family history of AS, psoriasis, or back pain at an early age? (patients with AS often have a family history of the condition)
These questions help to uncover a component of AS in the IBD patient, or vice versa. Since both conditions can frequently manifest in the same patient, gastroenterologists and rheumatologists need a high index of suspicion for concomitant inflammatory bowel disease and spondyloarthropathies. Each specialty had some helpful advice for the other as well.
Suggestions for the Rheumatologist
Below is a list of gastrointestinal perspectives for a rheumatologist treating the AS patient who might have IBD:
NSAIDs (such as ibuprofen) and IBD don’t mix – research shows that they can cause the formation of ulcers in the bowel, and lead to IBD flares. There is a particular class of NSAIDs, called COX-II inhibitors, which do not seem to increase the risk of a flare in patients with ulcerative colitis, but these COX-II inhibitors still have the same kidney and cardiovascular risks as traditional NSAIDs.
In spondyloarthropathies, a detailed gastrointestinal history can help identify those patients with IBD symptoms. Physicians should choose biologic agents with care when treating AS. For example, etanercept is associated with a numerically but not statistically higher risk of IBD flareups in AS patients who also have IBD.
It’s a good idea to use sulfasalazine instead of 5-ASA to manage UC patients who also have a spondyloarthropathy as sulfasalazine is effective in treating peripheral arthritis associated with AS, however, it has not been shown to have any effects on the axial disease.
Suggestions for the Gastroenterologist
Here is a list of rheumatological perspectives for gastroenterologists treating IBD patients who may have a spondyloarthropathy:
Be mindful of the risk of osteoporosis when prescribing steroids to patients, especially those with AS who are prone to osteoporosis already. Don’t forget vitamin D, calcium, and bisphosphonates.
In IBD patients, a detailed history with a focus on spondyloarthropathy can help identify those who might have co-existing AS.
If a patient has bad inflammation in a particular joint, then injections into the joint might be a good idea to avoid the use of NSAIDs.
Further valuable discussion followed regarding the co-management of those patients who have both IBD and spondyloarthropathy. The evening was an excellent tool to help raise awareness of concomitant inflammatory conditions, and to provide a framework within which to treat these difficult patients. It is also important for physicians to have a high index of suspicion that there may be more than one inflammatory condition in the person with IBD or AS. Good communication between specialties is vital for effective co-management.
Co-Managing Inflammatory Diseases: a complex prescription. Reprinted by permission of the Canadian Society of Intestinal Research. First published in The Inside Tract® Newsletter, Issue 171, Spring 2009, pages 8-10. http://www.badgut.org.