Q&A With Healio Rheumatology

For IBD-associated arthritis, disease control is becoming a team sport

David Karp, MD
David Karp

Rheumatologists are generally familiar with complicated case patients who require management across specialties. The same goes for gastroenterologists. But a little more communication never hurts. In this case, a closer look at patients with inflammatory bowel disease-associated arthritis — known commonly as enteropathic arthritis — may be beneficial.

David Karp, MD, PhD, chief of the division of rheumatic diseases at the University of Texas Southwestern Medical Center, and Nikolaos T. Pyrsopoulos, MD, PhD, chief of the division of gastroenterology and hepatology, and medical director of liver transplantation at Rutgers New Jersey Medical School University Hospital, sat down with Healio Rheumatology and explained the basics.

Nikolaos T. Pyrsopoulos

In short, ankylosing spondylitis and peripheral arthritis commonly occur in IBD, and IBD frequently accompanies ankylosing spondylitis. But a deeper look reveals myriad associations between IBD, ankylosing spondylitis, uveitis and psoriasis.

Q: Patients with IBD sometimes exhibit a type of arthritis that presents similarly to rheumatoid arthritis. How can clinicians distinguish between enteropathic arthritis and RA?

Pyrsopoulos: One of the extraintestinal manifestations of IBD is arthritis, which can be detected in up to 30% of IBD patients in the form of seronegative spondyloarthropathy. This can occur in the axial joints, peripheral joints, or occasionally in both types of joints at the same time. Patients diagnosed with peripheral type I form of pauci/oligoarticular arthritis or type II polyarticular arthritis have been described to have an estimated 1% to 6% chance of progressing to ankylosing spondylitis.

 
For IBD-associated arthritis, disease control is becoming a team sport.
Source: Adobe

Clinicians should be aware that in these patients, the rheumatoid factor is not detectable, and usually there is no erosive or deforming component, which is seen in patients with rheumatoid arthritis. Additionally, there is an association with the human leukocyte antigen HLA-B27.

Karp: About 40% of enteropathic arthritis looks like RA. The other 60% looks very different. If someone had a diagnosis of Crohn’s or ulcerative colitis, we would immediately think about IBD-associated arthritis. It would be at the top of the list. As a rheumatologist, a typical workup for someone with an inflammatory polyarthritis is a blood test that would be present in 80% or 85% for people with RA, but which would be absent in patients with IBD-associated or enteropathic arthritis.

In rheumatology, our diagnoses are made by a clinical picture. For example, the majority of patients with RA would have involvement of multiple joints, including the hands, knees and feet. In patients with IBD-associated enteropathic arthritis, they may have a picture with just knee involvement or just ankle arthritis, and that inflammation would be present at the same time the IBD was active. Other things we can look out for in patients with IBD-associated arthritis are erythema nodosum and pyoderma gangrenosum. Uveitis may also be present.

Q: What about the differences between enteropathic arthritis and ankylosing spondylitis?

Pyrsopoulos: Enteropathic arthritis can present as inflammatory back pain like ankylosing spondylitis. However, its presentation usually correlates with inflammation in the gut. Moreover, enteropathic arthritis is a diagnosis of exclusion. Interestingly, it has been strongly associated with a specific gene, HLA-DR103, which controls the immune response. This is a rare HLA allele that has been associated with seronegative spondyloarthritides.

Conversely, the diagnosis of ankylosing spondylitis can be made in the absence of IBD with the presence of inflammatory back pain and specifically, sacroiliac joint inflammation that is confirmed radiologically through plain radiography or MRI of the sacroiliac joints. There may also be a genetic predisposition in ankylosing spondylitis. There is increasing evidence that the microbiome may be involved as well, but that has not been confirmed.

Q: How about the challenge in managing uveitis, which occurs frequently in both IBD and ankylosing spondylitis?

Pyrsopoulos: These are comorbidities we always need to have in mind. As soon as the patient is complaining of photophobia of the eye, you need to be very proactive in sending these patients for evaluation by specialists. Intestinal manifestations can be cured, but we do not want to wait until it is too late to deal with these issues in the eye, so patients should be referred to an ophthalmologist right away.

Q: What can rheumatologists look for in a patient they suspect has enteropathic arthritis?

Pyrsopoulos: Unfortunately, gold standard criteria are lacking, and the diagnosis is made based on clinical criteria. As soon as patients develop pain in the abdominal tract, blood in the stool, fever and diarrhea, they should be referred to a gastroenterologist. The gastroenterologist will proceed with an endoscopic evaluation to try to identify lesions in the bowel. A careful medical history is also crucial in order to identify extraintestinal manifestations of IBD because intraluminal gut manifestations of IBD may lag behind symptoms such as arthralgias or eye pain. Often, arthritis or even uveitis can be the first manifestation of IBD.

Rheumatologists should also understand that the laboratory evaluation, especially of nonspecific inflammatory markers, such as ESR and CRP, might be confounding, as elevations in these markers can be associated with the activity of the underlying IBD and not just due to inflammation of joints. Another consideration for these patients is that they might not respond very well to NSAIDs. Their arthritis may improve, but NSAIDs have been associated with flares in IBD. The European Spondyloarthropathy Study group has published criteria, which may be helpful in assisting in the diagnosis and management of some forms of enteropathic arthritis.

Q: How about distinguishing between IBD and IBS?

Karp: Although I would generally consider that to be a question for a GI, for most general internists, there should be no trouble distinguishing between the two. IBD usually features abdominal pain, diarrhea or bloody stools, fever, symptoms of inflammation, and other flu-like symptoms. A colonoscopy will reveal inflammation, as will a biopsy.

The pathology is different in different types of IBD: Meaning, Crohn’s vs. ulcerative colitis. Regardless of the histology, it should be obvious to both rheumatologists and gastroenterologists when a patient has IBD. IBS, on the other hand, is a functional problem with gastrointestinal motility. The speed of motility can be too quick, causing diarrhea, or too slow, causing constipation. These patients will have a normal colonoscopy.

Pyrsopoulos: The laboratory evaluation of an IBD patient can reveal an increase in CRP and ESR anemia, or the presence of fecal calprotectin. The endoscopic findings of IBD include ulcerations and hemorrhage of the mucosa. On the other hand, the endoscopic appearance of the mucosa in IBS usually appears normal. Extraintestinal manifestations such as pyoderma gangrenosum, erythema nodosum, episcleritis, scleritis, uveitis, iritis, aphthous stomatitis, primary sclerosing cholangitis, and thromboembolism can be seen in addition to the gut-specific symptoms of IBD and is not seen in IBS.

Q: What medications should clinicians avoid in treating patients who may have undiagnosed IBD?

Pyrsopoulos: It is essential to screen these patients for potential IBD and diagnose the disease as early as possible. In general, as I mentioned before, NSAIDs should be avoided in patients with active IBD, as it has been associated with flares.

Karp: NSAIDs also have been associated with increased bleeding in IBD.

Q: How about biologics? Are there concerns with using them in IBD?

Pyrsopoulos: Biologics are often used to treat moderate-to-severe disease states in IBD. Prior to the use of biologics, patients must be tested for infections — for example, hepatitis B and tuberculosis — as cases of hepatitis B reactivation and tuberculosis have been reported. The risk of opportunistic infections, including fungal, parasitic and viral infections is increased. In addition, we need to investigate the possibility of allergic reactions.

Additionally, jaundice, multifocal leukoencephalopathy and malignancies are a recognized concern with long term use of biologics as well as in combination with other forms of immunosuppression. Frequent monitoring of the patient is needed while on biologics to ensure the risks and benefits of biologic medications are being weighed and that assessments for the formation of autoantibodies and loss of response are occurring as well.

Karp: Just like in rheumatology, there are society guidelines that suggest a stepwise approach to the treatment of IBD. This often includes oral medications first, and then if that fails or if the patients’ disease is severe, biologics may be used. Biologics are used significantly in IBD, the same as in psoriatic arthritis or rheumatoid arthritis. These patients are treated with TNF inhibitors like infliximab (Remicade, Janssen), etanercept (Enbrel, Amgen), and adalimumab (Humira, Abbvie).

Q: Given that patients with IBD-associated arthritis may be seen by clinicians in more than one specialty, can you discuss any contrasting guidelines or discrepancies in treatment algorithms?

Pyrsopoulos: Patients with established IBD and associated enteropathic arthritis should be followed by an interdisciplinary team that is made up experts in both gastroenterology and rheumatology. These specialists should adhere to their respective society guidelines in caring for the patient. Unfortunately, not all societies have published guidelines, which might make individual cases more challenging to manage. Perhaps relevant societies should participate in a coordinated effort to draft guidelines and algorithms for the co-management of these complex patients.

Karp: In most of these cases, you need a team of providers to take care of these patients. It is almost always a collaboration. Most of the medications that will help with the bowel inflammation will also help with arthritis treatment. Admittedly, the TNF drugs are expensive, but they can work in both conditions. In those cases, there is no contrasting guidelines or treatment algorithms. However, in some cases, medications may not lead to clinical improvement in the IBD or the arthritis. At this point, the GI needs to refer to a rheumatologist, or vice versa, depending on who is taking the lead in the patient. Either way, collaboration between specialists leads to the best result for the patient. The British societies of rheumatology and gastroenterology came up with guidelines for these patients. This is something that needs to be done much more often. Managing complex patients is often a team sport. – by Rob Volansky

For more information:

  • David Karp, MD, can be reached at 5323 Harry Hines Blvd., Dallas, TX 75390; email: Remekca.Owens@UTSouthwestern.edu.
  • Nikolaos T. Pyrsopoulos , MD, PhD, can be reached at 185 S. Orange Avenue, MSB H Rm - 536 Newark, NJ 07101-1709; email: pyrsopni@njms.rutgers.edu.

Disclosure: Karp and Pyrsopoulos report no relevant financial disclosures.

David Karp, MD
David Karp

Rheumatologists are generally familiar with complicated case patients who require management across specialties. The same goes for gastroenterologists. But a little more communication never hurts. In this case, a closer look at patients with inflammatory bowel disease-associated arthritis — known commonly as enteropathic arthritis — may be beneficial.

David Karp, MD, PhD, chief of the division of rheumatic diseases at the University of Texas Southwestern Medical Center, and Nikolaos T. Pyrsopoulos, MD, PhD, chief of the division of gastroenterology and hepatology, and medical director of liver transplantation at Rutgers New Jersey Medical School University Hospital, sat down with Healio Rheumatology and explained the basics.

Nikolaos T. Pyrsopoulos

In short, ankylosing spondylitis and peripheral arthritis commonly occur in IBD, and IBD frequently accompanies ankylosing spondylitis. But a deeper look reveals myriad associations between IBD, ankylosing spondylitis, uveitis and psoriasis.

Q: Patients with IBD sometimes exhibit a type of arthritis that presents similarly to rheumatoid arthritis. How can clinicians distinguish between enteropathic arthritis and RA?

Pyrsopoulos: One of the extraintestinal manifestations of IBD is arthritis, which can be detected in up to 30% of IBD patients in the form of seronegative spondyloarthropathy. This can occur in the axial joints, peripheral joints, or occasionally in both types of joints at the same time. Patients diagnosed with peripheral type I form of pauci/oligoarticular arthritis or type II polyarticular arthritis have been described to have an estimated 1% to 6% chance of progressing to ankylosing spondylitis.

 
For IBD-associated arthritis, disease control is becoming a team sport.
Source: Adobe

Clinicians should be aware that in these patients, the rheumatoid factor is not detectable, and usually there is no erosive or deforming component, which is seen in patients with rheumatoid arthritis. Additionally, there is an association with the human leukocyte antigen HLA-B27.

Karp: About 40% of enteropathic arthritis looks like RA. The other 60% looks very different. If someone had a diagnosis of Crohn’s or ulcerative colitis, we would immediately think about IBD-associated arthritis. It would be at the top of the list. As a rheumatologist, a typical workup for someone with an inflammatory polyarthritis is a blood test that would be present in 80% or 85% for people with RA, but which would be absent in patients with IBD-associated or enteropathic arthritis.

In rheumatology, our diagnoses are made by a clinical picture. For example, the majority of patients with RA would have involvement of multiple joints, including the hands, knees and feet. In patients with IBD-associated enteropathic arthritis, they may have a picture with just knee involvement or just ankle arthritis, and that inflammation would be present at the same time the IBD was active. Other things we can look out for in patients with IBD-associated arthritis are erythema nodosum and pyoderma gangrenosum. Uveitis may also be present.

PAGE BREAK

Q: What about the differences between enteropathic arthritis and ankylosing spondylitis?

Pyrsopoulos: Enteropathic arthritis can present as inflammatory back pain like ankylosing spondylitis. However, its presentation usually correlates with inflammation in the gut. Moreover, enteropathic arthritis is a diagnosis of exclusion. Interestingly, it has been strongly associated with a specific gene, HLA-DR103, which controls the immune response. This is a rare HLA allele that has been associated with seronegative spondyloarthritides.

Conversely, the diagnosis of ankylosing spondylitis can be made in the absence of IBD with the presence of inflammatory back pain and specifically, sacroiliac joint inflammation that is confirmed radiologically through plain radiography or MRI of the sacroiliac joints. There may also be a genetic predisposition in ankylosing spondylitis. There is increasing evidence that the microbiome may be involved as well, but that has not been confirmed.

Q: How about the challenge in managing uveitis, which occurs frequently in both IBD and ankylosing spondylitis?

Pyrsopoulos: These are comorbidities we always need to have in mind. As soon as the patient is complaining of photophobia of the eye, you need to be very proactive in sending these patients for evaluation by specialists. Intestinal manifestations can be cured, but we do not want to wait until it is too late to deal with these issues in the eye, so patients should be referred to an ophthalmologist right away.

Q: What can rheumatologists look for in a patient they suspect has enteropathic arthritis?

Pyrsopoulos: Unfortunately, gold standard criteria are lacking, and the diagnosis is made based on clinical criteria. As soon as patients develop pain in the abdominal tract, blood in the stool, fever and diarrhea, they should be referred to a gastroenterologist. The gastroenterologist will proceed with an endoscopic evaluation to try to identify lesions in the bowel. A careful medical history is also crucial in order to identify extraintestinal manifestations of IBD because intraluminal gut manifestations of IBD may lag behind symptoms such as arthralgias or eye pain. Often, arthritis or even uveitis can be the first manifestation of IBD.

Rheumatologists should also understand that the laboratory evaluation, especially of nonspecific inflammatory markers, such as ESR and CRP, might be confounding, as elevations in these markers can be associated with the activity of the underlying IBD and not just due to inflammation of joints. Another consideration for these patients is that they might not respond very well to NSAIDs. Their arthritis may improve, but NSAIDs have been associated with flares in IBD. The European Spondyloarthropathy Study group has published criteria, which may be helpful in assisting in the diagnosis and management of some forms of enteropathic arthritis.

PAGE BREAK

Q: How about distinguishing between IBD and IBS?

Karp: Although I would generally consider that to be a question for a GI, for most general internists, there should be no trouble distinguishing between the two. IBD usually features abdominal pain, diarrhea or bloody stools, fever, symptoms of inflammation, and other flu-like symptoms. A colonoscopy will reveal inflammation, as will a biopsy.

The pathology is different in different types of IBD: Meaning, Crohn’s vs. ulcerative colitis. Regardless of the histology, it should be obvious to both rheumatologists and gastroenterologists when a patient has IBD. IBS, on the other hand, is a functional problem with gastrointestinal motility. The speed of motility can be too quick, causing diarrhea, or too slow, causing constipation. These patients will have a normal colonoscopy.

Pyrsopoulos: The laboratory evaluation of an IBD patient can reveal an increase in CRP and ESR anemia, or the presence of fecal calprotectin. The endoscopic findings of IBD include ulcerations and hemorrhage of the mucosa. On the other hand, the endoscopic appearance of the mucosa in IBS usually appears normal. Extraintestinal manifestations such as pyoderma gangrenosum, erythema nodosum, episcleritis, scleritis, uveitis, iritis, aphthous stomatitis, primary sclerosing cholangitis, and thromboembolism can be seen in addition to the gut-specific symptoms of IBD and is not seen in IBS.

Q: What medications should clinicians avoid in treating patients who may have undiagnosed IBD?

Pyrsopoulos: It is essential to screen these patients for potential IBD and diagnose the disease as early as possible. In general, as I mentioned before, NSAIDs should be avoided in patients with active IBD, as it has been associated with flares.

Karp: NSAIDs also have been associated with increased bleeding in IBD.

Q: How about biologics? Are there concerns with using them in IBD?

Pyrsopoulos: Biologics are often used to treat moderate-to-severe disease states in IBD. Prior to the use of biologics, patients must be tested for infections — for example, hepatitis B and tuberculosis — as cases of hepatitis B reactivation and tuberculosis have been reported. The risk of opportunistic infections, including fungal, parasitic and viral infections is increased. In addition, we need to investigate the possibility of allergic reactions.

Additionally, jaundice, multifocal leukoencephalopathy and malignancies are a recognized concern with long term use of biologics as well as in combination with other forms of immunosuppression. Frequent monitoring of the patient is needed while on biologics to ensure the risks and benefits of biologic medications are being weighed and that assessments for the formation of autoantibodies and loss of response are occurring as well.

PAGE BREAK

Karp: Just like in rheumatology, there are society guidelines that suggest a stepwise approach to the treatment of IBD. This often includes oral medications first, and then if that fails or if the patients’ disease is severe, biologics may be used. Biologics are used significantly in IBD, the same as in psoriatic arthritis or rheumatoid arthritis. These patients are treated with TNF inhibitors like infliximab (Remicade, Janssen), etanercept (Enbrel, Amgen), and adalimumab (Humira, Abbvie).

Q: Given that patients with IBD-associated arthritis may be seen by clinicians in more than one specialty, can you discuss any contrasting guidelines or discrepancies in treatment algorithms?

Pyrsopoulos: Patients with established IBD and associated enteropathic arthritis should be followed by an interdisciplinary team that is made up experts in both gastroenterology and rheumatology. These specialists should adhere to their respective society guidelines in caring for the patient. Unfortunately, not all societies have published guidelines, which might make individual cases more challenging to manage. Perhaps relevant societies should participate in a coordinated effort to draft guidelines and algorithms for the co-management of these complex patients.

Karp: In most of these cases, you need a team of providers to take care of these patients. It is almost always a collaboration. Most of the medications that will help with the bowel inflammation will also help with arthritis treatment. Admittedly, the TNF drugs are expensive, but they can work in both conditions. In those cases, there is no contrasting guidelines or treatment algorithms. However, in some cases, medications may not lead to clinical improvement in the IBD or the arthritis. At this point, the GI needs to refer to a rheumatologist, or vice versa, depending on who is taking the lead in the patient. Either way, collaboration between specialists leads to the best result for the patient. The British societies of rheumatology and gastroenterology came up with guidelines for these patients. This is something that needs to be done much more often. Managing complex patients is often a team sport. – by Rob Volansky

For more information:

  • David Karp, MD, can be reached at 5323 Harry Hines Blvd., Dallas, TX 75390; email: Remekca.Owens@UTSouthwestern.edu.
  • Nikolaos T. Pyrsopoulos , MD, PhD, can be reached at 185 S. Orange Avenue, MSB H Rm - 536 Newark, NJ 07101-1709; email: pyrsopni@njms.rutgers.edu.

Disclosure: Karp and Pyrsopoulos report no relevant financial disclosures.