Long-Term Risk of Inflammatory Bowel Disease in IBS Patients

Studies suggest that individuals with IBS may be at increased risk of being subsequently diagnosed with IBD. Although most individuals with symptoms of IBD are actually diagnosed with IBD, not IBS, the goal of treatment for IBS is very different from that of IBD, and a delay in accurate diagnosis of IBD can result in serious harm to the patient. Diagnosis of IBS is typically approached as a working diagnosis that is occasionally revisited either because of a change in the patient’s symptoms, identification of a red flag that necessitates further evaluation, or because of findings of inflammation as evidenced by objective testing.

Why It Matters

Many patients with IBS and IBD present with overlapping symptoms but it is crucial that they not be treated as the same disease. IBS is a functional gut-brain interaction disorder characterized by the absence of tissue inflammation, ulcers or injury on routine testing, but significant symptoms which can be bothersome or disabling. Treatment of IBS focuses on control of the symptoms and can include diet and fiber modification, sleep and stress management, and select use of gut-directed psychological/psychiatric interventions. When pain and diarrhea predominate, pain management and medications to decrease diarrhea are used. When constipation predominates, medications to decrease constipation are used. When abdominal bloating predominates, medications and diet which decrease gas production and symptoms of gas are used. In contrast, IBD (Crohn’s disease and ulcerative colitis) is an immune-mediated disease that results in intestinal inflammation which can cause injury to the bowel lining including bleeding, ulcers, narrowing of the bowel (strictures), abnormal connections between the bowel and other organs (fistulas) and nutritional complications. Typical treatment includes anti-inflammatory medications, immune-modifying medications, and regular monitoring of symptoms of worsening disease and complications of Crohn’s disease and ulcerative colitis.

From a patient perspective it is important to understand your risk for the development of IBD symptoms over time. Recognizing early warning signs of IBD and beginning appropriate diagnostic workup in a timely fashion is critical since delay in treatment can result in a poor disease course. Patients with IBD commonly present with symptoms that may mimic irritable bowel syndrome (IBS) early in the course of disease, such as intermittent abdominal pain, loose stools, urgency, fatigue and/or bloating. Early awareness of these common and nonspecific gastrointestinal and general symptoms is therefore important for patients and physicians alike in terms of IBD diagnosis and management prior to development of complications of IBD such as marked weight loss, anemia, ulceration and extensive disease. In general patients with IBD are best treated with early diagnosis and management leading to effective control of disease, less use of steroids, and fewer hospitalizations.

There is no perfect diagnostic test for IBS, but there are some screening tests and approaches that have some evidence to support their use. However, there is a limit to how much benefit there is in over-testing of all patients who say that they have IBS, and in fact it can be potentially harmful. Colonoscopy is a safe procedure for most patients, but it is invasive, it requires bowel preparation, it results in significant time lost from usual activities and occupation, and although rare, there are potential complications. Clearly a system perspective must be taken into account when considering the appropriate use of endoscopy. Tests such as endoscopy take up slots in busy practices and should not be used to delay further evaluation of a patient who has been told they need urgent evaluation for IBS. The current evidence does not support a policy of routinely repeating invasive tests on patients with stable IBS, but does support a risk-stratified approach in deciding if some patients might benefit from periodic follow-up.

With advances in noninvasive diagnostics and an ever-increasing workload in medical specialties, a risk-stratified approach to managing children with chronic gastrointestinal symptoms is increasingly important. Stool inflammatory markers such as calprotectin and lactoferrin, and simple blood tests such as a full blood count and inflammatory markers can help distinguish between active inflammatory bowel disease and functional irritable bowel symptoms in the majority of children. Although not 100% accurate, they can help the clinician decide who needs urgent referral for possible IBD and who can be safely managed with conservative management and surveillance.

These issues have implications for the advice provided to patients with diagnosed IBS, e.g. that there is a small risk of developing IBD. Many patients with IBS have had many years of symptoms before diagnosis. They will have had a full investigation and multiple referrals to general practitioners and hospital specialists before diagnosis of IBS. They will have had different advice about their diet and tried different drugs for their symptoms. They will be anxious to have any new health concerns addressed promptly. The message that there is a small risk of developing IBD requires careful explanation. Patients need to be told two things: firstly that the absolute risk of developing IBD in people who have been diagnosed with IBS is small; and secondly that they should be aware of changes in their symptoms that may indicate possible IBD as well as other serious disease red flags. This approach to safety-netting IBS symptoms (clearing explaining the reasons for and limits of investigation and management) can reduce fear of serious disease and provide the patient with much needed reassurance and a safety-net.

Finally, our findings are relevant to future payer policy and guideline development, as choices about which non-invasive tests for inflammation to cover will shape whether the most practical triage strategy is facilitated or not. Without easy access to and reimbursement for such tests, providers will default to either doing nothing or performing colonoscopies, rather than intermediate tests. However, with appropriate monitoring in primary care, many cancer detections can be identified before referral for colonoscopy, preventing unnecessary colonoscopies. Moreover, any move to more repeated testing will put additional pressure on gastroenterology workload unless this is offset by strengthening of primary care pathways.

Who It Affects

Patients already diagnosed with IBS are the most directly affected by distinguishing this condition from IBD. They need to know that they do not have IBD and that their risk for developing IBD in the future, although present, is small. Many will never develop IBD and their focus should remain on symptom management. Others will have a greater long-term risk for IBD and could benefit from a more clear follow-up plan and earlier introduction of objective testing. Patients would like to know what to watch out for and how quickly they can be re-evaluated if their symptoms change.

Although certain clinical presentations are more likely than others to prompt the clinician to re-consider the diagnosis, diarrhea-predominant IBS is a very common clinical presentation that can occasionally mimic the presentation of early IBD, microscopic colitis, bile acid malabsorption or celiac disease. In such patients, the clinician should consider the possibility of an alternative diagnosis in patients with diarrhea-predominant IBS who wake from sleep for bowel movements, have persistent diarrhea, or increasing urinary urgency. Although the risk of an alternative diagnosis is not limited to patients with diarrhea-predominant IBS, patients with worsening symptoms warrant individualized consideration of alternative diagnoses.

Health care providers in primary care have a crucial role in the long-term management of patients with IBS. They are primarily responsible for diagnosing and treating IBS and for making decisions about further evaluation and therapy. This is typically where patients return to when their symptoms worsen. Providers must decide whether to use noninvasive biomarkers and empiric IBS-directed therapy and when to refer patients to gastroenterologists for further evaluation and management. Additionally, many of these patients have one or more overlapping conditions such as anxiety and depression, thyroid illness, medication side effects and food and nutrient sensitivities that affect their IBS symptoms.

For gastroenterologists and their staff, decreased thresholds for patient follow-up translate into increased referrals and a greater demand for endoscopy. Patients are seen at times of uncertainty; for example, when a patient fails medical therapy for symptoms or low grade elevation of inflammation indices just short of the normal range, or presents with concern for a more serious diagnosis. The doctor must weigh potential risks versus benefits of proceeding with endoscopy and decide between various modalities for imaging and endoscopic assessment. The gastroenterologist must establish an appropriate course of treatment for a patient diagnosed with IBD and then counsel the patient and family regarding the lifelong follow-up needed to manage the disease.

What are the costs to health systems and payers of these evolving trends in testing for patients with symptoms that could indicate IBD? On the one hand, the use of a fecal inflammatory marker for selective screening, and strategic repeat testing, may initially add costs, but potentially prevent more costly complications of IBD by facilitating an earlier diagnosis and treatment. Practices with limited endoscopy capacity must strategically consider a triage approach to avoid a logjam of patients awaiting procedures. Moreover, health plans’ coverage policies inadvertently could delay diagnosis for the patients who need the fastest trajectory of care.

Patients experiencing inequity are potentially harmed by delays as they are less likely to have timely re-assessment as their condition changes. Many patients face barriers to accessing general practice including: distance to the practice, low health literacy, high out-of-pocket costs for treatment or large gaps between seeing the doctor and having tests, or being time poor and under pressure to return to work. Patients in rural locations face particularly long wait times to access gastroenterology and endoscopy services. What begins as a minor course of treatment can quickly turn into a serious disease trajectory if a patient is unable to re-enter care in a timely manner.

What Changes

The new clinical guidelines for IBS emphasize the point that IBS can be a stable diagnosis for many patients, and at the same time, they state that the diagnosis should be revisited when clinical symptoms change. The earlier guidelines recommended close follow up for development of inflammatory disease that was overly prolonged and nonsensible. In contrast, the new guidelines for the diagnosis of IBD emphasize a thoughtful approach to reevaluation of symptoms at a time that makes sense for diagnosis.

1) Risk-stratified follow-up becomes standard practice

Simple follow-up plans can be initiated at the time of the diagnosis of IBS. Simple follow-up plans allow the clinician to compare the patient’s current clinical state to their baseline state. The patient’s baseline frequency and form of stool, weight, vital signs, family history of IBD, celiac disease or colorectal cancer and initial tests can be recorded. As the patient’s clinical symptoms change, the patient’s and clinician’s understanding of these changes can be compared to the recorded baseline. In addition, the clinician can establish triggers for reassessment at the time of the initial diagnosis of IBS.

Patients with higher-risk features for misdiagnosis or for having inflammatory disease or another organic condition should be evaluated for and diagnosed promptly. Red flags include: visible blood in stool; unexplained weight loss; persistent fever; new nocturnal diarrhea; iron deficiency anemia; progressive fatigue; persistent elevation of inflammatory markers (e.g., anemia of inflammation, elevated CRP); new onset of symptoms in an older patient; or a strong family history of IBD. Patients whose symptoms have not improved or have worsened on a therapeutic regimen targeted for IBS diagnosis should have their diagnosis reconsidered, especially if their IBS pattern is changing.

2) Noninvasive testing is used more strategically

Use fecal inflammatory markers and basic blood tests to triage patients to separate out patients who are likely to have functional symptoms versus those with likely inflammatory disease. These tests are useful to assess whether symptoms have changed, worsened or to give the clinician and patient some objective evidence that supports referral or avoids the need for colonoscopy in stable patients with IBS and no red flags. Patients with new diarrhea, worsening pain, or unexplained fatigue will benefit from these simple noninvasive tests to support timely diagnosis and treatment.

Test results must be considered in the context of the clinical history and examination findings. A single test with results mildly elevated on a single occasion could be due to recent gastrointestinal infection or medication as well as more serious causes of gastrointestinal inflammation. It should not lead to a diagnosis of IBD in isolation. Instead the results should be considered alongside the history and examination findings. A single test may be repeated if appropriate. Normal results should not be used as a gatekeeper to precluding further investigation for IBD, particularly in patients with alarm features.

3) Clear patient education and safety-netting reduce harm

Patients with IBS should leave your office with a plan and an understanding of their IBS. Patients and their families should have a sense of the “call us quickly” symptoms. Many patients with IBS feel that their symptoms are not taken seriously by their physician. It is important to acknowledge the impact of the patient’s symptoms, but also to explain the evidence-based reasons for a functional diagnosis. Patients and their families should have a clear sense of what they can expect in terms of symptoms, and what the indications are for urgent follow-up. Some examples of “call us quickly” symptoms include: rectal bleeding, black stools, persistent fever, change in stool at night, fainting, severe dehydration, significant weight loss, persistent vomiting, or new symptoms of anemia, i.e. shortness of breath at rest.

Patients and their carers should be informed about the reassessment pathway for IBS. They should be given details on how to access this as well as information about the administration including contact details, the information required to book an appointment and an estimate of waiting time (if red flags are identified). A symptom record either to be completed at review or as a self-monitoring tool could be useful in the management of IBS and detection of IBD. It helps to reduce uncertainty and improves the quality of follow up.

4) Clinical decision-making becomes more dynamic

IBS is a working diagnosis that is most likely to be correct until contrary evidence arises. Follow-up scheduling for patients whose IBS symptoms are more severe or have a change in pattern; Assessing response to IBS therapy when indicated; Using objective tests when the diagnosis of IBS is uncertain, the patient’s symptoms have changed or the clinical scenario has changed. Avoiding mistakes such as missing early inflammatory disease and over testing the stable patient with well characterized IBS.

Patients differ in risk tolerance and burden tolerance. Some patients may want an earlier diagnosis for peace of mind and others may strongly decline all invasive testing. Let the patients know that the majority of patients with IBS do not have IBD, and reassure them that your plan is designed to catch those who do. Then educate the patients as to the plan and have them partner with you to follow the plan and report any changes as they occur.

5) Health systems and payers need to be aligned with relevant policies and capacity to ensure effective health financing. Health systems and payers should be engaged in the policy-making process to design and implement financial protection strategies.

Ensure that coverage and workflow decisions allow for referral for targeted noninvasive testing and timely referral for specialist evaluation for objective markers or red flags indicating increased risk for gastrointestinal cancer. Health systems recommending the use of fecal inflammatory markers as triage tools should have sufficient infrastructure and resources to process the test in a timely fashion, notify clinicians of test results in a timely fashion, and educate clinicians about the test results. As referral thresholds are decreased for the detection of gastrointestinal cancer, endoscopy capacity and scheduling by gastroenterology departments need to be planned accordingly so that the highest risk patients are not delayed for months waiting for endoscopy.

We would like alarm elevation protocols to be as precise as possible to avoid performing colonoscopies on patients for whom it is not indicated, and to ensure that patients with worsening or progressively severe inflammatory disease are diagnosed as promptly as possible, rather than delayed. This would require the same processes and the same electronic order sets, as well as support from primary care and gastroenterology. In addition, we would like to make sure that high risk populations with poor access to monitoring and evaluation are supported, including referral processes and follow up on abnormal results for which no action is taken.

6) Research priorities focus on better prediction tools

Future research could focus on identifying better biomarkers and prediction models to distinguish patients with IBS symptoms who are at greatest risk of subsequent IBD from those who are not. Such advances could help prevent under-diagnosis of IBD and over-investigation for other diagnoses. Validations in additional patient cohorts of noninvasive biomarkers such as clinical characteristics, the microbiome, and blood-based immune signatures would be particularly useful. Establishment of long-term patient registries could facilitate the identification of patients with IBS symptoms at risk of subsequent IBD, and provide insight into specific IBS symptoms that are associated with an increased risk of IBD. This information could then be incorporated into guidelines for the management of IBD symptoms in a pragmatic fashion.

7) Practical guidance for patients and clinicians

The message for the patient is optimistic. Initially, many patients will attribute changes in their bowel habits and other gastrointestinal symptoms to IBS and should not be dissuaded from expressing their concerns as their condition changes. They should be encouraged to keep a simple diary of their symptoms and come back for evaluation if red flags appear. The message for the clinician is equally optimistic. Initially, IBS will be the correct diagnosis for the majority of patients with gastrointestinal symptoms. However, with careful documentation of the initial evaluation and the use of simple noninvasive tests to evaluate patients with change in symptoms, most patients with an underlying inflammatory disease will be identified and referred for appropriate diagnosis and treatment before delay occurs. Moreover, the majority of patients with IBS will require management with dietary approaches, fiber manipulation, selective use of medications, and psychosocial therapy. It is critical that these patients be identified and receive the appropriate diagnosis and treatment as quickly as possible.

Maintaining calibration between vigilance and alarm is a significant challenge. The clinician wants to remain alert for the possibility of IBD at the earliest sign and be confident that appropriate management of IBS is being delivered in the patients in the functional disorder category. This meeting will discuss triage tools and strategies for improved safety-netting and systems to help reduce diagnostic delay whilst addressing endoscopy capacity and the occasional problematic investigation.

References:

https://pubmed.ncbi.nlm.nih.gov/ibs-inflammatory-bowel-disease-progression