Symptoms of IBS in Patients With Inflammatory Bowel Disease
Symptoms of IBS in Patients With Inflammatory Bowel Disease
This observational study demonstrates that IBS-type symptoms are significantly more common in female IBD patients, are associated with high anxiety levels and can occur in patients with no active inflammation. Together, these features are similar to those exhibited by 'true' IBS occurring in the general population, and suggest that in some IBD patients the same condition may be responsible for producing their symptoms.
The absence of an objective biomarker for diagnosing IBS has meant that observational studies examining the phenomenon of IBS in IBD patients have all used symptom-based criteria to define its presence. As a result, it is unclear whether this is 'true IBS' or whether there are alternative pathologies causing similar symptoms that simply meet the criteria for a diagnosis of IBS.
An obvious consideration in IBD is whether active inflammation may be responsible; even those patients in clinical remission may have ongoing sub-clinical inflammation. The only previous study to evaluate this hypothesis found that FC levels were significantly higher in patients in clinical remission with IBS-type symptoms compared with those without. Although this finding contrasts with our own results, which showed no significant difference between the respective clinical remission groups, the current study was not powered directly towards testing this hypothesis and so our analysis may be subject to a type II statistical error. However, further information regarding the distribution of FC values can be gained from inspection of the frequency polygon in Figure 2. This demonstrates that there is a much higher proportion of patients with IBS-type symptoms who have mildly elevated FC levels (100–200 μg/g), and it is feasible that this low level inflammation may account for the symptoms experienced in some patients. Nevertheless, the observation that 31% of the 48 patients with very low FC levels (<90 μg/g) have IBS-type symptoms suggests that sub-clinical inflammation does not account for a substantial number of cases in our cohort.
Interestingly, in this study the duration and extent of disease were not associated with IBS-type symptoms, a finding that is shared by other surveys. This appears to counter the theory that functional symptoms result from chronic inflammation modulating the intestinal physiology. In this scenario it would be expected that more extensive inflammation, occurring over a longer period of time would yield increased IBS-type symptoms.
Previous studies have demonstrated a trend for IBS-type symptoms to be more common in female IBD patients (prevalence range 43–58%) compared with males (25–45%), but our results are the first in which this difference has been statistically significant. The 45% prevalence found in our female patients is similar to earlier reports, but the 13% prevalence in males is much lower. This was the case in both CD (6%) and UC (17%). The positive association between concurrent IBS-type symptoms and mood disorders identified in our IBD patients has been replicated in several other research papers. This alludes to the fundamental role of the brain–gut axis in producing these symptoms in IBD patients. The higher prevalence of IBS-type symptoms observed in IBD patients compared with the general population may partly be due to the increased anxiety levels that are recognised in this patient group.
There has been concern that IBS-type symptoms may influence the clinical assessment of disease activity, with patients exhibiting a high burden of functional symptoms appearing to have active disease when they are actually in remission. The results of this study show that the frequency of a correct clinical diagnosis of remission was slightly higher in those patients without IBS symptoms (86% vs. 67%); however, the overall level of agreement between clinical and biochemical assessments was very similar in patients with IBS-type symptoms compared to those without.
Faecal calprotectin has been shown to perform well in distinguishing active from inactive disease in both UC and CD, and to correlate with the endoscopic assessment of disease activity. Yet, uncertainty remains as to the optimum FC cut-off value that should be used to determine remission in IBD. The level of 90 μg/g was applied in this study as it is the value used to screen young adults with functional symptoms and has a high sensitivity for excluding inflammation in this situation. The relationship between this biochemical definition of remission and the clinical assessment equated to a less than moderate level of agreement as measured by the kappa statistic. This limited correlation between symptom-based activity indices and actual mucosal inflammation has been highlighted previously, especially in CD, and emphasizes the importance of also using objective markers of inflammation, such as FC to improve clinical judgement.
The generalisation of the results of this study may be limited by several factors. It is a single-centre study and 16% of the potentially eligible patients declined to participate. In addition, 36% of the 169 patients included in the study did not provide a stool sample for FC analysis. Although faecal calprotectin is an established diagnostic tool, the gold standard for assessing IBD activity is ileo-colonoscopy with biopsy specimens and this was not performed in our patients at the time of the study to confirm disease activity. Lastly, complications of IBD, including bile acid malabsorption (BAM), lactose intolerance and small bowel bacterial overgrowth (SBBO) were not excluded, and it is recognised that these conditions may lead to symptoms similar to IBS. BAM and SBBO are more common following small bowel resection and could potentially account for the higher rate of IBS-type symptoms found in patients with a history of previous surgery (47% vs. 22%, P = 0.09). Indeed, over 80% of the patients with a prior history of surgery had right hemicolectomy performed, thereby predisposing to BAM.
In summary, our results have shown that IBD patients with IBS-type symptoms share similar characteristics to people diagnosed with IBS in the general community, thereby suggesting that these conditions are not mutually exclusive and may be coexisting in a considerable number of IBD patients. Sub-clinical inflammation may play a role in a proportion of cases, and it is likely that other conditions, such as BAM and SBBO will also contribute. This multifactorial nature may account for the apparent increased prevalence of IBS-type symptoms in IBD patients compared with that seen in the normal Western population. Our results highlight the substantial number of patients who experience IBS-type symptoms, despite having normal calprotectin levels. Clinicians need to be aware that healing inflammation is not necessarily the end point in therapy, and that further management of symptoms may be required.
Recognising IBS in these circumstances may help direct interventions more appropriately. Dietary adjustments, antispasmodics, antidepressants and psychotherapy have all been shown to be effective in treating IBS. The effectiveness of these strategies in unselected IBD patients has been limited, but their therapeutic efficacy may be increased if suitable target populations are identified. Dietary modifications and psychotherapy have already shown promise in improving specific symptoms, such as fatigue and abdominal pain. Further randomised controlled trials are required to determine whether those therapies that are effective in treating IBS are also useful in the management of IBS-type symptoms in IBD patients.
Additional research is also needed to evaluate the contribution of non-inflammatory factors, such as SBBO, BAM and lactose intolerance in causing IBS-type symptoms. Until objective biomarkers are available that can enable clinicians to positively diagnose IBS, this will remain a complex scenario to assess with patients requiring a systematic diagnostic approach.
Discussion
This observational study demonstrates that IBS-type symptoms are significantly more common in female IBD patients, are associated with high anxiety levels and can occur in patients with no active inflammation. Together, these features are similar to those exhibited by 'true' IBS occurring in the general population, and suggest that in some IBD patients the same condition may be responsible for producing their symptoms.
The absence of an objective biomarker for diagnosing IBS has meant that observational studies examining the phenomenon of IBS in IBD patients have all used symptom-based criteria to define its presence. As a result, it is unclear whether this is 'true IBS' or whether there are alternative pathologies causing similar symptoms that simply meet the criteria for a diagnosis of IBS.
An obvious consideration in IBD is whether active inflammation may be responsible; even those patients in clinical remission may have ongoing sub-clinical inflammation. The only previous study to evaluate this hypothesis found that FC levels were significantly higher in patients in clinical remission with IBS-type symptoms compared with those without. Although this finding contrasts with our own results, which showed no significant difference between the respective clinical remission groups, the current study was not powered directly towards testing this hypothesis and so our analysis may be subject to a type II statistical error. However, further information regarding the distribution of FC values can be gained from inspection of the frequency polygon in Figure 2. This demonstrates that there is a much higher proportion of patients with IBS-type symptoms who have mildly elevated FC levels (100–200 μg/g), and it is feasible that this low level inflammation may account for the symptoms experienced in some patients. Nevertheless, the observation that 31% of the 48 patients with very low FC levels (<90 μg/g) have IBS-type symptoms suggests that sub-clinical inflammation does not account for a substantial number of cases in our cohort.
Interestingly, in this study the duration and extent of disease were not associated with IBS-type symptoms, a finding that is shared by other surveys. This appears to counter the theory that functional symptoms result from chronic inflammation modulating the intestinal physiology. In this scenario it would be expected that more extensive inflammation, occurring over a longer period of time would yield increased IBS-type symptoms.
Previous studies have demonstrated a trend for IBS-type symptoms to be more common in female IBD patients (prevalence range 43–58%) compared with males (25–45%), but our results are the first in which this difference has been statistically significant. The 45% prevalence found in our female patients is similar to earlier reports, but the 13% prevalence in males is much lower. This was the case in both CD (6%) and UC (17%). The positive association between concurrent IBS-type symptoms and mood disorders identified in our IBD patients has been replicated in several other research papers. This alludes to the fundamental role of the brain–gut axis in producing these symptoms in IBD patients. The higher prevalence of IBS-type symptoms observed in IBD patients compared with the general population may partly be due to the increased anxiety levels that are recognised in this patient group.
There has been concern that IBS-type symptoms may influence the clinical assessment of disease activity, with patients exhibiting a high burden of functional symptoms appearing to have active disease when they are actually in remission. The results of this study show that the frequency of a correct clinical diagnosis of remission was slightly higher in those patients without IBS symptoms (86% vs. 67%); however, the overall level of agreement between clinical and biochemical assessments was very similar in patients with IBS-type symptoms compared to those without.
Faecal calprotectin has been shown to perform well in distinguishing active from inactive disease in both UC and CD, and to correlate with the endoscopic assessment of disease activity. Yet, uncertainty remains as to the optimum FC cut-off value that should be used to determine remission in IBD. The level of 90 μg/g was applied in this study as it is the value used to screen young adults with functional symptoms and has a high sensitivity for excluding inflammation in this situation. The relationship between this biochemical definition of remission and the clinical assessment equated to a less than moderate level of agreement as measured by the kappa statistic. This limited correlation between symptom-based activity indices and actual mucosal inflammation has been highlighted previously, especially in CD, and emphasizes the importance of also using objective markers of inflammation, such as FC to improve clinical judgement.
The generalisation of the results of this study may be limited by several factors. It is a single-centre study and 16% of the potentially eligible patients declined to participate. In addition, 36% of the 169 patients included in the study did not provide a stool sample for FC analysis. Although faecal calprotectin is an established diagnostic tool, the gold standard for assessing IBD activity is ileo-colonoscopy with biopsy specimens and this was not performed in our patients at the time of the study to confirm disease activity. Lastly, complications of IBD, including bile acid malabsorption (BAM), lactose intolerance and small bowel bacterial overgrowth (SBBO) were not excluded, and it is recognised that these conditions may lead to symptoms similar to IBS. BAM and SBBO are more common following small bowel resection and could potentially account for the higher rate of IBS-type symptoms found in patients with a history of previous surgery (47% vs. 22%, P = 0.09). Indeed, over 80% of the patients with a prior history of surgery had right hemicolectomy performed, thereby predisposing to BAM.
In summary, our results have shown that IBD patients with IBS-type symptoms share similar characteristics to people diagnosed with IBS in the general community, thereby suggesting that these conditions are not mutually exclusive and may be coexisting in a considerable number of IBD patients. Sub-clinical inflammation may play a role in a proportion of cases, and it is likely that other conditions, such as BAM and SBBO will also contribute. This multifactorial nature may account for the apparent increased prevalence of IBS-type symptoms in IBD patients compared with that seen in the normal Western population. Our results highlight the substantial number of patients who experience IBS-type symptoms, despite having normal calprotectin levels. Clinicians need to be aware that healing inflammation is not necessarily the end point in therapy, and that further management of symptoms may be required.
Recognising IBS in these circumstances may help direct interventions more appropriately. Dietary adjustments, antispasmodics, antidepressants and psychotherapy have all been shown to be effective in treating IBS. The effectiveness of these strategies in unselected IBD patients has been limited, but their therapeutic efficacy may be increased if suitable target populations are identified. Dietary modifications and psychotherapy have already shown promise in improving specific symptoms, such as fatigue and abdominal pain. Further randomised controlled trials are required to determine whether those therapies that are effective in treating IBS are also useful in the management of IBS-type symptoms in IBD patients.
Additional research is also needed to evaluate the contribution of non-inflammatory factors, such as SBBO, BAM and lactose intolerance in causing IBS-type symptoms. Until objective biomarkers are available that can enable clinicians to positively diagnose IBS, this will remain a complex scenario to assess with patients requiring a systematic diagnostic approach.
Source...