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For medical professionals
only, this article summarizes the difficulties and points of diagnosis and treatment
: Functional bowel diseases (FBDs) are considered to be abnormalities in intestinal-brain interaction caused by a combination of factors, resulting in hypersensitivity of internal organs, resulting in a series of gastrointestinal symptoms associated with defecation
。 Irritable bowel syndrome with diarrhea (IBS-D) and functional diarrhea (FDr), characterized by diarrhoea, are characterized by a high incidence, but questions remain about the optimal diagnostic pathway and targeted management
.
At the recent 2022 Asia-Pacific Gastroenterology Academic Week, Professor Hou Xiaohua from Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology delivered a keynote report entitled "Optimizing the Diagnosis and Treatment of IBS-D and Functional Bowel Diseases", focusing on the challenges and new directions
in the diagnosis and treatment of functional bowel diseases represented by IBS and FDr.
IBS-D and FDr are two FGIDs
with a higher incidence.
A large survey study in 26 countries published in 2021 showed an overall incidence of 40.
3% for all FGIDs, 4.
7% for FDr based on the Rome IV diagnostic criteria, and 1.
2%
for IBS-D.
The incidence of FGIDs in China was 34.
4%, compared with 2.
3% for IBS and 5.
6% for FDr
.
Figure 1.
Overall global prevalence of FGID[1].
▌ Low diagnosis rate and delayed
diagnosis A study in China in 2018 showed that among all patients who went to the gastroenterology clinic for related symptoms and were diagnosed with IBS, only 5.
8% of patients were diagnosed with IBS first, and 94.
2% were diagnosed for the first time
.
In addition, 43% of patients did not confirm the diagnosis
of IBS until 5 years after the onset of gastrointestinal symptoms.
▌Low diagnostic accuracy
A 2015 survey study conducted among European general practitioners (GP, n=104), gastroenterologists (n=100) and specialists specializing in IBS diagnosis and treatment showed that the correct diagnosis rate of IBS-D by GP was only 64%, the misdiagnosis rate was 14%, and another 22% of cases could not be clearly diagnosed; The diagnosis of IBS-D by gastroenterologists and specialists was 72% correct, and misdiagnosis occurred in 12% of cases; Even 8% of patients treated by IBS specialists are misdiagnosed with other diseases
.
Figure 2.
Percentage of patients diagnosed with constipated irritable bowel syndrome (IBS-C), irritable bowel syndrome with diarrhea (IBS-D), inflammatory bowel disease (IBD), and chronic constipation (CC) based on patient history and physical examination [2].
Confusion about the application of the Roman criteria in routine care includes the following: the main evidence-based evidence for the Rome criteria comes from the West, which differs from the actual situation in different regions: according to the Roman criteria, only Bristol types I and II are considered constipation, while in Asians, Bristol type III is also considered constipation; The Rome standard requires patients to record fecal traits for two consecutive weeks, and the requirements for patient compliance are high and clinically difficult to achieve
.
▌Rome IV.
vs Rome III: Stricter diagnostic criteria In a large online survey of 14 countries (n=29,606), the overall prevalence of IBS was 3.
8% according to the Rome IV criteria and 10.
1% according to the Rome III criteria
(Table 1)
。 The prevalence of IBS based on the diagnostic criteria of Rome IV in various countries is only 24%~57%
of the prevalence of Rome III.
Table 1.
Comparison of prevalence (95% CI) of IBS based on Rome III and Rome IV diagnostic criteria (n=29,606)[1]
In 352 patients in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, when IBS was diagnosed using Rome III.
criteria, The positivity rate was 12.
4%, compared to only 6.
1%
using the Rome IV criteria.
Roma IV-positive patients are mainly patients with more severe symptoms of Rome III-positive IBS (Figure 3).
It can be seen that the Rome IV standard has stricter requirements for symptoms than the Rome III standard, and can be carried out in research, but is not suitable for clinical practice
.
Fig.
3.
The positive proportion and distribution of subtypes of IBS diagnosed by Rome III and Rome IV.
criteria in patients attending gastroenterology in China (a) Rome III criteria, (b) Rome IV criteria [3].
Changes in the incidence of FGIDs under the Rome III and Rome IV criteria
▌Patients with alarm signs of IBS diagnosed as IBS and with alarm signs
have a significantly increased chance of organic disease detected by colonoscopy, including: age > 40 years, blood in the stool, positive fecal occult blood test, nocturnal bowel movements, anemia, abdominal mass, ascites, fever, Unintentional weight loss, colorectal cancer, and family history of IBD [5].
▌IBS and Colon Organic Diseases
A 2015 Canadian cross-sectional survey [6] included 559 patients with IBS diagnosed based on Rome III criteria.
The proportion of patients with IBS-D-like symptoms with colonic organic disease was 31.
1%, the highest among
all subtypes of IBS.
Fig.
7.
Incidence of colonic organic disease in patients with different subtypes of IBS[6]The
diagnostic strategy of IBS and FDr is based on the diagnosis of symptoms rather than exclusionary diagnosis, and auxiliary tests
should be selected if necessary.
Diagnosis can be made as follows: when the patient has chronic abdominal pain (more than 3 months) or associated symptoms and/or abnormal bowel movements:
(1) a thorough history should be taken, symptoms should be assessed, and signs of IBS alert should be excluded;
(2) Conduct necessary laboratory tests (including complete blood count, CRP, celiac disease serology, and fecal calprotectin);
(3) phenotypic analysis of the disease (IBS-D or FDr) and initiation of appropriate treatment based on the results of the initial assessment;
(4) If symptoms are persistent, severe, and/or exacerbated or treatment is ineffective, further testing
should be recommended.
Colonoscopy + random biopsy is recommended to rule out organic disease, particularly in patients over 40 to 50 years of age with associated risk factors, alarm signs, and/or abnormal laboratory findings;
(5) For patients who do not respond to drug therapy, capsule endoscopy (VCE) can also be considered to better identify possible small bowel diseases; SeHCAT testing or other biomarkers are recommended to identify bile acid diarrhea
.
Figure 8.
Diagnostic pathways for IBS-D and FDr [8].
▌Lifestyle
dietary factors can induce or aggravate IBS symptoms, but they are not related to IBS subtypes, and the impact of diet on IBS incidence is mainly related
to intestinal intolerance to food 。 Foods rich in fermented oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) play an important role in the pathogenesis of IBS, mainly related to its difficulty in being absorbed by the small intestine and fermenting in the colon to produce gas, thereby causing abdominal pain, bloating, abdominal discomfort and other symptoms [5], Western IBS high FODMAP diet is the most common trigger, and the trigger for IBS patients in China is mostly cold, spicy, greasy diet
.
A 2017 meta-analysis published in Nutrients [7] that included six RCTs and six cohort studies combined the results and showed that a low-FODMAP diet improved IBS symptoms, particularly abdominal pain, compared with traditional IBS diets and moderate/high-FODMAP-based dietary patterns , flatulence and diarrhea
.
Table 3.
Meta-analysis results [7]▌The goal of treatment with IBS is to improve symptoms and improve quality of life, and individualized comprehensive treatment
measures
are required.
China's 2020 Chinese expert consensus recommendation on irritable bowel syndrome [5]: antispasmodics can improve the symptoms of abdominal pain in IBS; Antidiarrheal agents can improve diarrhea symptoms in IBS-D patients, and intestinal antibiotics that are not absorbed can improve overall symptoms and abdominal distension and diarrhea symptoms in non-IBS-C patients; Probiotics have a certain effect
on improving the symptoms of IBS.
Traditional Chinese medicine also has a certain effect on improving IBS symptoms, such as pain diarrhea granules can improve the spasm of ex vivo smooth muscle, increase the sensory threshold of internal organs, and help relieve the pain and diarrhea symptoms
of IBS-D patients.
A multicentre controlled study of dysphorinol granules in patients with IBS-D was treated with 360 patients in the experimental group and 120 patients in the control group, all with a duration of 3 weeks
.
The results showed that compared with the control group, the rate of diarrhea (healing rate + apparent efficiency) was 56.
23% vs 23.
89%, and the incidence of abdominal pain was 46.
2% vs 16.
81%, respectively, the difference was statistically significant, and no obvious adverse reactions were seen during taking Painstropic Granules [8].
Neurotransmitter-modifying drugs may be beneficial in improving IBS symptoms, so tricyclic antidepressants (TCAs) are recommended for the treatment of IBS-D
.
Table 4 summarizes the IBS-D therapeutic drugs recommended by the American Society of Gastroenterology (ADA), some of which have not yet been marketed
in China.
Table 4.
Recommendations in clinical practice guidelines for pharmacotherapy for IBS-D (ADA, 2022) [9].
Diagnosis of IBS-D and FDr should be based on the patient's symptoms and do not need to fully comply
with the Roman criteria.
Rome III standards are more applicable to Asian populations
.
Diagnosis of IBS-D and FDr should focus on excluding organic disease and focusing on alarm signs rather than underlying biological markers
.
Dietary risk factors for IBS-D and FDr are different
from those in Western populations.
At present, the drug treatment goals of IBS and FDr are mainly to improve symptoms, and the efficacy is not good
.
The therapeutic effects of TCM in many ways may be beneficial
for IBS and FDr.
Professor Hou Xiaohua, an audit expert
only, this article summarizes the difficulties and points of diagnosis and treatment
: Functional bowel diseases (FBDs) are considered to be abnormalities in intestinal-brain interaction caused by a combination of factors, resulting in hypersensitivity of internal organs, resulting in a series of gastrointestinal symptoms associated with defecation
。 Irritable bowel syndrome with diarrhea (IBS-D) and functional diarrhea (FDr), characterized by diarrhoea, are characterized by a high incidence, but questions remain about the optimal diagnostic pathway and targeted management
.
At the recent 2022 Asia-Pacific Gastroenterology Academic Week, Professor Hou Xiaohua from Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology delivered a keynote report entitled "Optimizing the Diagnosis and Treatment of IBS-D and Functional Bowel Diseases", focusing on the challenges and new directions
in the diagnosis and treatment of functional bowel diseases represented by IBS and FDr.
01
Incidence of IBS-D and FDr
IBS-D and FDr are two FGIDs
with a higher incidence.
A large survey study in 26 countries published in 2021 showed an overall incidence of 40.
3% for all FGIDs, 4.
7% for FDr based on the Rome IV diagnostic criteria, and 1.
2%
for IBS-D.
The incidence of FGIDs in China was 34.
4%, compared with 2.
3% for IBS and 5.
6% for FDr
.
Figure 1.
Overall global prevalence of FGID[1].
02
Challenges in IBS-D care
▌ Low diagnosis rate and delayed
diagnosis A study in China in 2018 showed that among all patients who went to the gastroenterology clinic for related symptoms and were diagnosed with IBS, only 5.
8% of patients were diagnosed with IBS first, and 94.
2% were diagnosed for the first time
.
In addition, 43% of patients did not confirm the diagnosis
of IBS until 5 years after the onset of gastrointestinal symptoms.
▌Low diagnostic accuracy
A 2015 survey study conducted among European general practitioners (GP, n=104), gastroenterologists (n=100) and specialists specializing in IBS diagnosis and treatment showed that the correct diagnosis rate of IBS-D by GP was only 64%, the misdiagnosis rate was 14%, and another 22% of cases could not be clearly diagnosed; The diagnosis of IBS-D by gastroenterologists and specialists was 72% correct, and misdiagnosis occurred in 12% of cases; Even 8% of patients treated by IBS specialists are misdiagnosed with other diseases
.
Figure 2.
Percentage of patients diagnosed with constipated irritable bowel syndrome (IBS-C), irritable bowel syndrome with diarrhea (IBS-D), inflammatory bowel disease (IBD), and chronic constipation (CC) based on patient history and physical examination [2].
03
The Rome Standard: Application Dilemma in Practice
Confusion about the application of the Roman criteria in routine care includes the following: the main evidence-based evidence for the Rome criteria comes from the West, which differs from the actual situation in different regions: according to the Roman criteria, only Bristol types I and II are considered constipation, while in Asians, Bristol type III is also considered constipation; The Rome standard requires patients to record fecal traits for two consecutive weeks, and the requirements for patient compliance are high and clinically difficult to achieve
.
▌Rome IV.
vs Rome III: Stricter diagnostic criteria In a large online survey of 14 countries (n=29,606), the overall prevalence of IBS was 3.
8% according to the Rome IV criteria and 10.
1% according to the Rome III criteria
(Table 1)
。 The prevalence of IBS based on the diagnostic criteria of Rome IV in various countries is only 24%~57%
of the prevalence of Rome III.
Table 1.
Comparison of prevalence (95% CI) of IBS based on Rome III and Rome IV diagnostic criteria (n=29,606)[1]
In 352 patients in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, when IBS was diagnosed using Rome III.
criteria, The positivity rate was 12.
4%, compared to only 6.
1%
using the Rome IV criteria.
Roma IV-positive patients are mainly patients with more severe symptoms of Rome III-positive IBS (Figure 3).
It can be seen that the Rome IV standard has stricter requirements for symptoms than the Rome III standard, and can be carried out in research, but is not suitable for clinical practice
.
Fig.
3.
The positive proportion and distribution of subtypes of IBS diagnosed by Rome III and Rome IV.
criteria in patients attending gastroenterology in China (a) Rome III criteria, (b) Rome IV criteria [3].
Table 2 presents the diagnostic criteria
for IBS-D and FDr in Rome IV.
Although the Rome IV criteria had little effect on the prevalence of FGIDs compared with the Rome III criteria (20.
9 versus 20.
7 percent), using Rome IV as a diagnostic criterion not only reduced the positive rate of IBS, but also increased the diagnostic rate of FDr (3.
3 versus 1.
2 percent).
Therefore, clinical admission to patients with suspected FGIDs should not be limited to Roman criteria, but should be based
on the patient's symptoms.
Table 2.
Rome IV criteria for the diagnosis of IBS-D and FDr [4].
Changes in the incidence of FGIDs under the Rome III and Rome IV criteria
04
Diagnosis of IBS-D and FDr
▌Patients with alarm signs of IBS diagnosed as IBS and with alarm signs
have a significantly increased chance of organic disease detected by colonoscopy, including: age > 40 years, blood in the stool, positive fecal occult blood test, nocturnal bowel movements, anemia, abdominal mass, ascites, fever, Unintentional weight loss, colorectal cancer, and family history of IBD [5].
▌IBS and Colon Organic Diseases
A 2015 Canadian cross-sectional survey [6] included 559 patients with IBS diagnosed based on Rome III criteria.
The proportion of patients with IBS-D-like symptoms with colonic organic disease was 31.
1%, the highest among
all subtypes of IBS.
Fig.
7.
Incidence of colonic organic disease in patients with different subtypes of IBS[6]The
diagnostic strategy of IBS and FDr is based on the diagnosis of symptoms rather than exclusionary diagnosis, and auxiliary tests
should be selected if necessary.
Diagnosis can be made as follows: when the patient has chronic abdominal pain (more than 3 months) or associated symptoms and/or abnormal bowel movements:
(1) a thorough history should be taken, symptoms should be assessed, and signs of IBS alert should be excluded;
(2) Conduct necessary laboratory tests (including complete blood count, CRP, celiac disease serology, and fecal calprotectin);
(3) phenotypic analysis of the disease (IBS-D or FDr) and initiation of appropriate treatment based on the results of the initial assessment;
(4) If symptoms are persistent, severe, and/or exacerbated or treatment is ineffective, further testing
should be recommended.
Colonoscopy + random biopsy is recommended to rule out organic disease, particularly in patients over 40 to 50 years of age with associated risk factors, alarm signs, and/or abnormal laboratory findings;
(5) For patients who do not respond to drug therapy, capsule endoscopy (VCE) can also be considered to better identify possible small bowel diseases; SeHCAT testing or other biomarkers are recommended to identify bile acid diarrhea
.
Figure 8.
Diagnostic pathways for IBS-D and FDr [8].
05
Treatment of IBS-D and FDr
▌Lifestyle
dietary factors can induce or aggravate IBS symptoms, but they are not related to IBS subtypes, and the impact of diet on IBS incidence is mainly related
to intestinal intolerance to food 。 Foods rich in fermented oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) play an important role in the pathogenesis of IBS, mainly related to its difficulty in being absorbed by the small intestine and fermenting in the colon to produce gas, thereby causing abdominal pain, bloating, abdominal discomfort and other symptoms [5], Western IBS high FODMAP diet is the most common trigger, and the trigger for IBS patients in China is mostly cold, spicy, greasy diet
.
A 2017 meta-analysis published in Nutrients [7] that included six RCTs and six cohort studies combined the results and showed that a low-FODMAP diet improved IBS symptoms, particularly abdominal pain, compared with traditional IBS diets and moderate/high-FODMAP-based dietary patterns , flatulence and diarrhea
.
Table 3.
Meta-analysis results [7]▌The goal of treatment with IBS is to improve symptoms and improve quality of life, and individualized comprehensive treatment
measures
are required.
China's 2020 Chinese expert consensus recommendation on irritable bowel syndrome [5]: antispasmodics can improve the symptoms of abdominal pain in IBS; Antidiarrheal agents can improve diarrhea symptoms in IBS-D patients, and intestinal antibiotics that are not absorbed can improve overall symptoms and abdominal distension and diarrhea symptoms in non-IBS-C patients; Probiotics have a certain effect
on improving the symptoms of IBS.
Traditional Chinese medicine also has a certain effect on improving IBS symptoms, such as pain diarrhea granules can improve the spasm of ex vivo smooth muscle, increase the sensory threshold of internal organs, and help relieve the pain and diarrhea symptoms
of IBS-D patients.
A multicentre controlled study of dysphorinol granules in patients with IBS-D was treated with 360 patients in the experimental group and 120 patients in the control group, all with a duration of 3 weeks
.
The results showed that compared with the control group, the rate of diarrhea (healing rate + apparent efficiency) was 56.
23% vs 23.
89%, and the incidence of abdominal pain was 46.
2% vs 16.
81%, respectively, the difference was statistically significant, and no obvious adverse reactions were seen during taking Painstropic Granules [8].
Neurotransmitter-modifying drugs may be beneficial in improving IBS symptoms, so tricyclic antidepressants (TCAs) are recommended for the treatment of IBS-D
.
Table 4 summarizes the IBS-D therapeutic drugs recommended by the American Society of Gastroenterology (ADA), some of which have not yet been marketed
in China.
Table 4.
Recommendations in clinical practice guidelines for pharmacotherapy for IBS-D (ADA, 2022) [9].
| New or updated recommendations | Recommended strength | Level of evidence |
| 1. In IBS-D patients, AGA recommends the use of eluxadoline (eluxadoline is contraindicated in patients without gallbladder or drinking more than 3 alcoholic beverages per day). | Conditional | medium |
| 2a. For IBS-D patients, AGA recommends rifaximin | Conditional | medium |
| 2b. In IBS-D patients who have an initial response to rifaximin and develop recurrent symptoms, AGA recommends resuming rifaximin therapy | Conditional | medium |
| 3. In IBS-D patients, AGA recommends the use of alosetron | Conditional | medium |
| 4. In IBS-D patients, AGA recommends loperamide | Conditional | Very low |
| 5. In patients with IBS, AGA recommends TCA | Conditional | low |
| 6. In IBS patients, AGA is not recommended to use SSRIs | Conditional | low |
| 7. In IBS patients, AGA recommends the use of antispasmodics | Conditional | low |
06
summary
Diagnosis of IBS-D and FDr should be based on the patient's symptoms and do not need to fully comply
with the Roman criteria.
Rome III standards are more applicable to Asian populations
.
Diagnosis of IBS-D and FDr should focus on excluding organic disease and focusing on alarm signs rather than underlying biological markers
.Dietary risk factors for IBS-D and FDr are different
from those in Western populations.At present, the drug treatment goals of IBS and FDr are mainly to improve symptoms, and the efficacy is not good
.
The therapeutic effects of TCM in many ways may be beneficial
for IBS and FDr.
Diagnosis of IBS-D and FDr should be based on the patient's symptoms and do not need to fully comply
with the Roman criteria.
Rome III standards are more applicable to Asian populations
.
Diagnosis of IBS-D and FDr should focus on excluding organic disease and focusing on alarm signs rather than underlying biological markers
.
Dietary risk factors for IBS-D and FDr are different
from those in Western populations.
At present, the drug treatment goals of IBS and FDr are mainly to improve symptoms, and the efficacy is not good
.
The therapeutic effects of TCM in many ways may be beneficial
for IBS and FDr.
Professor Hou Xiaohua, an audit expert
Doctor of Gastroenterology, Wuhan Union Medical College Hospital, Chief Physician, Professor, Doctoral Supervisor, Director of the Institute of Gastroenterology
He enjoys the government allowance of the State Council, a young and middle-aged expert with outstanding contributions from the National Health and Family Planning Commission, a leading medical talent in Hubei Province, a standing director of the Asian Association of Neurogastroenterology and Dynamics, and a member of the International Society of Gastrointestinal Electrophysiology
Vice President of Gastroenterologist Branch of Chinese Medical Doctor Association
Vice Chairman of the Digestive and Nutrition Professional Committee of the Chinese Physiological Society
Member of the Gastroenterology Society of the Chinese Society of Gastroenterology, leader of the Gastrointestinal Functional Diseases Collaborative Group
Chairman of the Gastroesophageal Reflux Disease Committee of the Gastroenterologist Branch of the Chinese Medical Doctor Association
Vice President of Hubei Medical Association and Chairman of Hubei Gastroenterology Society
References:
[1] Sperber AD, Bangdiwala SI, Drossman DA, et al.
Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.
Gastroenterology.
2021; 160(1):99-114.
e3.
[2] Andresen V, Whorwell P, Fortea J, Auzière S.
An exploration of the barriers to the confident diagnosis of irritable bowel syndrome: A survey among general practitioners, gastroenterologists and experts in five European countries.
United European Gastroenterol J.
2015; 3(1):39-52.
[3] Bai T, Xia J, Jiang Y, Cao H, et al.
Comparison of the Rome IV and Rome III criteria for IBS diagnosis: A cross-sectional survey.
J Gastroenterol Hepatol.
2017; 32(5):1018-1025.
[4] Savarino E, Zingone F, Barberio B, et al.
Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility.
United European Gastroenterol J.
2022; 10(6):556-584.
[5] Gastrointestinal Functional Diseases Collaborative Group of Gastroenterology Branch of Chinese Medical Association, Gastrointestinal Kinetics Group of Gastroenterology Branch of Chinese Medical Association.
Expert consensus opinion on irritable bowel syndrome in China in 2020[J].
Chinese Journal of Digestion,2020,40(12):803-818.
[6] Patel P, Bercik P, Morgan DG, et al.
Prevalence of organic disease at colonoscopy in patients with symptoms compatible with irritable bowel syndrome: cross-sectional survey.
Scand J Gastroenterol.
2015; 50(7):816-23.
[7] Altobelli E, Del Negro V, Angeletti PM, Latella G.
Low-FODMAP Diet Improves Irritable Bowel Syndrome Symptoms: A Meta-Analysis.
Nutrients.
2017; 9(9):940.
[8] Painstaking granules research collaboration group.
A randomized, double-blind, placebo-controlled multicenter trial of Dysphorinol granules in the treatment of irritable bowel syndrome with diarrhea [J] .
Chinese Journal of Digestion,2010,30( 05 ): 327-330.
[9] Lembo A, Sultan S, Chang L, et al.
AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Diarrhea.
Gastroenterology.
2022; 163(1):137-151.
