Constipation-type irritable bowel syndrome, are you really diagnosed correctly?

Only for medical professionals to read for reference.
For Chinese patients with constipation-type irritable bowel syndrome, the corresponding diagnosis and treatment can be carried out according to the main symptoms of the patients
.

Irritable bowel syndrome (IBS) is a common disease worldwide, with abdominal pain, bloating or abdominal discomfort as the main symptoms, which are related to bowel movements or accompanied by changes in bowel habits such as frequency and/or stool characteristics [1]
.

According to the main stool characteristics of patients with abnormal bowel movements, IBS can be divided into diarrheal IBS (IBS-D), constipation IBS (IBS-C), mixed IBS (IBS-M) and unspecified IBS (IBM-U) 4 subtypes [1]
.

 IBS-C is an important subtype of IBS, and its main symptoms are abdominal pain/bloating and constipation[1].
IBS-C in China accounts for about 24.
9% of IBS[2]
.

IBS-C seriously affects the quality of work and life of patients
.

The results of a questionnaire survey in the United States showed that IBS-C symptoms can significantly affect the daily activities of patients, and cause patients to absent from work or attendance, but their work is affected by the disease (Figure 1) [3]
.

Another study also showed that more than 50% of IBS-C patients said that due to disease-related symptoms, they cannot enjoy daily activities, travel, and avoid going to places without toilets, leaving home, making plans, and even feeling unnatural.
, Hate yourself [4]
.

 Figure 1.
IBS-C affects work and patients' daily lives.
In view of the heavy burden that IBS-C brings to patients, timely and accurate diagnosis and treatment have become particularly important
.

The etiology of IBS is more complicated, and the clinical diagnosis is often based on the Roman standard[1]
.

With the continuous updating of disease awareness in recent years and the deepening of clinical practice of IBS in China, we have a new understanding of the diagnosis of IBS-C
.

 Difficulties: The diagnosis of IBS-C faces many challenges.
Although IBS is a common gastrointestinal disease, its diagnosis is not optimistic
.

Clinical IBS patients are only the tip of the iceberg, and 94.
2% of IBS patients have not been formally diagnosed [5]
.

At the same time, IBS also has a low rate of visits and delays in diagnosis [6-7]
.

On the other hand, 72% of non-expert doctors regard IBS as a diagnosis of exclusion, using too many diagnostic tests [8]
.

 When we further paid attention to the IBS-C population in IBS, we found that its clinical characteristics brought many challenges to diagnosis
.

The currently applied IBS diagnostic framework Rome IV standard considers that functional constipation (FC) and IBS-C are different diseases, but there is overlap and mutual conversion between the two, which makes it difficult to type and diagnose [9]
.

A study showed that patients diagnosed with FC and IBS-C at the time of enrollment, after 1 year of follow-up, 33% of IBS-C patients converted to FC, and 32% of FC patients converted to IBS-C or IBS-M (Figure 2 ) [10]
.

In addition, there are differences in functional gastrointestinal diseases (FGIDs) between the East and the West.
In China, patients with IBS not only have lower abdominal pain, but also have symptoms of upper abdominal pain [11].
These differences are also based on the Rome IV diagnostic criteria established based on data from Western countries.
The clinical application in China has brought difficulties
.

 Figure 2.
Interconversion between IBS-C and FC patients Adapt to local conditions: Rome IV criteria are more suitable for clinical research, and the clinical diagnosis of IBS-C in China should be based on symptoms.
The updated Rome IV criteria in 2016 brought about significant changes in the diagnostic criteria for IBS
.

Compared with the Rome III standard, the Rome IV standard deletes "abdominal discomfort"; raises the diagnostic threshold of IBS from at least 3 days a month to at least 1 day a week; and reduces the relationship between abdominal pain episodes and accompanying symptoms [12 ]
.

But does the new Rome IV diagnostic criteria apply to China? Epidemiological studies of Asian patients with IBS have shown that the most commonly reported symptom of patients is abdominal distension [13], and abdominal distension is not included in the Rome IV standard, which makes the application of Rome IV standard to Asian patients prone to missed diagnosis
.

On the other hand, the research basis for raising the diagnostic threshold of IBS is only based on the results of American epidemiological studies, while studies in Asian countries have shown that the frequency and intensity of abdominal pain in patients with IBS are relatively low [13], which makes Rome IV criteria applicable to Asian patients Sensitivity may be slightly lower
.

 In addition, a cross-sectional study in a tertiary hospital in China showed that the diagnostic positive rate of Rome IV in China is only half of that of Rome III [14]
.

Another Chinese population study showed that among 1117 patients with FGIDs, 292 cases (26.
14%) were diagnosed as IBS by Rome III criteria, while only 58 cases (5.
19%) were diagnosed as IBS by Rome IV criteria [15]
.

Therefore, whether the Rome IV standard is applicable to clinical diagnosis in China needs further investigation
.

Abdominal pain, abdominal discomfort, and abdominal distension are the main clinical symptoms of Chinese IBS patients (Figure 3) [16]
.

For patients with IBS-C, abdominal discomfort is the main reason for their medical treatment [17-18]
.

So, how should Rome IV standard be applied to clinical diagnosis practice of IBS-C in China? Figure 3.
The ranking of distressing symptoms of Chinese IBS patients.
The 2016 Rome IV Consensus pointed out that clinicians are encouraged to make a diagnosis of IBS based on symptoms and emphasize that IBS is not a diagnosis of exclusion [19]
.

At the 2019 China IBS-C diagnosis and treatment progress expert meeting, experts also pointed out that in clinical practice, for patients whose symptom frequency and severity do not meet the Rome IV standard, corresponding diagnosis and treatment can be carried out according to the main symptoms of the patient, without being stuck.
Whether it fully meets the Rome IV standard
.

However, in future epidemiological investigations, clinical studies, and evaluation of the efficacy of new drugs, it is recommended to refer to the Rome IV standard for academic exchanges and research publications [20]
.

The original intention of the Rome Standard is to enable scholars from all over the world to use uniform standards for epidemiological investigations, clinical studies, and evaluation of the efficacy of new drugs, and to make research results more comparable [20]
.

The promulgation of the Rome IV standard is of great significance to the diagnosis of FGIDs, but how to adapt to local conditions and grasp the actual clinical application of the Rome IV standard according to the characteristics of patients in different regions is very important
.

The current clinical diagnosis of Chinese patients with IBS-C should still be based on the diagnosis of symptoms
.

A clinical randomized study on IBS diagnostic methods also showed that the diagnostic effect of symptom-based positive strategies is not lower than that of exclusionary diagnosis (difference 0.
64, 95% CI: -2.
74~1.
45); and the direct cost of symptom-based positive strategies Lower [21]
.

Therefore, the Rome IV standard should be used flexibly in clinical practice to optimize the diagnosis process of IBS-C, and give a positive diagnosis as soon as possible, so that patients can benefit earlier
.

 Breaking through the limitations: Linaclotide can comprehensively improve the constipation of IBS-C patients, and relieve the symptoms of abdominal pain in IBS patients
.

For patients with IBS, a treatment plan needs to be selected based on the main symptoms
.

The main clinical symptoms of IBS-C are abdominal pain/bloating, constipation, etc.
Domestic and foreign guidelines have pointed out that the main purpose of treating IBS-C is to relieve abdominal pain and other discomforts and increase bowel movements[1,22]
.

 The traditional treatment of IBS-C mainly targets a single symptom and cannot cover abdominal pain and constipation at the same time.
Some drugs may even increase the symptoms of abdominal distension/abdominal pain
.

For example, in the treatment of constipation, volumetric laxatives may aggravate abdominal distension and abdominal pain symptoms, irritant laxatives can cause abdominal cramps, osmotic laxatives (such as lactulose) can increase abdominal distension symptoms; and irritant laxatives have many adverse reactions, not Long-term use [1]
.

Medications to relieve abdominal pain, such as smooth muscle antispasmodics, can prolong the transit time of the patient’s colon [23]
.

These traditional treatment schemes cannot meet the treatment goals of IBS-C, and there is an urgent clinical need for IBS-C treatment drugs that can simultaneously improve abdominal pain/bloating, increase bowel frequency, and have good safety and long-term use
.

 On January 15, 2019, the National Medical Products Administration (NMPA) of China approved the world's first guanylate cyclase-C (GC-C) receptor agonist linaclotide to be marketed for the treatment of adult IBS -C, provides better treatment options for patients with IBS-C in China
.

 Linaclotide has a unique dual mechanism of action.
After it binds to intestinal GC-C, it increases the concentration of intracellular/external cyclic guanosine phosphate (cGMP), thereby accelerating gastrointestinal motility, increasing the frequency of bowel movements; and reducing Pain sensory nerve signal transmission, alleviate the symptoms of abdominal pain (Figure 4) [24,25], and at the same time solve the two major problems of defecation and relief of abdominal pain/abdominal distension
.

 Figure 4.
The unique mechanism of action of linaclotide.
The global multi-center phase III clinical study of linaclotide and a number of evidence-based medical evidence show that linaclotide has a rapid effect on IBS-C and can significantly improve constipation and abdominal pain.
/Symptoms of abdominal distension, with stable curative effect and good safety [26-29]
.

In Chinese patients with IBS-C, Linaclotide has also shown excellent efficacy and good safety in significantly improving constipation and abdominal pain/bloating [30]
.

Based on this, authoritative guidelines at home and abroad unanimously recommend linaclotide as the preferred drug for the treatment of IBS-C[1,25,31]
.

 Conclusion Linaclotide can significantly improve constipation, relieve abdominal pain, has good safety, high treatment satisfaction and more cost-effectiveness.
It is an effective treatment for IBS-C
.

At present, Linaclotide has been included in the national medical insurance catalogue, bringing good news to the vast number of IBS-C patients in China, helping patients return to a normal life without pain and ease! References: [1] Gastrointestinal Functional Diseases Collaboration Group, Chinese Medical Association Gastroenterology Branch, Gastrointestinal Dynamics Group, Chinese Gastroenterology Branch.
Chinese Journal of Digestion, 2020; 40(12):803-818.
[ 2] Zhao Y, et al.
Aliment Pharmacol Ther.
2010 Aug;32(4):562-72.
[3] DiBonaventura, et al.
CurrMed Res Opin.
2011 Nov;27(11):2213-22.
[4 ] Courtney McMahon, et al.
Presentation Number Sa1943; 2019 DDW[5] Tao Bai, et al.
Presentation Number: Su1585; 2018DDW[6] Gastrointestinal Functional Diseases Collaboration Group, Chinese Medical Association Digestion Gastrointestinal Dynamics Group of the Chinese Society of Diseases.
Chinese Journal of Digestion.
2016;36(5):299-312[7] Hulisz D, et al.
J Manag Care Pharm.
2004 Jul-Aug;10(4):299-309 .
[8] Spiegel BM, et al.
Am J Gastroenterol.
2010 Apr;105(4):848-58[9] Douglas A.
Drossman, Fang Xiucai, etc.
Rome 4: Functional Gastroenterology Abnormal intestine-brain interaction.
Science Press; 1st edition [10] Wong RK, et al.
Am J Gastroenterol.
2010; 105(10):2228-2234[11] Shi Quan, et al.
Functional gastrointestinal disease Symptom characteristics: research based on Asia Rome III questionnaire.
2012 Chinese Gastroenterology Conference [12] Schmulson MJ, Drossman DA.
J Neurogastroenterol Motil.
2017 Apr 30;23(2):151-163.
[13] Ghoshal UC, et al.
J Neurogastroenterol Motil.
2017 Jul 30;23(3):334-340.
[14] Bai T, et al.
J Gastroenterol Hepatol.
2017 May;32(5):1018-1025 [15] Bin Wang, et al.
Presentation Number: Sa1955; 2019 DDW[16] Xiong Lishou et al.
Chinese Journal of Digestion 2015, 35(7); 476-477.
[17] Heidelbaugh J.
Am J Gastroenterol.
2015; 110: 580.
[18] Huan Wang, Xiaohua Hou, et al.
2016 CGC[19] Lacy BE, et al.
Gastroenterology.
2016; 150:1393-1407[20 ] Yuan Yaozong.
Chinese Journal of Digestion, 2019,39(3):197-198[21] Begtrup LM, et al.
Clin Gastroenterol Hepatol.
2013 Aug;11(8):956-62.
e1[22] Johnston JM,et al.
Curr Med Res Opin.
2013 Feb;29(2):149-60[23] Bouchoucha Met al.
Biomed Pharmacother.
2000 Aug;54(7):381-7.
[24] Thomas RH, Luthin DR.
Pharmacotherapy 2015; 35(6):613-630.
[25] Ford AC, Moayyedi P, Lacy BE, et al.
Am J Gastroenterol 2014; 109 Suppl 1: S2-26; quiz S27.
[26] Chey WD, Lembo AJ , Lavins BJ, et al.
AmJ Gastroenterol.