The Mexican consensus on irritable bowel syndrome · 17/06/2015 · Desde la publicación de las...

Revista de Gastroenterología de México. 2016;81(3):149---167

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REVISTA DE

DE MEXICOGASTROENTEROLOGIA´

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REVIEW ARTICLE

The Mexican consensus on irritable bowel syndrome�

R. Carmona-Sáncheza,∗, M.E. Icaza-Chávezb, M.V. Bielsa-Fernándezc,O. Gómez-Escuderod, F. Bosques-Padillae, E. Coss-Adamef, F. Esquivel-Ayaneguig,Á.R. Flores-Rendónh, M.A. González-Martínez i, F. Huerta-Iga j, A. López-Colombok,T.H. Méndez-Gutiérrez l, A. Noble-Lugom, J.R. Nogueira-de Rojasn, R.H. Rana-Garibayo,J.M. Remes-Trochep, F. Roesch-Dietlenq, M.J. Schmulsonr, J.C. Soto-Pérezs,J.L. Tamayot, L.F. Uscangau, M.Á. Valdovinosu, J. Valerio-Urenav, M.R. Zavala-Solaresw

a Private Practice. San Luis Potosí, S.L.P., Mexicob Hospital Star Médica de Mérida, Yucatán, Mexicoc Unit of Patients Under Study, Universidad Autónoma de Guadalajara, Zapopan, Jalisco, Mexicod Gastroenterology Clinic, Gastrointestinal Endoscopy, and Gastrointestinal Motility, Hospital Ángeles Puebla, Puebla, Puebla,Mexicoe School of Medicine of the Universidad Autónoma de Nuevo León and Internal medicine Division Administration,Instituto Tecnológico y de Estudios Superiores de Monterrey, Monterrey, Nuevo León Mexicof Department of Gastroenterology and Gastrointestinal Motility Laboratory of the Instituto Nacional de Ciencias Médicas yNutrición Salvador Zubirán (INCMNSZ), Mexico City, Mexicog Endoscopy Administration, ‘‘Hospital General Dr. Miguel Silva’’ SSM, Morelia, Michoacán, Mexicoh Gastroenterology and Gastrointestinal Endoscopy Service of the Instituto de Seguridad y Servicios Sociales para los Trabajadoresdel Estado y Municipios de Baja California ISSSTECALI, Hospital Mexicali, Mexicali, North Territory of Baja California, Mexicoi Gastrointestinal Motility Laboratory, Department of Endoscopy, Hospital de Especialidades del Centro Médico Nacional Siglo XXIIMSS Mexico City, Mexicoj Endoscopy and Gastrointestinal Physiology Administration, Hospital Ángeles Torreón, Torreón, Coahuila, Méxicok Health Education and Research Administration, UMAE Hospital de Especialidades CMN Manuel Ávila Camacho,Instituto Mexicano del Seguro Social, Puebla, Puebla, Mexicol Gastroenterology Service, Hospital Ángeles Xalapa, Xalapa, Veracruz, Mexicom Department of teaching and Research, Hospital Espanol de México, Mexico City, Mexicon Private practice, Irapuato, Guanajuato, Mexicoo Gastroenterology Service, Hospital Espanol de México, Mexico City, Mexicop Gastrointestinal Motility and Physiology Laboratory, Institute of Medical and Biologic Research, Universidad Veracruzana (UV),Veracruz, Mexicoq Department of Gastroenterology, Institute of Medical and Biologic Research, UV, Veracruz, Ver. Mexicor Liver, Pancreas and Motility Laboratory (HIPAM)-Experimental Medicine Research Unit, School of Medicine-Universidad NacionalAutónoma de México (UNAM), Hospital General de México, Mexico City, Mexico

� Please cite this article as: Carmona-Sánchez R, Icaza-Chávez ME, Bielsa-Fernández MV, Gómez-Escudero O, Bosques-Padilla F, Coss-AdameE, et al. Consenso mexicano sobre el síndrome de intestino irritable. Revista de Gastroenterología de México. 2016;82:149---167.

∗ Corresponding author. Arista 931, interior 5, Col. Tequisquiapán, CP 78250, San Luis Potosí, S.L.P. México. Phone: +4448292790.E-mail address: [email protected] (R. Carmona-Sánchez).

2255-534X/© 2016 Asociacion Mexicana de Gastroenterologıa. Published by Masson Doyma Mexico S.A. This is an open access article underthe CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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150 R. Carmona-Sánchez et al.

s Gastroenterology and Gastrointestinal Endoscopy Service of the Hospital Central Sur de Alta Especialidad de PetróleosMexicanos, Gastrointestinal Physiology Clinic Administration of the Hospital Ángeles Metropolitano, Mexico City, Mexicot Gastroenterology and GI Endoscopy Administration at the Health Sciences Research and Teaching Center, Centro de Investigacióny Docencia en Ciencias de la Salud, Universidad Autónoma de Sinaloa, Hospital Civil de Culiacán, Culiacán, Sinaloa, Mexicou Department of Gastroenterology of the INCMNSZ, Mexico City, Mexicov Department of Teaching, Hospital de Alta Especialidad de Veracruz-SESVER, Veracruz, Mexico, Gastroenterology and SurgicalPathology Chair of the UV Faculty, School of Medicine campus Veracruz, Veracruz, Mexicow Doctorate Program in Medical Sciences, Postgraduate Unit, UNAM, Department of Gastroenterology INCMNSZ, Mexico City,Mexico

Received 17 June 2015; accepted 22 January 2016Available online 28 April 2016

KEYWORDSIrritable bowelsyndrome;Consensus;Review;Diagnosis;Treatment;Mexico

AbstractBackground: Since the publication in 2009 of the Guidelines on the Diagnosis and Treatment ofIrritable Bowel Syndrome of the Asociación Mexicana de Gastroenterología (2009 Guidelines),there have been significant advances in our knowledge of the epidemiology, pathophysiology,diagnosis, and treatment of this disease.Aims: To present a consensus review of the most current knowledge of IBS, updating the 2009Guidelines by incorporating new internationally published scientific evidence, with a specialinterest in Mexican studies.Methods: The PubMed literature from January 2009 to March 2015 was reviewed and comple-mented through a manual search. Articles in English and Spanish were included and preferencewas given to consensuses, guidelines, systematic reviews, and meta-analyses. Statementsreferring to the different aspects of the disease were formulated and voted upon by 24 gastroen-terologists employing the Delphi method. Once a consensus on each statement was reached,the quality of evidence and strength of recommendation were determined through the GRADEsystem.Results: Forty-eight statements were formulated, updating the information on IBS and addingthe complementary data that did not appear in the 2009 Guidelines regarding the importanceof exercise and diet, diagnostic strategies, and current therapy alternatives that were analyzedwith more stringent scientific vigor or that emerged within the last 5 years.Conclusions: We present herein a consensus review of the most relevant advances in the studyof IBS, updating and complementing the 2009 Guidelines. Several studies conducted in Mexicowere included.© 2016 Asociacion Mexicana de Gastroenterologıa. Published by Masson Doyma Mexico S.A. Thisis an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PALABRAS CLAVESíndrome de intestinoirritable;Consenso;Revisión;Diagnóstico;Tratamiento;México

Consenso mexicano sobre el síndrome de intestino irritable

ResumenAntecedentes: Desde la publicación de las guías de diagnóstico y tratamiento del síndrome delintestino irritable (SII) de la Asociación Mexicana de Gastroenterología en el 2009 (Guías 2009)se han producido avances significativos en el conocimiento de la epidemiología, fisiopatogenia,diagnóstico y tratamiento de esta enfermedad.Objetivos: Presentar una revisión consensuada del estado actual de los conocimientos sobre elSII que actualicen las Guías 2009, integrando las nuevas evidencias científicas publicadas a nivelmundial con énfasis en estudios realizados en México.Métodos: Se realizó una revisión de la bibliografía en PubMed de enero del 2009 a marzo del2015, que se complementó en forma manual. Se incluyeron todas las publicaciones en inglésy espanol, con preferencia por los consensos, guías, revisiones sistemáticas y metaanálisis. Segeneraron enunciados en los diferentes aspectos de la enfermedad que fueron votados por 24gastroenterólogos con el método Delphi. Una vez consensuado cada enunciado, se calificó elnivel de la evidencia y se otorgó la fuerza de la recomendación utilizando el sistema GRADE.











The Mexican consensus on irritable bowel syndrome 151

Resultados: Se generaron 48 enunciados que actualizaron la información sobre el SII y comple-mentaron la información que no había sido incluida en las Guías 2009 con referencia al papel delejercicio y la dieta, las estrategias diagnósticas, así como alternativas de tratamiento existentesque fueron evaluadas con mayor rigor o que surgieron en los 5 últimos anos.Conclusiones: Presentamos una revisión consensuada de los progresos más relevantes en el SII,que actualizan y complementan las Guías 2009. Se incluyen diversos estudios realizados enMéxico.© 2016 Asociacion Mexicana de Gastroenterologıa. Publicado por Masson Doyma Mexico S.A.Este es un artıculo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Introduction

Irritable bowel syndrome (IBS) is the most frequently diag-nosed gastrointestinal disorder in clinical practice.1 It isa functional disorder characterized by abdominal pain ordiscomfort that is associated with bowel habit alterationsand other gastrointestinal symptoms, such as bloating anda sensation of abdominal inflammation, incomplete bowelmovement, urgency, straining, and tenesmus.2---4 It is a clin-ical condition whose symptoms cannot be explained byorganic, metabolic, or underlying infectious causes.

In 2009 the Asociación Mexicana de Gastroenterologíabrought together a group of gastroenterologists that for-mulated the Guidelines on the Diagnosis and Treatment ofIBS.2---4 One year later, under the auspices of the same Asso-ciation, a broad review of the pharmacologic treatment ofIBS was published.5 Since then, there have been significantadvances in different aspects of the disease, including epi-demiology, pathophysiology, the role of the microbiota anddiet, the use of probiotics, novelties in the use of diag-nostic biomarkers, quality studies on the effectiveness ofcombined drugs and medications, as well as new drugs,some of which have recently arrived in Mexico. Innovativethemes have also emerged in the international literature,such as fecal microbiota transplantation. All these advancesjustify the elaboration of a document complementing the2009 Diagnosis and Treatment Guidelines. In January of2015, the Asociación Mexicana de Gastroenterología sum-moned a group of experts to carry out a review of theadvances made in relation to different aspects of IBS,evaluate the evidence, reach a quality consensus, and for-mulate statements for understanding the current status ofIBS.

The aim of the 2015 Mexican Consensus on IBS is topresent a consensus review of the current status of IBS tobring the 2009 Guidelines on the Diagnosis and Treatment ofIBS up-to-date by incorporating the new internationally pub-lished scientific evidence, with a special interest in studiesconducted in Mexico.

Methods

The Delphi method was used to prepare this consensus.6

The consensus coordinators found the published articlesto be reviewed through the search words ‘‘irritable

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owel syndrome’’ and ‘‘IBS’’ combined with the fol-owing terms: ‘‘diagnosis’’ ‘‘diet’’, ‘‘epidemiology’’,‘fecal transplant’’, ‘‘FODMAP’’, ‘‘gluten’’, ‘‘guidelines’’,‘hypnotherapy’’, ‘‘hypnosis’’, ‘‘incidence’’, ‘‘meta-nalysis’’, ‘‘microbiota’’, ‘‘prevalence’’, ‘‘probiotic’’,‘psychological’’, ‘‘review, ‘‘symptoms’’, ‘‘therapy’’,‘management’’ and ‘‘treatment’’, as well as the equiv-lent terms in Spanish. The search was conducted usinghe PubMed database and included articles in both Englishnd Spanish that were published within the time framef January 2009 to March 2015. Preference was given toonsensuses, guidelines, systematic reviews, and meta-nalyses, but was not limited to these types of articles.omplementary online and manual searches were alsoarried out using the archives of the Revista de Gastroen-erología de México and any of the publications that theoordinators felt were relevant up to March 2015.

After the review of each theme, a series of state-ents were formulated that covered the main aspects of

he disease. These were then sent to all the 2015 IBSonsensus panel members for the first anonymous votingrocess carried out electronically, voting ‘‘in agreement’’r ‘‘in disagreement’’ for each statement. When agree-ent equal to or greater than 75% was reached, it wasetermined that the statement could remain unchanged,assing to the next round of voting. Statements with dis-greement of 75% or higher were eliminated from theonsensus. The statements with less than 75% agreementr disagreement were restated by the coordinator of eachorking group, taking into account the comments of thearticipants. Three rounds of voting were carried outy email and an in-person vote was held at Boca delío (Veracruz), in March 2015. In the final voting pro-ess, the votes were cast using a 6-point scale: A) inomplete agreement; B) in agreement, with minor reser-ations; C) in agreement, with major reservations; D) inisagreement, with major reservations; E) in disagreement,ith minor reservations; or F) in complete disagree-ent. In the present review, consensus was consideredhen 67% of the participants or more were in agreement

A, B, or C).Once the final consensus statements were determined,

he coordinators established the level of evidence that sup-orted each statement and a recommendation grade when
ppropriate, using the Grading of Recommendations, Assess-ent, Development and Evaluation (GRADE) system.7 This
ystem came about through an international initiative toptimize the evaluation of quality of evidence and the











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Table 1 GRADE system: Classification of the quality of evi-dence and the strength of recommendation.

Quality of evidence Code

High AModerate BLow CVery low D

Strength of recommendation Code

Strong, in favor of the intervention 1Weak, in favor of the intervention 2Weak, against the intervention 2Strong, against the intervention 1

Modified from the Onate-Ocana et al.8 and Sanabria et al.9 ref-

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rading of strength of recommendation, in an effort to over-ome the limitations of previous systems. In the GRADEystem, the quality of evidence is not rated solely on studyesign or methodology, but in relation to a clearly poseduestion about a clearly formulated outcome measure.8

ven though, in general, the best evidence comes fromontrolled clinical trials and their meta-analyses, as wells from high quality cohort studies, whereas lower qual-ty evidence comes from case-control studies, case series,ross-sectional surveys, and expert opinions, the GRADE sys-em classifies the quality of evidence based on the designsed to answer the specific question that has been posed ariori.8,9 In such a manner, the study methodology requireds different, depending on the question, and its quality isudged according to the response to that question. Thus theuality of evidence can be high, moderate, low, or very low.t is defined as ‘‘high’’, when more research will not mod-fy our confidence in the estimated effect, ‘‘moderate’’,hen more research may modify our confidence in the esti-ated effect, ‘‘low’’ when more research will most likely

mportantly affect our confidence in the estimated effect,nd ‘‘very low’’ when any estimated effect is highly uncer-ain. In addition, the GRADE system establishes strengthf recommendation as strong or weak, for or against thentervention or statement. It employs a code for the qual-ty of evidence, using capital letters followed by a numbero indicate the strength of recommendation for or againsthe intervention or statement.8,9 Table 1 shows the GRADEystem codes.

The consensus statements by section are listed below:

efinition, pathophysiology, and epidemiologyf irritable bowel syndrome in adults

rritable bowel syndrome is a functional disorderharacterized by abdominal pain or discomforthat is associated with changes in bowel movement
requency or appearance
BS is defined as a chronic and recurring functional disor-er that is characterized by abdominal pain or discomfort,

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R. Carmona-Sánchez et al.

ssociated with changes in bowel movement frequency orppearance.2---4,10 It is considered one of the most commonunctional disorders, is presently incurable, and can affectatient quality of life to varying degrees.11

GRADE level of evidence and strength of recommenda-ion: C1, strong, in favor of the statement

Level of agreement: In complete agreement 92%.In agreement with minor reservations: 8%.

BS incidence in Mexico is unknown and there areo reports on this subject

ven though several good quality studies have been con-ucted in Mexico on IBS etiology, none of them establisheshe number of new cases of the disease having emergedt a given period of time, and therefore the incidencef this functional disorder in our country is presentlynknown.12---15GRADE level of evidence and strength of rec-mmendation: D1, strong, in favor of the statement.

Level of agreement: In complete agreement 100%

he reported prevalence of IBS in Mexico variesrom 4.4 to 35%

his wide variation in the epidemiologic results in Mex-co is largely explained by the criteria used to define theresence of IBS. Some studies have pointed out that theome III questionnaires appear to have low sensitivity inhe community for identifying IBS cases.15---17 In accordanceith this, Amieva-Balmori et al.15 reported a prevalencef 4.4% using the Rome III criteria, whereas prevalencesf up to 35% have been obtained in studies using theome II criteria.12---14GRADE level of evidence and strengthf recommendation: C1, strong, in favor of the state-ent.Level of agreement: In complete agreement 96%.In agreement with minor reservations: 4%.

here is a higher IBS prevalence in women,egardless of the diagnostic criteria used

s in the rest of the world, IBS in Mexico is more preva-ent in women, regardless of the subtype. This fact has beenonsistently reported in epidemiologic studies conducted inur country.12---15GRADE level of evidence and strength ofecommendation: B1, strong, in favor of the statement.


BS has a more negative impact on quality of life inoung adults than in older adults

ifferent studies conducted on Mexican patients coincideith the fact that IBS negatively affects quality of life, wheneasured through different instruments.18---22 At least one

tudy conducted in the United States showed that youngdults with this functional disorder have worse quality ofife than older adults.23 This datum has not been reportedn national studies.

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The Mexican consensus on irritable bowel syndrome

GRADE level of evidence and strength of recommenda-tion: C1, strong, in favor of the statement.

Level of agreement: In complete agreement 75%.In agreement with minor reservations 24%.In agreement with major reservations 1%.

The most frequent IBS subtypes in Mexico arethose with a predominance of constipation and themixed subtype

Studies in Mexico have found that the most frequent subtypeof this disorder is the one in which there is a predominanceof constipation (IBS-C), followed by the alternate or mixedsubtype (IBS-M).12,13,15 Only one study has reported a higherfrequency in the diarrhea-prominent subtype (IBS-D) than inthe IBS-M subtype, but it still found the greatest frequencyin IBS-C.14

GRADE level of evidence and strength of recommenda-tion: B1, strong, in favor of the statement.

Level of agreement: In complete agreement 96%.In agreement with minor reservations 4%.

IBS pathophysiology is multifactorial and variesamong the affected individuals. At present, nouniversal factor has been established

Numerous and different mechanisms intervene in IBS patho-physiology, among which are motor disorders, visceralhypersensitivity, gut microbiota alterations or dysbio-sis, post-infectious intestinal dysfunction, small intestinalbacterial overgrowth, low-grade inflammation, immune reg-ulation alterations, food intolerance and hypersensitivity,bile acid malabsorption, and psychosocial factors, but upto the present, no common factor for all cases has beenestablished. 24---27

GRADE level of evidence and strength of recommenda-tion: C1, strong, in favor of the statement.

Level of agreement: In complete agreement 100%.

The ingestion of lactose and other fermentableoligosaccharides, disaccharides, monosaccharides,and polyols (FODMAPs) may be associated withgreater production of gas, visceralhypersensitivity, and perception of bloating,especially in the subgroup of patients withdiarrhea-predominant IBS

Some foods have been described that possibly aggravateIBS symptoms. A Mexican study showed that intoler-ance to fructose may be responsible for gastrointestinalsymptoms in at least half of the patients with IBS, espe-cially in those with IBS-D.28 Other authors report thatlactose intolerance is more prevalent in patients withIBS-D than in healthy subjects, 29 and that they alsohave greater mucosal immunity activation and greatervisceral hypersensitivity after lactose ingestion.29,30 One
Mexican study found statistically significant improvementin 3 evaluated symptoms (abdominal pain, bloating, andflatulence) in the comparison of pre-low-FODMAP and post-low-FODMAP diet values.31 However, that study had the
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imitation of not having a control group that includedhe average or regular diet of the study population;nother limitation was that both diets did not havehe same nutritional content.32 Those findings concurredith other international studies reporting that FODMAPsppear to induce some symptoms in patients with IBShrough increased luminal distension and if there is visceralypersensitivity.33

GRADE level of evidence and strength of recommenda-ion: C1, strong, in favor of the statement.


he prevalence of small intestinal bacterialvergrowth in patients with IBS is quite variable,epending on the test and methodology employed

he presence of small intestinal bacterial growth has beenointed out, based on breath tests measuring the hydro-en in the exhaled breath of IBS patients. The reportedrevalence is varied and depends on the type of test andethodology used: 28 to 84% with a lactulose breath test,

to 31% with a glucose breath test, and a lower prevalence2 to 6%) when intestinal fluid cultures are used.27


Level of agreement: In complete agreement 88%.In agreement with minor reservations 8%.In disagreement with major reservations 4%.

he incidence of post-infectious IBS is from 9 to0%. The reported prevalence of post-infectious

BS varies from 3 to 17% and decreases in the yearsollowing the gastrointestinal infection

ost-infectious IBS (PI-IBS) incidence has been reported at0% (range 4-36%) and prevalence varies from 3 to 17%nd decreases in the years following the gastrointestinalnfection.24,34,35 A recently published systematic review andeta-analysis that included 6 studies determined that the

verall incidence of PI-IBS was 5.4% in patients that had pre-ented with traveler’s diarrhea compared with 1.4% of theontrol subjects, and the overall relative risk was 3.35 (95%I: 2.22-5.05).36



n relation to PI-IBS, bacterial etiology is the bestocumented, but viral and parasitic causes alsoppear to be risk factors for developing PI-IBS

I-IBS has been studied in numerous cohort studies that
onducted follow-up analyses of epidemic outbreaks ofacterial gastroenteritis and therefore this etiology is theest documented. Studies on acute gastroenteritis due toiruses and parasites have also been published, but these

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tudies are much fewer and include a small number ofatients.27



BS has been associated with different intestinalnd extraintestinal symptoms and syndromes

ome community-based surveys have confirmed that IBSrequently overlaps with functional dyspepsia and with gas-roesophageal reflux symptoms, especially in nonerosiveeflux disease. IBS has also been associated with a varietyf psychological disorders, but the evidence of an actualssociation is less solid. It has been suggested that psy-hopathology be considered a cofactor that, if present,ill modify the response to the different IBS symptoms

n each individual.37 In a study conducted in Mexico Citytilizing the Rome II questionnaire, the researchers foundhat heartburn and other reflux symptoms were more fre-uent in patients with IBS than in controls, regardless ofheir body mass index.38 Another study also conducted inur country on patients with IBS showed differences inymptom association depending on the IBS subtype, usinghe Rome III questionnaire. Thus, the IBS-M subtype had aigher association with symptoms such as halitosis, vom-ting, and greater intensity early satiety, and IBS-C wasssociated with straining and tenesmus, whereas IBS-D wasssociated with urgent bowel movements and daytime orighttime fecal incontinence.39 Patients with inflammatoryowel disease (IBD) have also been reported to have areater frequency of symptoms consistent with IBS com-ared with controls (non-IBD subjects), even among patientshat appeared to be in remission. In addition, IBS symp-oms were more frequent in patients with Crohn’s diseasehan in those with ulcerative colitis (UC) and in those withctive disease.40 These findings are very similar to thosehat have been reported in patients with celiac diseaseCD).41



rritable bowel syndrome diagnosis in adults

ymptom-based diagnostic criteria enable positiveBS diagnosis to be made in those patients with nolarm symptoms or risk factors. Nevertheless,heir sensitivity and specificity is variable andome patients with organic disease have diagnosticBS criteria, demonstrating the need for their

odification in order to have greater diagnostic
ccuracy
here is clear evidence of the limitations of theome clinical criteria in diagnosing IBS. 42---45 Another

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ystematic review that included studies published over aroad period of time that evaluated the 3 versions of theome criteria, as well as the Manning criteria, found thathe latter had been more accurate and validated moreften, whereas the Rome III criteria had not been vali-ated or widely adopted in clinical research, up to theresent.42 Among patients evaluated with Rome III criteria,.3% were observed to have Crohn’s disease, 6.1% ulcer-tive colitis, and 2.3% cancer of the colon.45 Fifty-ninelinicians and researchers participating in an internationalurvey were asked to review the diagnostic criteria and7% stated that the Rome criteria did not adequatelyeflect IBS in their community or medical practice and0% stated that new multinational diagnostic criteria wereeeded.46

GRADE level of evidence and strength of recommenda-ion: B1, strong, in favor of the statement.


here is insufficient evidence for recommending atandard group of diagnostic tests in all patientseeting the symptom-based IBS criteria

ue to the fact that IBS is a frequent illness in the gen-ral population, its diagnostic evaluation is costly. Sometudies systematically carrying out tests on subjects withBS clinical criteria have shown an increased frequency ofbnormal results, but these findings do not modify the diag-osis or clinical behavior of the disease.47---49 A systematiceview of the theme determined that the existing evidences insufficient for recommending the routine use of a bat-ery of diagnostic tests in patients meeting the IBS clinicalriteria.50

GRADE level of evidence and strength of recommenda-ion: C1, strong, against the intervention.


t is recommendable to carry out complementaryiagnostic tests in all patients that meet theymptom-based IBS clinical criteria and thatresent with alarm symptoms, refractoryymptoms, or risk factors. Diagnostic test selectionhould be carried out individually, considering thelinical characteristics of IBS and the pre-testikelihood of organic diseases (e.g. celiac disease,nflammatory bowel disease, neoplasias, etc.)

hen patients presenting with IBS clinical criteria are firsteen, a systematic search must be performed to rule outed flags, such as nocturnal symptoms, visible blood intool, anemia, and significant weight loss; physical exam-nation abnormalities, such as palpable masses; and riskactors, such as a family history of colorectal cancer, theecent appearance of symptoms, onset after 50 years ofge, male sex, and recent antibiotic use.51 The positive
redictive value of alarm symptoms is known to be lownd 11-15 patients with these ‘‘red flags’’ need to betudied in order to detect one patient with colorectalancer, inflammatory bowel disease, or malabsorption.52 A

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systematic review and meta-analysis that included 15 stud-ies and over 19,000 patients showed that alarm symptomshad low sensitivity and specificity for diagnosing colorectalcancer.53 Therefore, it is indispensible that test selectionbe done individually, taking into account the characteris-tics and risk factors of each patient, as well as the localprevalence of the organic diseases that are being lookedfor.10,50,54 The evidence supporting this statement comesmainly from case series, case-control studies, and clinicalguidelines.

GRADE level of evidence and strength of recommenda-tion: C1, strong, in favor of the intervention.


It is recommendable to study celiac disease inpatients with clinical criteria for IBS with diarrheaand in those with IBS with refractory symptoms

In some cases, IBS and CD can have a similar clinical pre-sentation. IBS symptom prevalence in patients with CD is38% and the risk for presenting with such symptoms is threetimes as great in those patients that do not adhere to agluten-free diet.41 CD prevalence in patients meeting theIBS clinical criteria has been estimated to be 10 timeshigher than in the general public.50 However, a detailedanalysis of the bowel habit of these patients is important,because the prevalence of antibodies associated with CDin IBS patients without constipation has been found to besimilar to that of asymptomatic controls.55 For a long time,CD was considered a rare condition in Mexico, but severalstudies analyzing the prevalence of antibodies associatedwith CD in different settings (university population, type 1diabetes mellitus patients, blood donors) suggest that theprevalence of this disease in our country is comparable tothat found in other populations.56,57 A study conducted onMexican patients with IBS (Rome III) found they had a preva-lence of positive serology for CD that was twice as high asthat of healthy controls and that the risk for presenting withCD confirmed by duodenal biopsy was 1.5 times higher.58

They also found that the prevalence of positive antibodiesrelated to CD was even higher in the patients with IBS-D.Obviously, more and better studies are required in order toknow the real CD prevalence in the general Mexican pop-ulation and to distinguish our risk groups, but given theevidence we have at the present time, we recommend CDscreening in patients with IBS clinical criteria, especially inthose presenting with a predominance of diarrhea that aretreatment-refractory.

GRADE level of evidence and strength of recommenda-
tion: C1, strong, in favor of the intervention.
Level of agreement: In complete agreement 92%.In agreement with minor reservations: 4%.In complete disagreement: 4%.

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olonoscopy should be performed in patients withBS criteria that have risk factors for colon cancer,ymptom onset at late stages of life, changes inowel habit pattern, presence of blood in stool,nd in all patients that do not respond toreatment. Colon biopsy should be performed inatients with refractory IBS-D, even in the absencef lesions, to intentionally search for microscopicolitis

systematic search should be carried out in all patientsith IBS clinical criteria that present with alarm symptoms,

uch as nocturnal symptoms, visible blood in stool, anemia,nd significant weight loss; physical examination abnormal-ties, such as palpable masses; and risk factors, such as aamily history of colorectal cancer, recently appearing symp-oms, onset after 50 years of age, male sex, and recentntibiotic use. 51 There is evidence of greater detectionf organic disease in patients presenting with IBS clinicalriteria with alarm symptoms and in patients with IBS-Dr IBS-M criteria.59 The American College of Gastroenter-logy proposes the performance of screening tests for theetection of colorectal cancer in patients above 50 years ofge.60 Some authors have suggested the intentional searchor microscopic colitis in subjects with IBS-D criteria.61,62 Ateast 2 studies conducted in Mexico have found an increasedrevalence of microscopic colitis in patients fitting the clin-cal criteria of IBS and IBS-D, in whom colon biopsies wereystematically taken.63,64 It is important that the search foricroscopic colitis in these patients be carried out throughiopsies of all the segments of the colon, even in the pres-nce of normal mucosa and when there is no evidence ofesions.

GRADE level of evidence and strength of recommenda-ion: B1, strong, in favor of the intervention.


maging studies (barium enema, ultrasound,omputerized tomography, magnetic resonance,tc.) are of little use in patients with IBS symptomsn the absence of alarm symptoms or comorbidities

adiologic studies are not necessary in patients that do notresent with alarm symptoms, but they should be consid-red when these symptoms are present. The choice of studyhould be individualized and determined by the predominantymptoms. Routine abdominal ultrasound in IBS patients isnnecessary.65 A recent review determined that there is aurprising lack of information on the usefulness of imaging
tudies in IBS.66


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here is insufficient evidence for recommendinghe routine use of tests for detecting smallntestinal bacterial overgrowth in patients with IBS

s mentioned beforehand, a recent systematic review foundhat the presence of small intestinal bacterial overgrowth inBS patients varies widely and the methodology for makinghis diagnosis has not been standardized.27 In addition, its not possible to establish with certainty the cause-and-ffect relation between symptoms and the presence of smallntestinal bacterial overgrowth.67



here is insufficient evidence for recommendinghe routine use of tests for detecting carbohydratentolerance in all IBS patients

he same as with small intestinal bacterial overgrowth,he prevalence of intolerance to different carbohydratesn patients with IBS varies widely and the methodologyor making this diagnosis has not been standardized,28,68

or is it possible to establish with certainty the cause-nd-effect relation between symptoms and the presencef food intolerance.29,67 However, some experts state thathese tests could be useful in patients with refractory symp-oms for the purpose of carrying out a potentially beneficialietary intervention.67


Level of agreement: In complete agreement 96%.In agreement with major reservations: 4%.

he questionnaires for evaluating quality of liferovide a profile of state of health and can detectspects of the disease that require specialttention (e.g. physical function, emotional role,ental health). Symptom intensity is correlatedith a negative impact on quality of life

ymptom severity and intensity has a consistently negativeffect on the quality of life of these patients. Quality ofife is an important measure in the integrated managementf the patient with IBS. Because it is a functional disorderith no organic marker, clinical decisions are dependent onsking the patient to evaluate and communicate, throughifferent instruments, how he or she perceives his or hertate of health.69,70GRADE level of evidence and strength ofecommendation: B1, strong, against the intervention.


t present, there are no biomarkers for
stablishing IBS diagnosis
biomarker is an objective biologic indicator of normalunction, pathogenic processes, or pharmacologic responses

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o a therapeutic intervention. The potential usefulness ofiomarkers in IBS has been studied in 3 respects: in the dif-erential diagnosis through the detection of organic diseaseinflammatory, infectious, or neoplastic) manifested as non-pecific clinical data that substitute ‘‘limited study’’; in theiagnosis made a priori through the detection of genetic pat-erns, molecular dysfunction markers, and histologic dataf intestinal permeability or low-grade infection that areeen in IBS; and as response predicters.71 Fecal biomarkersf inflammation, such as calprotectin, lactoferrin, protein100A12, polymorphonuclear elastase, myeloperoxidase, M2yruvate kinase, granins, defensins, and matrix metallopro-einases, among others, have been analyzed for establishinghe differential diagnosis of IBS with inflammatory bowelisease, but not ruling out other diagnostic possibilities.71---73

ecently, the detection of anti-CdtB and anti-vinculin serumntibodies has been evaluated and validated for the diag-osis made a priori of patients with IBS-D with apparentlyood results.74 Unfortunately, these antibodies are notetectable in all patients with IBS-D and their prevalencen IBS patients is unknown. Antibody expression dependsn the immunologic condition of the host and they havenly been validated in healthy controls and in patientsith CD and inflammatory bowel disease, without taking

nto account other possibilities, such as microscopic col-tis, parasitosis, or neoplasias. Only one determined ageange was included and the results cannot be extrapo-ated to all populations. Even though there have been greatdvances in the development of biomarkers for the diag-osis of IBS in a subgroup of patients (e.g. IBS-D) and its clear that in the future costs could be reduced in theare of these patients, contributing to the development ofrugs, some experts believe that they are not yet readyor practical application.75,76GRADE level of evidence andtrength of recommendation: B1, strong, against the inter-ention.


rritable bowel syndrome treatment in adults

BS treatment should be directed at the mostothersome symptom or at the pathophysiologicechanisms of the disease

iven that there is no single medication for treating allhe patients with IBS, two types of strategies have beenecommended: directing treatment at the symptom thats the most bothersome for the patient (pain, bloating,onstipation, diarrhea) or at the pathophysiologic mech-nisms involved in the production of symptoms, such asisceral hypersensitivity, motor alterations, dysbiosis, smallntestinal bacterial overgrowth, fluid homeostasis, andeuroplasticity.4,77---79GRADE level of evidence and strength
f recommendation: C2, weak, in favor of the interven-ion.

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An adequate doctor-patient relationship haspositive effects on overall improvement, symptomimprovement, symptom severity grade, and qualityof life of the patients with IBS. In addition, itreduces the number of medical consultations andincreases patient satisfaction. The doctor-patientrelationship is the most robust component of theplacebo effect

The approach to IBS centered on the patient and the effec-tive communication between the physician and patientis associated with therapeutic benefit. Asking open ques-tions that allow the patient to express his or her needs,to be actively listened to, and to be shown empathyto strengthen the doctor-patient relationship are use-ful strategies.80 Calming the patient’s fears regarding hisor her disease during the initial medical visit has beendemonstrated to significantly reduce the self-perception ofdisability.81 An attentive, warm, and confidence-inspiringdoctor-patient relationship has been shown to have amore intense positive effect on the symptoms of thepatients.82

GRADE level of evidence and strength of recommenda-tion: C2, weak, in favor of the intervention.


Two controlled studies showed that exercise(20-60 min, 3-5 times per week) producesimprovement in IBS symptom grade, inIBS-associated quality of life, and that it reducesthe risk for symptom worsening

Even though the controlled studies are few, they are goodquality and have demonstrated improvement in IBS symp-tom severity compared with controls. Exercise was capableof preventing symptom progression in the patients.83 Thisimprovement persisted over time, given that the patientswith an exercise plan maintained their symptom grade andquality of life improvement after 5.2 years.84

GRADE level of evidence and strength of recommenda-tion: C2, weak, in favor of the intervention.

Level of agreement: In complete agreement 88%.In agreement with minor reservations: 8%.In agreement with major reservations: 4%.

Soluble fiber ingestion is beneficial in IBS. Braningestion does not improve IBS symptoms

Dietary fiber supplementation has a long history in the treat-ment of gastrointestinal disorders. However, caution hasbeen expressed in regard to its use, due to the possibil-ity that fiber can exacerbate some symptoms in certainpatients.85,86 The recent meta-analysis of randomized andcontrolled studies by Moayyedi et al.87 showed the benefitof fiber in IBS symptoms, but only in the case of soluble fiberand not bran. It should be noted that no significant adverse
effects were demonstrated with the use of bran. On theother hand, no beneficial effects of linseed in relation toIBS have been detected, but there is only one quality studyon this topic.87
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GRADE level of evidence and strength of recommenda-ion:

For soluble fiber A2, strong, in favor of the intervention.For bran B2, weak, against the intervention.Level of agreement: In complete agreement 96%.In agreement with minor reservations: 4%.

low-FODMAP diet can improve overall symptoms,he perception of bloating, abdominal pain, andowel habit in some patients with IBS

he fermentable oligosaccharides, disaccharides, monosac-harides, and polyols are the so-called FODMAPs and theynclude fructose, lactose, fructans, and fructooligosaccha-ides present in common foods such as fruits, legumes,nd wheat. After several non-controlled studies on dietaryODMAP content and its effect on IBS symptoms,88 Halmost al., 89 in a randomized and blind study, demonstratedmprovement in IBS symptom grade, bloating, pain, and flat-lence with the use of a low-FODMAP diet. A recent studyonducted in Mexico showed significant beneficial results inymptoms of patients on a low-FODMAP diet. 31

GRADE level of evidence and strength of recommenda-ion: B1, weak, in favor of the intervention.


low-FODMAP diet reduces symptoms in IBSatients with a self-reported sensitivity to glutennd no celiac disease, regardless of its glutenontent

any patients today associate IBS symptoms with thengestion of products that contain gluten, suspendingheir consumption and reporting symptom improvement.his has been named non-celiac gluten sensitivity. Sometudies have shown that the reintroduction of gluten inatients with non-celiac gluten sensitivity that are wellontrolled with a gluten-free diet causes a reappearancef symptoms that includes abdominal pain and fatigue.90

iesiekierski et al.91 put patients with IBS and this sensi-ivity on a low-FODMAP diet and in a blind manner gavehem different doses of gluten or placebo. The effectf gluten on symptoms or fatigue could not be demon-trated.

GRADE level of evidence and strength of recommenda-ion: C1, weak, in favor of the intervention.


here is indirect evidence that the use of bile acidequestrants, such as cholestyramine, available inexico, produces symptom improvement in IBSith diarrhea

t has been documented that some patients with IBS-D canave bile acid malabsorption.92---95 A systematic review thatncluded 1,223 patients with IBS-D that had a TauroH-23-(Se)elena-25-homocholic acid (SeHCAT) test for diagnosing bile

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cid diarrhea found that 26, 32, and 10% had mild, moder-te, and severe bile acid malabsorption, respectively.92 Thisroup of patients may benefit from bile acid sequestrants,uch as cholestyramine (available in Mexico), colestipol,olesevelam, aluminum hydroxide, or obeticholic acid.94,95

owever, the evidence is indirect,96 given that there are notudies that specifically evaluate the use of cholestyraminen IBS-D.



ntispasmodic drugs are more efficacious thanlacebo for abdominal pain improvement, overall

mprovement, and symptom scores in IBS

ntispasmodics are a group of medications that competeith acetylcholine in the parasympathetic postganglionicerve terminals or block the calcium channels, inhibi-ing smooth muscle contraction.97 Several subgroups ofntispasmodics have been described5: 1) direct relaxinggents (mebeverine, trimebutine); 2) scopolamine deriva-ives (butylhyoscine, levsin, hyoscyamine, cimetropium);) ammonium derivatives (that also block calcium chan-els, such as otilonium bromide and pinaverium bromide);nd 4) calcium antagonists (alverine citrate, fenoverine,ociverine, pirenzepine, peppermint). A meta-analysis thatncluded 29 studies and a total of 2,333 patients com-ared antispasmodics with placebo and reported thatntispasmodics as a group were superior in abdominal painmprovement (58% of the patients treated with antispas-odics improved, compared with 46% of the control group,

< 0.001), overall improvement (57% of the patients treatedith antispasmodics improved, compared with 39% that

eceived placebo, p < 0.001), and in symptom score (37%f those treated with antispasmodics improved, comparedith 22% with placebo, p < 0.01), with a number necessary to

reat (NNT) of 7, 5, and 3, respectively.98 Another system-tic review and meta-analysis99 with 23 studies and 2,585atients showed similar findings. Some sub-analyses haveemonstrated improvement in particular outcomes withpecific antispasmodics: otilonium bromide (reduced defe-ation alterations and overall improvement) and pinaveriumromide (reduced defecation discomfort).100 Other studiesave shown improvement with an antispasmodic (mebev-rine) only in non-controlled studies with placebo.99,100

eppermint oil is a drug that has been considered alternativeherapy. However, it has calcium antagonist properties101

nd has been shown to be superior to placebo in aecent systematic review and meta-analysis in pain improve-ent and overall symptom improvement.102 Nevertheless,

he majority of the studies have observed short-termmprovement (6-8 weeks) and the presence of side effectsncreases with use. There is limited evidence in relationo long-term benefit in the main outcome measures, ateast in one study that used otilonium bromide for 15
eeks.103
GRADE level of evidence and strength of recommenda-ion: A1, strong, in favor of the intervention.


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he combination of simethicone/dimethicone withntispasmodics appears to improve abdominal painnd distension

imethicone/simethicone reduces the surface tension ofas bubbles, causing their coalescence. The combination ofimethicone with certain antispasmodics has been shown toe effective, particularly in the improvement of abdominalain and distension. In the meta-analysis by Martínez-ázquez, this same combination was superior to placebo

n overall symptom improvement.99 The combination ofinaverium bromide with dimethicone and alverine withimethicone has also been superior to placebo in themprovement of abdominal distension.99,104,105 The combi-ation of trimebutine/simethicone has not been specificallyvaluated and so there is no evidence for recommending itsse.



-HT3 receptor antagonists, such as alosetron andndansetron, improve the consistency, frequency,nd urgency of bowel movements in IBS withiarrhea. Alosetron is not available in Mexico and

ts use is restricted due to serious side effects

edications that act on the serotonin or 5-ydroxytriptamine (5-HT) receptors owe their effecto stimulation or antagonsim. The 5-HT3 receptor antago-ists attenuate bowel transit and increase fluid absorption,hus improving IBS-D symptoms. A systematic review andeta-analysis that included 11 studies and 7,216 patients

valuated the efficacy of this group of medications.106

losetron proved to be superior to placebo (8 studies, = 4,987), with a NNT of 7 (overall improvement) and 8symptom persistence), but its use is restricted due toerious side effects (number needed to harm = 10) thatnclude severe constipation and ischemic colitis, and its not available in Mexico.101 In that review, cilansetronlso showed improvement over placebo in overall symp-om reduction (3 studies, n = 2,229), with a NNT of 6nd practically no side effects, but it is not availablen Mexico either.106 Ondansetron, which is available inexico, is another 5-HT3 antagonist that has been usedainly as an antiemetic, but there is evidence of its

sefulness in IBS-D.107 A crossover and placebo-controlledtudy that was conducted for 5 weeks in 120 patients withBS-D concluded that ondansetron, titrated to response,mproved the consistency (p < 0.001), frequency (p = 0.02),nd urgency of bowel movements (p < 0.001), in additiono improving bloating (p < 0.001) in those patients withBS-D.106

ion: B1, strong, in favor of the intervention.

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GRADE level of evidence and strength of recommenda-tion: A1, strong, in favor of the intervention.



Certain 5-HT4 receptor agonists can improvesymptoms in IBS-C. Tegaserod has been shown tobe effective, but it should not be used in subjectsabove 55 years of age or with other cardiovascularrisks

The 5-HT4 receptor agonists increase colon motility, as wellas the secretion of fluids and electrolytes, and thus canbe useful in IBS-C. Tegaserod has shown benefit in overallimprovement (NNT = 14), abdominal pain, and improvementin bowel habit (NNT = 20) in patients with IBS-C.108 In thesystematic review by Ford, tegaserod was associated withless symptom persistence compared with placebo, with aNNT of 10.106 A sub-analysis showed a greater effect in men(p = 0.003). The frequency of side effects, such as diarrhea,had a number necessary to harm of 20. However, tegaserodwas taken off most of the international markets in 2007,due to a statistically higher frequency of adverse cardiovas-cular effects, such as acute myocardial infarction, unstableangina pectoris, cerebrovascular disease, and sudden death(0.11 vs 0.01%). The hypothetical interaction mechanism isat the 5-HT1B/D receptor level in the coronary arterioles,although it was later demonstrated that tegaserod did nothave that type of agonism. It was reintroduced in the UnitedStates in July 2007 under a treatment investigational newdrug protocol for IBS-C and chronic idiopathic constipationin women under the age of 55 years that had no risk forcertain cardiovascular events. However, tegaserod was notapproved for later use due to the opinion of the Committeefor Medicinal Products for Human Use that the benefit wasnot superior to placebo and did not outweigh its risks.109

In Mexico, based on the recommendations of a group ofexperts from the Asociación Mexicana de Gastroenterología,the Federal Commission Against Health Risks restricted itsuse to patients under 55 years of age and with no cardio-vascular risk (e.g. hypercholesterolemia, arrhythmias, highblood pressure, or the use of other medications that canhave an effect on the QT segment of the electrocardio-gram). Two other 5-HT4 agonists available in Mexico areprucalopride and mosapride. Prucalopride has shown benefitin chronic idiopathic constipation, but has not been evalu-ated in IBS-C.110 There is little evidence of the usefulness ofmosapride in IBS, but a placebo-controlled pilot study with37 IBS-C patients showed a reduction in the pain thresh-old and rectal perception in response to the barostat testafter the administration of mosapride.111 Some drugs canhave a mixed 5-HT4 agonist and 5-HT3 antagonist effect,such as cisapride and renzapride. The former, similar totegaserod, was taken off the majority of markets due toa risk for arrhythmias associated with QT segment prolon-gation, but it is still available in Mexico. The latter is notavailable in Mexico and there is little evidence of benefit inIBS.106

GRADE level of evidence and strength of recommenda-tion: B1, strong, in favor of the intervention.


159

olyethylene glycol can be useful for managingonstipation in IBS, although it is not superior tolacebo in pain or distension management

olyethylene glycol (PEG) 3350 (or macrogol) is an osmoticaxative that has been used for the treatment of chroniconstipation in children and adults, including chronic idio-athic constipation. Numerous studies have confirmed itsfficacy and safety. There is less evidence in relation to itsse in IBS-C, but a recent study compared PEG 2250 pluslectrolytes vs placebo in a group of patients with IBS-Cn = 68 and n = 71, respectively). An increase in the num-er of spontaneous bowel movements (SBMs) was observedn the two groups from the beginning of treatment, butrom week 4 the PEG group had a statistically significantncrease in the number of SBMs, complete spontaneousowel movements, stool consistency, and straining sever-ty. Nevertheless, no improvement in the severity of painr abdominal distension was observed with respect tolacebo.112



inaclotide improves IBS-C symptoms, includinghe frequency of spontaneous bowel movements,omplete spontaneous bowel movements, stoolonsistency, straining severity, bloating, gas, andbdominal discomfort

inaclotide, available in Mexico, is a guanylate cyclase agonist that acts by inducing an increase in cGMP

evels, causing accelerated gastrointestinal transit, aug-ented intestinal secretion, and a decrease in visceral

ypersensitivity. Two pivotal studies evaluated linaclotidesefulness in the main symptoms of IBS-C. The so-calledtudy 31 was a double-blind, placebo-controlled analysisith crossover at 12 weeks, in which linaclotide signifi-antly improved IBS symptoms, including SBM and completeBM frequency (p < 0.0001), consistency, strain severity, andbdominal symptoms (subjective bloating, gas, and discom-ort) (p = 0.0003).113 The second study, called Study 302, hadhe same design and evaluated the same outcomes at 26eeks.114 The therapeutic gain over placebo was 17% and

ignificant improvement was observed in all the endpointsnd visual symptom scale and quality of life scale scores,ith a NNT of 5.1 (overall response), 7 (pain), and 4 (com-lete SBMs).114 Later systematic reviews have confirmedhese findings.115

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ubiprostone is beneficial in overall improvement,loating, pain, stool form, and frequency of bowelovements in patients with IBS-C, but it is

urrently unavailable in Mexico

ubiprostone is a drug that activates the type 2 chlorinehannels, increasing gastrointestinal secretion and motility.ven though there is greater experience in chronic idiopathiconstipation, its efficacy in IBS-C is supported by 3 studies.he first 2 show that the drug was superior to placebo inverall symptom improvement, pain, bloating, stool form,nd frequency of bowel movements after follow-up at 1 and

months.116 In the third study, the same cohort was treatedor 36 weeks and followed for 52 weeks and, again, lubipros-one was associated with a greater frequency of spontaneousowel movements and lower scores for pain and abdomi-al distension, compared with placebo.117 This drug is noturrently available in Mexico.



here is insufficient evidence for recommendinghe use of mesalazine in the treatment of IBS

esalazine (or mesalamine) is a topical salicylate with annknown action mechanism. It has been shown to modulateroinflammatory cytokine production, reduce NF-kappa-branscriptional activity and tumor necrosis factor activa-ion, and inhibit prostaglandin and leukotriene synthesis.118

he use of mesalazine may be associated with improve-ent in low-grade inflammation of the colonic mucosa and

hanges in the gut microbiota profile.119 However, thesenti-inflammatory changes have not resulted in clinicalmprovement in patients with IBS. A recent pilot studyhowed no significant changes compared with placebo inymptoms that included pain, bloating, or bowel habit, norn overall improvement or quality of life in patients withI-IBS.120

GRADE level of evidence and strength of recommenda-ion: C2, weak, against the intervention.


n general, antidepressants, including the tricyclicntidepressants and selective serotonin reuptakenhibitors, have been shown to be effective inverall improvement of IBS symptoms

ntidepressants have been evaluated for IBS treatmentue to their visceral analgesic properties and have beenhown to be useful mainly in the treatment of abdomi-al pain and overall symptom imporvement.121 In a recent
eta-analysis,98 antidepressants in general were superior tolacebo for abdominal pain improvement (p = 0.03, NNT = 5),verall improvement (p < 0.001, NNT = 4), and symptomcore (p = 0.001, NNT = 4). Two analyses by Ford, published
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n 2009 and 2014, confirmed the same findings.122,123 Thericyclic antidepressants (e.g. amitriptyline [available inexico], imipramine, desipramine), as well as the selective

erotonin reuptake inhibitors (e.g. sertraline, citalopram,aroxetine, fluoxetine [all available in Mexico]), have shownhis benefit: both groups are superior to placebo in over-ll symptom improvement, but the tricyclic antidepressantsre superior to the selective serotonin reuptake inhibitorsn pain improvement.98 Their benefit is obtained 4-6 weeksfter treatment and can be limited by side effects.121

he tricyclic antidepressants are associated with constipa-ion, somnolence, and dry mouth, whereas the selectiveerotonin reuptake inhibitors are associated with nauseand diarrhea, making antidepressant selection dependentn IBS subgroup, side effects, and patient tolerance.he selective norepinephrine reuptake inhibitors, such asuloxetine and venlafaxine, have been used for pain ineuropathy and fibromyalgia, but there are no studies inBS.124

GRADE level of evidence and strength of recommenda-ion: A1, strong, in favor of the intervention.


ifaximin produces overall improvement inon-constipation IBS, including abdominalistension and perception of bloating, as well as

oose/watery stool consistency, with no significantdverse effects

ue to the possible abnormalities in the gut microbiota inatients with IBS, treatment with poorly absorbable antibi-tics and luminal antibiotics has the potential to modulatehe bacterial composition of the gastrointestinal tract andlter the natural history of the disease in the short term.ifaximin is a broad-spectrum, synthetic, non-absorbablentibiotic that has been shown to be useful in small intesti-al bacterial overgrowth and has recently been evaluated inhe management of IBS without constipation. Two random-zed, double-blind, and placebo-controlled studies, calledARGET 1 and TARGET 2, analyzed a total of 1,260 patientshat were given 550 mg of rifaximin three times a dayor 2 weeks, with follow-up at 10 weeks.125,126 In bothtudies, rifaximin was significantly superior to placebo,n overall symptom improvement (p < 0.001), in the per-eption of bloating (p < 0.001), and in stool consistencymprovement, with a NNT of 10.2 and no significant adverseffects.125---127 In addition, approximately half of the patientsith IBS had a negative lactulose breath test after rifax-

min treatment, which was associated with a decrease in IBSymptom intensity.27 Effectiveness in patients that requireetreatment with rifaximin has been shown to be simi-ar to that of the first treatment, even in evaluations ofwo retreatments, and with a mean effect duration of 4onths.128

GRADE level of evidence and strength of recommenda-ion: A1, strong, for intervention.


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Some probiotics or their combinations have beenefficacious as IBS treatment in overall symptomimprovement, as well as in relief from abdominalpain and bloating. However, it is not known whichspecies or strains are the effective ones

Changes in the gut microbiota of patients with IBS havebeen described. The differences in the composition of themicrobiota are significant in patients with IBS comparedwith controls.129 From 23 randomized and controlled stud-ies with different probiotics compared with placebo, it isconcluded that probiotics significantly reduce the risk forsymptom persistence. Even though the meta-analyses sug-gest that probiotics have beneficial effects on the gradingof overall symptoms, as well as on abdominal pain, bloat-ing, and flatulence, we still do not know which species orindividual strains are the most beneficial.130

GRADE level of evidence and strength of recommenda-tion: B2, weak, in favor of the intervention.


There is insufficient evidence for recommendingthe use of prebiotics and synbiotics in IBS

The randomized and placebo-controlled studies for eval-uating the effectiveness of prebiotics and the studies onsynbiotics have heterogeneous results and therefore theirefficacy cannot be affirmed.130

GRADE level of evidence and strength of recommenda-tion: D2, strong, against the intervention.


Fecal microbiota transplantation in IBS has beeninvestigated in non-controlled studies with resultsshowing symptom improvement. The use of fecalmicrobiota transplantation in IBS should berestricted to research protocols

Fecal microbiota transplantation has progressed dramati-cally in the last few years, together with the developingknowledge of the gastrointestinal microbiota. Differenceshave been shown in the microbiota of individuals withIBS compared with healthy subjects. However, we do notknow if the administration of the fecal microbiota fromhealthy individuals can revert symptoms in the long term.131

Non-controlled open studies on the use of fecal micro-biota transplantation for IBS have shown cure or symptomimprovement in 52 to 69% of cases and thus have beenreviewed.132 Fecal microbiota transplantation has poten-tial risks, such as communicable disease transmission, andthere are reports of the appearance of autoimmune dis-eases in the long-term follow-up after transplantation.133

Therefore, fecal microbiota transplantation for the treat-ment of IBS should only be carried out under strict researchprotocol.

GRADE level of evidence and strength of recommenda-tion: D2, weak, for intervention.

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n patients with IBS, the application of truecupuncture has shown no significant differencesompared with the application of shamcupuncture, in relation to symptom severity oruality of life

omplementary and alternative medicine is used by anmportant number of patients with functional gastrointesti-al disorders, corresponding to 51% in patients with IBS.134

ue to the safety of acupuncture and the fact that we doot have highly effective treatments for IBS improvement,ts evaluation is relevant.135 There is not a clear definitions to the meaning of placebo in acupuncture. It usuallynvolves placing the needles in zones that are not consid-red the correct ones for acupuncture or not penetratinghe skin with them (sham acupuncture). Studies controlledith sham acupuncture have shown no benefits in relation

o IBS symptoms.135

GRADE level of evidence and strength of recommenda-ion: D2, weak, against the intervention.

Level of agreement: In complete agreement 87%.In agreement with minor reservations: 4%.In disagreement with minor reservations: 4%.In disagreement with major reservations: 4%.

here is not enough evidence to recommendoxibustion for the treatment of IBS

oxibustion is a technique associated with acupuncture thatses the burning of herbal preparations on acupunctureoints. The systematic review and meta-analysis of ran-omized and placebo-controlled studies show inconsistentesults and a high risk for bias, thus its usefulness cannot beffirmed.136



here is not enough evidence to conclude whetheromeopathy has any beneficial effects in IBSreatment

hree randomized and controlled studies conducted morehan 25 years ago showed very poor evidence due to the lowuality of the reports, the high or unknown risk for bias,

short-term follow-up, and sparse data. Therefore theres no evidence for affirming or ruling out the usefulness ofomeopathy in the treatment of IBS.137

ion: D2, weak, against the intervention.

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ognitive behavioral therapy, multicomponentsychological therapy, and dynamic psychotherapydministered by qualified personnel have beenhown to improve IBS symptoms

atients with IBS present with higher levels of psychologi-al comorbidity compared with healthy controls. Therefore,sychological therapies have been proposed as alternativesor IBS treatment.138,139 Even though there are randomizednd controlled studies, the large majority are biased due tohe impossibility of conducting blind studies.122

GRADE level of evidence and strength of recommenda-ion: C2, weak, in favor of the intervention.


elaxation therapy, self-administered or minimumontact behavioral therapy, cognitive behavioralherapy administered online, stress managementherapy, multicomponent psychological therapy byelephone, and mindfulness therapy have not beenhown to be effective in improving IBS symptoms

he application of numerous psychological treatments inBS has been reported. Nevertheless, the meta-analysesf randomized and placebo-controlled studies have shownmportant heterogeneity in the results, the number ofatients included in the studies is small, and it is impossibleo conduct blind studies due to the nature of the treatment.n addition, these studies have the disadvantage that theyo not report adverse effects, which potentially exist in anyreatment.122,140



ypnotherapy performed by qualified personnel isfficacious in IBS treatment

he meta-analysis of 5 randomized studies showed theffectiveness of hypnotherapy in the improvement of IBSymptoms compared with controls.140



onclusion

BS is the most frequently diagnosed gastrointestinal dis-rder in daily practice and therefore it is of the utmostmportance for the physician to be up-to-date in regard to all
he changes and advances that have been made in the knowl-dge of this disease in the last few years. We present herein
consensus review of the most relevant progress in thenderstanding of this disorder, updating and complementing

TbfiF


he 2009 Clinical Guidelines on the Diagnosis and Treatmentf Irritable Bowel Syndrome of the Asociación Mexicana deastroenterología.

inancial disclosure

inancial support was received from Laboratorios Alfaassermann to partially cover the costs of the in-person

ote meeting (transportation and accommodations). Theuthors received no remuneration for their participation.

onflict of interest

amón Carmona-Sánchez is a Member of the Advisory Boardf Mayoly-Spindler and a Speaker for Mayoly-Spindler andsofarma.

María Eugenia Icaza-Chávez a Member of the Advisoryoard of Mayoly-Spindler and a Speaker for Mayoly-Spindlernd Asofarma.

María Victoria Bielsa-Fernández is a Speaker for Alfaassermann and Almirall and a Member of the Advisoryoard of Alfa Wassermann.

Octavio Gómez-Escudero is a Member of the Advisoryoeard of Laboratorios Almirall and a Speaker for Labora-orios Takeda, Astra-Zéneca, Almirall, Asofarma, and Alfaassermann.

Francisco Bosques-Padilla is a member of the Advisoryoard of Laboratorios Takeda and a Speaker for Laboratoriosbvie, Janssen, and Bristol-Myers Squibb México.

Enrique Coss-Adame is a Speaker for Laboratoriosakeda de México and has been a Consultant for and col-aborates Laboratorios Asofarma de México.

Francisco Huerta-Iga is a Speaker for Takeda and Aso-arma.

Aurelio López-Colombo is a Speaker for Laboratoriosakeda de México.

Alejandra Noble-Lugo is a Speaker for Laboratoriosakeda de México.

José Ramón Nogueira-de Rojas is a Speaker forstraZeneca and HealthPro and participates in a clinicalesearch project with Laboratorios Senosiain.

José María Remes-Troche is a Member of the Advi-ory Board of Takeda Pharmaceuticals, Alfa Wassermann andlmirall and a Speaker for Takeda, Asofarma, Alfa Wasser-ann, Almirall, and Astra-Zeneca.Max J. Schmulson has been a Speaker for Alfa Wasser-

ann and Takeda Mexico. He has received financial supportnd carried out research projects for Alfa Wassermann andakeda México. He has been a Consultant and Member ofhe Advisory Boards of Alfa Wassermann, Commonwealthaboratories Inc., and Senosiain.

José Luis Tamayo-de la Cuesta is a Speaker and Externalonsultant for Alfa Wassermann, Asofarma, Malloly Spindlernd Takeda de México.

Miguel A. Valdovinos is a speaker for Laboratoriosakeda de México and Laboratorios Ferrer. He is a Mem-
er of the Advisory Board of Mayoly-Spindler. He is receivingnancial support for a research project from Laboratorioserrer.


Francisco Esquivel-Ayanegui, Ángel Ricardo Flores-Rendón, Marina Alejandra González-Martínez, TomásHéctor Méndez-Gutiérrez, Ricardo Huberto Rana-Garibay,Federico Roesch-Dietlen, Julio César Soto-Pérez. Luis F.Uscanga, Joaquín Valerio-Urena, and Mónica R. Zavala-Solares declare that they have no conflict of interest.

Acknowledgements

The authors wish to thank Dr. Francisco Javier Bosques-Padilla, President of the Asociación Mexicana de Gas-troenterología and the administrative personnel of theAssociation for the favorable conditions provided us duringthe preparation of this consensus.

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The Mexican consensus on irritable bowel syndrome · 17/06/2015 · Desde la publicación de las...

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