- Email: [email protected]
Functional gastrointestinal disorders: what's new for Rome IV?
Comment
registries, primary care, hospitals, and social care,9 but the lack of standardisation and quality of data remain major limitations. There is much information now available about the organisation and cost of health-care systems,10 although this is largely limited to developed nations, and the depth of the data is too thin to be able to explore variation in services, approaches, and outcomes below a national level. For example, for pancreatic diseases we know little about the distribution of specialist centres and their effect on outcome. Retrospective audits give some information, but more timely and nationally comparable information is needed to make progress in this digital age.
2
3 4
5 6 7 8
9
*John G Williams, Stephen E Roberts Swansea University Medical School, Swansea, UK [email protected] We declare no competing interests. 1
10
Roberts SE, Samuel DG, Williams JG, et al. Survey of Digestive Health across Europe. Part one: The burden of gastrointestinal diseases and the organisation and delivery of gastroenterology services across Europe. Vienna: United European Gastroenterology, 2014. McNamara D. Pancreatic diseases. Aliment Pharmacol Ther 2003; 18 (suppl 3): 60–65. Kiczek C, Larson J, Tompsett ET, Wang L. Case study on point of care electronic data systems for ART clinics in Malawi: Baobab Health Trust. http://globalhealth.mit.edu/wp-content/uploads/2011/04/MIT-SloanPOC-EDS-Business-Case-March-2009.pdf (accessed June 19, 2016). Carpenter I, Bridgelal-Ram M, Croft G, Williams J. Medical records and record keeping standards. Clin Med 2007; 7: 328–31. SNOMED CT. The global language of healthcare. http://www.ihtsdo.org/ snomed-ct (accessed June 19, 2016). Schneeweiss S. Learning from big health care data. New Engl J Med 2014; 370: 2161–63. Volterra Partners. Sustaining universal healthcare in the UK: making better use of information. Sept 2014. http://volterra.co.uk/wp-content/ uploads/2014/09/Final-EMC-Volterra-Healthcare-report-web-version.pdf (accessed June 15, 2016). Public Health Research Data Forum. Enabling data linkage to maximise the value of public health research data. Final Report to the Wellcome Trust. March 2015. https://wellcome.ac.uk/sites/default/files/enabling-datalinkage-to-maximise-value-of-public-health-research-data-phrdf-mar15. pdf (accessed June 15, 2016). Mossialos E, Wenzl M, Osborn R, Sanark D. International profiles of healthcare systems, 2015, The Commonwealth Fund, January 2016. http://www.commonwealthfund.org/publications/fund-reports/2016/jan/ international-profiles-2015 (accessed June 15, 2016).
Xiao AY, Tan MLY, Wu LM, et al. Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol 2016; published online June 28. http://dx.doi.org/10.1016/S24681253(16)30004-8.
Functional gastrointestinal disorders: what’s new for Rome IV? Since publication of the Rome III criteria in 2006, there has been a marked and exciting expansion in the science of functional gastrointestinal disorders (FGIDs), which has led to improved understanding and better treatments. The Rome IV updates, published in May, 2016, include a redefinition of FGIDs and diagnostic criteria, addition of newly recognised disorders, and major changes in criteria for existing disorders.1 These changes reflect our growing understanding of FGIDs, including the relation between the microbiome, food, and nutrition and gastrointestinal function, and the role of genetics in responses to pharmaceutical treatments. Rapid growth in our knowledge of the role of sex, age, society, and culture are also integrated into the latest Rome update. Further, the broad range of biophysical processes—ie, the biomedical and psychosocial factors that affect a patient’s illness—have been recognised. The definition of FGIDs changed with Rome III from previous concepts relating to the absence of structural disease to a more appropriate disorder of gastrointestinal 6
functioning. Now to reach a more meaningful scientific approach to these disorders, Rome IV expanded on this concept with a new definition: disorders of gut– brain interaction. These disorders are classified by gastrointestinal symptoms related to any combination of: motility disturbance; visceral hypersensitivity; altered mucosal and immune function; altered gut microbiota; and altered central nervous system (CNS) processing. This definition is consistent with our evolving understanding of the pathophysiological processes that, in part or together, determine the symptom features of FGIDs. It also moves us away from traditional beliefs that functional means not structurally based, or even psychiatric. Thus diagnoses have been modified from Rome III: functional fecal incontinence is now fecal incontinence and functional abdominal pain syndrome (FAPS) is now centrally mediated abdominal pain syndrome (CAPS). Yet we do retain this term when it is needed to distinguish from clear structural diagnoses, for example, functional heartburn is not associated with increased acid reflux or acid sensitivity. www.thelancet.com/gastrohep Vol 1 September 2016
Comment
www.thelancet.com/gastrohep Vol 1 September 2016
Type 2 Type 3
Constipation
Type 1
Bristol stool type
The Rome IV criteria sees the addition of new diagnoses with known aetiologies, including: reflux hypersensitivity syndrome (in which a patient has heartburn with normal physiological degrees of reflux); cannabinoid hyperemesis (in which there are episodes of vomiting like cyclic vomiting syndrome, caused by cannabis); narcotic bowel syndrome (a centrally mediated hyperalgesia from opioids); and opioidinduced constipation (related to the peripheral effects of opioids on μ receptors producing constipation). Several disorders have been removed, revised, or merged in this latest update. For instance, the sphincter of Oddi disorder (SOD) criteria have been revised. Evidence for performing biliary sphincterotomy on the basis of clinical criteria for presumed sphincter of Oddi pain was not convincing. As a result, balancing the benefits of symptomatic relief with the potential risks of pancreatitis, bleeding, and perforation was challenging. The Rome IV criteria feature a reclassification of these disorders, providing a more rational treatment algorithm, and the previous type III SOD categorisation has been removed. Furthermore, the previous entities of chronic idiopathic nausea and functional vomiting have been combined as a new diagnosis—chronic nausea vomiting syndrome. This change reflects the lack of evidence for different diagnostic approaches and management of nausea compared with vomiting, and the clinical observation that these two symptoms are commonly associated. Although we recognise patients may present with nausea only, the clinical approach to diagnosis and management is not affected. Other major changes likely to affect a large portion of patients include removal of the term “discomfort” from the irritable bowel syndrome (IBS) diagnostic criteria, which previously accepted discomfort or pain. Discomfort has been removed because the term can incorporate a variety of symptoms and has different meanings in different cultures, and is therefore not specific enough to be a diagnostic criterion. Furthermore, we now recognise that functional bowel disorders exist on a spectrum of symptom presentations related to pain and stool consistency (figure). Thus, for patients with little or no pain, the diagnosis may be of functional diarrhoea or constipation, but in those with greater degrees of pain, patients are classified as having IBS-C or IBS-D, respectively. This concept is supported by
Constipation
Functional constipation Bloating
Type 4
Mixed
Type 5
Distension
Type 6 Type 7
Functional diarrhoea
IBS with...
Diarrhoea Pain
Figure: Association of stool consistency and degree of pain in defining functional bowel disorders
evidence that patients often migrate across categories over time. Finally, there is also a change in how to identify the IBS subtypes. The Rome III IBS classification used the proportion of total stools that were abnormal (ie, loose/ watery or hard/lumpy) to classify the different subtypes of the disorder. However, patients can have large periods of time with normal stool consistency, and many patients were therefore deemed to have unclassified IBS. Based on this observation and the results of a Rome Foundation normative symptom study,2 the criteria have been changed and now relate to the proportion of days with symptomatic stools rather than all stools (including normal ones). This change will result in a notable reduction in the number of patients deemed to have IBS unclassified. Looking ahead, the Rome Foundation has begun new initiatives not only to enhance our knowledge of these disorders but also to provide innovative learning tools to help clinicians in the care of their patients. For instance, we are beginning a global epidemiology study, which will help us understand not only the prevalence of these disorders but also cross-cultural differences in health perceptions and behaviours, including healthcare seeking. We have initiated three working teams to update knowledge and provide evidence-based recommendations on the use of brain imaging in clinical research and care, on post-infection IBS, and on the use of centrally targeted medications in treating painful FGIDs. Finally, we are developing educational initiatives including the use of intelligent software and innovative educational tools to help clinicians in the diagnosis and management of patients with these disorders. 7
Comment
Douglas A Drossman
DAD is president of the Rome Foundation.
Center for Education and Practice of Biopsychosocial Care, Drossman Gastroenterology, Chapel Hill, NC, USA; Center of Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA; and Rome Foundation, Chapel Hill, NC, USA [email protected]
1
2
Drossman DA, Chang L, Chey WD, Kellow J, Tack J, Whitehead WE (eds). Rome IV functional gastrointestinal disorders: disorders of gut-brain interaction. Raleigh, NC: Rome Foundation, 2016. Palsson OS, Whitehead WE, van Tilburg NA, et al. Development and validation of the Rome IV diagnostic questionnaire in adults. Gastroenterology 2016; 150: 1481–91.
End-stage liver disease in eastern Europe and central Asia: action is needed Eastern Europe and central Asia have a high burden of end-stage liver disease, and age-standardised mortality for liver cirrhosis is alarming (for those aged over 15 years, the highest rates for men are 99·3 per 100 000 in Kyrgyzstan, 94·9 per 100 000 in Turkmenistan, 82·6 per 100 000 in Kazakhstan, 56·7 per 100 000 in Ukraine, and 48·7 per 100 000 in the Russian Federation; whilst the highest rates for women are 66·9 per 100 000 in Turkmenistan, 52·4 per 100 000 in Uzbekistan, 45·1 per 100 000 in Tajikistan, 26·1 per 100 000 in the Russian Federation, and 25·5 per 100 000 in Belarus).1 The main aetiological factor is alcohol consumption, which in women accounts for almost three-quarters of deaths from liver cirrhosis in Ukraine, the Russian Federation, and Belarus, and in men for 70·8% of cirrhosis deaths in Kazakhstan, and around half of those in Uzbekistan, Belarus, and the Russian Federation.2 These countries have some of the heaviest burdens of alcoholic liver disease in the world. Hepatitis viruses also play an important part. Although data are incomplete due to weak or non-existent surveillance systems, adult prevalence of anti-hepatitis C virus (HCV) antibodies in the general population ranges from 1·3% in Belarus to 11·3% in Uzbekistan with a viraemic rate between 69% and 39·2%,3 and HBsAg seroprevalence ranges from 1·45% in Ukraine to 10·3% in Kyrgyzstan.4 Hepatitis D virus (HDV) infection is also highly prevalent in central Asia5 and in some areas of the Russian Federation.6 Although data are scarce, non-alcoholic fatty liver disease (NAFLD) probably constitutes an additional contributing factor, considering the progressive increase in overweight and obesity in recent years7 and the prevalence of metabolic risk factors and diabetes.8 Lastly, the role of HIV infection cannot be overlooked; the epidemic in eastern Europe still prevails in people 8
who inject drugs (PWID) but the rate of heterosexual transmission is growing and the seasonal labour migration from central Asian and Caucasian countries to Russia is a contributing factor.9 The interplay of these causes is complex. For instance, alcohol use and HCV infection act synergistically to provoke faster and more frequent progression of fibrosis, and the prevalence of metabolic syndrome and visceral adiposity increases among overweight and obese individuals who misuse alcohol, causing more prevalent and severe liver disease. HIV itself might contribute independently to liver disease, since advanced fibrosis can be found in HIV-infected patients without underlying viral hepatitis or alcohol misuse,10 and individuals coinfected with hepatitis B virus (HBV) or HCV can have accelerated progression of fibrosis and an increased risk of hepatic decompensation and hepatocellular carcinoma. So how can we reduce the burden of end-stage liver disease in eastern Europe and central Asia? At present, not enough is being done. In an analysis of the relation between the sale of different alcoholic beverages (beer, wine, vodka) and age-standardised mortality data for liver cirrhosis for 1970 to 2005, vodka alone seemed to be associated with liver cirrhosis mortality in the Russian Federation.11 Making vodka less affordable through differential taxation could be important and has been an essential component of the alcohol policy in Russia in recent years, where official alcohol sales, especially for vodka, have steadily decreased.12 Evidence exists for a decrease in mortality related to acute trauma, homicides, suicides, and car accidents as a result of these policies, but mortality from liver cirrhosis is unchanged in Belarus and has only decreased modestly in Russia, probably because of mortality www.thelancet.com/gastrohep Vol 1 September 2016
registries, primary care, hospitals, and social care,9 but the lack of standardisation and quality of data remain major limitations. There is much information now available about the organisation and cost of health-care systems,10 although this is largely limited to developed nations, and the depth of the data is too thin to be able to explore variation in services, approaches, and outcomes below a national level. For example, for pancreatic diseases we know little about the distribution of specialist centres and their effect on outcome. Retrospective audits give some information, but more timely and nationally comparable information is needed to make progress in this digital age.
2
3 4
5 6 7 8
9
*John G Williams, Stephen E Roberts Swansea University Medical School, Swansea, UK [email protected] We declare no competing interests. 1
10
Roberts SE, Samuel DG, Williams JG, et al. Survey of Digestive Health across Europe. Part one: The burden of gastrointestinal diseases and the organisation and delivery of gastroenterology services across Europe. Vienna: United European Gastroenterology, 2014. McNamara D. Pancreatic diseases. Aliment Pharmacol Ther 2003; 18 (suppl 3): 60–65. Kiczek C, Larson J, Tompsett ET, Wang L. Case study on point of care electronic data systems for ART clinics in Malawi: Baobab Health Trust. http://globalhealth.mit.edu/wp-content/uploads/2011/04/MIT-SloanPOC-EDS-Business-Case-March-2009.pdf (accessed June 19, 2016). Carpenter I, Bridgelal-Ram M, Croft G, Williams J. Medical records and record keeping standards. Clin Med 2007; 7: 328–31. SNOMED CT. The global language of healthcare. http://www.ihtsdo.org/ snomed-ct (accessed June 19, 2016). Schneeweiss S. Learning from big health care data. New Engl J Med 2014; 370: 2161–63. Volterra Partners. Sustaining universal healthcare in the UK: making better use of information. Sept 2014. http://volterra.co.uk/wp-content/ uploads/2014/09/Final-EMC-Volterra-Healthcare-report-web-version.pdf (accessed June 15, 2016). Public Health Research Data Forum. Enabling data linkage to maximise the value of public health research data. Final Report to the Wellcome Trust. March 2015. https://wellcome.ac.uk/sites/default/files/enabling-datalinkage-to-maximise-value-of-public-health-research-data-phrdf-mar15. pdf (accessed June 15, 2016). Mossialos E, Wenzl M, Osborn R, Sanark D. International profiles of healthcare systems, 2015, The Commonwealth Fund, January 2016. http://www.commonwealthfund.org/publications/fund-reports/2016/jan/ international-profiles-2015 (accessed June 15, 2016).
Xiao AY, Tan MLY, Wu LM, et al. Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol 2016; published online June 28. http://dx.doi.org/10.1016/S24681253(16)30004-8.
Functional gastrointestinal disorders: what’s new for Rome IV? Since publication of the Rome III criteria in 2006, there has been a marked and exciting expansion in the science of functional gastrointestinal disorders (FGIDs), which has led to improved understanding and better treatments. The Rome IV updates, published in May, 2016, include a redefinition of FGIDs and diagnostic criteria, addition of newly recognised disorders, and major changes in criteria for existing disorders.1 These changes reflect our growing understanding of FGIDs, including the relation between the microbiome, food, and nutrition and gastrointestinal function, and the role of genetics in responses to pharmaceutical treatments. Rapid growth in our knowledge of the role of sex, age, society, and culture are also integrated into the latest Rome update. Further, the broad range of biophysical processes—ie, the biomedical and psychosocial factors that affect a patient’s illness—have been recognised. The definition of FGIDs changed with Rome III from previous concepts relating to the absence of structural disease to a more appropriate disorder of gastrointestinal 6
functioning. Now to reach a more meaningful scientific approach to these disorders, Rome IV expanded on this concept with a new definition: disorders of gut– brain interaction. These disorders are classified by gastrointestinal symptoms related to any combination of: motility disturbance; visceral hypersensitivity; altered mucosal and immune function; altered gut microbiota; and altered central nervous system (CNS) processing. This definition is consistent with our evolving understanding of the pathophysiological processes that, in part or together, determine the symptom features of FGIDs. It also moves us away from traditional beliefs that functional means not structurally based, or even psychiatric. Thus diagnoses have been modified from Rome III: functional fecal incontinence is now fecal incontinence and functional abdominal pain syndrome (FAPS) is now centrally mediated abdominal pain syndrome (CAPS). Yet we do retain this term when it is needed to distinguish from clear structural diagnoses, for example, functional heartburn is not associated with increased acid reflux or acid sensitivity. www.thelancet.com/gastrohep Vol 1 September 2016
Comment
www.thelancet.com/gastrohep Vol 1 September 2016
Type 2 Type 3
Constipation
Type 1
Bristol stool type
The Rome IV criteria sees the addition of new diagnoses with known aetiologies, including: reflux hypersensitivity syndrome (in which a patient has heartburn with normal physiological degrees of reflux); cannabinoid hyperemesis (in which there are episodes of vomiting like cyclic vomiting syndrome, caused by cannabis); narcotic bowel syndrome (a centrally mediated hyperalgesia from opioids); and opioidinduced constipation (related to the peripheral effects of opioids on μ receptors producing constipation). Several disorders have been removed, revised, or merged in this latest update. For instance, the sphincter of Oddi disorder (SOD) criteria have been revised. Evidence for performing biliary sphincterotomy on the basis of clinical criteria for presumed sphincter of Oddi pain was not convincing. As a result, balancing the benefits of symptomatic relief with the potential risks of pancreatitis, bleeding, and perforation was challenging. The Rome IV criteria feature a reclassification of these disorders, providing a more rational treatment algorithm, and the previous type III SOD categorisation has been removed. Furthermore, the previous entities of chronic idiopathic nausea and functional vomiting have been combined as a new diagnosis—chronic nausea vomiting syndrome. This change reflects the lack of evidence for different diagnostic approaches and management of nausea compared with vomiting, and the clinical observation that these two symptoms are commonly associated. Although we recognise patients may present with nausea only, the clinical approach to diagnosis and management is not affected. Other major changes likely to affect a large portion of patients include removal of the term “discomfort” from the irritable bowel syndrome (IBS) diagnostic criteria, which previously accepted discomfort or pain. Discomfort has been removed because the term can incorporate a variety of symptoms and has different meanings in different cultures, and is therefore not specific enough to be a diagnostic criterion. Furthermore, we now recognise that functional bowel disorders exist on a spectrum of symptom presentations related to pain and stool consistency (figure). Thus, for patients with little or no pain, the diagnosis may be of functional diarrhoea or constipation, but in those with greater degrees of pain, patients are classified as having IBS-C or IBS-D, respectively. This concept is supported by
Constipation
Functional constipation Bloating
Type 4
Mixed
Type 5
Distension
Type 6 Type 7
Functional diarrhoea
IBS with...
Diarrhoea Pain
Figure: Association of stool consistency and degree of pain in defining functional bowel disorders
evidence that patients often migrate across categories over time. Finally, there is also a change in how to identify the IBS subtypes. The Rome III IBS classification used the proportion of total stools that were abnormal (ie, loose/ watery or hard/lumpy) to classify the different subtypes of the disorder. However, patients can have large periods of time with normal stool consistency, and many patients were therefore deemed to have unclassified IBS. Based on this observation and the results of a Rome Foundation normative symptom study,2 the criteria have been changed and now relate to the proportion of days with symptomatic stools rather than all stools (including normal ones). This change will result in a notable reduction in the number of patients deemed to have IBS unclassified. Looking ahead, the Rome Foundation has begun new initiatives not only to enhance our knowledge of these disorders but also to provide innovative learning tools to help clinicians in the care of their patients. For instance, we are beginning a global epidemiology study, which will help us understand not only the prevalence of these disorders but also cross-cultural differences in health perceptions and behaviours, including healthcare seeking. We have initiated three working teams to update knowledge and provide evidence-based recommendations on the use of brain imaging in clinical research and care, on post-infection IBS, and on the use of centrally targeted medications in treating painful FGIDs. Finally, we are developing educational initiatives including the use of intelligent software and innovative educational tools to help clinicians in the diagnosis and management of patients with these disorders. 7
Comment
Douglas A Drossman
DAD is president of the Rome Foundation.
Center for Education and Practice of Biopsychosocial Care, Drossman Gastroenterology, Chapel Hill, NC, USA; Center of Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA; and Rome Foundation, Chapel Hill, NC, USA [email protected]
1
2
Drossman DA, Chang L, Chey WD, Kellow J, Tack J, Whitehead WE (eds). Rome IV functional gastrointestinal disorders: disorders of gut-brain interaction. Raleigh, NC: Rome Foundation, 2016. Palsson OS, Whitehead WE, van Tilburg NA, et al. Development and validation of the Rome IV diagnostic questionnaire in adults. Gastroenterology 2016; 150: 1481–91.
End-stage liver disease in eastern Europe and central Asia: action is needed Eastern Europe and central Asia have a high burden of end-stage liver disease, and age-standardised mortality for liver cirrhosis is alarming (for those aged over 15 years, the highest rates for men are 99·3 per 100 000 in Kyrgyzstan, 94·9 per 100 000 in Turkmenistan, 82·6 per 100 000 in Kazakhstan, 56·7 per 100 000 in Ukraine, and 48·7 per 100 000 in the Russian Federation; whilst the highest rates for women are 66·9 per 100 000 in Turkmenistan, 52·4 per 100 000 in Uzbekistan, 45·1 per 100 000 in Tajikistan, 26·1 per 100 000 in the Russian Federation, and 25·5 per 100 000 in Belarus).1 The main aetiological factor is alcohol consumption, which in women accounts for almost three-quarters of deaths from liver cirrhosis in Ukraine, the Russian Federation, and Belarus, and in men for 70·8% of cirrhosis deaths in Kazakhstan, and around half of those in Uzbekistan, Belarus, and the Russian Federation.2 These countries have some of the heaviest burdens of alcoholic liver disease in the world. Hepatitis viruses also play an important part. Although data are incomplete due to weak or non-existent surveillance systems, adult prevalence of anti-hepatitis C virus (HCV) antibodies in the general population ranges from 1·3% in Belarus to 11·3% in Uzbekistan with a viraemic rate between 69% and 39·2%,3 and HBsAg seroprevalence ranges from 1·45% in Ukraine to 10·3% in Kyrgyzstan.4 Hepatitis D virus (HDV) infection is also highly prevalent in central Asia5 and in some areas of the Russian Federation.6 Although data are scarce, non-alcoholic fatty liver disease (NAFLD) probably constitutes an additional contributing factor, considering the progressive increase in overweight and obesity in recent years7 and the prevalence of metabolic risk factors and diabetes.8 Lastly, the role of HIV infection cannot be overlooked; the epidemic in eastern Europe still prevails in people 8
who inject drugs (PWID) but the rate of heterosexual transmission is growing and the seasonal labour migration from central Asian and Caucasian countries to Russia is a contributing factor.9 The interplay of these causes is complex. For instance, alcohol use and HCV infection act synergistically to provoke faster and more frequent progression of fibrosis, and the prevalence of metabolic syndrome and visceral adiposity increases among overweight and obese individuals who misuse alcohol, causing more prevalent and severe liver disease. HIV itself might contribute independently to liver disease, since advanced fibrosis can be found in HIV-infected patients without underlying viral hepatitis or alcohol misuse,10 and individuals coinfected with hepatitis B virus (HBV) or HCV can have accelerated progression of fibrosis and an increased risk of hepatic decompensation and hepatocellular carcinoma. So how can we reduce the burden of end-stage liver disease in eastern Europe and central Asia? At present, not enough is being done. In an analysis of the relation between the sale of different alcoholic beverages (beer, wine, vodka) and age-standardised mortality data for liver cirrhosis for 1970 to 2005, vodka alone seemed to be associated with liver cirrhosis mortality in the Russian Federation.11 Making vodka less affordable through differential taxation could be important and has been an essential component of the alcohol policy in Russia in recent years, where official alcohol sales, especially for vodka, have steadily decreased.12 Evidence exists for a decrease in mortality related to acute trauma, homicides, suicides, and car accidents as a result of these policies, but mortality from liver cirrhosis is unchanged in Belarus and has only decreased modestly in Russia, probably because of mortality www.thelancet.com/gastrohep Vol 1 September 2016