Gastroenterology GPSI Dr Jamie Dalrymple rounds up the latest developments in this area
1. Measuring calprotectin levels to diagnose IBD
This simple, non-invasive test promises to be an easy way of monitoring and optimising therapy in inflammatory bowel disease.
Calprotectin is a protein found in neutrophils and has antimicrobial properties. It is probably involved in the regulations of inflammatory reactions.
As calprotectin is resistant to enzymatic degradation, its presence can be measured in the stool by a simple, near-patient ELISA test that can be performed in primary care. Measurement of calprotectin is a surrogate marker of neutrophil influx into the bowel lumen and therefore a sensitive test of intestinal inflammation. Furthermore, elevated levels of calprotectin are a much better predictor of relapse than standard inflammatory markers (CRP, ESR, Hb).
The significance of calprotectin in primary care is twofold. First, faecal calprotectin has been shown to consistently differentiate inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS) because it has a high negative predictive value in ruling out inflammatory bowel disease in undiagnosed, symptomatic patients. Alternatively the faecal calprotectin level allows for the early identification of disease activity in inflammatory bowel disease.
Earlier this year an evidence review by the NHS Purchasing and Supply Agency confirmed its value as a diagnostic aid.
NHS Purchasing and Supply Agency. Value of calprotectin in screening out IBS. January 2010
2. Treatment for IBS: beyond the NICE guidelines
The 2008 NICE guidelines (CG61) on the diagnosis and treatment of IBS introduced a number of new approaches to diagnosis and treatment. First-line treatment included advice to reduce dietary fibre and that dietary fibre should be soluble. However, the advice on the use of antispasmodics, antimotility and laxatives was not as didactic. Second-line treatment advised low-dose tricyclic antidepressants or SSRIs in resistant cases.
American College of Gastroenterology Task Force on Irritable Bowel Syndrome. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol 2009;104;S1-35
3. Alarm symptoms and non-cancer diagnoses
In 2007, Jones et al published a paper on the positive predictive value (PPV) of dysphagia and rectal bleeding in diagnosing gastrointenstinal cancer. These results supported the concept that alarm symptoms are associated with an increased risk of malignant disease.
They developed this concept further with a paper published in 2009 measuring the association between alarm symptoms and the identification of clinically relevant, non-cancer diagnoses in the same cohort. Further analysis demonstrated that for all presentations about 20% of the population had an associated diagnosis at 90 days and nearly half of all patients at three years.
For patients presenting with dysphagia, significant diagnoses included acid-related conditions such as oesophagitis and peptic ulceration but also rarer conditions such as myasthenia gravis and scleroderma. Three years after presentation, for all ages, the PPV for any diagnosis was 39.4% for men and 33.6% for women.
Three years after presenting with rectal bleeding 32.3% of men and 32.4% of women had a significant diagnosis. Again there were a number of conditions diagnosed at 90 days and three years that were clinically relevant. These included diverticulitis and haemorrhoids, but there were also a significant number of cases of IBD.
These papers show that not only do red-flag symptoms predict the presence of cancer at a level that supports the concept of urgent referral under the two-week rule, but also that a negative result should not stop us from seeking alternative explanations for these symptoms.
Jones R, Charlton J, Latinovic R et al. Alarm symptoms and identification of non-cancer diagnoses in primary care: cohort study. BMJ 2009;13;339:b3094
4. Liver disease: the sleeping epidemic
The incidence of liver disease is increasing in the UK. It is the fifth most common cause of death in England, after cancer and heart, respiratory and cerebrovascular diseases. But it is the only one for which the mortality and morbidity are steadily rising.
The three main risk factors for this increase in liver disease are alcohol consumption, obesity and viral hepatitis.
Models for the progression to liver disease suggest that excess alcohol intake leads to alcoholic liver disease, with 10-35% of patients developing cirrhosis over 15 to 20 years.
Some 60-90% of obese people will have non-alcoholic fatty liver. Although less than 5% progress to non-alcoholic steatohepatitis, 35% of these patients will develop cirrhosis.
The important message is that all the risk factors are modifiable or at the very least amenable to effective treatment if recognised at an early stage.
A recent study commissioned by the Department of Health suggests that primary care is not ready to meet this challenge. The main findings of the report show that GPs:
• have a poor understanding of liver disease
• consider liver disease to be less of a health risk than other common conditions
• feel liver disease is difficult to diagnose and fail to diagnose liver disease early
• report that there are no clear referral pathways and poor access to specialist advice
• feel that more education is required.
There is no doubt that liver diseases are going to represent a significant workload for GPs in the future and primary care needs to be prepared to meet this growing problem.
Report to the Primary Care Reference Group. National Liver Disease Programme – personal communication 2010
Thomson SJ, Westlake S, Rahman TM et al. Chronic liver disease – an increasing problem: a study of hospital admission and mortality rates in England, 1979-2005, with particular reference to alcoholic liver disease. Alcohol Alcohol 2008;43:416-22
5. Targeted and opportunistic screening for coeliac disease
The population prevalence for gluten sensitivity by testing serology from blood donations has been calculated to be one in 100. This compares with the known prevalence of coeliac disease of between 0.1% and 0.4%. The implication of this is not clear – some people with positive serology will not have clinically significant coeliac disease, but there is undoubtedly a large number of people with undiagnosed coeliac disease. Although the case for opportunistic screening for the condition has not been proven, NICE has recently produced advice on targeted screening.
Historically, the presenting symptoms of coeliac disease were gastrointestinal, but increasingly other symptoms have been recognised as being associated with coeliac disease – and, in some people, no symptoms at all. Furthermore, coeliac disease is associated with a number of conditions, such as autoimmune thyroid disease and dermatitis herpetiformis, and often coexists with other conditions, such as Down's syndrome or epilepsy.
These coexisting signs and symptoms act as a guide for the screening of coeliac disease but such screening must be considered within the clinical context of the presentation. In conditions that share signs and symptoms of coeliac disease and in other associated conditions, it is routine to screen first-degree relatives for the disease. In other situations it would be appropriate to screen for coeliac disease provided the patient is taking gluten in their diet as the prevalence of this condition is high.
NICE Guideline Group. Coeliac disease: recognition and assessment of coeliac disease. NICE, 2009 www.nice.org.uk/CG086
Dr Jamie Dalrymple is chair of the Primary Care Society for Gastroenterology, a GPSI in gastroenterology in Norwich and hospital practitioner in gastroenterology at the Norfolk and Norwich University Hospital
The PCSG supports and represents all primary care professionals with an interest in gastroenterology and celebrates its 25th anniversary this year. The first year's membership is now free and includes attendance at the regional meeting and annual scientific meeting in Harrogate in October. For details on how to join go to the PCSG website
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