Coeliac Disease ( CD ) is an immune-mediated intestinal enteropathy that is triggered by exposure to dietary gluten in genetically predisposed individuals ( The Oslo definition for coeliac disease and related terms Jonas F Ludvigsson et al ) Dietary gluten is a storage protein found in wheat , rye and barley and is widely used in food processing to give dough the desired baking properties, add flavors and improve texture.
How common ? CD is one of the most common cause of chronic malabsorption the prevalence of CD is thought to be around 1 % American Journal of Gastroenterology in 2013 reported that CD remains under-diagnosed in the US NICE also informs that CD is under-diagnosed particularly when patients are seen in primary care or other non-specialist settings ( NICE 2016 ) The incidence has been increasing steadily in the last 5- yrs – possibly due to better awareness , better diagnostic tools and probable real increases in incidence The female-to-male ratio ranges from 1:3 to 1.5 : 1 CD can affect any age group including the elderly ,usual age of presentation now is 10-40 yrs Current understanding does not support population level screening.
What happens ? ingestion of gluten is pre-requisite for the development of CD gliadin ( alcohol-soluble portion of gluten ) in people with CD occasionally passes through the epithelial layer of the intestine and stimulates an immune response leading to chronic inflammation injury to small intestine ( mucosal inflammation , villous strophy and crypy hperplasia ) with loss of absorptive surface area reduction of digestive enzymes ( both luminal and pancreatic ) impaired absorption of micronutrients like fat-soluble vitamins , iron , possibly b12 and folate inflammation – cause net secretion of fluid which can cause diarrhoea weight loss- possibly due to failure of absorption of calories abdominal pain and bloating- due to malabsorption abdominal pain may also happen due to intermittent intussusceptio and IBS CD should be considered as a systemic disease rather than just a disease of the GI tract.
Strong associations –The frequency of CD is substantially increased in patients with a positive family history -first degree relatives of people with CD are at an increased risk The precise risk is highest in monozygous twins , next in HLA matched siblings and finally in parents and children of patients with CD There is a close association between CD and human leukocyte antigens ( HLA ) variant named HLA-DQ2.5 – not all people with with HLA will develop CD but the absence of HLA in person with suspected CD means that they do not have and will never develop CD ( NICE 2015 ) Genome wide association studies have so far identified 40 loci outside of HLA with genes predisposing to or protecting against CD children breastfed at or beyond gluten introduction may be a lower risk of developing CD in childhood ( not conclusive ) conversely exposure of large amount of gluten without ongoing breast feeding may increase the risk CD is substantially more common in patients with type 1 diabetes auto-immune thyroid disease Down’s & Turner’s syndrome GI infections , drugs , interferon alpha and surgery have also been implicated as trigger factors.
Presentation –CD can present with a wide variety of symptoms ( or asymptomatic ) for ease of understanding we can divide then into intestinal and extra-intestinal.
Intestinal manifestations –Classic malabsorption symptoms as diarrhoea steatorrhoea , weight loss or failure to thrive these are often more common in children Symptoms suggestive of irritable bowel syndrome
Extraintestinal manifestations of celiac disease –Dermatitis herpetiformis – cutaneous manifestation of CD , herpetiform clusters of pruritic urticated papules and vesicles on the skin and granular IgA deposits in the dermal papillae Gluten ataxia -idiopathic sporadic ataxia in association with positive coeliac serology with or without enteropathy Iron deficiency anaemia Other deficiencies as Vit b12 , D , folate , zinc , Vit B6 Fatigue Recurrent apthous ulcers Elevated hepatic transaminases ( Celiac hepatitis ) Short stature Delayed puberty / menarche Amenorrhoea Osteopenia / osteoporosis Dental enamel hypoplasia Peripheral neuropathy Hyposplenism Adverse pregnancy out comes Lymphoma.
Tests Diagnosis is by serological testing and biopsy in adults with suspected CD A serological test to investigate CD is only accurate if a gluten -containing diet has been followed for at least 6 weeks NICE recommends testing for total immunoglobulin A ( IgA ) and IgA tissue transglutaminase ( tTG ) as the first choice A positive test result is defined as 1 unambiguously + ve IgA tTG alone 2 weakly + ve IgA tTG and + ve endomyseal antibodies ( EMA ) 3 in people with IgA deficiency a serologically + ve result can be derived from any one of the IgG antibodies Further testing to confirm a diagnosis may involve an edoscopic biopsy ( in adults ) an IgA EMA test to cnfirm serological positivity ( in children < 16 ) HLA testing -CD is associated with specific HLA types in virtually all populations.
Serological tests should be done in the following groups as per NICE –NICE recommends a serological testing for CD in the following people persistent unexplained abdominal or GI symptoms faltering growth prolonged fatigue unexpected weight loss severe or persistent mouth ulcers unexpained iron , vit B12 or folate deficiency type 1 diabetes , at diagnosis auto-immune thyroid disease , at diagnosis adults who meet irritable bowel syndrome criteria 1st degree relatives relatives of people newly diagnosed with CD.
Diagnosis –The diagnosis of CD requires duodenal biopsy consistent with CD positive serological testing and / or response to a gluten free diet ( GFD ) A positive CD-specific ( TTG , DGP and EMA ) in patients with villous atrophy confirms the diagnosis of CD
Common differentials-Crohn’ disease Ulcerative colitis Malignancy Infections for e.g HIV or TB Irritable bowel syndrome CMPA.
Complications –Gastrointestinal complications malabsorption Inestinal lyphomas Collagenous sprue Other GI malignancies eg gastrointestinal lymphomas Nutrient and mineral deficiencies Osteoporosis / osteomalacia Dental defects Idiopathic pulmonary hemosiderosis Glomerular IgA nephropathy Infertility Hyposplenism Venous thromboembolism Cardiomayopathy / myocarditis Neurophsychiatric- symptoms as headache , peripheral neuropathy , ataxia , depression , dysthymia , anxiety and epilepsy.
Gluten Free Diet ( GFD ) there is currently no cure for CD patients with CD should adhere to a gluten free diet for life GFD will lead to resolution of symptoms and repair of intestinal damage risk of osteoporosis is reduced with good strict adherence and reduction in intestinal villous atrophy and BMD increases during the 1st year of GFD adherence Oats -position is unclear and CKS suggests that patients can include pure , uncontaminated oats in their diet Patient education is important as here is evidence that compliance with a GFD is improved in those who are more knowledgeable bout CD and the diet .
Ensure that enough advice and information has been rendered to the patient Check adherence – to GFD Review for symptoms and signs of CD , its complications and associated conditions Assess and manage osteoporosis risk Monitor BMI Arrange annual blood tests for Coeliac serology- helps monitor adherence FBC Thyroid function tests Liver function tests Vit D , B12 , folate and bone profile Us & Es Offer immunisation as indicated for e.g if splenic dysfunction present All patients with CD should have an annual review All newly diagnosed patients should be seen by a dietitian who specializes in CD .
Refer for further investigations if –poor response to GFD If symptoms persist despite GFD consider the following lactose intolerance pancreatic insufficiency wheat/ malt intolerance Lymphoma Microscopic colitis Bacterial overgrowth Irritable bowel syndrome Refractory CD weight loss on GFD GI malignancy is suspected onset of unexplained abdominal pain difficulty in assessing if the person is adhering to GFD or poor adherence is suspected
LINKS AND RESOURCES
Coeliac UK – a large UK charity https://www.coeliac.org.uk/home/
An explainer page from BUPA https://www.bupa.co.uk/health-information/digestive-gut-health/coeliac-disease
Coeliac Disease Foundation US-based charity https://celiac.org/about-celiac-disease/what-is-celiac-disease/
GUTS Charity- pdf on celiac disease https://gutscharity.org.uk/wp-content/uploads/2018/11/Guts-UK-Coeliac-Disease-Leaflet.pdf
GFD from Dudley group NHS Foundation Trust http://www.dgft.nhs.uk/wp-content/uploads/2014/09/The-gluten-free-diet-V3.pdf
Beyond CD.org https://www.beyondceliac.org/celiac-disease/
INFORMATION FOR CLINICIANS ON COELIAC DISEASE
American College of Gastroenterology- an easy to read -the concise page on CD https://gi.org/topics/celiac-disease/
Refractory CD from National Organization for Rare Diseases https://rarediseases.org/rare-diseases/refractory-celiac-disease/
Making the diagnosis of CD from RACGP https://www1.racgp.org.au/ajgp/2018/january-february/interpreting-tests-for-coeliac-disease-(1)
Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology https://gut.bmj.com/content/63/8/1210
- ACG Clinical Guidelines : Diagnosis and Management of Celiac Disease Rubio-Tapia et al American Journal of Gastroenterology : May 2013 – Volume 108 – Issue 5 – p 656-767
Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology by Jonas F Ludvigsson via https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112432/pdf/gutjnl-2013-306578.pdf
Tests for Coeliac disease https://celiac.org/about-celiac-disease/screening-and-diagnosis/screening/
- NICE guideline on Coeliac Disease https://www.nice.org.uk/guidance/qs134/resources/coeliac-disease-pdf-75545419042501
- Spotlight Coeliac Disease British Journal of Family Medicine July 2019 https://www.bjfm.co.uk/coeliac-disease-management-in-primary-care
- European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders by Abdullah Al-Toma et al European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders https://journals.sagepub.com/doi/full/10.1177/2050640619844125
- Advances in Diagnosis and Management of Celiac Disease Ciaran P Kelly et al https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409570/
- The Oslo definitions for coeliac disease and related terms Jonas F Ludvigsson et al https://gut.bmj.com/content/62/1/43?ijkey=b5bb23430eca7af890facee2605e477145587c48&keytype2=tf_ipsecsha
- CKS NHS Coeliac disease https://cks.nice.org.uk/coeliac-disease#!scenario
- Celiac disease Diagnosis and Management JAMA 2011 Oct 12 ; 306 ( 14) : 1582-1592 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373262/
- Celiac Disease: Diagnosis and Management AFP Timothy D Pelkowski et al https://www.aafp.org/afp/2014/0115/p99.html