TABLE 1

Summary of main auto-immune GI diseases ¹

Clinical features

Coeliac disease

An enteropathy-associated multisystem disorder

Environmental factors In both diseases , environmental factors can be responsible for triggering the condition . Such triggers include social stress , a fast-paced lifestyle , smoking and diet . In addition , low levels of vitamin D have been associated with IBD . ⁶

Immune dysregulation CD40 and its ligand CD40L are overexpressed in both forms of IBD , suggesting that they play a key role in the pathophysiology of the disease . ⁷

Crohn ’ s disease Genetic susceptibility Several genetic variations have been associated with CD . For example , nucleotide-binding oligomerization domain ( Nod ) 2 gene mutations are associated with its development . ^{1 , 8}

Clinical presentation and prognosis CD typically presents as bloody diarrhoea , weight loss , fever , iron deficiency , chronic and post-prandial abdominal pain and lack of rectal urgency . ¹

CD can affect any part of the gut from the mouth to the anus . The most affected areas are the terminal ileum , the colon , and the small bowel ( in 55 % of patients ). The hallmarks of CD are transmural inflammation and the presence of ‘ skip lesions ’ ( patchy areas of inflammation separated by unaffected areas ). This inflammation can result in fibrosis and luminal narrowing , leading to stricture formation . Transmural inflammation can also lead to fistula formation with any adjacent organ or other parts of the bowel . ⁸

It is a lifelong condition , typified by periods of relapse and remission with recurrent cycles of inflammation . ⁹ A review by Peyrin-Biroulet and colleagues of CD in adults found ¹⁰ :

• The location of the disease ( ileitis , colitis , or ileo-colitis ) tended to remain stable over time

• Annually , 20 % of people were admitted to hospital

• Approximately 50 % of people underwent surgery within ten years of their diagnosis and approximately 50 % of these had a recurrence of symptoms within ten years of diagnosis . ¹⁰ Factors indicative of a poor prognosis include :

• Early disease onset

• A history of more than one surgical resection

• A history of complicated disease , such as abscess , fistulising or penetrating disease . ¹¹

Ulcerative colitis Clinical presentation and prognosis UC is a lifelong condition , characterised by periods of relapse and remission and recurrent cycles of mucosal inflammation . It typically affects only the innermost lining of the bowel . Hallmarks of the condition are tenesmus and bloody diarrhoea ; patients might also report tenderness , lower abdominal cramping , and fatigue ( due to blood loss ). ¹

A systematic review found the all-cause mortality rate for people with UC is slightly higher than in the general population . ¹² Ford and colleagues showed that 50 % of people are in remission at any one time , and 90 % of people have a relapsing and remitting disease course . ¹³ Factors indicative of a poor prognosis include :

• Severe symptoms and widespread disease

• Age younger than 50 years

• Childhood-onset disease

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• Poor compliance with drug treatment .

Genetic susceptibility In UC , the DR2 , DR9 and DRB1 * 0103 ( HLA class II genes ) have been identified as conferring susceptibility . DRB1 * 0103 is associated with extensive disease . ¹⁵

Intestinal microbial flora An imbalance of the intestinal microbiota , such as a reduction in specific Firmicutes bacteria and an increase in Bacteroidetes bacteria and facultative anaerobes , is a factor in the pathogenesis of UC . ¹⁶

Coeliac disease Clinical presentation and prognosis Coeliac disease occurs in genetically predisposed individuals whereby ingestion of gluten triggers damage in the small intestine . The key genetic elements ( human leukocyte antigens HLA-DQ2 and HLA-DQ8 ), the autoantigen involved ( tissue transglutaminase ; tTG ), and the environmental trigger ( gluten ) are all well-known in coeliac disease . ¹⁷

Coeliac disease can be classified as ‘ typical ’ or ‘ atypical ’. People with typical coeliac disease can be further classified as responding , resistant ( or non-responsive ) or refractory . Those with the atypical form can also be further classified as silent ( which includes intestinal and extraintestinal features but having less marked histological features than the typical

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