Malabsorption Syndrome

Question 1

How common is Coeliac disease?

Answer 1

Affects ~ 1% of UK population

Question 2

What is Coeliac disease?

Answer 2

• intolerance to gluten
• in particular, gliadin, the alcohol-free fraction of gluten, is the disease-producing component
• gluten is found in wheat, barley and rye

Question 3

What is the brief pathogenesis of coeliac disease?

Answer 3

• not fully understood
• thought that gliadin triggers inappropriate activation
• of intestinal T cells
• in genetically susceptible individuals (ppl w/ HLA-DQ2 and HLA-DQ8 haplotypes)
• resulting in damage to epithelial cells

Question 4

Now explain in more detail what happens in patients with coeliac when gluten is digested in comparison to a healthy individual?

Answer 4

• gluten digested by luminal and brush-border enzymes in small intestine
• into aino acids + peptides, incl 33AA gliadin peptide
• gliadin is deamidated in mucosa by tissue transglutaminases (tTG)
• in those w/ HLA-DQ2 and HLA-DQ8 haplotypes, deamidated gliadin closely fits the MHC II grooves
• gliadin presented to T helper cells by antigen presenting cells
• initiates a Th2-predominant immune response
• generates cytotoxic T cells against gliadin
• cytotoxic T cells migrate into intestinal epithelium, visible on biopsy as intraepithelial lymphocytes
• the T cells damage + destroy epithelial cells resulting in progressive villous atrophy
• as a result, crypts become hyperplastic to compensate for cell loss
• loss of normal small bowel fxn -> malabsorption
• also a humoral immune response w/ generation of antigliadin, antiendoymysial and antiTTG antibodies - useful antibodies diagnostically

Question 5

What is the clinical presentation of coeliac disease?

Answer 5

• at any age, most commonly in childhood or middle age
• symptoms of malabsorption (diarrhoea, steatorrhoea, weight loss, lethargy, bloating, abdo pain)
• non-specific symptoms: eg. anaemia (usually iron def), irritable bowel syndrome-like symptoms, altered bowel habit, abdo pain
• in children, coeliac disease is an important cause of failure to thrive and delayed puberty
• an intensely itchy and blistering rash over elbows + buttocks - dermatitis herpetiformis
• some pts are asymptomatic and diagnosis is discovered incidentally

Question 6

How is coeliac disease diagnosed?

Answer 6

• history and examination
• gluten-containing diet better to be consumed during diagnostic process
• serology tests: total IgA and IgA tissue transglutaminase antibodies are currently the preferred first line test (owing to its high sensitivity and negative predictive value)
• IgA anti-endomysial (EMA) antibodies can be used if IgA tTG is weakly positive
• gold standard ix: endoscopy and duodenal biopsy

Question 7

What does tissue biopsy for positive coeliac show?

Answer 7

• villous atrophy
• crypt hyperplasia
• prominent intraepithelial lymphocytes

Generally agreed that duodenal biopsy should be performed on all adult patients to confirm the diagnosis

Question 8

What is the treatment for coeliac?

Answer 8

• Life-long gluten-free diet
• Those with coeliac disease (+ fam members, carers) should be given sources of info on the disease, including a national and local specialist coeliac groups and dietiticans with a specialist knowledge of coeliac disease

Question 9

What are complications of coeliac disease?

Answer 9

• Malabsorption (-> anaemia + deficiencies)
• Osteopenia/osteoporosis
• Dermatitis herpetiformis
• Lymphoma

Question 10

Why do patients with coeliac develop osteopenia/osteoporosis? How can this be investigated and treated?

Answer 10

• most pts w/ coeliac disease are osteopenic (reduced bone density)
• bc they fail to reach their peak bone mass during young adult life
• due to malabsorption of calcium
• reduction in bone density is usually mild, most pts are only osteopenic
• however, some are actually osteoporotic w/ associated risk of fracture
• at dx, pts given lifestyle advice + basline DEXA scan to assess bone mineral density
• pts should maintian adequate calcium and vit D intake
• a gluten-free diet should prevent further bone loss and may improve bone density

Question 11

Why do coeliac patients develop dermatitis herpetiformis?

Answer 11

• intensely itchy chronic blistering skin condition
• typically occurs symmetrically on extensor surfaces (buttocks, back of neck, knees, elbows etc)
• it’s not related to herpes virus
• rather, associated w/ coeliac disease although exact mechanism not fully understood
• may be due to autoantibodies to epidermal transglutaminase