Coeliac Disease Flashcards
Coeliac Disease
Coeliac disease is caused by sensitivity to the protein gluten. Repeated exposure leads to villous atrophy which in turn causes malabsorption. Conditions associated with coeliac disease include dermatitis herpetiformis (a vesicular, pruritic skin eruption) and autoimmune disorders (type 1 diabetes mellitus and autoimmune hepatitis).
Coeliac Disease - Diagnosis
Diagnosis is made by a combination of immunology and jejunal biopsy. Villous atrophy and immunology normally reverses on a gluten-free diet.
NICE issued guidelines on the investigation of coeliac disease in 2009. If patients are already taking a gluten-free diet they should be asked, if possible, to reintroduce gluten for at least 6 weeks prior to testing.
Immunology
tissue transglutaminase (TTG) antibodies (IgA) are first-choice according to NICE
endomyseal antibody (IgA)
anti-gliadin antibody (IgA or IgG) tests are not recommended by NICE
anti-casein antibodies are also found in some patients
Jejunal biopsy villous atrophy crypt hyperplasia increase in intraepithelial lymphocytes lamina propria infiltration with lymphocytes
Rectal gluten challenge has been described but is not widely used
NB If patient is suspected to be IgA deficient, they will test negative for Coeliac so alternative test = IgG TTG antibodies - Selective IgA Deficieny = False negative)
Coeliac Disease - Example Question
A 23 year old female presents with a 4 month history of diarrhoea with pale stools, and ‘tingling’ sensations in her fingers. There are intermittent episodes of mild ‘tummy pain’ but she is particularly aware that she no longer fits into dresses she wore 18 months ago. She has noticed a few mouth ulcers during this time but is not particularly distressed by them. She denies fevers or bloody stools. She has a family history of Crohns disease, with her mother diagnosed with the condition in her 30s. A friend encouraged her to abstain from wheats, ryes and oats, which she remembers to have helped. Over the past 6 months, she reports significant stresses on her university masters course and personal problems with her boyfriend. Her only travel history is a recent trip to India 3 months ago.
She had recently seen her GP for these symptoms: her anti-endomysial antibody however, was negative on serological testing and an initial colonscopy was non-diagnostic due to poor bowel preparation. Unfortunately, her sample for serum tissue transglutaminase antibody was lost. On examination, her abdomen is soft and non-tender, she appears pale and BMI = 14.7. She awaits a second colonoscopy. What is the most likely diagnosis?
Crohns disease Irritable bowel syndrome > Coeliac disease Ulcerative colitis Tropical sprue
The patient presents with vague symptoms of abdominal malabsorption that improves with abstinence to wheat and rye. The key to understanding this scenario is that although anti-endomysial antibody is extremely specific for celiac disease, it should be remembered that Coeliac disease also results in an IgA deficiency, which anti-endomysial antibodies (EMA) are. Therefore, positive anti-EMA is very diagnostic of Coeliac disease, a negative one is not. On the other hand, IgG tissue transglutaminase will be positive in this patient but was unfortunately lost.
There are a number of distractors in this scenario. IBS is a possibility but the improvement with diet change goes against this. The travel to India occurred after onset of symptoms and there is little to suggestive inflammatory bowel disease. Mouth ulcers can ulcer in Coeliac disease and are not synonymous with Crohns disease.
Coeliac Disease Definitive Diagnosis - Example Question
A 33-year-old lady was referred to the outpatient gastroenterology clinic by her GP who had diagnosed Irritable Bowel Syndrome refractory to symptomatic management. Her symptoms commenced six months ago with central abdominal cramping bloating made worse with eating wheat and oat based foods. She also noticed that the onset of the abdominal cramping was often associated with faecal urgency. Despite a prolonged trial of mebeverine, hyoscine butylbromide and peppermint oil there was no improvement in her symptoms. Her symptoms were however alleviated by avoiding the precipitating foods. She had not lost any weight and did not pass any blood per rectum; other than a family history of maternal depression there was no family history of note. Her past medical history was comprised depression for which she was prescribed citalopram 40mg OD; this was increased recently following worsening of her mood over the last few weeks.
Examination revealed the presence of a well 33-year-old lady. Her blood pressure was 112/72mmHg, heart rate 78 bpm and temperature 36.6ºC. Examination of her cardiovascular and respiratory systems was unremarkable. Examination of her gastrointestinal system was similarly unremarkable with no organomegaly, normal bowel sounds and the absence of lymphadenopathy. Examination of her forearms revealed the presence of multiple superficial lacerations.
Investigations conducted by her GP are as shown:
Hb 105 g/l
MCV 81 fl
Platelets 224 * 109/l
WBC 8.2 * 109/l
Bilirubin 19 µmol/l ALP 142 u/l ALT 33 u/l Protein 81 g/l Albumin 39 g/l
ESR 9 mm/hr CRP 12 mg/l TSH 0.75 (NR 0.4-3.6mu/ml) FT4 11.6 (NR 4.5-13.6 mcg/dl) IgG 7.2 (NR 5.8-15.4g/l) IgA 0.2 (NR 0.64-2.97g/l) IgM 1.2 (0.75-2.20g/l) B12 224 (NR 160-900 ng/l) Anti-endomysial antibody negative
What is the next most appropriate management option?
Organise oesophageal motility studies > Organise upper GI endoscopy and biopsy Commence trial with low dose amitriptyline Commence gluten exclusion diet Commence trial with domperidone
This lady has a history strongly suggestive of coeliac disease which GP the erroneously diagnosed as IBS; a common mistake to make. Of note her anti-endomysial antibody screening test was negative. This test has a sensitivity rate of 90% but of significance here is the incidental finding of selective IgA deficiency; as anti-endomysial antibody is IgA based, deficiency of IgA will result in a false negative finding and therefore this test has no negative predictive capability in this scenario. The next step is therefore to proceed to OGD and biopsy; whilst a gluten exclusion diet will aid her symptoms it is important to make a definitive diagnosis where possible.
Coeliac Disease - Example Question
A 20-year-old girl complains of feeling tired. She has no past medical history and takes no regular medications.
The following blood tests were obtained:
Hb 84g/L
MCV 70fL
WBC 8x10^9/L
Platelets 460x10^9/L
Blood film analysis comments on hypochromic anaemia with pencil cells, target cells, acanthocytes and Howell Jolly bodies.
What is the most likely diagnosis?
> COELIAC DISEASE
Sickle cell anaemia Hereditary spherocytosis Thalassaemia trait Iron deficiency anaemia Coeliac disease
The blood film shows hypochromic anaemia with the presence of pencil cells that indicates the patient has iron deficiency anaemia. Target cells, acanthocytes and Howell Jolly bodies are features of hyposplenism. Iron deficiency and functional hyposplenism are both seen in coeliac disease, which is therefore the most likely unifying diagnosis. Thalassaemia trait is associated with mild reduction in haemoglobin, low MCV and low MCH; there would not be evidence of hyposplenism on the film in thalassaemia trait. Hereditary spherocytosis is due to a deficiency in spectrin, which leads to an abnormal red blood cell cytoskeleton. The film would show spherocytic red blood cells and reticulocytes. In sickle cell anaemia MCV is usually normal and sickle cells would be seen on the blood film.
Coeliac Disease - Example Question
A 27-year-old man presents to the gastroenterology clinic with weight loss. He has a past medical history of coeliac disease diagnosed four years ago. Since then he has been advised to strictly comply with a gluten-free diet. His current weight is 69kg, reduced from 72kg two months ago. He has had an increase in the frequency of diarrhoea but has no other symptoms. On discussing his diet, he states that he typically eats rice, potatoes, oatmeal, fish, meats, chicken and dairy. He also drinks roughly four pints of beer per week. Which blood test is most useful in this situation?’
Liver function tests Thyroid function tests > IgA tissue transglutaminase or IgA deamidated gliadin peptide (coeliac serology) Full blood count (FBC) Ferritin
The correct answer is IgA tissue transglutaminase or IgA deamidated gliadin peptide (coeliac serology). He is a patient with coeliac disease who is having a diet which includes oatmeal, which is commonly contaminated with gluten, and continues to drink beer which commonly has high gluten levels. This means that a continued intake of gluten has lead to recurrence of symptoms; diarrhoea and weight loss in this case. Coeliac serology can be used to help monitor compliance in such patients.
The other blood tests would assess for complications and associated diseases in coeliac patients and should be tested for on an annual basis:
FBC and ferritin to look for anaemia
Thyroid function tests to look for autoimmune thyroiditis
Liver function tests to look for autoimmune hepatitis
Source:
‘Scenario: Management of Confirmed Coeliac Disease.’ Clinical Knowledge Summaries. National Institute for Health and Care Excellence, Mar. 2016
Coeliac Disease - Definitive Diagnosis: Example Question
A 23-year-old woman has been referred to the gastroenterology clinic. She has been found to have positive IgA tissue transglutaminase following investigations for chronic diarrhoea and weight loss. She has no other past medical history and takes no regular medications. As the diagnosis of coeliac disease was suspected she has omitted gluten over the last month. Which further investigation is recommended in confirming coeliac disease?
No further investigations are needed HLA DQ2 testing HLA DQ8 testing Endoscopic intestinal biopsy urgently > Endoscopic intestinal biopsy after re-introducing gluten for six weeks
The correct answer is endoscopic intestinal biopsy after re-introducing gluten for six weeks. This is a patient which symptoms matching coeliac disease who has tested positive with immunological studies. However, a diagnosis of coeliac disease requires a biopsy. To increase the diagnostic yield of the biopsy gluten should be re-introduced prior to the biopsy. HLA testing is only recommended in cases where biopsy would not be possible, but if the patient refuses biopsy it can be considered an option.
Source:
‘Coeliac disease: recognition, assessment and management.’ NICE guideline [NG20]. The National Institute for Health and Care Excellence, September 2015.
Coeliac and Osteomalacia - Example Question
A 28-year-old woman presents to the gastroenterology clinic for review. She has been diagnosed with coeliac disease some 2 years earlier, and has been suffering from severe tiredness, muscle aches and proximal weakness for the past few months. On examination her blood pressure is 112/70 mmHg, pulse is 75 beats per minute and regular. You confirm proximal muscle weakness.
Investigations
Ca++ 2.0 mmol/l
Alkaline phosphatase 275 IU/l
Which of the following is the most useful next investigation?
CK Parathyroid hormone > Vitamin D Muscle biopsy Electromyography
Coeliac disease is known to interfere with absorption of fat soluble vitamins, including vitamin D, and the low calcium and elevated alkaline phosphatase, coupled with symptoms of proximal myopathy fits with a diagnosis of osteomalacia. Vitamin D levels are therefore the next investigation of choice.
CK and muscle biopsy are indicated for possible inflammatory myositis, and the limited proximal weakness seen here, coupled with low calcium is much more consistent with osteomalacia. Parathyroid hormone may be elevated, but this is secondary to low vitamin D and calcium. Electromyography is most useful for assessment of motor neuropathy, which doesn’t fit with the painful proximal muscle weakness seen here.
Coeliac Complications
- Anaemia (Iron, folate, vit B12 deficiency, folate more common than B12)
- Hyposplenism
- Osteoporosis
- Osteomalacia
- Lactose intolerance
- Enteropathy-assoc T cell lymphoma of SI
- Subfertility
- Unfavourable pregnancy outcomes
- Rare = oesophageal Ca, Other malignancies
Coeliac Disease - Mx
Mx = GLUTEN FREE DIET
Gluten containing foods:
- Wheat: bread, pasta, pastry
- Barley, beer
- Rye
- Oats
NB Whisky is made using malted barley, proteins such as gluten however are removed during distillation process
Some notable Gluten free foods:
- Rice
- Potatoes
- Corn (maize)
Tissue transglutaminase antibodies may be checked to check compliance w gluten free diet
NB: Pts with coeliac disease often have a degree of Functional Hyposplenism, for this reason all patients with coeliac disease are offered pneumococcal vaccine. Influenza vaccine given on an individual basis
Jejunal Atrophy
Whilst Coeliac disease is the classical cause of Jejunal Villous Atrophy there are also a number of other causes you need to be aware of:
- Coeliac disease
- Tropical Sprue
- Hypogammaglobulinaemia
- Gastrointestinal lymphoma
- Whipple’s disease
- Cow’s milk intolerance
Coeliac Disease and Vitamin D
Coeliac disease is known to interfere with absorption of fat soluble vitamins, including vitamin D
If low calcium, elevated alkaline phosphatase, coupled with symptoms of proximal myopathy = fits with a diagnosis of osteomalacia.
Parathyroid hormone may be elevated secondary to low vitamin D and calcium.
Coeliac Disease - Blood Film
Blood film analysis comments on hypochromic anaemia with pencil cells, target cells, acanthocytes and Howell Jolly bodies.
Hypochromic anaemia with the presence of pencil cells that indicates the patient has iron deficiency anaemia. Target cells, acanthocytes and Howell Jolly bodies are features of hyposplenism. Iron deficiency and functional hyposplenism are both seen in coeliac disease.
