Celiac Disease Flashcards
What is celiac disease?
An auto-immune disease which results in the permanent sensitivity to gluten resulting in damage to intestinal mucosa
–> we dont necessarily know the trigger, and there is not cure
What is the genetic and autoimmune linkage of celiac disease?
- if 1 in 22 1st degree relatives, the risk goes up
- Major genes HLA-DQ2 and HLA-DQ8 in 95% of patients
- However having these genes doent necessarily mean that we will encounter the trigger which will cause CD, but the risk is there
What is the incidence of CD?
- Estimated 0.9% but no Canadian data
- 0.9% of Canadian children would be 16540
Prevalence of CD?
- Estimated at >1%
- About 330,000 Canadian
Who is at risk for celiac disease?
- 9-14% of those with symptomatic iron deficiency have CD
- 1-3% of those with osteoporosis evident have CD
Median age of diagnosis of CD in Canada?
40-49
–> However, diagnosis is done throughout the lifespan and depends on when the trigger was realized
What is the mean delay in diagnosis of CD?
11.7 years
Risk factors for CD?
- Dermatitis herpetiformis
- First-degree relative with CD
- Autoimmune thyroid disease
- Down syndrome
- T1DM
Which risk factors has a 100% prevalence of CD?
Dermatitis herpetiformis
When does an active state occur in CD?
-Occurs when the gluten from wheat, rye, malt and barley are eaten and is digested to yield alpha-gliadin. Causes the infiltration of WBC and production of IgA antibodies
What are the theories for the development of CD?
- Young age of introduction
- Short duration of breast-feeding
- Viral infections in infancy
What is the only treatment for CD?
A Gluten-free diet
How are many CD patients misdiagnosed?
With IBS or IBD
What is dermatitis herpetifomis?
- Found on 100% of those with CD
- The enzymes which our immune system become confused with with not only attack the GI tract, but will also attack the skin which results in the formation of the blister
Why autoimmune thyroid disease in CD?
-The same enzymes in the confused immune system that target the GI will also target the thyroid
Do people die from CD?
Yes, therefore we must intervene and therapy is important
(T/F) Gluten can trigger the development of CD (i.e. by triggering the pre-disposing gene)
F
Gluten will only trigger AFTER the CD is already established. Gluten will trigger and active diseased state
What may cause a false negative diagnosis of CD?
When they are deficient in IgA antibodies, but they still are CD
Key gluten containing foods?
- Wheat
- Rye
- Malt
- Barley
Discuss the pathophysiology of CD
- The gluten is broken down into gliadin protein
- The gliadin protein will become deaminated gliadin with the tissue transaminanse enzyme
- The deaminiated gliadin is picked up by the APC, which is presented to the naive-T cells in the payers patch and lymphnodes of the GI.
- This produces an inflammatory response, and there are killer T-cells now primed against the deaminated gliadin
- Cytokines are then released by WBC
Where is the IgA antibodies?
Found on the luminal mucosa of the GI tract, the “immune system” of the intestinal mucosa
Pathophysiological consequence of CD?
- Damage to villi, reduced height and flattened microvilli
- Decreased enzyme function and surface area
- Consequential maldigestion and malabsorptions
Which tissues have tissue transaminase?
-Thyroid
-Brain
-Pancreas
-Skin
Where the immune cells will also attack these tissues and will cause issues q
What is notable of the diarrhea in CD?
it originates in the small intestine, rather than within the bowel
What are the classical manifestation of Celiac Disease?
-Diarrhea, abdominal pain, cramping, bloating and gas
What are the “atypical” (but now more commonly acknowledged) clinical manifestations of CD?
- Bone and joint pain
- Muscle cramping and fatigue
- Peripheral neuropathy and seizures
- Skin rash
- Mouth ulcerations
- Higher risk of lymphoma and osteoporosis
–>Now more used regularly in the diagnosis
Common signs and symptoms of CD?
- Diarrhea
- Fatigue
- Borborygmus
- Abdominal Pain
- Weight loss
- Abdominal Distention
- Flatulence
Uncommon signs and symptoms of CD?
- Osteopenia and osteoporosis
- Abnormal liver function
- Iron-deficiency anemia
- Neurologic dysfunction
- Constipation
- Nausea
Up to___ of CD are asymptomatic
38%
Common sign and symptoms of celiac disease?
- Diarrhea
- Fatigue
- Borborygmus
- Abdominal pain
- Weight loss
- Abdominal distention
- Flatulence
Uncommon signs and symptoms of celiac disease?
- Osteopenia/osteoporosis
- Abnormal liver function
- Vomiting
- IDA
- Neurologic dysfunction
- Constipation
- Nausea
Up to ___ have non-classical symptoms
85%
What are the MOST common presenting symptoms?
- Abdominal pain
- Diarrhea
- Weight loss
What may be the reason for the mean delay in diagnosis?
- The mean delay in diagnosis is 11.7 years
- Not all symptoms follow the “classic” pattern, thus can delay diagnosis
What are common diagnoses made prior to celiac disease?
- Anemia
- Stress
- Irritable bowel syndrome
- Sometimes osteoporosis
How does CD often present clinically in children?
As PEM
- Leading to failure to thrive and issues with neurological deficiencies
- IDA in newborns is worse than IDA in utero
What is a clinical sign of iron deficiency?
Koilonychia or spoon shaped nails
What other clinical signs may be present in CVD?
- Finger clubbing
- Although cause is unclear
- Also associated with CF, Celiac disease, IBD and hepatic diseases
What is important to consider about symptoms and celiac disease?
Those with outward symptoms are fewer than those asymptomatic, or with less specific symptoms
- Often those with classical celiac disease are only 1:4500
- Those with atypical, silent or latent CD are 1:250
- Therefore screening is extremely important
In adults, which types of CD are the most problematic?
Silent and Latent, as if they go undetected and untreated may go on and develop cancer
What does the diagnosis of CD consist of? Why is the order of diagnosis important?
1) Physical exam and blood testing for the tTG antibodies
2) Duodenal biopsy
3) Implementation of the gluten-free diet
- -> Order is important, as if e start with the gluten-free diet other tests will simply come back negative
What is refractory CD?
- Due to a co-existing disease
- Does NOT respond to a gluten-free diet
What antibodies are tested for in CD?
- Gliadin antibodies
- IgA Endomysial antibodies
- IgA tTG antibodies
Which antibody test is NO longer recommended? Why?
- Gliadin antibodies
- Low sensitivity and specificity for celiac disease
What is the sensitivity and specificity to IgA endomysial and tTG antibodies?
- > 95%
* *However, the individual must be producing IgA, some people do not produce IgA**
If following normal treatment and it is effective, how can we suspect IgA endomysial and tTG antibodies to react?
- They should return to normal if treatment adhered to after 3-12 months
- If detected after, it may suggest non-compliance or hidden gluten
What is the recommended single serologic test for CD screening in the primary care setting?
- tTG antibody test
- less costly as it uses an enzyme-linked immunosorbent assay
What is the positive predicative value in the tTG antibody test?
- 7%
- ->If we have a normal tTG test, it is likely correct
What is the negative predictive value of the tTG antibody test?
99.9%
(T/F) The prevalence of CD is low in the general population, the risk of a false-positive result is high even with an accurate test
T
–> Therefore, confirmatory testing, including the small bowel biopsy is advised
What are the 3 types of IgA antibodies in CD?
- Anti-gliadin
- Anti-endomysial
- Anti-tTG
What may produce a false negative in testing for CD in blood work?
When there is an IgA deficiency
What may produce a false positive in testing for CD in bloodwork?
A positive tTG, as it is also present in IBD
-Has a specificity of 97-98%
tTG IgA negative for CD?
<4.0 U/ml
tTG IgA weak positive for CD?
4.0-10.0 U/ml
tTG IgA positive for CD?
> 10.0 Y/ml
What is required to confirm the biopsy in most?
Small intestine biopsy
When should a small intestine biopsy be considered?
- In most to confirm the diagnosis
- Patients with negative serological results, but are at high risk
- When the physician strongly suspects celiac disease
Discuss the mucosal changes expected to be observed upon tissue biopsy for someone with CD
- Partial to total villous atrophy
- Subtle crypt lengthening
- Increased epithelial lymphocytes
How can false negative results on the endoscopic biopsy be avoided?
By providing at least 4 tissue samples, which will increase the sensitivity of the test
How do patients need to prep for the endoscopy?
- Will likely be sedated
- May have to fast
- Will require to eat gluten diet and check, then do one without gluten and check again and seethe comparison
What does the Marsh scoring system help us grade?
The progression in the destruction of the villi or GI specimen which can help us interpret the absorption and our nutritional intervention
–> 0 is considered absent, and 4 is considered severe
How does the lymph-node involvement impact our nutritional intervention?
Will cause inflammation on both the gut-mucosa and lamina propria sides
–> This will eventually cause lots of inflammation and will heavily impact any absorption capabilities
Silent presentation of celiac disease?
- No signs or symptoms
- Positive Ab
- Abnormal biopsy
Latent presentation of celiac disease?
- No signs or symptoms
- Positive Ab
- Normal biopsy
- OR in remission
- -> This means that we want them to get to the latent stage to get remission.
Someone with silent CD says that they eat gluten but feel fine. What is your impression?
The nature of their atypical disease presentation means that this is normal, however it does not mean that there isn’t the trigger of the autoimmune response internally. Therefore, they still need to adhere to a GF diet even if they do not present with external signs and symptoms
What are the co-morbidities associate with CD?
- Osteoporosis
- Thyroid dysfunction
- Deficiencies in folic acid, vitamin B12, fat-soluble vitamins and iron
- Cancers
Why is there increased mortality in CD?
- Due to high risk of malignancy
- 3-6x more likely to develop non-hodgkin’s lymphoma
- Common cancers include oropharyngeal, esophageal and small intestinal adenocarcinoma
What is the gluten challenge?
If the patient is following a GF diet prior to dx, the standard of care is to consume two serving of gluten containing foods per day for up to 8 weeks and then return of serological testing and duodenal biopsy.
What did the short-course 14-28 days on a 3-7.5 g gluten diet per day study show?
- Resulted 20 adults biopsy proven to have celiac disease
- As little as 3 g of gluten per day induces damage to the GIT based on histological assessments
- Caused decreased villous height to crypt death ration and increased intraepithelial lymphocyte counts
What are key elements successful to the treatment of CD?
- The motivation of the patient
- Physician treatment of co-morbidities
- Formal consultation with a registered dietitian is necessary
What did the NIH identify as the six key elements essential to treating celiac disease once it is diagnosed? (CELIAC Acronym)
- Consultation with a skilled registered dietitian
- Education about the disease
- Lifelong adherence to a gluten-free diet
- Identification an treatment of nutritional deficiencies
- Access to an advocacy group
- Continuous, long-term follow-up
What are the effects of the gluten-free diet?
- Relief of outward symptoms in 2-3 weeks and in 70-90% of patients
- GIT and nutrient deficiencies may take more time
What should be considered when some patients continue to experience symptoms, including intestinal damage despite following a gluten-free diet?
- Consider the contamination sources
- May have refractory celiac disease due to another condition
Which wheat derivatives also include gluten?
-Bulgar, couscous, mataza, seitan, semolina, triticale, spelt, kamut, einkorn, emmer and anything with wheat in title
(T/F) Buckwheat is gluten-free
T
In Canada, what is considered gluten free?
- When <20 ppm gluten or 20 mg/kg
- There is 10 mg of gluten in 1/8th tsp of wheat flour
- Equivalent to 1/350th slice of bread
What is considered GF in USA & Europe?
<20 ppm of gluten
What are other considerations for GF?
- Imported foods
- Travel
- Contamination of gluten
Typical foods to avoid on the gluten-free diet?
- Barley
- Beer, ale, lager
- Bulgur, couscous , croutons, farine
- Hydrolyzed wheat protein
- Rye bread and flour
- Wheat bran, wheat flour, wheat germ and wheat starch
- Malt vinegar
Other names for wheat?
- Dinkel (Spelt)
- Durum, Einkorn
- Emmer, Farro
what is other names for spelt?
Farro and dinkel
Other less common gluten containing foods?
-Atta (chapatti flour)
-Brewers yeast
-Communion wafers
Fu (used as a protein supplement in Asian dishes)
-Graham flour
-Malt
-Matzoh
-Oats
Are oats gluten free?
Oats are contaminated unless they are certified GF
Which grains are OK in GF diet?
- Corn
- Rice
- Buckwheat
- Wild rice
- Amaranth
- Quinoa
- Teff
- Millet
- Sorghum
Which other foods are safe in a GF diet?
-All vegetables, legumes, fruit, natural meats, fish, shellfish, eggs, naturally dairy, nuts potatoes, tapioca and arrowroot
Why must natural meats be used?
Potential gluten or wheat containing preservatives in deli meats
How much
uncontaminated oats is safe per day?
Up to 50 g/day which an OLD recommendation, no no conclusive evidence for a certain amount tolerated
Canadian Position on Gluten Free Oats?
- <20 ppm define uncontaminated oats
- Can be safely ingested by most patients
- No conclusive evidence of a certain amount tolerate each day
- Should have a stabilization phase before introducing uncontaminated oats 60 months after GFD minimum
- Long-term follow-up of patients consuming gluten-free oars is not different from regular practice
What is the issue with most gluten-free foods on the market?
Most are NOT fortified with the proper vitamins and mineral
How has the popularity of the gluten-free diet saturated the restaurant market in the recent 2018 meta analysis?
Median prevalence of gluten-free foods available in about 50-80% of establishments depending the study
What is the cost of a gluten free diet?
- On average, 242% more expensive
- GF mean unit price: $1.71
- Regular products: $0.61
Assessment in CD?
- Body weight
- Micronutrient deficiencies
- Fibre, as wheat is omitted
Common micronutrient deficiencies in CD?
- Folate (RBC folate)
- Ferritin
- 25-hydroxy vitamin D
- Vitamin A
- Vitamin B12
Management of CD?
- GF diet which is often nutrient dense, and weight-gain is a common outcome
- Common to recommend a MV or mineral supplement, especially iron, calcium, vitamin D and fibre
Which teaching components regarding nutritional education should be considered upon the first initial visit?
- Defining celiac disease, reviewing symptoms and treatment
- Define gluten and identify common sources
- Discuss diet modification, limitations, eating out, potential barriers
- Diet fortification and supplementation if required
What should be considered in follow-up in a GF consult?
- Re-evaluate food record
- Labs: iron studies, vitamin B12 and hemoglobin to make sure they return to normal
- Vitamin D for increased risk of osteopenia
- Weight
- Overall compliance, affordability, barriers to compliance, accessibility
What is the CSI?
Celiac Symptom Index
–> Consists of a 16-item questionnaire
What does as CSI with a score of less than 30?
- Associated with a high quality of life and excellent GFD adherence
- Suggestive of clinical remission
What does a CSI score greater than 45 indicate?
- Associated with relatively poor quality of life and worse GFD adherence
- Suggesting ongoing active celiac disease
What would be a classic presentation s/p gastroduodensocopy in a celiac patient?
- Grooving in the second part of the duodenum
- Biopsy revealing increased intraepithelial lymphocytes and crypt hyperplasia
A 15 y/o F is referred to you with IDA, normal menstrual cycles and no typical complaints of the GI tracts consited with CD or IBS. Upon review of he 24 hr recall, iron intake seems to be sufficient, same with folate. She also regularly took B12 supplements. What is your impression?
- The IDA is likely due to CD, and not ID from the diet. As an RD, we can refer to MD to confirm CD.
- In the meantime, we can suggest an iron supplement
A 38 y/o W is referred for colonoscopy due to complaints of post-natal diarrhea. She has a low BMI of 17, low albumin, elevated liver enzymes (which is common in GI issues). After failed supplements to increase weight, she is referred to the RD. What is your intervention?
- Low gluten and low-lactose diet with pancreatic supplements
- Rationale as the sum of the poor digestion together with the hypoalbuminemia ca worsen absorption. Pancreatic enzymes would be a possible effective solution in this case.
- However, we could suggest CD testing by the physician, which was positive.
Discuss key points regarding the Canadian perspective in living with celiac disease
- Women report significantly greater emotional response of GFD, more accepting than men
- Difficulties and negative emotions were experienced less frequently by those on the diet >5 years
- Frustration and isolation were the most common negative emotions experienced
From a study requiring participants to identify GF foods, which ones where the most frequently falsely identified as OK to eat?
- Imitation crab meat
- Egg noodles
- Spelt
From a study requiring participants to identify GF foods, which ones where the most frequently falsely identified as NOT OK to eat?
- Modified corn starch
- Glutinous rice
- Molasses
In the study, what was knowledge of identification of gluten by patients linked to?
- NOT linked to duration of disease, sex, education, grocery shopping, family member with celiac disease or education by an RD
- Higher if member of Canadian Celiac Association
What is the bottom line of the patient burden of gluten free diet?
- They have and high treatment burden due to dietary therapy, but have excellent overall health status in comparison with other chronic medical conditions.
- Therefore, the significant burden of dietary therapy argues fo the need of a safe adjuvant therapy, as well as intervention to lower the perceived burden of GFD
