Gi 13: Gluten Sensitivity Disorders

Front 1

What are the symptoms of "Classic" Celiac Disease?

Back 1

- Diarrhea, bloating, abdominal pain and weight loss
- This is a less typical presentation presently (however still considered the "classic presentation"

Front 2

What are the symptoms of "Atypical" Sprue?

Back 2

"Atypical Sprue"
- Iron deficiency
- Osteoporosis
- Dermatitis herpetiformis
- IBS
- DM type 1
- Elevated LFTs

Front 3

What are the characteristics of "Asymptomatic" Sprue?

Back 3

- Relative of Sprue patient
- Positive antibodies (IgA EMA or tTG positive) and intestinal mucosal abnormality but NO SYMPTOMS

Front 4

What defines someone "above the blue line" in the celiac disease iceberg?

Back 4

They are positive for antibodies (IgA EMA or tTG positive) and have intestinal mucosal abnormality, however the symptoms differ from having no symptoms to having the classic symptoms

Front 5

How common is Celiac Disease?

Back 5

~1 in 100 in Norther European descent

Front 6

If you have a first-degree relative, what is your risk for Celiac Disease?

Back 6

1 in 10

Front 7

If you have a second-degree relative, what is your risk for Celiac Disease?

Back 7

1 in 39

Front 8

If you have a monozygotic twin, what is your risk for Celiac Disease?

Back 8

70-80%

Front 9

If you have an HLA identical sibling, what is your risk for Celiac Disease?

Back 9

40%

Front 10

When must you screen for Celiac Disease?

Back 10

1st degree relatives of patients with Celiac Disease which can help diagnose asymptomatic Celiac Disease

Front 11

Which part of the GI tract is most affected by Celiac Disease?

Back 11

Duodenum (it receives the most gluten)

Front 12

What are the non-GI complaints associated with Celiac Disease?

Back 12

- Unexplained iron-deficiency anemia (3% to 15%)
- Folic acid or vitamin B12 deficiency 
- Reduced serum albumin 
- Unexplained elevated LFTs (2% to 9%)

Front 13

What auto-immune disorders are associated with Celiac Disease?

Back 13

• Type 1 diabetes mellitus (2% to 15%)
• Thyroid dysfunction (2% to 7%)
• Addison disease
• Primary Biliary Cirrhosis
• Sjogren’s Disease
• Autoimmune hepatitis (3% to 6%)

Front 14

What genetic diseases are associated with Celiac Disease?

Back 14

(6-14%)
- Down Syndrome
- Turner Syndrome

Front 15

Which deficiency is associated with Celiac Disease?

Back 15

Selective IgA deficiency
- 2-5% of all patients w/ CD have IgA deficiency
- 9% of all IgA-deficient patients have CD

Front 16

What skin finding has a high association (~85%) with Celiac Disease? Symptoms?

Back 16

Dermatitis Herpetiformis
- Pruritic
- Papulovesicles
- Found on extensor surfaces of the extremities and on the trunk

Front 17

What are you thinking if you see pruritic papulovesicles on the extensor surfaces of the extremities and on the trunk?
How do you work up this patient?

Back 17

Dermatitis Herpetiformis - check for Celiac Diseases because ~85% have CD

Front 18

What is the most common non-GI presentation of Celiac Disease?

Back 18

Osteopenia and Osteoporosis

Front 19

How common is Osteopenia in Celiac Disease?

Back 19

- ~70% of patients with untreated CD
- ~30% of silent CD

Front 20

How common is Osteoporosis in Celiac Disease?

Back 20

>25% of all CD patients

Front 21

What should all newly diagnosed CD patients have tested? Why?

Back 21

Bone density test to look for Osteopenia and Osteoporosis

Front 22

How common is Celiac Disease in patients with osteoporosis? Should you screen them for CD?

Back 22

- ~3% of patients with osteoporosis have CD
- Controversial if new osteoporosis patients should be screened for CD

Front 23

What are the neurological symptoms of Celiac Disease? Specific causes when relevant?

Back 23

- Ataxia (likely B12 deficiency)
- Night blindness (Vitamin A deficiency)
- Seizures
- Headaches
- Epilepsy
- Mood disturbances
- Peripheral neuropathies

Front 24

What are the gynecologic and fertility issues associated with patients with Celiac Disease?

Back 24

- Amenorrhea in 1/3 untreated CD 
- Infertility common in untreated CD
- Common to become pregnant shortly after commencing a gluten free diet (may need to start birth control)
- Spontaneous abortions
- Intrauterine fetal growth retardation 
- Male infertility reported
- No clear recommendations on testing

Front 25

What is the pathogenesis of Celiac Disease?

Back 25

- Gluten comes in and is degraded by your enzymes into Gliadin
- Gliadin enters tissue and tissue transglutaminase (tTG) converts it to deamidated gliadin
- Deamidated gliadin is presented to APC
- Stimulates T cells, which release IFN-gamma
- Also stimulates B cells which release anti-gliadin, anti-endomysium, and anti-tTG antibodies which cause tissue inflammation

Front 26

What antibodies do B cells produce when presented with deamidated gliadin?

Back 26

- Anti-gliadin
- Anti-endomysium
- Anti-tTG (tissue transglutaminase)

Front 27

If you are suspecting Celiac Disease, how do you diagnose with serology?

Back 27

Screen for:
- IgA endomyseial antibody (EMA)
- IgA tissue transglutaminase (tTG)
- IgA and IgG Deaminated Gliadin Antibodies

(Anti-Gliadin antibodies of little value and IgA level is not technically recommended for screening)

Front 28

If you are suspecting Celiac Disease, what would you look for on small intestine biopsy / endoscopy?

Back 28

- “Scalloping” or “Notching” of the small bowel folds
- Small intestinal villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia

Front 29

When would you use an endoscopy / small intestine biopsy to look for Celiac Disease? Procedure?

Back 29

- Following positive serology
- Multiple biopsies should be obtained (total of six to eight biopsies probably optimal)

Front 30

What does this endoscopy show?

Back 30

- “Scalloping” or “Notching” of the small bowel (duodenum) folds
- Indicative of Celiac Disease

Front 31

What does this histology show?

Back 31

- Small intestinal villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia
- Indicative of Celiac Disease

Front 32

What are the pitfall in serologic tests for diagnosing Celiac Disease?

Back 32

False negatives for two reasons:
- Antibody levels fall on a gluten-free diet
- Celiac patient that is IgA deficient would not test positive for the antibodies you are screening for

Front 33

What happens to antibody levels when on a gluten free diet? Implications?

Back 33

- Fall within days in very mild disease
- Usually takes 6-8 weeks
- As long as a year in severe disease

- If someone has put themselves on a gluten-free diet it will be hard to know if they have Celiac Disease by screening for these antibodies because they will be decreased

Front 34

What are the implications of trying to diagnose a Celiac patient that is IgA deficient? Best tests / worst tests?

Back 34

- Makes IGA tTG and EMA, falsely negative
- IgG Abs useful in this situation
- IgG Deaminated Gliadin antibody best here
- Intestinal biopsy despite antibodies

Front 35

What are the pitfall in pathologic tests for diagnosing Celiac Disease?

Back 35

- Villous Atrophy may be patchy
• Were enough biopsies taken?
• Should we biopsy jejunum and ileum?

- Was patient on GFD?
• Takes 6 months to normalize
• May never normalize in adults.

- Not all Villous Atrophy is Celiac
• NSAIDs
• Infections
• IBD

Front 36

What are the genetic abnormalities are associated with Celiac Disease?

Back 36

Celiac Disease and HLA class II DQ
• 95% have DQ2 heterodimer
• 5% have DQ8 heterodimer

Essentially accounts for 100% of patients with Celiac Disease

Front 37

How common are positive DQ2 and DQ8 heterodimers in persons of European descent? What does this mean?

Back 37

~40% of persons of European ancestry are DQ2 or DQ8 positive (this does not mean that they all have Celiac Disease)

Front 38

What is the utility of evaluating if a patient is DQ2 or DQ8 heterodimer positive?

Back 38

- If negative, it can rule out Celiac Disease
- Useful for patients who want off a GFD

Front 39

What are the characteristics of a Gluten Free Diet?

Back 39

- Avoid all foods containing wheat, rye, and barley gluten
- Avoid malt
- Read all labels
- Beware of gluten in medications

Front 40

Why should we treat asymptomatic individuals?

Back 40

Long term prognosis:
- 4x increase in all causes of mortality (including cardiovascular disease and malignancy)
- Normalized with gluten free diet
- Normalizes risk of Enteropathy Associated T-Cell Lymphoma (20x increased risk w/o GFD)

Front 41

What are the malignant complications of Celiac Disease, even in asymptomatic individuals?

Back 41

Enteropathy Associated T-Cell Lymphoma:
- Most frequent malignant complication of Celiac Disease is High-grade T-Cell Non-Hodgkin Lymphoma

Front 42

What is the increased risk for Enteropathy Associated T-Cell Lymphoma in patients with Celiac Disease? Prognosis? How can you abate this risk?

Back 42

- 20x more common in CD than normal (although still rare)
- 5-year survival rate ~10%
- Risk normalizes on gluten free diet

Front 43

What is the effect of a gluten free diet on the extra-intestinal manifestations of Celiac Disease?

Back 43

- Osteoporosis - at least a partial improvement or prevention
- Iron Deficiency Anemia - improves
- Rashes - improve
- Avoid development of other auto-immune diseases
- Improves fertility

Front 44

What mediates a Wheat Allergy?

Back 44

IgE mediated

Front 45

What parts of the body are affected by a wheat allergy?

Back 45

- Skin
- GI tract
- Respiratory tract

Front 46

What are the symptoms of a wheat allergy?

Back 46

- Baker's asthma
- Rhinitis
- Contact urticaria
- Wheat-dependent, exercise-induced anaphylaxis (WDEIA)

Front 47

How common is a wheat allergy?

Back 47

0.5-2% although true anaphylaxis is rare

Front 48

What are the serological and endoscopic results in a wheat allergy?

Back 48

- Normal antibodies
- Normal intestinal mucosa

Front 49

How do you make a diagnosis of a wheat allergy?

Back 49

Allergy pin prick testing

Front 50

What is Non-Celiac Gluten sensitivity?

Back 50

- Patients who claim their symptoms (most commonly GI symptoms) feel better on a gluten free diet
- No evidence of Celiac disease
- Patients who have started a GFD without workup for Celiac Disease

Front 51

Why do Non-Celiac Gluten sensitivity patients feel better on a Gluten Free Diet?

Back 51

- Major change in dietary intake (lower carb, more fruit and veggies)
- Fructan fermentation by gut microbiota may cause symptoms (GFD may reduce ingestion of fructans)
- Withdrawal of fermentable oligosacchardies, disaccharides, monosaccharides, and polyols in IBS (FODMAP diet overlaps with GFD)

Front 52

How long is the interval between exposure to gluten and the onset of symptoms in:
- Celiac Disease
- Gluten Sensitivity
- Wheat Allergy

Back 52

- Celiac Disease: weeks to years
- Gluten Sensitivity: hours to days
- Wheat Allergy: minutes to hours

Front 53

What is the pathogenesis behind:
- Celiac Disease
- Gluten Sensitivity
- Wheat Allergy

Back 53

- Celiac Disease: auto-immunity (innate and adaptive immunity)
- Gluten Sensitivity: possibly innate immunity
- Wheat Allergy: allergic immune response

Front 54

What are the HLA findings in:
- Celiac Disease
- Gluten Sensitivity
- Wheat Allergy

Back 54

- Celiac Disease: restricted HLA-DQ2 or HLA-DQ8 (97% positive)
- Gluten Sensitivity: not restricted to HLA-DQ2 or -DQ8 (they are positive in 50% of patients)
- Wheat Allergy: not restricted to HLA-DQ2 or -DQ8 (positive in 35-40%, similar to general population)

Front 55

Presence of auto-antobidies:
- Celiac Disease
- Gluten Sensitivity
- Wheat Allergy

Back 55

- Celiac Disease: almost always present
- Gluten Sensitivity: always absent
- Wheat Allergy: always absent

Front 56

Enteropathy in:
- Celiac Disease
- Gluten Sensitivity
- Wheat Allergy

Back 56

- Celiac Disease: almost always present
- Gluten Sensitivity: always absent (slight increase in intraepithelial lymphocyte count)
- Wheat Allergy: always absent (eosinophils in lamina propria)

Front 57

Symptoms in:
- Celiac Disease
- Gluten Sensitivity
- Wheat Allergy

Back 57

- All have intestinal and extra-intestinal symptoms
- GI symptoms are not distinguishable from each other

Front 58

Complications in:
- Celiac Disease
- Gluten Sensitivity
- Wheat Allergy

Back 58

- Celiac Disease: co-existing (other auto-immune disorders) conditions, long-term complications
- Gluten Sensitivity: absence of co-existing conditions and long-term complications
- Wheat Allergy: absence of co-existing conditions, but presence of short term-complications (including anaphylaxis)

Front 59

What is the down side of a Gluten Free Diet?

Back 59

Not really any, except:
- May be inadequate iron, calcium, vitamin D, and B vitamins (usually resolved w/ multi-vitamin)
- Low fiber (watch for constipation)
- Difficult to eat out
- Social stigma
- No beer (but wine, most liquors, ciders, and spirits are allowed)
- Cost

Front 60

What did Environmental Enteropathy used to be called?

Back 60

Tropical Sprue

Front 61

What are the symptoms of Environmental Enteropathy / Tropical Sprue? Cause?

Back 61

Syndrome:
- Stunted growth
- Diarrhea (repeated bouts within first 2-3 years of life)

Cause:
- No infectious agent identified
- May be due to malnutrition because supplementary feeding and vitamin supplementation are able to reverse the syndrome
- Recurrent diarrhea establishes a cycle of mucosal injury, malnutrition, infection, and inflammation

Front 62

How common is Environmental Enteropathy?

Back 62

Affects >150 million children worldwide

Front 63

How does Environmental Enteropathy compare to Celiac Disease?

Back 63

Similar histologic features to severe diarrhea