Celiac's Disease Flashcards
What does the body lose tolerance to?
How is this substance processed in the gut?
Increased levels of de-amidated gliadin peptide
Gluten is comprised of gliadin
Gliadin converted to de-amidated gliadin by tissue transglutaminase once passage across the mucosa
What genetic predisposition towards autoimmunity is there?
What antibodies are produced?
HLA-DQ2 (95% have heterodimer) & HLA-DQ8 (5% have heterodimer) genes
Tissue transglutaminase, endomysium, gliadin peptide antibodies
What type of hypersensitivity reaction is involved?
What is the mechanism involved?
Type IV
Th1 increases IFNg which induces IgA and IgG plasma cells
Macrophage and PMN invasion
What are the signs of classic Celiac’s?
Is this representative?
Diarrhea, bloating, abdominal pain, weight loss
Possible growth retardation, failure to thrive
Actually atypical
What are the levels of CD?
What signs does each show?
Latent and healthy - Lack of antibodies
Silent celiac sprue - Show mucosal abnormalities
Atypical celiac sprue
Classic celiac sprue
Who is likely to have silent celiac sprue?
What is the risk for them?
Relative of Sprue patient
May be susceptible of progressing
What are the major symptoms of atypical celiac sprue?
Iron deficiency
Osteoporosis
Dermatitis Herpetiformis
IBS
T1DM
Elevated LFTs (idiopathic)
What is the prelavence of CD?
What are the risks for relatives?
1 in 100 northern European descent
Iron deficiency
Osteoporosis
Dermatitis Herpetiformis
IBS
T1DM
Elevated LFTs (idiopathic)
Where does CD affect in the GI?
Can affect any part of the intestine
Primarily occurs at duodenum – Highest exposure of gluten
What GI/nutrient related atypical issues can result from CD?
Unexplained iron-deficiency anemia (3 to 15%)
Folic acid or B12 deficiency
Reduced serum albumin
Unexplained Elevated LFTs
What autoimmune disorders are related to CD?
What genetic syndromes?
What immunodeficiency?
T1DM
Thyroid dysfunction
Addison’s
PBC
Sjogren’s Disease
Autoimmune Hepatitis
Down syndrome and Turner Syndrome (6-14%)
Selective IgA deficiency
What is dermatis herpetiformis?
How is it treated?
Pruritic, papulovesicles
Extensor surface of the extremities on the trunk
Regardless of cause, treated with gluten elimination
What is the most common non-GI presentation of CD?
What should all newly diagnosed CD patients have?
Should those with this presentation be screened for CD?
Bone Diseases (Osteopenia/Osteoporosis)
Bone Scan
Controversial
What neurologic symptoms do CD patients have?
Why?
Ataxia
Night blindness
Seizures
Headaches
Epilepsy
Mood disturbances
Peripheral neuropathies
Vitamin Malnutrition
What gynecologic and fertility problems are there wtih CD?
Amenorrhea 1/3 untreated CD
Female infertility common in untreated CD- Common to become pregnant shortly after commencing a GFD
Spontaneous abortions
Intrauterine fetal growth retardation
Male infertility reported (rarer)
What are the most useful tests for CD?
How about Anti-Gliadin Antibodies?
How about general IgA?
IgA Endomysial antibody (EMA)
IgA Tissue Transglutaminase (tTG)
IgA and IgG Deamidated Gliadin Antibodies
Little value, “CRP of the gut”
IgA Level – Technically not recommended for screening
What are the causes of false negatives in serology?
How can each be addressed?
Ab levels fall on a gluten-free diet
Within days in very mild disease
Usually takes 6-8 weeks
AS long as a year in severe disease
Celiac patient that is IgA deficient
IgG Abs useful in this situation
IgG deamidated Gliadin
Biopsy
What is seen on the small intestine biopsy of CD?
When is it done?
How many should be taken?
“Scalloping” or “Notching” of the small bowel folds
Small intestinal villous atrophy
Increase of intraepithelial lymphocytes
Crypt hyperplasia
Following positive serology
Multiple biopsies should be obtained – Total of 6 to 8
What issues are there with biopsies?
Villous atrophy can 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
What is the problem with genetic testing?
When is it useful?
40% of European ancestry are DQ2 or DQ8 positive
Most helpful in ruling out Celiac Disease
Useful for patients who want off a GFD
How do you treat CD?
Gluten Free Diet
What are the major things that need to be avoided on a GFD?
Avoid all food containing wheat rye and barley gluten
Avoid malt
Read all labels
Beware of gluten in medications
What are the down-sides of a GFD?
Not much
Iron, Calcium, Vitamin D, and B Vitamin deficiencies - Use a multivitamin
GFD is low fiber – Watch for constipation
Replacement with sugary foods, simple carbohydrates
Difficult to eat out/Social Stigma
Costly/Inability to maintain for long term if not necessary
Should asymptomatic individuals be treated with GFD?
What can it affect?
Four fold increase in all-cause mortality if untreated
Often CVD and malignancy likely normalized with GFD
Less likely to get Enteropathy Associated T-cell Lymphoma
Osteoporosis – Improvement on GFD
IDA – Improvement on GFD
Rashes improved
Avoid development of other autoimmune diseases
Improves fertility
What is enteropathy associated T-cell lymphoma?
How is survival?
What is the CD associated risk?
Malignant Complication
High-grade T-cell NHL
5 year survival rate ~10%
Occurs ~20x more frequently in patients with CD
Normalized risk with GFD
Where does wheat allergy affect?
What kind of disease it and what are the different types of it?
What is the prevalence?
What is the serology?
What is the biopsy?
How is it diagnosed?
Classic food allergy affecting Skin, GI, Respiratory tract
IgE Mediated Diseases
Baker’s asthma
Rhinitis
Contact urticarial
Wheat-dependent, exercise-induced anaphylaxis
Prevalence is about 0.5 to 2%
True anaphylaxis is rare
Normal antibodies
Normal intestinal mucosa
Diagnosis made by allergy pin prick testing
What is non-celiac gluten sensitivity?
How many people have tried a GFD?
Is this a fad?
Is it real?
What are the genetics?
Is there enteropathy?
Patients who claim symptoms feel better on a GFD
17 million people have tried a GFD
Patient driven and likely to stay - Massive growth of the gluten free diet
Literature is unclear but evidence appears to be growing that it is a real phenomenon
Not restricted to HLA-DQ2 or HLA-DQ8
Enteropathy – Almost always absent
Why do patients feel better?
Change in dietary intake: Lower carbs, more fruits and veggies, arguably “healthier” choices
Fermentable fructans may cause symptoms
Fermentation and gas production by gut microbiota
Reduction of gluten may inadvertently be reducing the ingestion of fructans
Withdrawal of fermentable oligosaccharides, disaccharides, monosaccharides which play a role in IBS
What is environemental enteropathy/tropical sprue?
Where does it affect?
Who does it affect?
What is the process of pathogenesis?
How does it manifest?
What is the histology?
- *Very Unlikely to be Tested On**
- *Just Added For Completeness**
Syndrome of stunted growth and diarrhea
Developing world
Affects > 150 million children worldwide
Malnutrition thought to make susceptible to pathogenesis
Thought to be reversible if fed/nutrition restored
Recurrent diarrhea establishes a cycle of mucosal injury, malnutrition, infection, inflammation
Repeated bouts of diarrhea within 2 or 3 years of life
No single infectious agent
Histiologic features similar to severe celiac disease
