Celiac's Disease

Question 1

Define Celiac Disease.

Answer 1

an autoimmune disease characterized by chronic intestinal inflammation and varying degrees of intestinal mucosal atrophy with associated malabsorption due to a reaction to non-digestible protein in wheat called gluten (not an allergy)

Question 2

What are the ‘classic’ celiac symptoms and what percentage of people exhibit these symptoms?

Answer 2

10% display classic symptoms of diarrhea with anemia

other presentations include severe steatorrhea, dissension and weight loss or failure to thrive, cramping and abdominal pain, flatulence, microcytic anemia without GI blood loss
symptoms get worse as day progresses

severe disease can occur with B12 deficiency- megaloblastic anemia, neurologic disease; infertility amenorrhea, osteoporosis and low vitamin D also possible

Question 3

At what point in the intestine do changes to the mucosa usually begin?

Answer 3

changes begin in the duodenum and extend distally (proximal bowel is more effected)

Question 4

List some extra intestinal manifestation of Celiac’s disease.

Answer 4

anemia (iron, folate, B12)
osteogenic bone disease (Ca, low Vit D)
muscle cramps, tetany (low Ca and Mg)
bleeding (vitamin K)
peripheral neuropathy
menstrual abnormalities, infertility

Question 5

What malignant disease does celiac’s put patients at risk for?

Answer 5

lymphoma- intestinal and extra intestinal
adenocarcinoma of the small bowel
squamous cell carcinoma of the esophagus

Question 6

What is the offending molecule in celiac disease?

Answer 6

gliadin: large polypeptide chain, a gliadin is the most reactive; is found in wheat, rye, barley

oat, rice are intermediate relatives

Question 7

What are the three variable that come together to produce celiac’s disease?

Answer 7

environmental trigger
genetic risk HLA DQ2/HLA DQ8
leaky gut

Question 8

Describe how an environmental trigger contributes to the pathogenesis of celiac’s disease.

Answer 8

gliadin is similar to adenovirus serotype 12, E1b protein– can act as an inflammatory trigger

Question 9

Describe the genetic predisposition that plays a role in celiac’s disease.

Answer 9

HLA DQ2 and HLA DQ8 are proteins on antigen presenting cells and they present gluten to helper T-cells, conferring greater sensitivity to the protein

Question 10

What causes the increased intestinal permeability in celiac’s disease?

Answer 10

tight junctions are opened by the messenger zonulin

Question 11

What is the action of tissue tranglutaminases in celiac’s disease?

Answer 11

tissue transglutaminase bind to the indigestible gluten fragments and form a complex with DQ2 and DQ8

transglutaminases are normally invovled in many functions such as tissue repair, signaling processes and cellular differentiation

they are found in the gut (TG2), skin (TG3) and brain (TG6)

Question 12

What is the end histological result of environmental trigger, genetic predisposition and leaky gut coming together?

Answer 12

increased number of intraepithelial lymphocytes in the small intestine; increased numbers of T-lymphocytes as well anti-gliadin antibodies are produced in the mucosa

Question 13

What antibody testing is done to diagnose celiacs?

Answer 13

IgA tissue tranglutaminase is the first line test, also check IgA levels to insure test is accurate in case of IgA deficiency; note if patient has been on a gluten free diet the test may be negative

IgG and IgA anti-gliadin antibodies can be helpful

Question 14

What would you find on PE in a patient with Celiacs?

Answer 14

completely normal PE on 90% patients

doughy abdomen, clubbing of nails, peripheral edema, ecchymosis, bone tenderness, peripheral neuropathy

Question 15

What will an endoscope reveal about the condition of the intestine?

Answer 15

scalloping or loss of circular folds in the duodenum which does not have its normal “shag carpet” appearance but is instead flat

proximal biopsy will reveal mucosal inflammation with chills atrophy and crypt hyperplasia with increased intraepithelial lymphocytes (these are not unique to this disease but are diagnostic in the right clinical context)

Question 16

What is the gold standard for diagnosis of celiac’s disease?

Answer 16

small bowel biopsy

Question 17

Describe the rash of dermatitis herpetiformis.

Answer 17

intensely pruritic, papulovesicular rash found on the extensor surfaces of the extremities, trunk, neck, scalp

80% of patients with DH have sprue, 10% of sprue patients have DH; it is treated with dapsone and a gluten free diet

Question 18

When and in who is dermatitis herpetiformis most often described?

Answer 18

typical onset in the teens or in the 3rd, 4th decade of life

2:1 male to female ratio, more common in caucasians and rare in people of african or asian descent

Question 19

What foods are known to contain gluten?

Answer 19

foods containing wheat, rye, barley, farina, gamut, triticale, spelt (initially avoid oat gluten (due to cross contamination)

beware gluten is often a food additive, emulsifier, stabilizer, hydrolyzed plant protein, starch, flavoring etc. e.g. ice cream, non-dairy creamer, hot dogs, peanut butter, stamp envelop blue, communion wafers

Question 20

What are common causes of treatment failure in celiacs?

Answer 20

contamination at home (i.e. of the toaster)
contamination while eating out
3-5% become refractory