celiac disease

mild celiac disease

Mild iron deficiency anemia Iron and folate deficiency

Latent celiac disease

Positive serology only -no abnormalities on biopsy

Endoscopic appearance and sprue

Scalping and decreased folds

Celiac disease antibody testing false negatives

Serologic Tests may be *falsely negative in patients with selective IgA deficiency* -2% of celiac patients

other names for celiac disease

Sprue Non Tropical Sprue Celiac Sprue Gluten Sensitive Enteropathy

Collagenous sprue

Subtype of refractory sprue, thick collagen band is seen in this sub mucosa on microscopy

Celiac disease pathophysiology

Tissue transglutaminase binds to the indigestible gluten fragment The fragment complex tightly binds to DQ2 or DQ8

Dermatitis Herpetiformis defined

Typical onset in the *teens or in the third or fourth decades of life. * -In the U.S., diagnosed cases about 1 in 10,000 -*male/female ratio of 2:1.* -More common in caucasians -rare in people of African or Asian descent.

Proximal bowel biopsy pathology seen

mucosal inflammation → villus atrophy → crypt hyperplasia → Increased Intraepithelial lymphocytes

Small Bowel Bx in Celiac Disease

same appearance with eosinophilic enteritis, tropical sprue, milk protein intolerance, lymphoma, etc.

Presentation of celiac disease

*Widely variable presentation * -from severe steatorrhea, distension and weight loss or failure to thrive to cramping and abdominal pain. -tympanitis doughy abdomen on exam -Some asymptomatic -*Microcytic anemia / iron deficiency without GI blood loss* -can present in children or adults

Celiac disease and osteoporosis

-*10 million in the U.S., 80% women* -18 million with osteopenia -Cost of 10 - 15 billion dollars

Extra intestinal manifestations of celiac disease

-*Anemia* - (iron, folate, B12) -*Osteogenic bone disease* (Ca, low vitamin D) -*Muscle cramps, tetany *(Low Ca++, Mg++) -*Bleeding *(vitamin K) -*Peripheral neuropathy* -Menstrual abnormalities, *infertility.*

Dermatitis herpetiformis

-*Celiac disease of the skin* -intensely pruritic, papulovasicular rash -typically seen on* extensor surfaces of the extremities*

Signs of celiac disease that may be seen on physical exam

-*MAY BE COMPLETELY NORMAL* -Emaciation +Doughy abdomen -Clubbing of nails -Peripheral edema -Ecchymosis +Bone tenderness -Angular cheilosis, glossitis -peripheral neuropathy

Complications of celiac disease due to tissue transglutaminase homologs

-*TG2 - predominantly GUT* -*TG3 - predominantly SKIN Dermatitis Herpetiformis* -*TG 6 - predominantly BRAIN* Brain Fog, ataxia, etc.

GI manifestations of celiac disease

-Diarrhea / Steatorrhea - increased osmotic load, bile malabsorption in ileum, poor motility, colon bacterial action (hydroxy fatty acids) -Flatulence -Weight loss -Distension, cramping

Celiac disease and cancer

-Disease may select out certain clones of immune cells so that transformation to lymphoma is simple -gluten-free diet lowers this risk -10% of patients develop cancer -patients also at higher risk for adenocarcinoma of the mouth, pharynx, esophagus, and small intestine

Refractory sprue

-Does not respond to removing gluten from the diet -*treatments is steroids, immunosuppressants, or complete bowel rest with total parenteral nutrition*

CD triad

-Environmental trigger -Genetic risk (HLA DQ2 / HLA DQ8( -Leaky gut

Laboratory Findings in celiac disease

-Fat malabsorption (quantitative testing) -Anemia -Prolonged INR -Low calcium, magnesium, zinc. -Low albumin

What to monitor while treating celiac disease

-IBS like symptoms -Anemia -Failure to thrive -Neurologic symptoms (Brain Fog) -Derm Manifestations

Foods that may contain gluten

-Ice cream -nondairy creamer -yogurt with fruit -cocoa mix -instant coffee/tea -bouillon cubes -soup mixes -canned soup -hot dogs/lunch meats -mustard, ketchup -tomato sauce -peanut butter -stamp/envelope glue -communion wafers

Differential diagnosis of celiac disease

-Infectious gastroenteritis/bacterial overgrowth -tropical sprue -eosinophilic enteritis -HIV -lymphoma -Zollinger-Ellison syndrome -ischemic/radiation damage -starvation

Gliadins

-Large, single polypeptide chains -Up to 40 different gliadins in a single variety of wheat. -Alpha gliadin is the most reactive subtype

Celiac disease and malignant complications

-Lymphoma - intestinal & extraintestinal -Adenocarcinoma of small bowel -Squamous Cell Ca of the Esophagus

Celiac disease and ulcerative jejunoileitis

-Multiple ulcers throughout the bowel can bleed or perforate -severe form this disease typically not responsive to diet change alone -may require medical therapy -concern is that it may progress to or mask lymphoma

Complications of celiac disease

-Osteoporosis -short stature -chronic anemia -microscopic colitis -pancreatic insufficiency -*lactose intolerance*

Incidence of celiac disease

-Reported incidence increased greatly in the 1960's. (Advent of peroral intestinal biopsy) -*Often appears at age of weaning (1-3 yo) and second peak 3rd or 4th decade.* -Ireland 1 in 300, Italy 1 in 250, Great Britain, N. Europe 1 in 400 to 2000 -Rare in Japan, Southeast Asia. -*incidence of Celiac Disease in the U.S. is as high as 1:125.*

Gold standard for diagnosis of celiac disease

-Small bowel biopsy from the duodenum or upper jejunum -classic findings are: * villi atrophy crypt hyperplasia increased intraepithelial lymphocytes* mucosal inflammation

CD Increased intestinal permeability

-Tight junctions opened by the messenger *zonulin* -Opens in certain disease states

Treatment Recommendations

-Use a team approach with motivated members -Registered Dietitian -Local Gluten intolerance chapters, patients, stores -National organizations -Internet sites

severe celiac disease

-megaloblastic anemia -neurologic disease (B12) -Infertility -Amenorrhea -Osteoporosis -Hypovitaminosis D

Facts about celiac disease

-reaction to a non-digestible protein in wheat called gluten -*not an allergy* -autoimmune disorder -lifelong - treatable with diet changes

Treatment of dermatitis herpetiformis

-sulfones (dapsone) -gluten free diet

Celiac disease etiology and immunology

-↑ intraepithelial lymphocytes (IEL cells) -↑ ratio gamma/delta T lymphocytes -Anti-gliadin (and other) antibodies are produced in the mucosa. (can be seen in other mucosal diseases)

Celiac disease antibody testing

1. *IgG and IgA Anti-gliadin antibodies* -Initial antibody test available *IgA* -Sensitivity 55-100% -Specificity 82 - 100% *IgG* -Sensitivity 55 - 78% -Specificity 71 - 87% 2. *IgA Tissue Transglutaminase (TtG)* -Sensitivity 77-100% -Specificity 91 - 100% 3. *IgA Anti - Endomysial antibodies* -Sensitivity 86-98%, -specificity 98 - 100% -IgG and IgA Anti-gliadin antibodies Variable sensitivity/specificity

Number of Americans affected by celiac disease

1.1 million >60% women -only 90,000 exhibit classic symptoms

Percent of patients with sprue who have Dermatitis herpetiformis

10%

Percent of patients with Dermatitis herpetiformis who have sprue

80%

Definition of celiac disease

An autoimmune disease characterized by chronic intestinal inflammation and varying degrees of intestinal mucosal atrophy with associated malabsorption. Or An antigen driven enteropathy of the small intestine, resulting from an inappropriate immune response to dietary gliadin, a component of wheat proteins.

Silent celiac disease

Asymptomatic, but *-Positive serology -Abnormal biopsy*

Spectrum of celiac disorders

Celiac Disease Celiac Disease Negative Gluten Sensitivity -'Gluten Intolerance' Refractory Celiac Disease Ulcerative Jejunoileitis Small Bowel Lymphoma, adenocarcinoma

Treatment of celiac disease

Complete avoidance of gluten -avoid foods containing wheat, rye, barley, farina, kamut, triticale, spelt -use only rice, corn, buckwheat, potato, soybean, or tapioca flowers -limit or avoid all milk and lactose -read all labels in processed foods -beware of gluten in food additives, emulsifiers, starchs, and flavoring

Celiac disease severity

Depends on the length of bowel affected -*changes begin in the duodenum and extend distally* -the proximal bowel is more affected

Appearance of celiac disease on endoscopy

Flattening of the circular folds as well as scalloping along the edges

Celiac disease environmental trigger

Gliadin similar to Adenovirus serotype 12 E1b protein

what is gluten?

Gluten = indigestible water-soluble protein -Gliadins & Glutenins - Major component of wheat endosperm. -Source of nitrogen to wheat embryo. -Elastic (good for bread, cookies, bagels, pizza...!) -*Only gliadins associated with sprue.*

Celiac disease genetic risk

*HLA DQ2/HLA DQ8 -Present in 95% of CD* -Proteins on antigen presenting cells -Presents gluten to helper T-cells

Highest percentage of celiac disease by ethnicity

*Irish/ Celtic descent* Northern Italian African American Sahawari Arab Laplander Norwegian