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CHAIRPERSON- Dr. Ardaman Singh PRESENTATION- Dr. Honey Sharma

Celiac disease truths n myths

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Page 1: Celiac disease  truths n myths

CHAIRPERSON-

Dr. Ardaman Singh

PRESENTATION-

Dr. Honey Sharma

Page 2: Celiac disease  truths n myths

What is Celiac disease?

Celiac disease Small intestinal malabsorption of nutrients

Seen after the ingestion of wheat gluten or

related proteins from rye and barley

Characterised by villus atrophy of the small

intestinal mucosa and prompt clinical and

histologic improvement following strict

adherence to a gluten-free diet

Clinical and histologic relapse when gluten is

reintroduced.

Page 3: Celiac disease  truths n myths
Page 4: Celiac disease  truths n myths

ATYPICAL CELIAC DISEASE- Fully expressed

gluten-sensitive enteropathy manifest only by

extraintestinal symptoms and signs including short

stature, anemia, osteoporosis, and infertility.

SILENT CELIAC DISEASE- Fully expressed gluten-

sensitive enteropathy usually found after serologic

screening in asymptomatic patients.

CLASSIC/TYPICAL CELIAC DISEASE- Fully

expressed gluten-sensitive enteropathy found in

association with the classic gastrointestinal symptoms of

malabsorption.

Page 5: Celiac disease  truths n myths

LATENT CELIAC DISEASE- Normal villusarchitecture on a gluten-containing diet but, at anothertime, have had or will have gluten-sensitive villus atrophy.

POTENTIAL CELIAC DISEASE- Never had a biopsyconsistent with celiac disease but show immunologicabnormalities characteristic for the disease- positive(Ig)Aantibody to endomysium (or tissue transglutaminase [tTG])or increased intraepithelial lymphocytes (IELs) in the smallintestine.

REFRACTORY/UNCLASSIFIED/INTRACTABLECELIAC SPRUE- Symptomatic, severe small intestinalvillus atrophy that mimics celiac disease but does notrespond to at least six months of a strict gluten-free diet.This is a diagnosis of exclusion that is not accounted for byinadvertent gluten ingestion, other causes of villusatrophy, or overt intestinal lymphoma.

Page 6: Celiac disease  truths n myths

Marked geographic variation

Rare in the predominantly rice-eating area of

southern India, prevalent in Punjab

provinces of northwest India, where wheat

rather than rice, for many generations, has

been staple diet.

Female-to-male ratio of 2 : 1 reported by

some where as some studies report as low as

1.3 : 1 ratio but still suggesting a FEMALE

predominance.

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Affects the Mucosa of the small intestine.

Examination of the small intestinal mucosal

surface- a flat mucosal surface with complete

absence of normal intestinal villi.

HISTOLOGIC EXAMINATION- Confirms this loss of

normal villus structure.

Intestinal crypts- Markedly elongated and open

onto a flat absorptive surface.

Total thickness of the mucosa is reduced only

slightly in most cases, because crypt hyperplasia

compensates for the absence or shortening of

the villi.

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Page 9: Celiac disease  truths n myths

CENTRAL MECHANISM OF VILLUS SHORTENING

Gliadin-associated toxic effect on maturing enterocytes that results in their premature loss into the intestinal lumen and a compensatory increase in enterocyte replication in the crypts.

Page 10: Celiac disease  truths n myths

Stage 0- Normal preinfiltrative

mucosa, IEL rise

Stage 1-lamina proprialymphocytosis

Stage 2- Crypt hyperplasia

Stage 3-Villous atrophy

Stage 4- total mucosal atrophy

Page 11: Celiac disease  truths n myths

Centre to pathogenesis- Interaction of the water-insoluble protein moiety (gluten) of certain cereal grainswith the mucosa of the small intestine in susceptiblepersons.

ENVIRONMENTAL FACTORS- wheat protein categorizedinto 4 groups.

Prolamins

Glutenins

Globulins

Minor albumins

• Gluten encompasses both the prolamins and the glutenins.

• Prolamins of wheat are referred to as gliadins.

• Prolamins from oats, barley, wheat, and rye haveimmunologic cross-reactivity because of their commonancestry.

• Grains that do not activate disease - rice, corn, sorghum,and millet.

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Page 13: Celiac disease  truths n myths

Concordance for celiac disease in first-

degree relatives 8%-18% and 70% in

monozygotic twins.

Celiac disease is associated with specific

HLA-DQ2 haplotypes. The HLA class II

molecule DQ2-more than 90% of persons with

celiac disease. HLA-DQ8 found in remaining.

Only a minority of persons who express DQ2

actually develop celiac disease. Much of the

genetic predisposition to celiac disease is

conferred by genes other than those

encoding HLA DQ molecules.

Page 14: Celiac disease  truths n myths

Antigliadin antibodies- nonspecific response tothe passage of incompletely digested antigenicgluten proteins across an abnormally permeableintestinal epithelium.

IgA antibodies to endomysium are virtuallypathognomonic for celiac disease .

The target autoantigen contained within theendomysium is the enzyme tTG-2.

Gliadin is a preferred substrate for thisubiquitous calcium-dependent intracellularenzyme, and tTG deamidates key neutralglutamine residues in gliadin and converts theminto negatively charged glutamic acid residues,which are preferred in positions 4, 6, and 7 ofthe nonapeptide antigen-binding groove of theHLA-DQ2 heterodimer thereby facilitatingantigen presentation.

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Page 17: Celiac disease  truths n myths

Steatorrhea with or without vomiting

Occ. cramping abdominal pain esp. in 1st and

2nd yr of life

Failure to thrive

Apathetic and Irritable child

Muscle wasting, Hypotonia, and Abdominal

distention

Watery diarrhea or occasionally constipation

Nutritional deficiencies, particularly anemia,

especially in older children.

Page 18: Celiac disease  truths n myths

Overall mean age at presentation- 45 years;approx. 25% of cases diagnosed in patients olderthan 60 years

G.i. symptoms including diarrhea, steatorrhea,flatulence, and weight loss

Diarrhea is episodic rather than continuous.Nocturnal, early morning, and postprandialdiarrhea are common.

Patients with extensive intestinal involvementcan have more than 10 stools per day.

The stools may be light tan or grayish and greasyin appearance, with a tendency to float anddifficult to flush.

Steatorrhea often is absent in patients withdisease limited to the proximal small intestine.

Page 19: Celiac disease  truths n myths

Weight loss

Malaise, lassitude, and fatigue

Occ., severe hypokalemia resulting fromfecal loss of potassium causes severe muscleweakness.

Vague abdominal discomfort and esp.abdominal bloating are extremely common

Severe abdominal pain can occur but isuncharacteristic in uncomplicated celiacdisease

Abdominal distention with excessive amountsof malodorous flatus is a common complaint.

Recurrent severe aphthous stomatitis maybe the sole presenting complaint.

Page 20: Celiac disease  truths n myths

Cutaneous- Ecchymosis, petechiae, edema,dematitis herpatiformis, follicularhyperkeratosis and dermatitis

Endocrinologic- Amenorrhoea, infertility,impotence, sec.hyperparathyroidism

Haematologic- Anaemia, haemorrhage,thrombocytosis

Muscular- Atrophy, tetany, weakness

Neurologic- Peripheral neuropathy, ataxia,demyelinating CNS lesions, seizures

Skeletal- Osteopenia, osteoarthropathy,pathologic fractures

Page 21: Celiac disease  truths n myths

Common manifestation in children and adults

Caused by impaired iron or folate absorption.

In severe disease with ileal involvement, vitamin

B12 absorption also is impaired.

Bleeding into the skin or mucous membranes or

hematuria, epistaxis, or vaginal or

gastrointestinal bleeding caused by a

coagulopathy resulting from impaired intestinal

absorption of fat-soluble vitamin K.

Evidence of hyposplenism with thrombocytosis,

deformed erythrocytes, and splenic atrophy,

occurs in up to 50% of adults with celiac disease

but only rarely is seen in children.

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Most common complication

Due to-

impaired calcium absorption

vitamin D deficiency

binding of intraluminal calcium and magnesium tounabsorbed dietary fatty acids (forming insolublesoaps, which are then excreted in the feces).

Present with-

Bone pain, esp. the lower back, rib cage, and pelvis.

Calcium and magnesium depletion can causeparesthesias, muscle cramps, and even frank tetany.With prolonged calcium malabsorption, patients maydevelop secondary hyperparathyroidism.

Page 23: Celiac disease  truths n myths

Caused by lesions of the central or peripheral

nervous system occasionally occur in patients

with celiac disease.

Progressive gait and limb ataxia may be the sole

manifestations of disease in some patients and is

referred to as GLUTEN ATAXIA, result from

immunologic damage to the cerebellum,

posterior columns of the spinal cord, and

peripheral nerves.

The associations of celiac disease and epilepsy,

frequently complex partial seizures, and

bilateral parieto-occipital cerebral calcification

is well recognized. The cause remains unclear.

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Common in women with untreated celiacdisease.

Amenorrhea occurs in one third of women ofchildbearing age and menarche is delayed,typically by one year, in untreated subjects.

A high prevalence of silent celiac disease hasbeen reported in women with recurrentspontaneous abortions, intrauterine fetalgrowth retardation.

Infertility secondary to impotence or anabnormally low sperm count can occur inmen with untreated celiac disease.

Page 25: Celiac disease  truths n myths

On average, Three inches shorter than their peers.

Evidence of weight loss- loose skin folds and muscle wasting

Clubbing and koilonychia

Pitting edema of the lower extremities secondary to hypoproteinemia.

Hypotension related to fluid and electrolyte depletion

The skin is dry with poor turgor, if dehydrated.

Increased skin pigmentation.

Aphthous stomatitis, angular cheilosis, and glossitis with decreased papillation of the tongue and Dental enamel defects.

Page 26: Celiac disease  truths n myths

Serum IgA EMA or tTG antibody and small intestinal biopsy are the most

reliable diagnostic tests.

SEROLOGY-IgA EMA and IgA tTG are based on the target antigen tTG, and IgA

and IgG AGAs are based on the target antigen gliadin.

IgA EMA sensitivity 90%, specificity 99%, and reproducibility 93% and currently

remains the gold standard.

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GENETIC TESTING

Almost all patients with

celiac disease are positive

for HLA DQ2 or DQ8.

HLA testing may be helpful

in excluding celiac disease

in specific clinical

situations, mainly before

embarking on a gluten

challenge or evaluating a

patient who has a celiac-

like enteropathy but

negative IgA tTG, EMA, and

DGP serologies.

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Page 29: Celiac disease  truths n myths

Biopsy of the small intestine- The standardtest to establish the diagnosis.

Multiple biopsies should be obtained (e.g., atotal of six to eight biopsies from the secondand third parts of the duodenum).

Increased IEL’s, flat villi, hyperplastic cryptsand inc. lymphocytes in lamina propria.

Scalloping or absence of duodenal foldsnoted.

Other endoscopic features include multiplefissures or a mosaic-like appearance wherethe fissures circumscribe areas of mucosalnodularity in a manner similar to thegrouting around a mosaic tile.

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Page 31: Celiac disease  truths n myths

Pancreatic insufficiency

Cholestatic liver disease

Terminal ileal disease or resection

Small intestinal bacterial overgrowth

Whipple's disease

Infiltration of the mucosa with Mycobacterium avium complex.

Parasitic infections- strongyloidiasis, coccidiosis, hookworm disease

Hypogammaglobulinemia

An acute viral gastroenteritis

Cow's milk or soy protein intolerance

Collagenous sprue

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Definite

•Bird-fancier’s lung

•Dermatitis hepatiformis

•DM Type1

•Down’s syndrome

•Epilepsy with cerebral calcification

•Fibrosing alveolitis

•Hypo/hyperthyroidism

•Idiopathic pulmonary hemosiderosis

•IG A deficiency

•IGA mesangial nephropathy

•IBD

•Microscopic colitis

•Recurrent pericarditis

•RA

•Sarcoidosis

Possible

•Addison’s disease

•AIHA

•Autoimmune liver disease

•Cavitory lung disease

•CHD

•Cystic fibrosis

•Immune thrombocytopenic purpura

•Iridiocyclitis/choroiditis

•Macroamylasemia

•Myasthenia gravis

•Polymyositis

•Schizophrenia

•Sjogren syndrome

•Systemic and cutaneous vasculitides

•SLE

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Page 34: Celiac disease  truths n myths

Avoid foods with wheat, rye, barley gluten.

Avoid all oats initially.

Avoid malt unless clearly labelled derived fromcorn.

Use only rice, corn, maize, millet, amaranth,sorghum, potato or potato starch, soyabean, andnut flours.

Wheat starch only used if it contains < 20ppmgluten and marked as gluten free.

Read labels and ingredients of processed foods.

Avoid beer unless labelled gluten free.

Wine, whiskey and brandy are allowed.

Beware of gluten in medications

Page 35: Celiac disease  truths n myths

Beers, Herbal tea

Soups, Gravy and soy sauses

Candy, Wafers

Lipstick and lip balms

Meat and sea food

Nutritional supplements

Salad dressings

Toothpaste

Page 36: Celiac disease  truths n myths

Key element

AVOIDWHEAT

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Consult a skilled dietician

Education about disease

Life long adherence to gluten free diet

Page 38: Celiac disease  truths n myths

Identify and treat nutritional deficiencies

Access to advocacy group

Continuous long term follow up

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Considerable variation among patients with

celiac disease in their ability to tolerate

gluten.

Some patients are exquisitely sensitive to

ingestion of even minute amounts of gluten

and can develop massive watery diarrhea

within hours of eating very small amounts of

gluten.

Occasionally, the diarrhea is so severe that it

can induce acute dehydration, termed

gliadin shock or celiac crisis.

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Appropriate supplemental therapy tocorrect nutritional deficiencies.

The risks of osteopenia and osteoporosisshould be explained and general adviceshould be given about weight-bearingexercises, dietary calcium and vitamin Dintake.

Glucocorticoids are not indicated in theroutine management of celiac disease butare reserved for severely ill patients whopresent with acute celiac crisis manifestedby severe diarrhea, dehydration, weight loss,acidosis, hypocalcemia, andhypoproteinemia.

Page 41: Celiac disease  truths n myths

The persistence of symptoms, signs, orlaboratory abnormalities typical of celiac diseasedespite adherence to a gluten-free diet for atleast six months.

Primary NRCD- Nonresponsive immediately afterthe initial diagnosis

Secondary NRCD- Nonresponsive following aperiod of response to the gluten-free diet

The single most common cause for NRCD-continued gluten ingestion, which is ofteninadvertent and occult.

A persisting elevation of anti-tTG is stronglyassociated with ongoing gluten exposure.

Intolerance to disaccharides (e.g., lactose,fructose) also is common, especially in primaryNRCD.

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Unclassified or intractable celiac disease-

defined as symptomatic, severe small

intestinal villus atrophy that mimics celiac

disease but does not respond to at least six

months of a strict gluten-free diet and is not

accounted for by other causes of villus

atrophy or overt intestinal lymphoma.

Uncommon in adults, extremely rare in

children, and largely a diagnosis of exclusion

Complications- Ulcerative jejunoileitis,

Cryptic intestinal T- cell lymphoma

Page 44: Celiac disease  truths n myths

Glucocorticoids

Immunosuppressive therapy- Azathioprine or 6-mercaptopurine used as a glucocorticoid-sparingagent if a dose of 10 mg of prednisolone or more/dayis required to keep the condition under control.

Other drugs- cyclosporine, infiximab

Oral budesonide is fast becoming a drug of firstchoice for treatment of refractory celiac disease.

Trial of immunosuppressive therapy is worthconsidering in all patients with refractory celiacdisease, caution must be used, because thesepatients often are malnourished and hyposplenic;hence prone to opportunistic infections.

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Small intestinal lymphoma- often multifocal anddiffuse, accounts for one half to two thirds ofthe malignancies complicating celiac disease andtypically occurs after 20 to 40 years of disease.

Typically of T-cell origin

In patients whose disease was previouslycontrolled on a gluten-free diet, recurrence ofgastrointestinal symptoms (e.g., abdominal pain,weight loss, diarrhea) should raise the clinicalsuspicion of lymphoma.

Carcinoma, particularly of the oropharynx,esophagus, and small intestine, account for onethird of the remaining malignancies complicatingceliac disease. The average patient affected-older than 50 years.

Page 46: Celiac disease  truths n myths

Excellent prognosis- if it is diagnosed early

and the patient adheres to a lifelong gluten-

free diet.

Conversely, if not recognized, patients can

develop marked malnutrition and debilitation

and can die of complications such as

intercurrent infection, hemorrhage, or

malignancy.

Past studies- mortality increased 1.9-3.4 fold

if nonadherence to gluten free diet.

Page 47: Celiac disease  truths n myths

Oral glutenases

Larazotide acetate- an octapeptide inhibitorof paracellular permeability derived from aprotein (zonula occludens toxin) secreted byVibrio cholerae

Genetic modification of wheat to deletetoxic peptides

tTG inhibitors are also being evaluated for their ability to reduce gluten toxicity.

Blockade of signals derived from IL-15- an attractive possibility in refractory celiac disease

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Page 49: Celiac disease  truths n myths

MESSAGE

KEEP HIGH CLINICAL

SUSPICION

PATIENT

COUNSELLING IS

EQUALLY IMPORTANT

AS DIETARY

TREATMENT

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