Celiac DiseaseCeliac Disease Gluten Sensitive Gluten Sensitive

EnteropathyEnteropathy

Celiac Disease:

Immune mediated enteropathy caused by permanent sensitivity to gluten in genetically susceptible individuals.

• Pathogenesis:– Gluten is the protein found in the grain of

wheat, barley, rye.– Gluten is a large complex molecule consist of

four heterogeneous classes of protein (Gliadin, Glutenine, Albumin & Globulin)

Celiac diseaseCeliac diseaseAutoimmune disorder with a prevalence of approximately Autoimmune disorder with a prevalence of approximately 0.5 to 1 percent . (1 in every 100-200 persons)0.5 to 1 percent . (1 in every 100-200 persons)

Inappropriate immune response to the dietary protein Inappropriate immune response to the dietary protein gluten, which is found in rye, wheat, and barley.gluten, which is found in rye, wheat, and barley.

After absorption in the small intestine these proteins After absorption in the small intestine these proteins interact with the antigen-presenting cells in the lamina interact with the antigen-presenting cells in the lamina propria causing an inflammatory reaction that targets the propria causing an inflammatory reaction that targets the mucosa of the small intestine.mucosa of the small intestine.

Manifestations range from no symptoms to overt Manifestations range from no symptoms to overt malabsorption with involvement of multiple organ malabsorption with involvement of multiple organ systems and an increased risk of some malignancies.systems and an increased risk of some malignancies.

Most patients with celiac disease express Most patients with celiac disease express human leukocyte antigen (HLA)-DQ2 or human leukocyte antigen (HLA)-DQ2 or HLA-DQ8, which facilitate the immune HLA-DQ8, which facilitate the immune response against gluten proteinsresponse against gluten proteins

Concordance rates of 70 to 75 % among Concordance rates of 70 to 75 % among monozygotic twins and 5 to 22 % among monozygotic twins and 5 to 22 % among first-degree relatives. first-degree relatives.

Associated Disorders with Celiac Associated Disorders with Celiac Disease(extraintestinal)Disease(extraintestinal)

Dermatitis Herpitiformis.Dermatitis Herpitiformis.Insulin Dependent -Diabetes MellitusInsulin Dependent -Diabetes Mellitus autoimmune thyroid disesae.autoimmune thyroid disesae.Selective IgA deficiencySelective IgA deficiencyIgA Nephropathy.IgA Nephropathy.Down’s Syndrome.Down’s Syndrome.Primary Biliary Cirrhosis & Sclerosing Cholangitis.Primary Biliary Cirrhosis & Sclerosing Cholangitis.Sjogren’s Syndrome, alopecia areata, Addison’s Sjogren’s Syndrome, alopecia areata, Addison’s disease, epilepsy and post. Cerebral calcification.disease, epilepsy and post. Cerebral calcification.First-degree relative with celiac diseaseFirst-degree relative with celiac disease

Clinical FeaturesClinical Features:: Age of onsetAge of onset: variable, most children present : variable, most children present

between one & five years of age but they may present between one & five years of age but they may present for the first time at any time from infancy to old age. for the first time at any time from infancy to old age. Classic GI pediatric cases usually appear in children Classic GI pediatric cases usually appear in children aged 9-18 months. aged 9-18 months.

““Latent intervalLatent interval”: the time period between the ”: the time period between the introduction of gluten into the diet and the introduction of gluten into the diet and the development of clinical manifestation, varies from development of clinical manifestation, varies from months to years. months to years.

Silent Silent Celiac Disease: Abnormal small bowel Celiac Disease: Abnormal small bowel mucosa characteristic of celiac disease but mucosa characteristic of celiac disease but the child is Asymptomatic.the child is Asymptomatic.

LatentLatent Celiac Disease: The small intestinal Celiac Disease: The small intestinal mucosa shows no flat villi but abnormal in the mucosa shows no flat villi but abnormal in the form of increasing intraepithelial lymphocyte form of increasing intraepithelial lymphocyte in addition to positive circulating antigliadin or in addition to positive circulating antigliadin or antiendomysial antibodies. antiendomysial antibodies.

Signs and SymptomsSigns and Symptoms

CommonCommon DiarrheaDiarrhea Fatigue and muscle Fatigue and muscle

wastingwasting BorborygmusBorborygmus Abdominal painAbdominal pain Weight loss, FTT and short Weight loss, FTT and short

staturestature Abdominal distentionAbdominal distention FlatulenceFlatulence

UncommonUncommon Osteopenia/ osteoporosisOsteopenia/ osteoporosis Abnormal liver functionAbnormal liver function Nausea and VomitingNausea and Vomiting Dental enamel hypoplasia Dental enamel hypoplasia Iron-deficiency anemia Iron-deficiency anemia

resistant to treatmentresistant to treatment Neurologic dysfunction:Neurologic dysfunction: ataxia, epilepsy, PNPataxia, epilepsy, PNP ConstipationConstipation Delayed pubertyDelayed puberty Psychiatric disordersPsychiatric disorders

Up to 38 % Asymptomatic

Diarrhea: Diarrhea:

The most common presentation The most common presentation Acute, chronic or recurrentAcute, chronic or recurrent Stool is characteristically pale, loose and Stool is characteristically pale, loose and very offensive, often one large bulky stool, very offensive, often one large bulky stool, but could more frequent, some children but could more frequent, some children might have recurrent attacks of more might have recurrent attacks of more severe diarrhea. Few children with CD severe diarrhea. Few children with CD have constipation.have constipation.

Diagnosis of Celiac DiseaseDiagnosis of Celiac DiseaseClinical picture.Clinical picture.Small intestinal biopsySmall intestinal biopsy: the gold standard.: the gold standard.

Serological markersSerological markers: : IgA Antiendomysial, IgA and IgG IgA Antiendomysial, IgA and IgG antigliadin ,and IgA Anti-tissue transglutaminase antigliadin ,and IgA Anti-tissue transglutaminase antibodies.antibodies.

+ Tissue transglutaminase (tTG) antibodies had sensitivity + Tissue transglutaminase (tTG) antibodies had sensitivity and specificity > 95%.and specificity > 95%.

+Testing for gliadin antibodies is no longer recommended +Testing for gliadin antibodies is no longer recommended because of the low sensitivity and specificity for celiac because of the low sensitivity and specificity for celiac disease.disease.

+The +The tTG antibodytTG antibody test is less costly because it uses an test is less costly because it uses an enzyme-linked immunosorbent assay; enzyme-linked immunosorbent assay; it is the it is the recommended single serologic test for celiac disease recommended single serologic test for celiac disease screening in the primary care setting.screening in the primary care setting.

SMALL BOWEL BIOPSYSMALL BOWEL BIOPSY

Required to confirm the diagnosis of celiac Required to confirm the diagnosis of celiac disease for most patients.disease for most patients.Should also be considered in patients with Should also be considered in patients with negative serologic test results who are at negative serologic test results who are at high risk or in whom the physician strongly high risk or in whom the physician strongly suspects celiac disease.suspects celiac disease.Findings:Findings:

-Short, flat villi -Short, flat villi -increased number of lymphocytes in the -increased number of lymphocytes in the

epithelial layer epithelial layer -crypt hyperplasia-crypt hyperplasia

Reported causes of flat small intestinal Reported causes of flat small intestinal mucosa in childhoodmucosa in childhood::

Celiac DiseaseCeliac Disease Cow’s milk and Soy protein allergy.Cow’s milk and Soy protein allergy. Gastroenteritis and post enteritis syndromes.Gastroenteritis and post enteritis syndromes. Giardiasis.Giardiasis. Autoimmune enteropathy.Autoimmune enteropathy. Microvillous atrophy.Microvillous atrophy. Acquired hypogammaglobulinemia.Acquired hypogammaglobulinemia. Protein-energy malnutrition.Protein-energy malnutrition.

Normal small intestine

Celiac Disease Villous atrophy

Normal villi

Differential Diagnosis of Celiac DiseaseDifferential Diagnosis of Celiac Disease

Anorexia nervosaAnorexia nervosaAutoimmune enteropathyAutoimmune enteropathyBacterial overgrowthBacterial overgrowthCollagenous sprueCollagenous sprueCrohn's diseaseCrohn's diseaseGiardiasisGiardiasisHuman immunodeficiencyHuman immunodeficiencyvirus enteropathyvirus enteropathyHypogammaglobulinemiaHypogammaglobulinemiaInfective gastroenteritisInfective gastroenteritisIntestinal lymphomaIntestinal lymphoma

Irritable bowel syndromeIrritable bowel syndromeIschemic enteritisIschemic enteritisLactose intoleranceLactose intolerancePancreatic insufficiencyPancreatic insufficiencySoy protein intoleranceSoy protein intoleranceTropical sprueTropical sprueTuberculosisTuberculosisWhipple's diseaseWhipple's diseaseZollinger-Ellison Zollinger-Ellison syndromesyndrome

Patient presents with symptoms of celiac disease

Perform serologic IgA tTG antibody testing

Positive Negative

Small bowel biopsy High clinical suspicion?

Positive NegativeSmall bowel biopsy

Low probability of celiacdisease; consider total IgA test to R/O IgA deficiencyDx confirmed,

Gluten-free diet

F/U and considerOther dx, considerRepeat bx Positive Negative

Tx and monitorCeliac ruled out,Look for other causeImprovement?

Yes No

Dx confirmed Evaluate for possible secondary cause of symptoms

YesNo

Evaluation for Celiac Disease

TreatmentTreatmentAvoidance of food products that contain gluten proteins Avoidance of food products that contain gluten proteins for life:for life:

Improve the appetite, Improve the appetite, decrease the diarrhea,decrease the diarrhea, reverse osteopenia, reverse osteopenia, prevent lymphoma, prevent lymphoma, enhance appropriate growth and pubertyenhance appropriate growth and puberty

Key elements to successful treatment include the Key elements to successful treatment include the motivation of the patient, the attentiveness of the motivation of the patient, the attentiveness of the physician to comorbidities that need to be addressed.physician to comorbidities that need to be addressed.Formal consultation with a trained dietitian is necessary.Formal consultation with a trained dietitian is necessary.National celiac disease support organizations can National celiac disease support organizations can provide patients invaluable resources for information and provide patients invaluable resources for information and support. support. Replacement of nutritional deficiencies as vitamins, iron, Replacement of nutritional deficiencies as vitamins, iron, caloriescalories

COMORBIDITIESCOMORBIDITIESOsteoporosis (common finding)Osteoporosis (common finding)Thyroid dysfunctionThyroid dysfunctionDeficiencies in folic acid, vitamin B12, fat-Deficiencies in folic acid, vitamin B12, fat-soluble vitamins, and ironsoluble vitamins, and ironIncreased mortality due to increased risk Increased mortality due to increased risk of malignancyof malignancy Intestinal lymphoma (3-6x more likely) Intestinal lymphoma (3-6x more likely) Most common is intestinal Most common is intestinal non- Hodgkin's non- Hodgkin's

lymphomalymphoma

ScreeningScreeningScreening an asymptomatic patient for celiac disease Screening an asymptomatic patient for celiac disease must be weighed against the psychological, emotional, must be weighed against the psychological, emotional, and economic impact of a false positive result.and economic impact of a false positive result.

Also, it would necessitate further evaluation with small Also, it would necessitate further evaluation with small bowel biopsy. bowel biopsy.

The need to follow a strict diet indefinitely can adversely The need to follow a strict diet indefinitely can adversely affect the patient's perceived quality of life.affect the patient's perceived quality of life.

Routine screening of the general population is not Routine screening of the general population is not recommended.recommended.

Persons at high risk for celiac disease who exhibit any Persons at high risk for celiac disease who exhibit any level of symptoms, appropriate testing is indicated. level of symptoms, appropriate testing is indicated.