celiac disease
TRANSCRIPT
CELIAC CELIAC DISEASEDISEASE
Iman Galal, MDIman Galal, MDAssistant Professor Pulmonary Assistant Professor Pulmonary
MedicineMedicineAin Shams UniversityAin Shams University
E-mail: [email protected]: [email protected]
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Objectives:Objectives:
Historical aspectHistorical aspect
DefinitionDefinition
EpidemiologyEpidemiology
PathogenesisPathogenesis
Pathology & pathological classificationPathology & pathological classification
Organ affection & clinical presentationOrgan affection & clinical presentation
DiagnosisDiagnosis
TreatmentTreatment
Follow-upFollow-up
PrognosisPrognosis
ScreeningScreening
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Historical Aspect:Historical Aspect:2,000 yrs ago, a Greek physician 2,000 yrs ago, a Greek physician
named named Aretaeus the Aretaeus the
CappadocianCappadocian provided the 1 provided the 1stst
known description of adult known description of adult
patients with celiac disease. The patients with celiac disease. The
name name ‘celiac’‘celiac’ is derived from the is derived from the
Greek for Greek for ‘suffering in the ‘suffering in the
bowels’.bowels’.
In October 5, 1887, In October 5, 1887, Dr. Samuel Dr. Samuel
GeeGee, an English Medical Lecturer , an English Medical Lecturer
gave to medical students a gave to medical students a
lecture on the ‘celiac affection’ & lecture on the ‘celiac affection’ &
this constitutes the modern this constitutes the modern
‘rediscovery’ of celiac disease. ‘rediscovery’ of celiac disease.
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Definition:Definition:
Celiac diseaseCeliac disease is an inflammatory autoimmune is an inflammatory autoimmune
condition of the small intestine, triggered by condition of the small intestine, triggered by
glutengluten in in genetically susceptiblegenetically susceptible individuals. individuals.
It has diverse multi-systemic clinical It has diverse multi-systemic clinical
manifestations rather than being a 1ry intestinal manifestations rather than being a 1ry intestinal
disease. disease.
Other terms for celiac disease include: Other terms for celiac disease include: Gluten Gluten
Sensitive EnteropathySensitive Enteropathy, , Non-Tropical Sprue Non-Tropical Sprue & &
Celiac Sprue.Celiac Sprue.
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Epidemiology:Epidemiology:Celiac diseaseCeliac disease is more commonly found among is more commonly found among
white Europeans or those of European descent.white Europeans or those of European descent.
It is recognized as a common disorder that can be It is recognized as a common disorder that can be
diagnosed at any age but commonly occurs at the diagnosed at any age but commonly occurs at the
age of 1-5 yrs old.age of 1-5 yrs old.
Estimates vary from one in 5,000 to as many as one Estimates vary from one in 5,000 to as many as one
in every 300 individuals.in every 300 individuals.
Celiac disease is Celiac disease is 2020 times more common among times more common among
type 1 diabetestype 1 diabetes patients than in the general patients than in the general
population, that it became recommended to apply population, that it became recommended to apply
screening programs for celiac disease among screening programs for celiac disease among
children recently diagnosed with type 1 diabetes. children recently diagnosed with type 1 diabetes.
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Pathogenesis:Pathogenesis:
Genetic Genetic predispositionpredisposition
HLA-DQ(DQ2 &/or DQ8) HLA-DQ(DQ2 &/or DQ8) genesgenes
Environmental Environmental triggertrigger DietaryDietary
Non-dietary?? Non-dietary??
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Immune Response in Celiac Immune Response in Celiac DiseaseDisease
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Pathological Spectrum of Small IntestinePathological Spectrum of Small Intestine
The classic pathology changes of celiac disease in the small bowel The classic pathology changes of celiac disease in the small bowel areare
categorized bycategorized by "Marsh Classification""Marsh Classification"::
Marsh stage 0:Marsh stage 0: normal mucosa normal mucosa
Marsh stage 1:Marsh stage 1: ↑↑ intra-epithelial lymphocytes >20/100 intra-epithelial lymphocytes >20/100
enterocytesenterocytes
Marsh stage 2:Marsh stage 2: proliferation of the crypts of Lieberkuhn proliferation of the crypts of Lieberkuhn
Marsh stage 3:Marsh stage 3: partial or complete villous atrophy partial or complete villous atrophy
Marsh stage 4:Marsh stage 4: hypoplasia of the small bowel architecture hypoplasia of the small bowel architecture
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Pathology of Celiac DiseasePathology of Celiac Disease
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Clinical Presentation:Clinical Presentation:
The most commonly recognized symptoms of celiac disease The most commonly recognized symptoms of celiac disease
relate to the improper absorption of food in the GIT. relate to the improper absorption of food in the GIT.
Patient presents with Patient presents with diarrhea (<50%)diarrhea (<50%), , steatorrheasteatorrhea,,
flatulenceflatulence,, distended abdomen distended abdomen,, weight loss weight loss, &, &
generalized weakness.generalized weakness.
Up toUp to 38 % 38 % of patients areof patients are asymptomatic. asymptomatic.
Unrecognized celiac disease may cause Unrecognized celiac disease may cause malabsorptionmalabsorption, , iron iron
deficiency anemiadeficiency anemia, , osteoporosisosteoporosis, , osteomalaciaosteomalacia causing causing
bone fractures, pain & bony deformities. bone fractures, pain & bony deformities.
People with celiac disease may also experience People with celiac disease may also experience lactose lactose
intoleranceintolerance due to due to lactase enzyme deficiency.lactase enzyme deficiency.
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Dermatitis HypertiformisDermatitis Hypertiformis
Dermatitis herpetiformis (DH)Dermatitis herpetiformis (DH) is the skin is the skin
manifestation of celiac disease. manifestation of celiac disease.
It is an It is an intensely itchy rashintensely itchy rash that occurs in the that occurs in the
hands, fingers, forearms, buttocks or scalp or hands, fingers, forearms, buttocks or scalp or
anywhere on the body.anywhere on the body.
The rash typically consists of intensely itchy, small The rash typically consists of intensely itchy, small
red dots that may develop into blisters or pimples. red dots that may develop into blisters or pimples.
Approximately Approximately 10%10% of patients with celiac disease of patients with celiac disease
have DH, & it is estimated that have DH, & it is estimated that > 85%> 85% of patients of patients
with DH have celiac disease .with DH have celiac disease .
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Dermatitis HypertiformisDermatitis Hypertiformis
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Celiac Disease & the Lung:Celiac Disease & the Lung:
The association between The association between celiac diseaseceliac disease & &
diffuse interstitial pulmonary diseasediffuse interstitial pulmonary disease has has
been suspected since been suspected since 1970.1970.
Extrinsic allergic alveolitisExtrinsic allergic alveolitis was found in was found in
combination with celiac disease & it may be combination with celiac disease & it may be
considered that both these diseases are based on considered that both these diseases are based on
one common immunologic disorder. one common immunologic disorder.
The association between The association between pulmonary pulmonary
hemosiderosishemosiderosis & celiac disease have been & celiac disease have been
reported 9 times in literature as an extremely rare reported 9 times in literature as an extremely rare
combination. combination.
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Other Presentations of Celiac Other Presentations of Celiac Disease:Disease:
NeurologicalNeurological symptoms e.g., symptoms e.g., peripheral peripheral
neuropathyneuropathy, , ataxiaataxia or or epilepsy. epilepsy.
Apthous ulcersApthous ulcers in the mouth is considered to be in the mouth is considered to be
an autoimmune disorder associated with celiac an autoimmune disorder associated with celiac
disease. disease.
Dental enamel defectsDental enamel defects are frequent. are frequent.
Patients with celiac disease may have Patients with celiac disease may have liver liver
diseases.diseases. Abnormal liver testsAbnormal liver tests are common at are common at
diagnosis & usually improve with treatment. diagnosis & usually improve with treatment.
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The Celiac IcebergThe Celiac Iceberg
SymptomaticSymptomaticCeliac DiseaseCeliac Disease
Silent Celiac Silent Celiac DiseaseDisease
Latent Celiac DiseaseLatent Celiac Disease
Genetic Genetic susceptibility: susceptibility: - DQ2, - DQ2, DQ8DQ8
Positive serologyPositive serology
Manifest Manifest mucosal lesionmucosal lesion
Normal Normal MucosaMucosa
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Diagnosis: SerologyDiagnosis: Serology
Serum IgA endomysial antibodies (EMA)Serum IgA endomysial antibodies (EMA) & &
serum IgA tissue transglutaminase (tTG) serum IgA tissue transglutaminase (tTG)
antibodiesantibodies have both have both sensitivitysensitivity & & specificity > specificity >
95%.95%.
Testing for Testing for gliadin antibodiesgliadin antibodies is no longer is no longer
recommended because of its recommended because of its low sensitivitylow sensitivity & &
specificityspecificity for celiac disease. for celiac disease.
The The tTG antibodytTG antibody is the is the recommended single recommended single
serologic test serologic test forfor celiac disease screening. celiac disease screening.
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Diagnosis: Small Bowel Diagnosis: Small Bowel BiopsyBiopsyRequired to confirm the diagnosis of celiac disease.Required to confirm the diagnosis of celiac disease.
Should also be considered in patients with Should also be considered in patients with negative negative
serologicserologic test results who are at test results who are at high riskhigh risk or in or in
whom the physician whom the physician strongly suspectsstrongly suspects celiac celiac
disease.disease.
Mucosal changes may vary from Mucosal changes may vary from partialpartial to to total total
villous atrophyvillous atrophy, or may be characterized by , or may be characterized by subtle subtle
crypt lengtheningcrypt lengthening or or increased epithelial increased epithelial
lymphocytes.lymphocytes.
To avoid false-negative results on endoscopic To avoid false-negative results on endoscopic
biopsy, it is recommend to obtain at least biopsy, it is recommend to obtain at least 4 tissue 4 tissue
samplessamples to increase the sensitivity of the test. to increase the sensitivity of the test.
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Endoscopy & Biopsy in Celiac Endoscopy & Biopsy in Celiac DiseaseDisease
Normal small intestine
Celiac Disease
Normal Villi
Villous Atrophy
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Diagnosis: HLA Genetic Diagnosis: HLA Genetic TypingTyping
Antibody testing & HLA testing have Antibody testing & HLA testing have similar similar
accuracies.accuracies.
TestTest SensitivitSensitivityy
SpecificitSpecificityy
HLA-DQ2HLA-DQ2 94%94% 73%73%
HLA-DQ8HLA-DQ8 12%12% 81%81%
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Evaluation of Celiac DiseaseEvaluation of Celiac Disease
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Differential Diagnosis of Celiac Disease:
Anorexia nervosaAnorexia nervosa
Autoimmune enteropathyAutoimmune enteropathy
Bacterial overgrowthBacterial overgrowth
Collagenous sprueCollagenous sprue
Crohn's diseaseCrohn's disease
GiardiasisGiardiasis
HIV enteropathyHIV enteropathy
HypogammaglobulinemiaHypogammaglobulinemia
Infective gastroenteritisInfective gastroenteritis
Irritable bowel syndromeIrritable bowel syndrome
Ischemic enteritisIschemic enteritis
Lactose intoleranceLactose intolerance
Pancreatic insufficiencyPancreatic insufficiency
Soy protein intoleranceSoy protein intolerance
Tropical sprueTropical sprue
TuberculosisTuberculosis
Whipple's diseaseWhipple's disease
Zollinger-Ellison syndromeZollinger-Ellison syndrome
Intestinal lymphomaIntestinal lymphoma
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Treatment Options:Treatment Options:
Option #1:Option #1:Remove the genesRemove the genes
Option #2:Option #2:Remove the grainsRemove the grains
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Dietary Management in Celiac Dietary Management in Celiac DiseaseDiseaseAt present, the only effective At present, the only effective
treatment is a treatment is a life-long gluten-life-long gluten-
free diet (GFD).free diet (GFD).
No medication exists that will No medication exists that will
prevent damage or prevent the prevent damage or prevent the
body from attacking the gut when body from attacking the gut when
gluten is present.gluten is present.
Strict adherence to the diet allows Strict adherence to the diet allows
the intestines to heal, leading to the intestines to heal, leading to
resolution of all symptoms in most resolution of all symptoms in most
cases and, depending on how soon cases and, depending on how soon
the diet is begun, can also the diet is begun, can also
eliminate the increased risk of eliminate the increased risk of
complications.complications.
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Dietary Management in Celiac Dietary Management in Celiac DiseaseDisease
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Follow-Up:Follow-Up:
Serologic markers Serologic markers (serum IgA tTG)(serum IgA tTG) used to monitor used to monitor compliancecompliance with GFD. with GFD.
Antibody levelsAntibody levels return to return to normalnormal within within 3-12 3-12 monthsmonths of starting a GFD but may take up to of starting a GFD but may take up to 30 30 monthsmonths if the initial titers are high. if the initial titers are high.
Repetition of small bowel biopsyRepetition of small bowel biopsy 3-4 months3-4 months after initiation of a GFD is after initiation of a GFD is not necessarynot necessary if the if the patient responds appropriately to therapy.patient responds appropriately to therapy.
If the patient does not respond as expected → revise If the patient does not respond as expected → revise the patient’s adherence to GFD, then the physician the patient’s adherence to GFD, then the physician should consider other differential diagnosis.should consider other differential diagnosis.
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Prognosis:Prognosis:Treating CD with a strict Treating CD with a strict GFDGFD is always is always completely effective.completely effective.
Gastrointestinal complaints & other symptoms resolve in almost Gastrointestinal complaints & other symptoms resolve in almost all patients. all patients.
Once the diet has been followed for several years, individuals Once the diet has been followed for several years, individuals with CD have with CD have similar mortality ratessimilar mortality rates as the general as the general population. However, about population. However, about 10 %10 % of patients with celiac disease of patients with celiac disease
develop develop lymphomalymphoma & & small bowelsmall bowel adenocarcinoma.adenocarcinoma.
A few patients develop a A few patients develop a refractory typerefractory type of CD, in which the of CD, in which the GFD no longer seems effective. GFD no longer seems effective.
Experts emphasize the need for Experts emphasize the need for lifelong adherence to the lifelong adherence to the GFDGFD to avoid the long-term complications of this disorder. They to avoid the long-term complications of this disorder. They point out that although the disease may have symptom-free point out that although the disease may have symptom-free periods if the diet is not followed, silent damage continues to periods if the diet is not followed, silent damage continues to occur. occur.
According to medical authorities, CD According to medical authorities, CD cannot be outgrown cannot be outgrown oror cured.cured.
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American Gastroenterological Association Institute American Gastroenterological Association Institute Recommendations for Celiac Disease Screening Recommendations for Celiac Disease Screening
Consider testing in symptomatic patients at high Consider testing in symptomatic patients at high
risk for Celiac Disease with any of the following risk for Celiac Disease with any of the following
conditions:conditions:
Autoimmune hepatitisAutoimmune hepatitis
Down syndromeDown syndrome
Premature onset of osteoporosisPremature onset of osteoporosis
Primary biliary cirrhosisPrimary biliary cirrhosis
Unexplained elevations in liver transaminase levelsUnexplained elevations in liver transaminase levels
Unexplained iron deficiency anemiaUnexplained iron deficiency anemia
Type 1 DMType 1 DM
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References: References:
Presutti J,Cangemi J, Cassidy H, Hill D, Celiac Presutti J,Cangemi J, Cassidy H, Hill D, Celiac Disease. American Family Physician. December Disease. American Family Physician. December 15, 2007: 1795-1802.15, 2007: 1795-1802.
Hadithi M, von Blomberg BM, Crusius JB, et Hadithi M, von Blomberg BM, Crusius JB, et al. (2007). "Accuracy of serologic tests and HLA-al. (2007). "Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease". Ann. DQ typing for diagnosing celiac disease". Ann. Intern. Med. 147: 294–302. Intern. Med. 147: 294–302.
Hood J, Mason AMS. Diffuse pulmonary disease Hood J, Mason AMS. Diffuse pulmonary disease with transfer defect occurring in coeliac disease. with transfer defect occurring in coeliac disease. Lancet 1970;1:445-47.Lancet 1970;1:445-47.
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