1. CELIAC DISEASECELIAC DISEASE
Iman Galal, MDIman Galal, MD
Assistant Professor Pulmonary MedicineAssistant Professor Pulmonary Medicine
Ain Shams UniversityAin Shams University
E-mail: dr.imangalal@gmail.comE-mail: dr.imangalal@gmail.com

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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 physician2,000 yrs ago, a Greek physician
namednamed Aretaeus the CappadocianAretaeus the Cappadocian
provided the 1provided the 1stst
known description ofknown description of
adult patients with celiac disease. Theadult patients with celiac disease. The
namename ‘celiac’‘celiac’ is derived from theis derived from the
Greek forGreek for ‘suffering in the bowels’.‘suffering in the bowels’.
In October 5, 1887,In October 5, 1887, Dr. Samuel GeeDr. Samuel Gee,,
an English Medical Lecturer gave toan English Medical Lecturer gave to
medical students a lecture on themedical students a lecture on the
‘celiac affection’ & this constitutes the‘celiac affection’ & this constitutes the
modern ‘rediscovery’ of celiac disease.modern ‘rediscovery’ of celiac disease.

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Definition:Definition:
Celiac diseaseCeliac disease is an inflammatory autoimmuneis an inflammatory autoimmune
condition of the small intestine, triggered bycondition of the small intestine, triggered by glutengluten inin
genetically susceptiblegenetically susceptible individuals.individuals.
It has diverse multi-systemic clinical manifestationsIt has diverse multi-systemic clinical manifestations
rather than being a 1ry intestinal disease.rather than being a 1ry intestinal disease.
Other terms for celiac disease include:Other terms for celiac disease include: Gluten SensitiveGluten Sensitive
EnteropathyEnteropathy,, Non-Tropical SprueNon-Tropical Sprue && Celiac Sprue.Celiac Sprue.

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Epidemiology:Epidemiology:
Celiac diseaseCeliac disease is more commonly found among whiteis more commonly found among white
Europeans or those of European descent.Europeans or those of European descent.
It is recognized as a common disorder that can be diagnosedIt is recognized as a common disorder that can be diagnosed
at any age but commonly occurs at the age of 1-5 yrs old.at any age but commonly occurs at the age of 1-5 yrs old.
Estimates vary from one in 5,000 to as many as one in everyEstimates vary from one in 5,000 to as many as one in every
300 individuals.300 individuals.
Celiac disease isCeliac disease is 2020 times more common amongtimes more common among type 1type 1
diabetesdiabetes patients than in the general population, that itpatients than in the general population, that it
became recommended to apply screening programs for celiacbecame recommended to apply screening programs for celiac
disease among children recently diagnosed with type 1disease among children recently diagnosed with type 1
diabetes.diabetes.

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Pathogenesis:Pathogenesis:
Genetic predispositionGenetic predisposition
HLA-DQ(DQ2 &/or DQ8) genesHLA-DQ(DQ2 &/or DQ8) genes
Environmental triggerEnvironmental trigger
 DietaryDietary
 Non-dietary??Non-dietary??

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Immune Response in Celiac DiseaseImmune Response in Celiac Disease

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Pathological Spectrum of Small IntestinePathological Spectrum of Small Intestine
The classic pathology changes of celiac disease in the small bowel areThe classic pathology changes of celiac disease in the small bowel are
categorized bycategorized by "Marsh Classification""Marsh Classification"::
Marsh stage 0:Marsh stage 0: normal mucosanormal mucosa
Marsh stage 1:Marsh stage 1: ↑↑ intra-epithelial lymphocytes >20/100 enterocytesintra-epithelial lymphocytes >20/100 enterocytes
Marsh stage 2:Marsh stage 2: proliferation of the crypts of Lieberkuhnproliferation of the crypts of Lieberkuhn
Marsh stage 3:Marsh stage 3: partial or complete villous atrophypartial or complete villous atrophy
Marsh stage 4:Marsh stage 4: hypoplasia of the small bowel architecturehypoplasia 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 relate to theThe most commonly recognized symptoms of celiac disease relate to the
improper absorption of food in the GIT.improper absorption of food in the GIT.
Patient presents withPatient presents with diarrhea (<50%)diarrhea (<50%),, steatorrheasteatorrhea,, flatulenceflatulence,,
distended abdomendistended abdomen,, weight lossweight loss, &, & generalized weakness.generalized weakness.
Up toUp to 38 %38 % of patients areof patients are asymptomatic.asymptomatic.
Unrecognized celiac disease may causeUnrecognized celiac disease may cause malabsorptionmalabsorption,, ironiron
deficiency anemiadeficiency anemia,, osteoporosisosteoporosis,, osteomalaciaosteomalacia causingcausing
bone fractures, pain & bony deformities.bone fractures, pain & bony deformities.
People with celiac disease may also experiencePeople with celiac disease may also experience lactoselactose
intoleranceintolerance due todue to lactase enzyme deficiency.lactase enzyme deficiency.

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Dermatitis HypertiformisDermatitis Hypertiformis
Dermatitis herpetiformis (DH)Dermatitis herpetiformis (DH) is the skinis the skin
manifestation of celiac disease.manifestation of celiac disease.
It is anIt is an intensely itchy rashintensely itchy rash that occurs in the hands,that occurs in the hands,
fingers, forearms, buttocks or scalp or anywhere on the body.fingers, forearms, buttocks or scalp or anywhere on the body.
The rash typically consists of intensely itchy, small red dotsThe rash typically consists of intensely itchy, small red dots
that may develop into blisters or pimples.that may develop into blisters or pimples.
ApproximatelyApproximately 10%10% of patients with celiac disease have DH,of patients with celiac disease have DH,
& it is estimated that& it is estimated that > 85%> 85% of patients with DH have celiacof patients with DH have celiac
disease .disease .

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Dermatitis HypertiformisDermatitis Hypertiformis

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Celiac Disease & the Lung:Celiac Disease & the Lung:
The association betweenThe association between celiac diseaseceliac disease && diffusediffuse
interstitial pulmonary diseaseinterstitial pulmonary disease has been suspectedhas been suspected
sincesince 1970.1970.
Extrinsic allergic alveolitisExtrinsic allergic alveolitis was found in combinationwas found in combination
with celiac disease & it may be considered that both thesewith celiac disease & it may be considered that both these
diseases are based on one common immunologic disorder.diseases are based on one common immunologic disorder.
The association betweenThe association between pulmonary hemosiderosispulmonary hemosiderosis &&
celiac disease have been reported 9 times in literature asceliac disease have been reported 9 times in literature as
an extremely rare combination.an extremely rare combination.

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Other Presentations of Celiac Disease:Other Presentations of Celiac Disease:
NeurologicalNeurological symptoms e.g.,symptoms e.g., peripheral neuropathyperipheral neuropathy,,
ataxiaataxia oror epilepsy.epilepsy.
Apthous ulcersApthous ulcers in the mouth is considered to be anin the mouth is considered to be an
autoimmune disorder associated with celiac disease.autoimmune disorder associated with celiac disease.
Dental enamel defectsDental enamel defects are frequent.are frequent.
Patients with celiac disease may havePatients with celiac disease may have liver diseases.liver diseases.
Abnormal liver testsAbnormal liver tests are common at diagnosis & usuallyare common at diagnosis & usually
improve with treatment.improve with treatment.

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The Celiac IcebergThe Celiac Iceberg
SymptomaticSymptomatic
Celiac DiseaseCeliac Disease
Silent CeliacSilent Celiac
DiseaseDisease
Latent Celiac DiseaseLatent Celiac Disease
GeneticGenetic susceptibility:susceptibility: - DQ2, DQ8- DQ2, DQ8
Positive serologyPositive serology
ManifestManifest
mucosal lesionmucosal lesion
NormalNormal
MucosaMucosa

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Diagnosis: SerologyDiagnosis: Serology
Serum IgA endomysial antibodies (EMA)Serum IgA endomysial antibodies (EMA) && serumserum
IgA tissue transglutaminase (tTG) antibodiesIgA tissue transglutaminase (tTG) antibodies havehave
bothboth sensitivitysensitivity && specificity > 95%.specificity > 95%.
Testing forTesting for gliadin antibodiesgliadin antibodies is no longeris no longer
recommended because of itsrecommended because of its low sensitivitylow sensitivity &&
specificityspecificity for celiac disease.for celiac disease.
TheThe tTG antibodytTG antibody is theis the recommended singlerecommended single
serologic testserologic test forfor celiac disease screening.celiac disease screening.

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Diagnosis: Small Bowel BiopsyDiagnosis: Small Bowel Biopsy
Required to confirm the diagnosis of celiac disease.Required to confirm the diagnosis of celiac disease.
Should also be considered in patients withShould also be considered in patients with negativenegative
serologicserologic test results who are attest results who are at high riskhigh risk or in whom theor in whom the
physicianphysician strongly suspectsstrongly suspects celiac disease.celiac disease.
Mucosal changes may vary fromMucosal changes may vary from partialpartial toto total villoustotal villous
atrophyatrophy, or may be characterized by, or may be characterized by subtle cryptsubtle crypt
lengtheninglengthening oror increased epithelial lymphocytes.increased epithelial lymphocytes.
To avoid false-negative results on endoscopic biopsy, it isTo avoid false-negative results on endoscopic biopsy, it is
recommend to obtain at leastrecommend to obtain at least 4 tissue samples4 tissue samples to increaseto increase
the sensitivity of the test.the sensitivity of the test.

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Endoscopy & Biopsy in Celiac DiseaseEndoscopy & Biopsy in Celiac Disease
Normal small intestine
Celiac Disease
Normal Villi
Villous Atrophy

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Diagnosis: HLA Genetic TypingDiagnosis: HLA Genetic Typing
Antibody testing & HLA testing haveAntibody testing & HLA testing have similar accuracies.similar accuracies.
TestTest SensitivitySensitivity SpecificitySpecificity
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 DiseaseDietary Management in Celiac Disease
At present, the only effective treatment isAt present, the only effective treatment is
aa life-long gluten-free diet (GFD).life-long gluten-free diet (GFD).
No medication exists that will preventNo medication exists that will prevent
damage or prevent the body fromdamage or prevent the body from
attacking the gut when gluten is present.attacking the gut when gluten is present.
Strict adherence to the diet allows theStrict adherence to the diet allows the
intestines to heal, leading to resolutionintestines to heal, leading to resolution
of all symptoms in most cases and,of all symptoms in most cases and,
depending on how soon the diet isdepending on how soon the diet is
begun, can also eliminate the increasedbegun, can also eliminate the increased
risk of complications.risk of complications.

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Dietary Management in Celiac DiseaseDietary Management in Celiac Disease

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Follow-Up:Follow-Up:
Serologic markersSerologic markers (serum IgA tTG)(serum IgA tTG) used to monitorused to monitor
compliancecompliance with GFD.with GFD.
Antibody levelsAntibody levels return toreturn to normalnormal withinwithin 3-12 months3-12 months ofof
starting a GFD but may take up tostarting a GFD but may take up to 30 months30 months if the initialif the initial
titers are high.titers are high.
Repetition of small bowel biopsyRepetition of small bowel biopsy 3-4 months3-4 months afterafter
initiation of a GFD isinitiation of a GFD is not necessarynot necessary if the patient respondsif the patient responds
appropriately to therapy.appropriately to therapy.
If the patient does not respond as expected revise the→If the patient does not respond as expected revise the→
patient’s adherence to GFD, then the physician shouldpatient’s adherence to GFD, then the physician should
consider other differential diagnosis.consider other differential diagnosis.

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Prognosis:Prognosis:
Treating CD with a strictTreating CD with a strict GFDGFD is alwaysis always completely effective.completely effective.
Gastrointestinal complaints & other symptoms resolve in almost allGastrointestinal complaints & other symptoms resolve in almost all
patients.patients.
Once the diet has been followed for several years, individuals with CD haveOnce the diet has been followed for several years, individuals with CD have
similar mortality ratessimilar mortality rates as the general population. However, aboutas the general population. However, about 1010
%% of patients with celiac disease developof patients with celiac disease develop lymphomalymphoma && small bowelsmall bowel
adenocarcinoma.adenocarcinoma.
A few patients develop aA few patients develop a refractory typerefractory type of CD, in which the GFD noof CD, in which the GFD no
longer seems effective.longer seems effective.
Experts emphasize the need forExperts emphasize the need for lifelong adherence to the GFDlifelong adherence to the GFD toto
avoid the long-term complications of this disorder. They point out thatavoid the long-term complications of this disorder. They point out that
although the disease may have symptom-free periods if the diet is notalthough the disease may have symptom-free periods if the diet is not
followed, silent damage continues to occur.followed, silent damage continues to occur.
According to medical authorities, CDAccording to medical authorities, CD cannot be outgrowncannot be outgrown oror cured.cured.

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American Gastroenterological Association InstituteAmerican Gastroenterological Association Institute
Recommendations for Celiac Disease ScreeningRecommendations for Celiac Disease Screening
Consider testing in symptomatic patients at high riskConsider testing in symptomatic patients at high risk
for Celiac Disease with any of the following conditions:for Celiac Disease with any of the following 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 Disease.Presutti J,Cangemi J, Cassidy H, Hill D, Celiac Disease.
American Family Physician. December 15, 2007: 1795-American Family Physician. December 15, 2007: 1795-
1802.1802.
Hadithi M, von Blomberg BM, Crusius JB, et al. (2007).Hadithi M, von Blomberg BM, Crusius JB, et al. (2007).
"Accuracy of serologic tests and HLA-DQ typing for"Accuracy of serologic tests and HLA-DQ typing for
diagnosing celiac disease". Ann. Intern. Med. 147: 294–diagnosing celiac disease". Ann. Intern. Med. 147: 294–
302.302.
Hood J, Mason AMS. Diffuse pulmonary disease withHood J, Mason AMS. Diffuse pulmonary disease with
transfer defect occurring in coeliac disease. Lancettransfer defect occurring in coeliac disease. Lancet
1970;1:445-47.1970;1:445-47.

29. Thank YouThank You