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MORPHOLOGICAL SPECTRUM OF MUCOSAL LESIONS IN CLINICALLY SUSPECTED CELIAC DISEASE AND COMPARISON WITH SEROLOGYDr. Nusrat Zahra

MBBS

Supervisor:

Professor Dr. Anwar-ul-Haque

Diplomat American Board of Pathology

Fellow College of American Pathologists

Pathology Department

Pakistan Institute of Medical SciencesDate: 22-02-10SUPERVISORS CERTIFICATE

I, hereby certify that Dr. Nusrat Zahra

Having enrolment number: F-03-24803And RTMC Registration number: HSP-2005-042-208

Has been working under my direct supervision with effect from: 01.03.06 to date.

In the department of Pathology

Of Training Institution: Pakistan Institute of Medical Sciences

In the City of: Islamabad

The dissertation titled, Morphological Spectrum of Mucosal Lesions in Clinically Suspected Celiac Disease and Comparison with Serology, was prepared according to the FCPS Dissertation Guidelines under my direct supervision. I have read the Dissertation and have found it satisfactory for FCPS part II examination in the subject of Pathology.

Signature of Supervisor:

Professor Dr: Anwar-ul-Haque

Official stamp:

Date: 22 -02-10I am indebted to Professor Anwar-ul-Haque who motivated and guided me through every step of the way. I would also like to thank the technical staff without whose help; the assignment would not have been possible. I have deep regards for the gastroenterology department who cooperated with me fully during my study.

I would also like to take this opportunity to thank my parents who have encouraged and believed in me throughout my life.

And most importantly, I would like to thank Allah Almighty, without whose will no vision can ever become a reality.TABLE OF CONTENTSCONTENTS

PAGE NO.

PART I

Acknowledgementiii

List of Tablesv

List of Figuresvi

List of Abbreviationsvii

PART II

Abstract 1

Introduction 3

Review of Literature

7

Objective

30

Operational definitions31

Material and Methods

32

Results

37

Discussion

54

Conclusion

65

References

66

Annexes 86

LIST OF TABLES

Serial No.Page No.

i. Table 1The Modified Marsh Classification36

ii. Table 2Frequencies of Comorbid Disease, and Symptoms for various Marsh grades40

iii. Table 3Patient age and frequencies of gender for various Marsh grades41

iv. Table 4Frequencies of positive and negative tTGA (IgA/M) serology for various Marsh grades42

v. Table 5Frequencies of positive and negative AGA (IgA) serology for various Marsh grades43

vi. Table 6Patient characteristics and Marsh grading in cases with High grade Marsh lesions and positive tTGA (IgA/M) serology44

vii. Table 7Patients with discordant Serology and Histology45

LIST OF FIGURESSerial No.Page No.

i. Figure 1Age- Distribution of Male Patients46

ii. Figure 2Age Distribution of Female Patients47

iii. Figure 3Gender distribution of clinical symptoms in patients clinically suspected of Celiac disease48

iv. Figure 4Duodenal Biopsy showing Modified Marsh Type 1 lesion49

v. Figure 5Duodenal Biopsy showing Modified Marsh Type 3a Lesion50

vi. Figure 6Duodenal Biopsy showing Modified Marsh Type 3b Lesion51

vii. Figure 7Duodenal Biopsy showing Modified Marsh Type 3c lesion52

viii. Figure 8Duodenal biopsy showing Modified Marsh Type 3c Lesion53

LIST OF ABBREVIATIONSi. AGAAntigliadin antibody

ii. AGAAmerican Gastroenterological Association

iii. ARA Antireticulin antibodies

iv. CD Celiac disease

v. CTComputerized tomography

vi. DHDermatitis herpetiformis

vii. EATLEnteropathy-associated T-cell lymphoma

viii. EGD

Esophagogastroduodenoscopy

ix. ELISA Enzyme-linked immunosorbent assay

x. EMAEndomysial antibody

xi. ESPGHAN European Society for Pediatric Gastroenterology, Hepatology and Nutrition

xii. GFD Gluten-free diet

xiii. GI Gastrointestinal

xiv. GSGluten-sensitivity

xv. H&E Hematoxylin and eosin

xvi. HLAHuman leukocyte antigen

xvii. IBSIrritable bowel syndrome

xviii. IDAIron deficiency Anemia

xix. IELs

Intraepithelial lymphocytes

xx. IgAImmunoglobulin A

xxi. IgG

Immunoglobulin G

xxii. IgMImmunoglobulin M

xxiii. NIHNational Institute of Health

xxiv. NSAIDsNonsteroidal anti-inflammatory drugs

xxv. NK cells Natural killer cells

xxvi. PASPeriodic acid Schiff

xxvii. PETPositron emission tomography

xxviii. PIMS

Pakistan Institute of Medical Sciences

xxix. SIBOsmall intestinal bacterial overgrowth

xxx. SPSSStatistical Package for Social Sciences

xxxi. TCRT cell receptor

xxxii. tTG

Tissue transglutaminase

xxxiii. tTGA Tissue transglutaminase antibody