Refractory Celiac Disease

Contents
Introduction
	References
Uncomplicated Celiac Disease
	Introduction
	Epidemiology
	Pathogenesis and Risk Factors
	Clinical Presentation
	Physical Examination Findings
	Diagnosis of Celiac Disease
	Video Capsule Endoscopy and Enteroscopy in Celiac Disease
	Follow-Up of Celiac Disease
	Conclusion
	References
Mechanisms of Lymphomagenesis in Celiac Disease: Lessons for Therapy
	Introduction
		The Long History of Intestinal Lymphoma in Celiac Disease
		The Intraepithelial Origin of Lymphoma Complicating Celiac Disease
		Analysis of the Transition from Uncomplicated CeD to Type 1 and Type 2 Refractory CeD and EATL
		Identification of the Intraepithelial Precursor(s) of RCD2 Lymphocytes from a Subset of Innate-like iCD3+ IEL (Fig. 1)
		JAK1-STAT3 Mutations in RCD2 Link Chronic Inflammation and Lymphomagenesis (Fig. 2)
		EATL Complicating RCD2 or Occurring De Novo in Celiac Disease or RCD1 Share a Mutational Landscape Dominated by JAK1 and STAT3 Mutations (Fig. 2)
		Lessons for Therapy in RCD2
		Conclusion and Perspectives
	References
From Unresponsive Celiac Disease to Refractory Celiac Disease: Epidemiological Data
	Introduction
	The Problems with Investigating Compliance
	Mucosal Healing and Outcome
	Epidemiology of RCD1
	Epidemiology of RCD2
	Concluding Remarks
	References
The Role of Endoscopy in Refractory Coeliac Disease
	Introduction
	Upper GI Endoscopy
	Small Bowel Capsule Endoscopy
	Device Assisted Enteroscopy
	Which Patients Should Undergo Endoscopy?
	Conclusions
	References
The Role of Pathologist in the Diagnosis of Refractory Coeliac Disease-and Enteropathy-Associated T Cell Lymphoma
	Introduction
	Refractory Coeliac Disease (RCD) Diagnosis
	Type 1 RCD (RCD1)
	Type 2 RCD (RCD2)
	Ulcerative Jejunoileitis
	Enteropathy-Associated T-Cell Lymphoma (EATL)
	Conclusion
	References
Laboratory Findings for the Diagnosis of Celiac Disease Related Complications
	Introduction
	Immunophenotypic Characteristics
		Phenotypical Characteristics of Intestinal Lymphocytes in the Normal Human Intestine, in CD and in RCD. Application for Diagnosis by Flow Cytometry
		Technical Aspects for Flow Immunophenotyping of Duodenal Biopsies
		Value of Flow-Cytometry in the Diagnostic Work-Up: Advantages and Limitations
	Genetic Characteristics of RCDII and EATL. Application for Diagnosis
		Immunogenetic Features: Clonality Assessment
			Rationale
			Clonality Assessment in Clinical Practice and Technical Considerations
			Future Developments
		Oncogenetic Features
			Cytogenetics
			Gene Sequencing
				Rationale
				Molecular Abnormalities in RCD and EATL
					JAK-STAT Pathway
					Other Genes Mutations
					Lessons from the VAFs
				Clinical Significance
				Technical Aspects
	Conclusion and Perspectives
	References
The Other Causes of Severe Enteropathy with Villous Atrophy Non-Responsive to a Gluten-Free Diet
	Environmental Enteropathy
	Autoimmune Enteropathy
	Common Variable Immunodeficiency Enteropathy
	Lymphoproliferative Disorders
		Drug/Iatrogenic Enteropathy
			Angiotensin Receptor Blockers
			Non-steroidal Anti-Inflammatories
			Mycophenolate Mofetil
			Methotrexate
			Azathioprine
			Monoclonal Antibodies
			Graft-Versus-Host Disease
			Chemotherapy
			Radiation
		Infectious Enteropathy
			Giardiasis
			Whipple’s Disease
			Human Immunodeficiency Virus
			Tropical Sprue
			Small Intestinal Bacterial Overgrowth
			Collagenous Sprue
			Eosinophilic Gastroenteritis
	References
Treatment of Refractory Celiac Disease
	Introduction
	Overview of the Drugs Investigated in Refractory Celiac Disease
		Immunosuppressive and Immunomodulatory Drugs
			Systemic Corticosteroids and Budesonide
			Cyclosporin
			Thiopurines
			IL-10
			Anti-TNF
			Mesalamine
		Cytoreductive Drugs
			Alemtuzumab
			Cladribine
			Stem Cell Transplantation
		Mesenchymal Stem Cell Transplantation
			Novel Approaches
	Conclusion
		Looking Back and Looking Forward: Future Perspectives on Treatment of Refractory Celiac Disease
	References
Prognosis of Refractory Coeliac Disease: The Prognostic Scores
	Introduction
		Defining Complicated Coeliac Disease
		Mortality in Complicated Coeliac Disease and Refractory Coeliac Disease
	Predictors and Risk Factors for Complicated Coeliac Disease
		Prognostic Score for Complicated Coeliac Disease: The PROCONSUL SCORE
	Predictors and Risk Factors for Poor Outcomes in Refractory Coeliac Disease
		Clinical and Molecular Classification of Refractory Coeliac Disease
		Scores to Predict Survival in Refractory Coeliac Disease
	Conclusions
	References
Enteropathy-Associated T-Cell Lymphoma
	Definition
	Epidemiology
	Pathology and Genetics
	Clinical Features
	Staging
	Prognosis
	Treatment
	Conclusion and Perspective
	References