New aspects in celiac disease

Table 1 Clinical manifestations of untreated celiac disease

Manifestations	Associated diseases	Genetic associated diseases
Classic symptoms:	Autoimmune diseases:	Down syndrome
		Turner syndrome
Abdominal pain	Type 1 diabetes	William syndrome
Anorexia	Thyroiditis	IgA deficiency
Diarrhea	Sjogren’s syndrome
Weight loss	IgA nephropathy
Short stature
Irritability	Neurologic disturbances:
Nonclassic symptoms:	Autism
	Depression
Dermatitis hepertiformis	Epilepsy
Hepatitis	Cerebellar ataxia
Anemia
Arthritis	Other diseases:
Constipation
Alopecia	Osteopenia/osteoporosis
Pubertal delay	Infertility
Vomiting	Intestinal adenocarcinoma
Inflammatory bowel disease	Non-Hodgkin lymphoma
Migraine headaches

Table 2 Diagnosis in celiac disease

Diagnostic criteria used in celiac disease	Diagnostic propose for celiac disease	Comments
Serological test:	With classical symptoms:	Positive serology supports a diagnosis of CD, but they are not
Tissue transglutaminase antibody (tTGA)	Serological test:	essential. Compatible with HLA-DQ2/D8 testing and identify
Endomysial antibody (EMA)	Tissue transglutaminase antibody (tTGA)	individuals for further biopsy evaluation. Small bowel biopsy
Gliadin antibodies (AGA)	Endomysial antibody (EMA)	is critical in symptomatic patients with negative serology for
Total IgA	Gliadin antibodies (AGA)	CD and with HLA compatible with the disease
Endoscopy	HLA-DQ2/DQ8 testing	Determination of HLA typing as a first step in diagnosis in CD family
	Capsule endoscopy (with adequate pathological interpretation)	Adequate number of biopsies and well oriented. Estimate lymphocyte infiltration and partial or total villus atrophy
	Without classical symptoms HLA-DQ2/DQ8 testing	Primordial role of HLA-typing if serology is negative and with biopsy refused or equivocal to identify individuals
	Serologic test:	Adequate number of biopsies and well oriented. Estimate
	Tissue transglutaminase antibody (tTGA)	lymphocyte infiltration and partial or total villous atrophy
	Endomysial antibody (EMA)
	Gliadin antibodies (AGA)
	Capsule endoscopy (with adequate pathological interpretation)

Table 3 Future directions in celiac disease

Unanswered questions	Future directions
Immunopathogenesis
How is oral tolerance broken?	Restoring immunological tolerance to gluten would represent the ideal cure for CD
Gluten-specific T cells	Gluten-specific T cells could be inactivated or deleted, tolerance to gluten should be restored
Diagnosis
What is the significance of the vast number of currently undiagnosed people with the disease?	The rate of the diagnosis will continue to increase with better diagnosis.
What is the significance of the increase number of people with extraintestinal symptoms or without classical symptoms in CD?	“the suspicion of the disease”
Genetics
Identify the genetic risk factors that predispose to CD	Polymorphic genes located in the MHC region and CD
	Genetic polymorphism of cytokine genes may influence the risk of CD
	Associated polymorphism with serological markers
	HLA-G polymorphism?