Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances

Figures & data

Table 1 Classification of CD subtypes

	Clinical symptoms	Serology	HLA markers	Pathology
Classic CD	Diarrhea, abdominal distension, failure to thrive, or weight loss	Positive	Positive	Villous atrophy always present
Atypical CD	Iron deficiency anemia, osteoporosis, short stature, arthritis, infertility, peripheral neuropathy, abnormal liver function tests	Positive	Positive	Variable degree of villous atrophy is present, more subtle microarchitectural changes
Silent CD	Asymptomatic	Positive	Positive	Villous atrophy
Latent CD	Vary from asymptomatic to symptoms seen in atypical CD	Positive or negative	Positive	No villous atrophy but cellular immune cells antibody infiltration seen

Abbreviations: CD, celiac disease; HLA, human leukocyte antigen.

Table 2 Oberhuber/Marsh classification³⁴

	Villous architecture	Crypt height	Intraepithelial lymphocytosis/ECa	Diagnostic of CD?
Type 0	Normal	Normal height	<40 IEL/100 EC	No
Type 1	Normal	Normal height	>40 IEL/100 EC	No
Type 2	Normal	Crypt hyperplasia	>40 IEL/100 EC	No
Type 3A	Mild villous flattening	Increased height	>40 IEL/100 EC	Yes
Type 3B	Marked villous flattening	Increased height	>40 IEL/100 EC	Yes
Type 3C	Total villous flattening (flat mucosa)	Increased height	>40 IEL/100 EC	Yes

a Notes: Recently this threshold was reduced to 25/100;⁷ the data displayed in this table have been collated from data in Oberhuber.³⁴

Abbreviations: CD, celiac disease; EC, enterocytes.

Table 3 Differential diagnosis of villous atrophy³⁹

Celiac disease Tropical sprue Adult-onset autoimmune enteropathy Hypogammaglobulinemia Idiopathic AIDS enteropathy Food protein hypersensitivity Eosinophilic gastroenteritis Whipple disease Abetalipoproteinemia Intestinal lymphoma Collagenous sprue Tuberculosis Giardiasis Crohn’s disease Small-bowel bacterial overgrowth Infectious enteritis Parasitic infestation Severe malnutrition Small-bowel ischemia

Note: Reproduced from: Rubio-Tapia A, Murray JA. Classification and management of refractory coeliac disease. Gut. 59:547–557. Copyright notice 2010 with permission of BMJ Publishing Group Ltd.³⁹

Abbreviation: AIDS, acquired immune deficiency syndrome.

Figure 1 Algorithm for the diagnosis of celiac disease.

Note: *Nutritional deficiencies include testing iron, folic acid, calcium, vitamin D, vitamin B12 and vitamin A.
Abbreviations: TTG, tissue transglutaminase; EGD, esophagogastroduodenoscopy; CD, celiac disease; GFD, gluten-free diet.

Figure 2 Nonresponsive celiac disease algorithm.

Abbreviations: CD, celiac disease; GFD, gluten-free object; HLA, human leukocyte antigen; CC, collagenous colitis; LC, lymphocytic colitis; EGD, esophagogastroduodenoscopy; TCR, T-cell receptor; UJ, ulcerative jejunitis; EATL, enteropathy associated T-cell lymphoma; IBS, irritable bowel syndrome.

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