Celiac Disease

CLINICAL CHARACTERISTICS

Celiac disease is a common systemic autoimmune disease that can develop in genetically susceptible individuals as a response to dietary gluten. Celiac disease can be associated with gastrointestinal findings (e.g., diarrhea, malabsorption, abdominal pain and distention, bloating, vomiting, and weight loss) and/or highly variable non-gastrointestinal findings (dermatitis herpetiformis, iron deficiency anemia, osteoporosis/osteopenia, other nutrient deficiencies, migraines, chronic fatigue, epilepsy, depression, attention-deficit/hyperactivity disorder, joint pain/inflammation, infertility and/or recurrent fetal loss, delayed puberty, growth deficiency, dental enamel hypoplasia, abnormal liver function, autoimmune disorders, and increased risk of cancer). Classical celiac disease, characterized by prominent gastrointestinal symptoms, is less common than non-classical celiac disease, characterized by mild or absent gastrointestinal symptoms. Some individuals with celiac disease have no symptoms despite the presence of immune reactivity to gluten; these individuals are referred to as having silent celiac disease.

DIAGNOSIS/TESTING: The diagnosis of celiac disease is established in an individual with positive celiac serologic testing results while on a gluten-containing diet (tissue transglutaminase immunoglobulin [Ig] A, anti-deamidated gliadin-related peptide IgA and/or IgG, or endomysial antibody IgA) and characteristic histologic findings on small bowel biopsy. Human leukocyte antigen (HLA) molecular genetic testing to detect celiac-associated and alleles is not necessary for initial diagnostic testing, but it is useful for diagnostic evaluation when serology or small biopsy results are inconclusive or discrepant. A negative result for celiac HLA genetic testing rules out celiac disease and a positive result identifies predisposition to celiac disease. Celiac HLA genetic testing is important for individuals who started a gluten-free diet before diagnostic evaluation.

MANAGEMENT

Lifelong adherence to a strict gluten-free diet (avoidance of wheat, rye, and barley). Nutrition assessment for those with persistent gastrointestinal manifestations despite removal of gluten from the diet; consider corticosteroids and immunosuppressants for refractory celiac disease; assess for malignancy in those with persistent poor weight gain and/or growth efficiency; consider dapsone for dermatitis herpetiformis; standard treatment for anemia if not responsive to gluten-free diet; standard treatment of osteoporosis; treatment of nutritional deficiencies (iron, zinc, calcium, fat-soluble vitamins, folic acid). Standard treatments for peripheral neuropathy, ataxia, seizures, migraines, poor school performance, psychiatric manifestations, joint pain and inflammation, fertility issues, pubertal delay, dental enamel hypoplasia, autoimmune disease, and cancer; evaluation for alternative causes of abnormal liver function if unresolved with gluten-free diet. For symptomatic individuals responsive to a gluten-free diet, abnormal celiac disease serologies should be followed to normalization; physical examination and assessment of growth, nutritional status, and non-gastrointestinal disease manifestations annually or as needed; measurement of hepatic profile and thyroid-stimulating hormone annually. Follow-up biopsy of intestinal villi can be considered for monitoring two years after diagnosis among individuals with a clinical and serologic response. Normalization of the intestinal biopsy is considered the aim of treatment with the diet. Dietary gluten. Celiac HLA genetic testing of first-degree relatives of a proband (including young children) for celiac-associated and alleles and determination of HLA-DQ status can be used to identify those who are susceptible to developing celiac disease and who would benefit from serologic testing to screen for celiac disease or silent celiac disease. Early diagnosis of celiac disease and treatment with a gluten-free diet can prevent secondary complications.

GENETIC COUNSELING

Celiac disease is a complex multifactorial disorder. The risk to family members of a proband with celiac disease depends on their HLA genetic risk (i.e., their HLA-DQ status, the strongest determinant of celiac disease susceptibility), less well-recognized variants in non-HLA genes, exposure to dietary gluten, and the involvement of additional environmental influences. Empiric risk for celiac disease can be estimated based on HLA-DQ status and familial relationship to the proband.