Celiac Disease

A chronic malabsorptive disease of the small intestine resulting from ingestion of gluten.

Celiac Sprue; Gluten-Sensitive Enteropathy; Herter Disease; Herter-Heubner Disease.

For symptomatic gluten-sensitive enteropathy, the incidence is 1:150-1000 in Europe, but a greater proportion of individuals (1:200-400) may have clinically silent disease. The incidence appears to be much lower in the black and Asian population, which is explained by a lower frequency of human leukocyte antigen (HLA)-DQ2 or HLA-DQ8.

Multifactorial. The causative genetic component involves an assortment of major histocompatibility complex genes interacting with environmental factors. Celiac disease is the first HLA-associated disease for which the “at-risk genotypes” have been delineated. In the vast majority (>93%) of patients with celiac disease, genetic susceptibility has been associated with the HLA-DQ2 heterodimer, encoded by the DQA1*0501 and DQB1*02 genes. The remaining minority not expressing DQ2 is positive for DR4 and shows the DQ8 heterodimer, which is encoded by DQA1*0301/DQB1*0302 genes. The two heterodimers DQ2 and DQ8 are located on the surface of antigen-presenting cells and are involved in binding of peptides to be presented to CD4+ T lymphocytes. This association supports the importance of CD4+ T lymphocytes in the pathogenesis of celiac disease, as a T-cell-mediated inflammatory response in the proximal small bowel is made responsible for the intestinal problems.

The mucosal lesion represents an immunologically mediated injury triggered by gluten. The amino acid residue of gliadin triggers the abnormal immune response. Gluten is found in wheat, rye, barley, triticale, and oats. The alcohol-soluble prolamine fraction is the component of gluten that is responsible for the symptoms of celiac disease. Depending on the cereal, this prolamine fraction has different names: gliadin in wheat, secalin in rye, avenin in oats, and hordein in barley (newer research suggests avenin is tolerated). Tissue transglutaminase, the major target of autoantibodies in celiac disease, converts glutamine residues of gluten to glutamic acid. This deamination results in significantly increased DQ binding and T-cell recognition.

Malabsorption usually begins at approximately 4 to 20 months of age (although later onset has been reported), but 10 to 20% of patients become “tolerant” to gluten during adolescence. The disease is permanent, even if no symptoms are present. The best combination of serologic tests for the diagnosis is anti-gliadin IgA, anti-gliadin IgG, and anti-endomysium IgA. The high serum count of intraepithelial lymphocytes suggests activated mucosal cell-mediated immunity. The final diagnosis of celiac disease must always rely on the results of an intestinal biopsy showing villous atrophy. Serologic tests usually are performed at the onset of clinical symptoms. If the results are positive, then an intestinal biopsy is indicated to confirm the diagnosis. Serologic tests can be used to control the response to treatment with a gluten-free diet.

Clinical signs start in early infancy a few weeks after a diet containing gluten is added to breast-feeding. Intestinal symptoms are variable, including diarrhea, nausea, vomiting, bloating, steatorrhea, and constipation. Other features include failure to thrive, anorexia, hypoprothrombinemia as a result of malabsorption of vitamin K, osteoporosis, defective enamel, skin rash (dermatitis herpetiformis Duhring; a papulovesicular skin condition), recurrent aphthous stomatitis, edema as a result of hypoproteinemia, decreased blood levels of vitamin A and E, anemia as a result of folate deficiency and/or iron deficiency, and rickets secondary to vitamin D malabsorption. Puberty may be delayed, and refractory epilepsy associated with brain calcifications has been reported in 5% of patients. Arthritis occurs frequently in adults (26%) and requires regular followup. Serum prolactin in patients with active celiac disease is significantly higher and can be correlated to the degree of mucosal atrophy. Celiac disease is more common in patients also suffering from other genetic or immune diseases (e.g., Down syndrome, selective IgA deficiency, IgA nephropathy, rheumatoid arthritis, thyroid diseases, insulin-dependent diabetes mellitus). Children with diabetes mellitus, even when asymptomatic, should be screened yearly for celiac disease. A significantly increased risk for intestinal adenocarcinomas, non-Hodgkin (T-cell) lymphomas, and squamous cell carcinomas of the oropharynx and esophagus has been reported in patients with long-standing celiac disease.

Preoperative blood work should include a complete blood count (anemia), total serum protein and albumin (hypoproteinemia), serum electrolytes (including calcium), and coagulation parameters (vitamin K-dependent coagulation factors). Depending on the clinical manifestation (diarrhea, vomiting), the volume status must be assessed and corrected if necessary. For patients with diabetes mellitus, either a blood glucose profile should be obtained or their personal serum glucose diary should be reviewed (if available). For patients with abnormal thyroid function, a preoperative check is recommended.

Regional anesthesia techniques are not contraindicated per se, but a review of the coagulation status is highly recommended.

The child must be managed as though he/she were hypovolemic and hypoproteinemic, so the dose of agents decreasing arterial blood pressure should be reduced. This also applies to drugs with high protein binding.