13.3 Celiac Disease & Malabsorption
Key Takeaways
- Celiac disease is an HLA-DQ2/DQ8-linked autoimmune enteropathy triggered by gluten, and it clusters with type 1 diabetes, autoimmune thyroiditis, Down syndrome, and selective IgA deficiency.
- First-line serology is tTG-IgA drawn while the child is still eating gluten; total serum IgA must be checked to avoid a false-negative result in IgA-deficient children.
- Duodenal biopsy remains the diagnostic gold standard, classically showing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes.
- Treatment is a strict, lifelong gluten-free diet; there is no medical cure and no safe threshold of ongoing gluten exposure.
- Cystic fibrosis, cow's milk protein allergy, and lactose intolerance are the key malabsorption mimics, each distinguished by its own history and confirmatory test.
Celiac Disease
Celiac disease is an immune-mediated enteropathy triggered by dietary gluten — the storage protein in wheat, barley, and rye — in genetically susceptible individuals, nearly all of whom carry the HLA-DQ2 or HLA-DQ8 haplotype. Gluten peptides are deamidated by tissue transglutaminase and presented to T cells in the lamina propria, driving an inflammatory response that damages the small intestinal mucosa. Celiac disease clusters with other autoimmune and genetic conditions — type 1 diabetes mellitus, autoimmune thyroiditis, Down syndrome, Turner syndrome, and selective IgA deficiency — and a stem describing a child with one of these conditions plus growth or gastrointestinal complaints is testing whether the candidate screens for celiac disease.
Clinical Presentation
Classic celiac disease presents in toddlers after gluten introduction with chronic diarrhea, abdominal distention, poor weight gain or weight loss, muscle wasting, and irritability — a malabsorptive picture reflecting villous damage. Increasingly, however, children present with atypical or extraintestinal features: isolated short stature or growth faltering, iron-deficiency anemia unresponsive to oral iron, dental enamel defects, delayed puberty, constipation rather than diarrhea, elevated transaminases, or the intensely pruritic vesicular rash of dermatitis herpetiformis, itself considered a cutaneous manifestation of celiac disease. Some children are entirely asymptomatic and identified only through screening because of a first-degree relative with celiac disease or an associated condition.
Diagnosis
Serologic testing is the first step, and the exam-critical rule is that the child must still be eating gluten at the time of testing — starting a gluten-free diet before testing is complete blunts antibody titers and can produce a false-negative result, delaying or obscuring diagnosis. The preferred initial test is IgA anti-tissue transglutaminase (tTG-IgA), which has high sensitivity and specificity. Because celiac disease is associated with selective IgA deficiency, a total serum IgA level should always be checked alongside tTG-IgA; if IgA is deficient, an IgG-based test (tTG-IgG or deamidated gliadin peptide IgG) is used instead, since an IgA-deficient child could otherwise have a falsely reassuring low tTG-IgA.
A positive serology is confirmed by esophagogastroduodenoscopy with duodenal biopsy, the diagnostic gold standard (some modern protocols allow biopsy-sparing diagnosis in select symptomatic children with very high tTG-IgA titers plus a positive endomysial antibody and compatible genetics, but classic teaching centers on biopsy confirmation). Histology follows the Marsh classification, with the fully developed lesion showing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes.
Treatment
The only effective treatment is a strict, lifelong gluten-free diet, which typically produces clinical improvement within weeks and normalization of serology and histology over months. Ongoing exposure to gluten, even in small amounts, perpetuates mucosal injury and raises long-term risk of osteoporosis, infertility, and, rarely, enteropathy-associated T-cell lymphoma, so dietary adherence and periodic serologic monitoring are lifelong priorities.
Other Causes of Pediatric Malabsorption
Celiac disease is one of several conditions a general pediatrician must distinguish when a child presents with chronic diarrhea, poor growth, or steatorrhea.
| Condition | Mechanism | Key clue |
|---|---|---|
| Celiac disease | Autoimmune villous injury from gluten | Positive tTG-IgA, growth faltering, associated autoimmune disease |
| Cystic fibrosis | Pancreatic exocrine insufficiency causing fat and protein maldigestion | Steatorrhea, recurrent respiratory infections, failure to thrive, meconium ileus history |
| Cow's milk protein allergy | Immune reaction to milk protein, not gluten | Younger infants, blood or mucus in stool, atopy, resolves with hydrolyzed formula |
| Lactose intolerance | Lactase deficiency, primary or post-infectious | Bloating and diarrhea temporally linked to dairy intake, improves with lactose avoidance |
| Short bowel syndrome | Reduced absorptive surface after resection | History of necrotizing enterocolitis, volvulus, or gastroschisis with prior bowel resection |
Cystic fibrosis (CF) deserves particular attention because it mimics celiac disease's growth failure but through a different mechanism: loss of pancreatic exocrine enzymes causes malabsorption of fat and fat-soluble vitamins (A, D, E, K), producing bulky, greasy, foul-smelling stools. Recurrent sinopulmonary infections, a history of meconium ileus, or a positive newborn screen or sweat chloride test distinguish CF from celiac disease.
Post-infectious lactose intolerance commonly follows an episode of viral gastroenteritis, as brush-border lactase — the most superficial and slowest-to-regenerate disaccharidase — is transiently lost; it resolves spontaneously over weeks as the mucosa heals and does not require the permanent dairy restriction that primary, genetic lactase deficiency does.
Follow-Up and Related Entities
After a confirmed celiac diagnosis, children are followed with growth monitoring and periodic tTG-IgA titers, which should trend down toward normal over 6-12 months on a genuinely gluten-free diet; a titer that fails to fall is the first clue to inadvertent gluten exposure or, rarely, refractory disease and should prompt a detailed dietary review before invasive workup. A related but distinct entity, non-celiac gluten sensitivity, causes gastrointestinal and sometimes extraintestinal symptoms that improve on gluten withdrawal but occurs without the HLA association, positive celiac serology, or villous atrophy that define true celiac disease — an important distinction because it does not carry celiac disease's long-term complication risks and does not require the same lifelong surveillance. Exam stems that describe symptom improvement on gluten avoidance but negative tTG-IgA and normal biopsy are testing this distinction rather than describing a false-negative celiac workup.
The exam pattern across this domain is consistent: match the growth trajectory, stool characteristics, associated conditions, and confirmatory test to the specific malabsorptive process rather than treating "chronic diarrhea plus poor weight gain" as a single diagnosis.
A 4-year-old with type 1 diabetes is being screened for celiac disease. Her mother recently placed her on a gluten-free diet after reading about the association. What is the most important issue with ordering tTG-IgA serology now?
A child with suspected celiac disease has a low total serum IgA level. Why is checking total IgA important before relying on the tTG-IgA result?
Duodenal biopsy in a child with a strongly positive tTG-IgA is most likely to show which histologic pattern?
A 5-year-old has poor growth, bulky and greasy stools, and recurrent sinopulmonary infections. Which feature most strongly favors cystic fibrosis over celiac disease as the cause of malabsorption?