“Misdiagnosis because pediatrician did not follow guidelines ?”
History
Emil presented at 10 years of age because of abdominal pain, and diarrhea since 3 months, weight loss of 1 kg
Physical examination: no abnormalities, height and weight for age: 60th percentile, BMI: 50th percentile.
Six months ago, his pediatrician diagnosed celiac disease. Since then Emil is keeping a strict gluten free diet (GFD).
Review of his diagnostic work-up prior start of GFD revealed the following results:
CeD-Serology at time of diagnosis (tissue transglutaminase antibodies=TGA, deaminateded gliadin peptides=DGP)
TGA-IgA = 30 U/ml (normal <20 U/ml) (Manufacturer: Euroimmun, Germany)
DGP-IgA = 104 U/ml (normal <25 U/ml), (Manufacturer: Euroimmun, Germany)
DGP-IgG = <10 U/ml (normal <25 U/ml) (Manufacturer: Euroimmun, Germany)
Total-IgA = 1.9 g/L (normal 0.5 – 2.0 g/l)
Other Lab values: CBC, ALT, AST, Lipase, Ca, Na, K: normal
No biopsies were performed.
Recommandation of Pediatricians: GFD because of CeD, follow up in 3 months with measurement of antibodies against EMA (Endomysium)
Work up at presentation
Upper Endoscopy &Sigmoidoscopy: Normal, Histopathology of duodenum: Marsh 0
TGA-IgA = 1.2 U/ml (normal <7 U/ml) (Manufacturer: ThermoFisher, Germany)
EMA-IgA negative (<1:5)
Stool: soft, pH 5.5, negative for pathogens, including parasites
Other Lab-values: normal
Dietary history revealed extensive consumption of milk (>500 ml/d), fruits, apple juice
Therapy and follow up:
- No juice, fruits after meals, switch to L-minus dairy products (Lactose free)
è Stool normalized, no abdominal pain
è H2 breath test with fructose: normal; with lactose – lactose intolerance
- After 4 weeks: gluten containing diet with lactose free/reduced dairy products
è No recurrence of diarrhea or abdominal pain, no other symptoms ocurred
è TGA-IgA after 3, 6, 12 and 24 months all < 2 U/ml (normal <7 U/ml) (Manufacturer: ThermoFisher), EMA-IgA remaineds negative
Final diagnosis: Lactose intolerance, no celiac disease
Identified mistakes and take home messages:
- Celiac disease was not diagnosed according to current guidelines1, 2
- TGA were only 1.5 times the upper limit of normal
- The child was not referred to a pediatric gastroenterologist when TGA-IgA tested positive
- Duodenal biopsies would have been obligatory with histopathology showing Marsh 2/3 to confirm the diagnosis of CeD
- The pediatricians was not familiar with the serological testing
- The applied test for TGA-IgA was from the manufacturer Euroimmun, Germany. This test is very sensitive and false positive results with low levels (here 1.5 x ULN) are more common than with test from other manufacturers 3.
- Testing for DPG-IgA and DGP-IgG were performed at initial work up. The new guidelines recommend against initial testing with other serological tests than TGA-IgA and total IgA in Serum 2.
- DGP-IgA is neither specific nor sensitive and should not be used at all.
- The pediatrician miss-interpreted the result with >100 U/ml as very high, not considering the type of test and cut off (personal communication)
- DGP-IgG should only be performed in cases with IgA-deficiency. They are less specific and are commonly positive in infants and young children after gluten introduction as a normal response and do not predict CeD in the absence of TGA-IgA4
FACIT: The child received the wrong diagnosis with all implications for him and the parents: induction of anxiety, unneeded gluten free diet and later upper endoscopy to prove normal mucosa prior gluten introduction, resulting in increased costs and decreased quality of life.
1. Husby S, Koletzko S, Korponay-Szabo IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54:136-60.
2. Husby S, Koletzko S, Korponay-Szabo I, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr. Jan 2020;70(1):141-156.
- Werkstetter KJ, Korponay-Szabo IR, Popp A, et al. Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice. Gastroenterology 2017;153:924-935.
- Dios A, Elek R, Szabo I, et al. Gamma-gliadin specific celiac disease anti-bodies recognize p31-43 and p57-68 alpha gliadin peptides in deamidation related manner as a result of cross-reaction. Amino Acids 2021;53:1051-1063.