“Refractory” celiac disease in a 4 year old girl

History at 22 months of age

Recurrent vomiting, constipation, 2 kg weight loss, iron deficiency anemia 

Mother has celiac disease 

CeD-Serology (tissue transglutaminase antibodies, TGA)

at pediatrician (Lab A)

• TGA-IgA   = >200 RE/ml (normal <20 U/ml)

at hospital (Lab B)

• TGA-IgA   = >128 U/ml (normal <7 U/ml),
• TGA-IgG 8.6 U/ml (normal <7)

Histopathology: Marsh 3c

Diagnosis: Celiac disease

Start of strict gluten free diet (GFD)

Follow up:  Vomiting and anemia resolved, good weight gain, but new symptoms: abdominal pain, bloating and diarrhea

CeD-Serology at pediatrician (Lab A):  8, 9, 13 und 15 months after starting strict GFD:

TGA-IgA   = >200 RE/ml (normal <20 U/ml) all 4 time points

EMA-IgA 1:1280 (15 months after start of GFD)

Age 3.5 years (20 months after starting strict GFD)

EGD & colonoscopy because of symptoms and no decline of CeD specific autoantibodies

Histopathology: Duodenum Marsh 3b,  other gastric and colonic biopsies normal

Diagnosis: Refractory celiac disease Type 1

Age 4 years: Referal to Celiac Center at Dr von Hauner Children’s Hospital, University of Munich, because of »refractory CeD« and continous diarrhea while keeping strict GFD since 2.2 years

Biopsies taken 6 months ago were reassessed by pathoolgists in Munich and  Marsh 3b was confirmed.

Physical examination: very active child, except little distended abdomen perfectly normal, growth since diagnosis along the 60^th percentile

BMI: increase from the 25^th to the 88^th percentile for age and sex  (Fig. 1)

Dietary assessment: No evidence of gluten ingestion, high intake of energy and fructose, 3 L of diluted apple juice/per day 

EGD: normal duodenal villi

Histopathology : Marsh 0

CeD-Serology: TGA-IgA 30 U/ml (normal <7I

Diagnosis Celiac disease in remission, Symptoms due to overfeeding and excess of juice with fructose malabsorption.

Treatment: Energy and fructose restrictions, symptoms resolved

Take home messages:

1. Refractory CeD does not exist in childhood.
2. Perform titration of TGA concentrations above measuring range to judge whether TGA concentrations decline during GFD.
3. Serology and histopathology may take up to 2.5 years to normalize in cases with total villous atrophy and very high TGA concentrations.
4. BMI development was against the diagnosis of „malabsorption syndrome“ as obligatory sign of refractory CeD.
5. Always consider other causes if „pieces of the puzzle“ do not fit in CeD. Clinical history (high juice intake) and physical examination (BMI during follow up) give the hind to solve the case.