Some Non-celiac Gluten Sensitivity Patients May Have 'Celiac Lite' Disease

By Marilynn Larkin

July 29, 2016

NEW YORK (Reuters Health) - A subset of patients with non-celiac gluten sensitivity (NCGS) may actually have a form of celiac disease, researchers in Spain report.

"The differential diagnosis of 'minor' forms of celiac disease and NCGS is difficult," Dr. Fernando Fernandez Banares of the University Hospital Mútua de Terrassa told Reuters Health by email. A diagnosis of NCGS requires ruling out celiac disease on the basis of negative celiac serology and a duodenal biopsy of normal villi (no villous atrophy) in a person who is currently on a diet that contains gluten, he explained. But those diagnostic criteria may need to be revisited.

Dr. Banares and colleagues conducted a small proof-of-concept study that aimed to demonstrate that gluten can trigger clinical symptoms in a subgroup of patients who currently fulfill the diagnostic criteria NCGS. Recent trials suggest that only a minority of those patients will exhibit symptoms in response to a gluten challenge, the authors note in PloS One, online July 8.

At the time of NCGS diagnosis, the 18 participants had all been on a gluten-containing diet, with lymphocytic enteritis on distal duodenum biopsy and gastrointestinal symptoms that fell within the clinical spectrum of celiac disease - but they had negative celiac disease serology. In addition, they all had genes that predispose to celiac disease (HLA-DQ2.5 and/or HLA-DQ8 haplotypes).

Other causes of lymphocytic enteritis such as parasitic infection, NSAID intake or Helicobacter pylori infection had been ruled out.

All participants also had clinical and histological remission after at least a year on a gluten-free diet.

Eleven patients were randomly assigned to take a sachet of 10 grams of gluten twice daily for six months; the other seven patients took placebo sachets twice daily.

In the gluten-challenge group, 10 patients (91%) had a clinical relapse within the first two weeks; including seven who "were prematurely withdrawn because of intolerable symptoms." By comparison, only two patients (28.5%) relapsed in the placebo group (p=0.01).

Clinical scores and quality of life worsened after gluten, but not after placebo (p<0.01).

"Since these patients (the 91%) were characterized by gastrointestinal clinical symptoms within the clinical spectrum of celiac disease, presence of HLA-DQ2/8+, Marsh stage 1 lesion (increased intraepithelial lymphocytes but no villous atrophy), and a clinical and histological response to a gluten-free diet, the question remains as to whether this condition should be considered a 'minor' or 'low-grade' celiac disease (also called 'celiac lite' by some authors) or NCGS," Dr. Banares said.

"Previous studies have shown that the intraepithelial lymphocyte (IEL) count and/or the presence of anti-transglutaminase (TG2) deposits in the mucosa are biomarkers of celiac disease," he continued. "In the present study, these tissue celiac markers were present in around 55% of patients at inclusion, despite their being on a gluten-free diet, suggesting a 'celiac lite' disease."

He added, "Previous studies of celiac disease with (villous) atrophy have shown a permanent increase in IEL, even after a gluten-free diet, (suggesting) that this marker may provide a clue for celiac disease diagnosis and offering the possibility of identifying celiac disease patients when they are on a gluten-free diet, even when histological examination of the biopsy shows recovered mucosa."

"This 'proof of concept' study suggests that there is a 'minor' form of celiac disease with negative celiac serology that should be taken into account in the differential diagnosis of NCGS. The presence of increased IEL count and/or TG2 deposits in the mucosa could be of help in the diagnosis of these patients," Dr. Banares observed.

"We are routinely using this diagnostic strategy in our outpatient clinic, and we think that the intraepithelial lymphogram study adds important information to the diagnostic work-up of these patients. Our recommendation is to use it in clinical practice," he concluded.

Commenting by email, Dr. Gina Sam, director of the Gastrointestinal Motility Center at the Mount Sinai Hospital in New York City said, "This study suggests that patients who do not have celiac disease but still have symptoms like a celiac patient (NCGS patients) do respond to a gluten-free diet. This is a groundbreaking study and supports that there is some type of inflammatory response that occurs with gluten in some patients. This is an amazing finding and suggests this is why IBS patients do well gluten free."

No commercial funding or conflicts of interest were reported.


PLoS One 2016.