Definition of non-celiac gluten sensitivity

  1. Definition of non-celiac gluten sensitivity
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Non-celiac gluten sensitivity (NCGS) manifests itself with non-specific symptoms that occur both intestinally and extra-intestinally and resemble the symptoms of celiac disease or wheat allergy. Diagnosis is made based on the response to a gluten-free diet, after celiac disease and wheat allergy have been ruled out.

There is a group of patients who react  to the consumption of food containing gluten with symptoms such as abdominal pain, fatigue, headaches, rashes, or mental confusion ("foggy mind"). However, neither celiac disease nor wheat allergy is present in these instances. When these patients avoid gluten, their symptoms improve within a few weeks; when they are re-exposed to gluten the symptoms return. Whether the gluten or some other component of wheat is actually responsible for the reactions is currently the subject of debate in the scientific community. The focus is not just on gluten, it also includes amylase trypsin inhibitors (ATI) and FODMAPs. For this reason, some experts in this field may refer to NCGS more broadly as non-celiac wheat sensitivity.

Comparative differences with to celiac disease and wheat allergy

All three gluten-related disorders - NCGS, celiac disease and wheat allergy - have similar symptoms and  therefore diagnosis can be difficult. However, there are differences, e.g. in terms of reaction times and pathogenesis. Celiac disease is an autoimmune enteropathy caused by gluten. Wheat allergy is an IgE-mediated response to wheat. Although people with NCGS develop symptoms similar to those observed in celiac disease after eating food containing gluten, the clinical presentation is generally less severe. However, in contrast to celiac disease, NCGS individuals usually do not present with  auto-antibodies, anti-tissue-transglutaminases or autoimmune concomitant diseases. In contrast to celiac disease patients, patients with NCGS exhibit little histological change or only lesions in the small intestine mucosa, which corresponds to 0 - 1 on the Marsh scale.

 

Overview of how to distinguish between celiac disease, NCGS and wheat allergy

Celiac diseaseGluten sensitivityWheat allergy
Period between exposure to gluten and onset of symptomsWeeks to yearsHours to daysImmediate reaction:
a few hours
Delayed reaction:
a few hours to two days
PathogenesisAutoimmune
(congenital + adaptive immunity)
Currently unclear immunological reactionIgE formation and IgE-mediated mediator release
HLAHLA DQ2/8
(approx. 95% of cases)
Unclear-
AutoantibodiesPositive
(high sensitivity and specificity)
Negative
(except anti-gliadin antibodies IgA and/or IgG)
Positive
EnteropathyTypicalMissing; occasionally IEL slightly elevated
(Marsh 0-1)
Missing
SymptomsIntestinal and extra-intestinalIntestinal and extra-intestinalIntestinal and extra-intestinal
ComplicationsConcomitant diseases, long-term complicationsNo concomitant diseases, long-term complications unknownNo concomitant diseases
TherapyLong-term implementation of a gluten-free diet is necessary

Persons with celiac disease may must avoid foods containing gluten, even those that contain only traces of gluten, for their entire life
The minimum time frame should be no less than one or two years

The minimum time frame should be no less than one or two years

The tolerance threshold of patients with NCGS varies, i.e. gluten intake must be adjusted individually
Temporary avoidance of wheat-based foods is sometimes sufficient

Administration of cortisone may be necessary