Extraintestinal Non Celiac Wheat Sensitivity
Condition: Non-celiac Gluten Sensitivity
MeSH terms: Hypersensitivity
Study type: Observational

Summary: 
      Non Celiac Gluten Sensitivity (NCGS), or, better, Non Celiac Wheat Sensitivity (NCWS), since
      it is not known the real pathogenetic component(s) of grain, is a syndrome characterized by a
      cohort of symptoms, both gastrointestinal and extraintestinal, related to the ingestion of
      gluten/wheat-containing food in subjects who are not affected by celiac disease (CD) or wheat
      allergy. In particular, the possibility of extraintestinal manifestations in this condition
      has been suggested by some reports. In most cases, they are characterized by vague symptoms,
      such as headache, 'foggy mind', fatigue, joint and muscle pain, leg or arm numbness (i.e.,
      fibromyalgia-like symptoms), even if more specific complaints have been described. A possible
      neurological involvement has been underlined by NCWS association with gluten encephalopathy,
      gluten ataxia, and gluten peripheric neuropathy. NCWS patients may show even psychiatric
      diseases, such as anxiety, depression, and psychosis. Other described extraintestinal
      manifestations are dermatitis, (eczema or skin rash), gynecological disorders, and anemia. In
      addition, the association of NCWS with autoimmune diseases, such as autoimmune thyroiditis,
      and presence of anti-nuclear or other autoantibodies has been demonstrated, suggesting that,
      similarly to CD, NCWS might be considered as an immune system-related disease, and this
      aspect should be of relevance. In conclusion, the novelty of this matter has generated an
      expansion of literature data about the clinical features of the disease, with the unavoidable
      consequence that some reports are often based on low levels of evidence. The aims of the
      present study were to: a) retrospectively evaluate the prevalence and kind of extraintestinal
      symptoms in a large cohort of NCWS patients; b) to research for a possible relationship
      between the clinical, serological, genetic and histological characteristics of the NCWS
      patients and the number and kind of extraintestinal manifestations. As control groups, the
      researchers used CD and Irritable Bowel Syndrome (IBS) patients unrelated to NCWS or other
      food allergies/intolerances.
    

Detailed description: 
      Non Celiac Gluten Sensitivity (NCGS), or, better, Non Celiac Wheat Sensitivity (NCWS), since
      it is not known the real pathogenetic component(s) of grain, is a syndrome characterized by a
      cohort of symptoms, both gastrointestinal and extraintestinal, related to the ingestion of
      gluten/wheat-containing food in subjects who are not affected by celiac disease (CD) or wheat
      allergy. In detail, NCWS is distinguished by symptoms that typically take place soon after
      gluten/wheat ingestion, withdraw with gluten/wheat exclusion, and relapse following
      gluten/wheat challenge (i.e., double-blinded placebo-controlled, DBPC, gluten/wheat
      challenge, used for diagnostic purpose) within hours or days. The gastrointestinal clinical
      picture of NCWS is a combination of irritable bowel syndrome (IBS)-like manifestations, such
      as abdominal pain, bloating, diarrhea, or constipation, or alternation of diarrhea and
      constipation, and dyspepsia like-symptoms, such as postprandial heaviness, early satiety, and
      epigastric pain or burning. However, the possibility of extraintestinal manifestations in
      this condition has been suggested by some reports. In most cases, they are characterized by
      vague symptoms, such as headache, 'foggy mind', fatigue, joint and muscle pain, leg or arm
      numbness (i.e., fibromyalgia-like symptoms), even if more specific complaints have been
      described. A possible neurological involvement has been underlined by NCWS association with
      gluten encephalopathy, gluten ataxia, and gluten peripheric neuropathy. NCWS patients may
      show even psychiatric diseases, such as anxiety, depression, and psychosis. Other described
      extraintestinal manifestations are dermatitis, (eczema or skin rash), gynecological
      disorders, and anemia. In addition, the association of NCWS with autoimmune diseases, such as
      autoimmune thyroiditis, and presence of anti-nuclear or other autoantibodies has been
      demonstrated, suggesting that, similarly to CD, NCWS might be considered as an immune
      system-related disease, and this aspect should be of relevance. In conclusion, the novelty of
      this matter has generated an expansion of literature data about the clinical features of the
      disease, with the unavoidable consequence that some reports are often based on low levels of
      evidence. Therefore, only studies performed on large samples, with the inclusion of control
      groups, may be able to clearly establish whether the large information from the literature
      regarding extraintestinal NCWS manifestations could be supported by evidence-based
      agreements. Therefore, the aims of the present study were to: a) retrospectively evaluate the
      prevalence and kind of extraintestinal symptoms in a large cohort of NCWS patients, diagnosed
      by DBPC gluten/wheat challenge; b) to research for a possible relationship between the
      clinical, serological, genetic and histological characteristics of the NCWS patients and the
      number and kind of extraintestinal manifestations. As control groups, the researchers used CD
      and IBS patients unrelated to NCWS or other food allergies/intolerances.
    

Intervention name(s): Evaluation of extraintestinal manifestations
Intervention type(s): Other
Intervention description(s): The researchers evaluated the prevalence and kind of extraintestinal symptoms in NCWS patients and the possible relationship between the clinical, serological, genetic and histological characteristics of the NCWS patients and the number and kind of extraintestinal manifestations, using, as control groups, CD and IBS patients.
Other intervention name(s): Extraintestinal manifestations
Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        The researchers evaluated the extraintestinal manifestations in 3 groups of patients: (1)
        100 patients with a definitive diagnosis of NCWS, based on DBPC gluten/wheat challenge; (2)
        50 patients affected with CD, sex- (± 5%) and age-matched (± 2 years) with the NCWS
        patients, selected at random during the study period; (3) 50 patients affected with IBS,
        according to the Rome IV criteria, not related to NCWS or other food
        allergies/intolerances, sex- (± 5%) and age-matched (± 2 years) with the NCWS patients,
        selected at random during the study period.
      
Keywords: Non-celiac Gluten Sensitivity; Celiac Disease; Irritable Bowel Syndrome