Fibromyalgia-like Joint/Muscle Pain and Synovitis in Non-celiac Wheat Sensitivity Patients

Study Overview
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Brief Summary
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Recently it has been reported that a consistent percentage of the general population consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term 'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes the symptoms in NCGS patients, and the investigators also showed that these patients had a high frequency of coexistent multiple food hypersensitivity. The clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and extra-intestinal and/or systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). Nowadays no data are available on the characteristic of 'rheumatologic' symptoms of NCWS patients. Therefore, the aims of the present study are: 1) to investigate the prevalence of fibromyalgia-like joint/muscle pain in NCWS patient, 2) to search for possible ultrasonographic alterations (i.e. synovitis) of hands and feet joints of NCWS patients, and 3) to evaluate modification of fibromyalgia-like joint/muscle pain in NCWS patients after a gluten free diet period of almost 6 months.

Detailed Description
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Recently it has been reported that a consistent percentage of the general population consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term 'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes the symptoms in NCGS patients, and the investigators also showed that these patients had a high frequency of coexistent multiple food hypersensitivity. CD is an immunological disorder whose best-known manifestations are gastrointestinal symptoms. However, early joint manifestations are common and frequently overlooked features of the disease. Similarly, the clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and extra-intestinal and/or systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). Nowadays no data are available on the characteristic of 'rheumatological' symptoms of NCWS patients. Therefore, the aims of the present study are: 1) to investigate the prevalence of fibromyalgia-like joint/muscle pain in NCWS patient, 2) to search for possible ultrasonographical alterations (i.e. synovitis) of hands and feet joints of NCWS patients, and 3) to evaluate modification of fibromyalgia-like joint/muscle pain in NCWS patients after a gluten free diet period of almost 6 months.

Official Title
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Fibromyalgia-like Joint/Muscle Pain and Synovitis in Non-celiac Wheat Sensitivity Patients

Conditions
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Non-celiac Wheat Sensitivity

Intervention / Treatment
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* Other: Gluten free diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All the patients met the recently proposed criteria: negative serum anti-tissue transglutaminase and antiendomysium (EmA) immunoglobulin (Ig) A and IgG antibodies absence of intestinal villous atrophy IgE-mediated immunoallergic tests negative to wheat and cow's milk protein (skin prick tests and/or serum specific IgE detection). Adjunctive criteria adopted in our patients were: resolution of the gastrointestinal and extra-intestinal symptoms on a standard elimination diet, without wheat, cow's milk, egg, tomato, chocolate, or other food(s) causing self-reported symptoms symptom reappearance on double-blind placebo-controlled (DBPC) wheat challenge, performed as described previously. DBPC cow's milk protein challenge will be also performed to diagnose cow's milk protein allergy. Exclusion Criteria: Exclusion criteria will be: age <18 years positive EmA in the culture medium of the duodenal biopsies, even if the villi to crypts ratio in the duodenal mucosa was normal self-exclusion of wheat from the diet and refusal to reintroduce it before entering the study other organic gastrointestinal diseases previously diagnosed rheumatic diseases nervous system disease and/or major psychiatric disorder physical impairment limiting physical activity menopause; steroid and sex steroid therapy, hormone replacement therapy or ovariectomy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NCWS patients<br>Fifty consecutive adult patients with an irritable bowel syndrome (IBS)-like clinical presentation, according to Rome III criteria, and a definitive diagnosis of NCWS. The patients will be recruited between January 2017 and January 2018 at 2 centers: the Department of Internal Medicine at the University Hospital of Palermo, Italy, and the Department of Internal Medicine of the Hospital of Sciacca, Agrigento, Italy. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo, Italy. | Other: Gluten free diet<br>* The investigators will evaluate the prevalence of fibromyalgia-like joint/muscle pain and the possible ultrasonographical alterations (i.e. synovitis) of hands and feet joints in NCWS patient at baseline (i.e. at the moment of diagnosis) and after a gluten free diet period of almost 6 months.<br>|
| No Intervention: CD patients<br>Fifty sex- and age-matched subjects with CD, diagnosed according to standard criteria during the same study period and enrolled, at the same 2 centers, as first control group. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo, Italy. | |
| No Intervention: IBS patients<br>Fifty sex- and age-matched subjects with IBS unrelated to NCWS or other food 'intolerance', diagnosed according to standard criteria during the same study period and enrolled, at the same 2 centers, as second control group. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of fibromyalgia-like joint/muscle pain in NCWS patients | Prevalence of fibromyalgia-like joint/muscle pain in NCWS patient using an ad hoc questionnaire and orientated clinical examination (tenders and triggers point evaluation) | up to 12 months | 
| Hands and feet joints ultrasonography alterations | Hands and feet joints ultrasonography alterations in NCWS patients. | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modification of fibromyalgia-like joint/muscle pain in NCWS patients after gluten free diet | Modification of fibromyalgia-like joint/muscle pain, by visual analogic scale, in NCWS patients after a gluten free diet period of almost 6 months. | up to 12 months | 
| Modifications of hands and feet joints ultrasonography alterations in NCWS patients after gluten free diet | Modifications of hands and feet joints ultrasonography alterations in NCWS patients after a gluten free diet period of almost 6 months. | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-celiac Wheat Sensitivity, fibromyalgia, synovitis