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Nickel Allergy and Systemic Nickel Allergy Syndrome in Non Celiac Wheat Sensitivity

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ClinicalTrials.gov Identifier: NCT02750735
Recruitment Status : Completed
First Posted : April 25, 2016
Last Update Posted : April 25, 2016
Sponsor:
Information provided by (Responsible Party):
Pasquale Mansueto, University of Palermo

Brief Summary:
In the last few years, a new clinical entity has emerged which includes patients who consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy. This clinical condition has been named non-celiac gluten sensitivity (NCGS), although in a recent article, the investigators suggested the term "non-celiac wheat sensitivity" (NCWS), because it is not known to date what component of wheat actually causes the symptoms. Nickel is the fourth most used metal and the most frequent cause of contact allergy in the industrialized world. As a natural element of the earth's crust small amounts are found in water, soil, and natural foods, especially plant ones. Nickel allergy not only affects the skin but also results in systemic manifestations. Systemic nickel allergy syndrome can have cutaneous (urticaria/angioedema, flares, itching), and/or gastrointestinal (meteorism, colic, diarrhoea) signs and symptoms. In this study, the investigators evaluated 1) the frequency of Nickel allergy and Systemic Nickel allergy syndrome in NCWS patients, and 2) the clinical, serological, and histological characteristics of NCWS patients with contact dermatitis Nickel positive in comparison to NCWS patients without contact dermatitis.

Condition or disease
Non Celiac Wheat Sensitivity

Detailed Description:

In the last few years, a new clinical entity has emerged which includes patients who consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy. This clinical condition has been named non-celiac gluten sensitivity (NCGS), although in a recent article, the investigators suggested the term "non-celiac wheat sensitivity" (NCWS), because it is not known to date what component of wheat actually causes the symptoms. Other areas of doubt in NCWS regard its pathogenesis, while some papers reported intestinal immunologic activation, others linked NCWS to the dietary short chain carbohydrate (fermentable oligo-di-monosaccharides and polyols, FODMAPs) load. The investigators recently demonstrated that higher proportions of patients with NCWS develop autoimmune disorders, are antinuclear antibodies (ANA) positive, and show DQ2/DQ8 haplotypes compared with patients with irritable bowel syndrome (IBS), supporting an immunologic involvement in NCWS. Furthermore, some papers reported also a high frequency, ranging from 22% and 35%, of coexistent atopic diseases in NCWS patients, and the investigators suggested that a percentage of NCWS patients could really suffer from non-IgE-mediated wheat allergy.

Nickel is the fourth most used metal and the most frequent cause of contact allergy in the industrialized world. As a natural element of the earth's crust small amounts are found in water, soil, and natural foods, especially plant ones. Nickel allergy not only affects the skin but also results in systemic manifestations. Systemic nickel allergy syndrome can have cutaneous (urticaria/angioedema, flares, itching), and/or gastrointestinal (meteorism, colic, diarrhoea) signs and symptoms.

Volta et al. reported that 15% of NCWS patients suffered from allergy to nickel, but they did not further characterize this subgroup of patients, neither posed the NCWS diagnosis by means the double-blind placebo controlled challenge (DBPCC), as recommended. In this study, the investigators evaluated 1) the frequency of Nickel allergy and Systemic Nickel allergy syndrome in NCWS patients, and 2) the clinical, serological, and histological characteristics of NCWS patients with contact dermatitis Nickel positive in comparison to NCWS patients without contact dermatitis.


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Study Type : Observational
Actual Enrollment : 200 participants
Observational Model: Case-Only
Official Title: Nickel Allergy and Systemic Nickel Allergy Syndrome in Non Celiac Wheat Sensitivity
Study Start Date : January 2001
Actual Primary Completion Date : June 2011
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy
Drug Information available for: Nickel

Group/Cohort
Retrospective NCWS patients
The clinical charts of NCWS patients attending the outpatient centers of the Department of Internal Medicine at the University Hospital of Palermo and the Department of Internal Medicine of the Hospital of Sciacca were retrospectively reviewed. Patients had all been diagnosed with NCWS between January 2001 and June 2011, by a DBPCC method, and included in a previously published study. These charts included specific sections for the presence of associated atopic diseases, including nickel allergy. In this way, the characteristics of the NCWS patients suffering from nickel allergy were compared with those of the NCWS patients who did not suffer from nickel allergy. Incomplete clinical charts were excluded.
Prospective NCWS patients
The investigators also prospectively surveyed adult patients with functional gastroenterological symptoms according to the Rome III criteria, and a definitive diagnosis of NCWS. The patients were recruited between December 2014 and March 2016 at 3 centers: the two already mentioned and the Gastroenterology Unit of the ARNAS Civico Hospital of Palermo, Italy. Most of the patients had been referred due to gastrointestinal symptoms, the onset of which, they reported, could be related to wheat ingestion. Again, the characteristics of the NCWS patients suffering from nickel allergy were compared with those of the NCWS patients who did not suffer from nickel allergy.
Retrospective NCWS control patients
To compare the frequency of nickel allergy in NCWS and non-NCWS patients, a control group composed of 70 irritable bowel syndrome (IBS) patients, was selected. These controls were randomly chosen by a computer-generated method from subjects diagnosed during the same period and age- (+/-2 years) and sex-matched (+/-5%) with the NCWS patients. The IBS controls had been receiving the same elimination diet as the NCWS patients and had not shown any clinical improvement; they belonged to the cohort of subjects the investigators had studied previously.
Prospective NCWS control patients
As for the retrospective study, to compare the frequency of nickel allergy in NCWS and non-NCWS patients, a control group composed of 70 patients with functional gastroenterological symptoms, was selected, with the same criteria adopted for the retrospective study.



Primary Outcome Measures :
  1. Nickel allergy and Systemic Nickel allergy syndrome in retrospective NCWS patients [ Time Frame: Up to 10 years ]
    Frequency of Nickel allergy and Systemic Nickel allergy syndrome in retrospective NCWS patients and controls

  2. Nickel allergy and Systemic Nickel allergy syndrome in prospective NCWS patients [ Time Frame: Up to 15 months ]
    Frequency of Nickel allergy and Systemic Nickel allergy syndrome in prospective NCWS patients and controls


Secondary Outcome Measures :
  1. Characteristics of retrospective NCWS patients with contact dermatitis Nickel positive in comparison to retrospective NCWS patients without contact dermatitis and controls. [ Time Frame: Up to 10 years ]
    Clinical, serological, and histological characteristics of of retrospective NCWS patients with contact dermatitis Nickel positive in comparison to retrospective NCWS patients without contact dermatitis and controls.

  2. Characteristics of prospective NCWS patients with contact dermatitis Nickel positive in comparison to prospective NCWS patients without contact dermatitis and controls. [ Time Frame: Up to 15 months ]
    Clinical, serological, and histological characteristics of prospective NCWS patients with contact dermatitis Nickel positive in comparison to prospective NCWS patients without contact dermatitis and controls.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
The study was divided into 2 different parts. In the first, the clinical charts of NCWS patients were retrospectively reviewed, comparing the characteristics of the ones suffering from nickel allergy with those who did not suffer from nickel allergy, using, as control group, 70 IBS patients. In the second, the investigators prospectively surveyed adult patients with functional gastroenterological symptoms (Rome III criteria) and a definitive diagnosis of NCWS, comparing the characteristics of the ones suffering from nickel allergy were compared with those who did not suffer from nickel allergy, using, as control group, 70 patients with functional gastroenterological symptoms.
Criteria

Inclusion Criteria:

All the patients met the recently proposed criteria:

  • negative serum anti-tissue transglutaminase and antiendomysium (EmA) IgA and IgG antibodies;
  • absence of intestinal villous atrophy;
  • IgE-mediated immunoallergy tests negative to wheat (skin prick tests and/or serum specific IgE detection).

Adjunctive criteria adopted in our patients were:

  • resolution of the gastrointestinal 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. As in previous studies, DBPC cow's milk protein challenge and other "open" food challenges were also performed.

Exclusion Criteria:

Exclusion criteria were:

  • 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 cutaneous and/or gastrointestinal diseases;
  • concomitant treatment with steroids and/or antihistamines.

Allergic contact dermatitis was diagnosed in patients showing local eczematous lesions on the skin in close contact with nickel-containing objects. Suspected systemic nickel allergy syndrome (SNAS), was defined as a reaction characterized not only by diffused eczematous lesions (systemic contact dermatitis) but also by extracutaneous signs and symptoms, mainly gastrointestinal, after ingestion of nickel-rich foods (i.e. tomato, cocoa, beans, mushrooms, vegetables, wheat flour, etc). In all cases, the diagnosis was confirmed by means of the epicutaneous patch tests which provoked delayed lesions.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02750735


Locations
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Italy
Antonio Carroccio
Sciacca, Agrigento, Italy
Pasquale Mansueto
Palermo, Italy, 90127
Sponsors and Collaborators
University of Palermo
Investigators
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Study Chair: Antonio Carroccio, PhD University of Palermo

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pasquale Mansueto, MD, University of Palermo
ClinicalTrials.gov Identifier: NCT02750735     History of Changes
Other Study ID Numbers: ACPM10
First Posted: April 25, 2016    Key Record Dates
Last Update Posted: April 25, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Hypersensitivity
Immune System Diseases
Nickel
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs