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

Completed

• Conditions: Non Celiac Wheat Sensitivity

• Registration Number: NCT02750735
• Lead Sponsor: 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.

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.

Study Timeline

• Study Start: 2001-01
• Primary Completion: 2011-06
• Study Completion: 2016-03
• Status Verified: 2016-04
• Study First Submitted: 2016-04-15
• Study First Submitted QC: 2016-04-20
• Last Update Submitted: 2016-04-20
• Study First Posted: 2016-04-25
• Last Update Posted: 2016-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Nickel allergy and Systemic Nickel allergy syndrome in retrospective NCWS patients	Up to 10 years	Frequency of Nickel allergy and Systemic Nickel allergy syndrome in retrospective NCWS patients and controls
Nickel allergy and Systemic Nickel allergy syndrome in prospective NCWS patients	Up to 15 months	Frequency of Nickel allergy and Systemic Nickel allergy syndrome in prospective NCWS patients and controls

Secondary Outcome Measures

Name	Time	Method
Characteristics of prospective NCWS patients with contact dermatitis Nickel positive in comparison to prospective NCWS patients without contact dermatitis and controls.	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.
Characteristics of retrospective NCWS patients with contact dermatitis Nickel positive in comparison to retrospective NCWS patients without contact dermatitis and controls.	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.

Trial Locations

Locations (2)

Pasquale Mansueto; 🇮🇹 Palermo, Italy

Antonio Carroccio; 🇮🇹 Sciacca, Agrigento, Italy