Overview
This International Archives of Allergy and Immunology study from the University of Verona (Departments of Clinical and Experimental Medicine and Maxillofacial Surgery / Odontostomatology) and the University of Palermo (Department of Clinical Medicine and Emerging Pathologies) tests whether nickel sensitization underlies recurrent aphthous stomatitis (RAS) in a large patient cohort. 380 consecutive RAS patients underwent patch testing for nickel and double-blind placebo-controlled oral nickel challenge. Among nickel-sensitive RAS patients, 45.7 percent had a positive DBPC oral nickel challenge, and 21 of 32 patients who followed a nickel-free diet experienced symptom improvement. The cohort is the largest controlled study of the nickel-RAS link and supports nickel sensitivity as a meaningful subset etiology for RAS that responds to dietary intervention.
Key numbers
| Measure | Result |
|---|---|
| RAS patients with positive nickel patch test | (subset of 380) |
| Positive DBPC oral nickel challenge among nickel-sensitive patients | 45.7 percent |
| Symptom improvement on nickel-free diet | 21 of 32 (65.6 percent) |
| Orthodontic-appliance-related onset | 28 of 380 (7.4 percent) |
| Chocolate/cocoa-aggravated symptoms | 352 of 380 (92.6 percent) |
Methods (brief)
Retrospective and prospective data analysis (1990-1999). All patients underwent standardized patch testing to nickel sulfate. DBPC oral nickel challenge with nickel sulfate vs placebo. Patients with positive challenge then followed nickel-free diet with structured outcome assessment.
Implications
- Certification: Demonstrates that a subset of RAS — a common oral mucosal disorder — has a nickel-mediated etiology amenable to dietary intervention. The 92.6 percent chocolate/cocoa-aggravated subset reinforces the cocoa-as-high-nickel-matrix framing on Cocoa and Chocolate.
- Microbiome / immunology: Oral mucosal allergic contact mucositis (ACM) is the parallel of cutaneous allergic contact dermatitis on the oral mucosa; both share type IV hypersensitivity mechanism.
- Courses: Standard reference for the nickel-RAS link and DBPC challenge methodology.
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Update history
The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.
| Commit | Date | Change | Description |
|---|---|---|---|
| a8052bb | 2026-08-09 | major | 6 sections added; narrative text revised |