BACKGROUND: This is the first randomized, double-blind, placebo-controlled trial 
(EUDRACT No. 2009-013923-43) evaluating nickel oral hyposensitizing treatment 
(NiOHT) in patients with "systemic nickel allergy syndrome" (SNAS), 
characterized by Ni-allergic contact dermatitis and systemic reactions after 
eating Ni-rich food.
METHODS: Adults with positive Ni-patch test, who reported symptoms suggesting 
SNAS, which improved after Ni-poor diet, and were positive to Ni-oral challenge 
were eligible. Patients were randomly assigned to three treatments (1.5 μg, 0.3 
μg, or 30 ng Ni/week) or placebo for a year, with progressive reintroduction of 
Ni-rich foods form the 5(th) month. Out of 141 patients randomized, 113 
completed the trial. Endpoints were efficacy and tolerability of treatment.
RESULTS: During Ni-rich food re-introduction, the 1.5 μg Ni/week group had a 
mean VAS score significantly higher than placebo (p = 0.044), with significant 
improvement of gastrointestinal symptoms (p = 0.016;) and significantly fewer 
rescue medications. Cutaneous manifestations also improved but without reaching 
statistical significance. After the treatment, oral challenge with higher Ni 
doses than at baseline were needed to cause symptoms to flare-up in 
significantly more patients given 1.5 μg Ni/week than placebo (p = 0.05). 
Patients reported no side-effects.
CONCLUSIONS: NiOHT is effective in SNAS, in particular on gastrointestinal 
manifestations, with trend toward improvement of cutaneous symptoms.