Some patients with nickel (Ni) allergic contact dermatitis suffer from systemic 
(intestinal or cutaneous) symptoms after ingestion of Ni-rich foods and 
experience symptoms reduction with low-Ni diet, a condition termed Systemic Ni 
Allergy Syndrome (SNAS). We aimed at evaluating whether oral administration of 
low nickel doses improved clinical conditions and modulated immunological 
aspects of SNAS, without significant side effects. Thirty-six SNAS patients were 
enrolled. Treatment started after 1-month of low-Ni diet and consisted in an 
incremental oral NiOH dose phase (0.3ng to 1.5 microg/week) followed by a 
12-months maintenance phase (1.5 microg/week). Randomly, twenty-four patients 
added Ni therapy to low-Ni diet and 12 remained with diet alone. All patients 
were allowed rescue medications (antihistamines and topical steroids). After 4 
months, Ni-rich foods were gradually reintroduced. In vitro allergen-driven 
IL13, IL5 and IFN-gamma release by peripheral blood mononuclear cells was 
evaluated before and after treatment. Twenty-three patients receiving NiOH and 
the 12 control patients completed the study. Evaluation of SNAS clinical 
severity (by VAS and drug consumption) showed a significant difference in favor 
of NiOH-treated patients compared to controls. Twenty of 23 patients in the NiOH 
group and none in the control group tolerated Ni-rich food reintroduction. 
Release of all studied cytokines in culture supernatants was significantly lower 
after NiOH treatment. In conclusion NiOH is effective in reducing symptoms and 
drug consumption in SNAS and is able to modulate inflammatory parameters.