Intrinsic atopic dermatitis shows high serum nickel concentration

Atopic dermatitis (AD) can be divided into two types,1 serum IgE-high extrinsic AD (EAD), occupying approximately 80% of total AD, and serum IgE-normal intrinsic AD (IAD). We have investigated various clinical and immunological aspects of IAD.2e5 Female predominate is noted in IAD. While Th2 cells are increased in the peripheral blood of EAD, the frequency of IFN-g-producing Th1 cells is high in IAD. ThemRNA expression of Th1 cytokines, such as interferon (IFN)-g, in lesional and nonlesional skin from IAD patients are significantly higher than EAD.6 IAD patients often suffer frommetal allergy. Given that protein antigens and metals/haptens give rise to Th2 and Th1 responses, respectively, metals are a candidate of causes for relatively Th1-skewing IAD. We have previously shown that the frequencies of positive patch tests to nickel, cobalt and chrome in IAD patients are 41.9%, 38.7% and 22.6%, respectively, and 61.3% of IAD patients show positive reactions to at least one of the three metals.7 This is 2.4-fold higher than that of EAD. A high nickel concentration in sweat of IAD patients was also found.7 Here, we measured nickel concentration of sera in patients with IAD and EAD, and healthy control (HC). We performed a dietary nickel loading study using a chocolate containing a high nickel dose. This study was approved by the humanmedical and ethics committees of both Hamamatsu University School of Medicine and Tohoku University. Patients gave written informed consent. Enrolled in this study were 17 AD patients and 17 HC volunteers. Leukocyte counts, eosinophil percentage, serum IgE, serum specific IgE to Dermatophagoides pteronyssinus (DP), serum CCL17/TARC were measured in AD patients. There is no uniform criteria for AD categorization. As previously reported, we classified AD into IAD and EAD by using serum IgE and IgE specific to DP.7 IAD was defined as serum IgE levels 200 kU/L or 200 < IgE 400 plus class 0 or 1 of IgE specific to DP and EAD was defined as 400 < IgE levels or 200 < IgE 400 plus class 2 or more of the specific IgE. Severity Scoring of AD index (SCORAD) and 100 mm visual analog scale (VAS) for pruritis were used for evaluation of clinical severity of AD. Eight filaggrin gene (FLG) mutations common to Japanese AD patients were analyzed as described previously.2,7 The nickel loads were applied by using chocolate bar containing a high dose nickel (Lindt chocolate excellence 85% cocoa, Lindt &Sprungli, Kilchberg, Switzerland). This chocolate contains 470 mg nickel per bar (National consumer affairs center of Japan, 2008). Participants ingested one-half chocolate bar containing 235 mg nickel per day for 4 consecutive days. The dose of