Metals used in the oral cavity have been reported to cause various allergic diseases of the skin and mucosa. Skin manifestations due to dental restorations appear not only in the oral cavity, but also on the hands, feet or the whole body, as in the cases of pustulosis palmoplantaris and lichen planus. These phenomena implicate different pathogeneses from that of conventional skin sensitization and tolerance. Therefore, we compared skin and oral mucosa sensitization with nickel and oral tolerance for nickel in a mouse model. Female C57BL/6J mice were sensitized by injection of NiSO 4 into the skin or oral mucosa. Allergic reactions were evaluated by the mouse ear swelling test and splenocyte proliferation and cytokine profiles. Skin and oral mucosa sensitization succeeded in all mice. Ear swelling was significantly greater in the skin-than in the oral mucosa-sensitized mice at 48 hr after challenge. Ear swelling was also suppressed by single oral administration of NiSO 4 in both the skin-and oral mucosa-sensitized mice to the level of that in nonsensitized mice. Splenocytes from skin-sensitized mice proliferated similarly to those from oral mucosa-sensitized mice. Splenocytes from orally-tolerized mice also showed similar proliferation activity to those from skin and oral mucosa-sensitized mice. In the challenge phase, IL-2, IFN-␥, and IL-10 production was induced in splenocytes from both skin-and oral mucosa-sensitized mice. However, IL-4 was induced only in those from skin-sensitized mice. In addition, IL-4 in splenocytes from oral mucosa-sensitized mice was up-regulated to the level in those from skin-sensitized mice by oral tolerance. These results suggest that sensitization sites in mice influence not only the degree of excitation, but also Th-1 and Th-2 balance in the challenge phase and oral tolerance.
The patch test is the most reliable method for diagnosing a metal allergy. However, interpretation of patch test results depends on the experience of the investigator and on the conditions of the individual patient. In the case of patch tests for metal salts, irritant reactions such as pustular or follicular reactions are quite common. Therefore, one must be careful not to interpret irritant reactions as allergic responses, and objective standards to evaluate erythema in patch tests need to be established. In the present study, we attempted to objectively evaluate patch test results for metal salts using an erythema index meter. We used the Erythema Index Difference (EID) (patch test site erythema index (EI) minus the mean EI of healthy skin outside the patch test area and at the unit tape site) rather than the EI itself in order to eliminate the effects of the patch test unit and individual differences. We measured the EID over time in patients with suspected metal allergies to various metals. Significant differences in EID were observed among ++ assessments, + assessments and irritant reactions based on International Contact Dermatitis Research Group (ICDRG) standards. In considering changes in EID over time, allergic and irritant reactions can be discriminated with high sensitivity (73.3%) and specificity (91.2%). These results suggest that the measurement of erythema over time with an erythema index meter is useful for the objective assessment of metal patch test reactions.
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