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In order to determine the inflammatory mechanisms of skin lesions in patients with drug hypersentivity, we examined eosinophil activation and interleukin-5 (IL-5) production in infiltrating lymphocytes. First, we showed that the number of peripheral eosinophils and the level of serum IL-5 at the eruption-active stage were both significantly higher than those in healed skin eruptions. Histological and immunohistological examination revealed that CD4+ T cells and eosinophils significantly more densely infiltrated drug eruptions than control skin lesions. The infiltrating eosinophils were also shown to be activated by immunostaining using anti-secreted formed eosinophilic cationic protein monoclonal antibody. The expression of mRNA for IL-5 in the infiltrating mononuclear cells at drug eruptions was shown by in situ hybridization. These results suggest that infiltrating CD4+ T cells might regulate both peripheral and tissue eosinophils and facilitate allergic inflammation at drug eruptions by means of IL-5 production.

It has been shown that CD4+ lymphocytes and eosinophils pathologically infiltrate the dermis in skin eruptions due to hypersensitivity to the administration of certain drugs associated with peripheral eosinophilia. However, the mechanisms involved in drug related skin eruptions with eosinophilia are largely unknown. There are several methods of diagnosing drug hypersensitivity, but no single in vitro method is available for the detection of the sensitizing drug. In order to elicit the mechanism of drug related skin eruption with eosinophilia and to establish effective methods for diagnosing drug hypersensitivity, we studied in vitro IL-5 production by peripheral mononuclear cells (PBMC) from patients with drug related skin eruptions (n = 8). Significant increase in IL-5 from exposure to drug alone (n = 3) and drug with PHA (n = 3) were noted, whereas PBMC from normal subjects (n = 7) exhibited no such stimulation. Six of the eight cases showed a significant decrease in the number of peripheral blood eosinophils when the skin eruptions healed compared with those at the onset. Histopathological features revealed mild to moderate infiltration of eosinophils. Immunohistopathologically, infiltration of CD4+ and CD8+ lymphocytes and CD4+ cells were predominant within the dermis of drug related skin eruption sites in all cases. This study suggested that the IL-5 production of sensitized mononuclear cells might be a critical mediator in drug hypersensitivity with eosinophilia and an important diagnostic marker.