Fixed drug eruption: pathogenesis and diagnostic tests

Purpose of review Fixed drug eruption is a simplified disease model for elucidating the mechanism(s) of how skin inflammation is induced by skin-resident T cells. In this review, we focus on how the presence of intraepidermal CD8(+) T cells resident in the fixed drug eruption lesions can provide exciting new clues to our understanding of pathomechanisms of inflammatory skin diseases. Recent findings Intraepidermal CD8(+) T cells with an effector-memory phenotype resident in fixed drug eruption lesions have a major contributing role in the development of localized tissue damage. Activation of these CD8(+) T cells is sufficient for triggering the lesion, however, but not sufficient to cause extensive tissue damage observed in the fully evolved lesions; additional recruitment of CD4(+) and CD8(+) T cells to a specific tissue site would also contribute to the late stage of lesion development. The influx of regulatory T cells into the epidermis observed in fully evolved lesions would serve to limit harmful immune reactions. Consistent with this, positive patch test reactions are only observed at the site of previous lesions harboring significant numbers of intraepidermal CD8(+) T cells. Summary Intraepidermal CD8(+) T cells may represent double-edged swords of the skin immune system with protective and destructive capacity.