Prolonged Imiquimod Treatment and Graft-versus-Host Reaction: Histological Mimicry in the Skin Infiltration Pattern of the Monocyte-Macrophage-Dendrocyte Lineage

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Abstract
Factor-XIIIa-positive dendrocytes belong to the monocyte-macrophage-dendrocyte (MMD) lineage which is considered to play a pivotal role in the skin response to the immune response modifier imiquimod. The same cells are also boosted in low-grade graft-versus-host reaction (GVHR) with skin manifestations. Both conditions are characterized by specific epidermal damage. The aim of the present study was to compare them using immunohistochemistry to identify MMD subsets and other inflammatory cells in the dermis. We compared 3 cases of long-term (4, 9 and 11 months) imiquimod topical applications on normal skin, 25 low-grade GVHR controlled by immunosuppressive therapy and 25 control cases with normal skin. Compared to the normal dermis, cells of the MMD lineage were considerably boosted in the dermis of GVHR and at the imiquimod-treated sites. By contrast, only minimal accumulations of lymphocytes and Langerhans cells were disclosed in the dermis. The pattern of dermal infiltration by MMD cells was similar in GVHR and after imiquimod treatment. However, intraindividual differences in densities were obvious irrespective of the skin condition. In conclusion, there is great mimicry in the MMD involvement in the dermis during low-grade GVHR and after chronic applications of imiquimod.