The concept of lichenoid tissue reactions (LTR) was proposed by Pinkus in 1973. 1 LTR refer to reactions in which epidermal keratinocytes are damaged by inflammatory cells infiltrating into the dermis, resulting in vacuolar or liquefaction degeneration of basal cells, and cell death/individual keratinization of keratinocytes. 1 LTR are classified into those with prominent (cell rich) and those with little (cell poor) cell infiltration. The prototype of the former reaction is lichen planus. 2 Programmed cell death 1 (PD-1) is expressed on lymphocytes, binds to its ligands, programmed cell death ligand 1 (PD-L1), and PD-L2, and suppresses the regulation of lymphocyte function. 3 PD-L1 is expressed on leukocytes, especially macrophages, stromal cells, and tumor cells, 4 and PD-L2 is mainly expressed on dendritic cells. 4PD-1 antagonists activate lymphocytes to treat malignant tumors.In recent years, immune checkpoint inhibitors (ICI), such as PD-1 and PD-L1 inhibitors, have been developed and used in the immunotherapy of solid cancers following malignant melanoma. With the use of ICI, a variety of immune-related adverse events (irAE), including lichen planus/lichenoid eruption, have been reported. 5 The aim of this study was to clarify the role of PD-1 and PD-L1 in the pathogenesis of lichen planus in the absence of ICI administration, using biopsy specimens.

Objectives Peripheral blood monocytes are categorized as classical (CD14++/CD16−) or nonclassical (CD14−/CD16+ and CD14+/CD16+) based on their CD14 expression and CD16 expression. Maturation of classical monocytes produces CD14+/CD16+ macrophages. Our aim was to clarify the in vivo distribution of CD14 and C16 monocytes/macrophages in three granulomatous skin diseases—sarcoidosis, granuloma annulare, and lupus miliaris disseminatus faciei. Methods CD14 and CD16 immunohistochemistry, and CD14/CD16, CD16/CD11c, CD16/CD68, and CD16/factor XIIIa dual labeling were performed in tissues sampled from three cases of sarcoidosis, four cases of granuloma annulare, and three cases of lupus miliaris disseminatus faciei. Results The main infiltrating cell types were CD14+/CD16+ and CD14−/CD16++ macrophages. A small number of CD14+/CD16− macrophages localized along the granuloma periphery. Dual immunofluorescence showed that CD16+ overlapped the most with CD68+ cells, partially overlapped with CD11c+ cells, and did not overlap with FXIIIa+ cells. Conclusions Inflammatory granulomatous skin diseases are characterized by CD16+, mature and inflammatory macrophages; some of which are in the process of maturation.

Osteopontin (OPN) was initially described as a protein involved in bone metabolism, but the roles played by OPN in the immune system and allergic reactions have attracted increasing attention. Here, we clarify the OPN‐related dynamics of severe cutaneous adverse drug reactions, and assess whether the OPN level has utility for classifying such reactions and serving as a biomarker of severity. Serum OPN levels in patients with drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and erythema multiforme‐type drug reaction (EM‐DR) were quantified by ELISA. The OPN sources were analyzed by dual immunofluorescence assay of DIHS, SJS/TEN and EM‐DR biopsy specimens. The serum OPN levels of DIHS/DRESS patients (489.1 ± 37.0 ng/mL) and SJS/TEN patients (508.5 ± 47.8 ng/mL) were significantly higher compared with controls (314.4 ± 14.3 ng/mL; p < 0.001). After treatment, the serum OPN level of DIHS/DRESS patients decreased to that of controls. In addition, OPN levels in DIHS/DRESS patients and SJS/TEN patients were higher than in patients with EM‐DR (Mann–Whitney U test, p < 0.05). However, when the Kruskal–Wallis test was used to compare the OPN levels among the three groups of patients, the difference was not significant (p = 0.055). Dual immunofluorescence assay revealed that T lymphocytes and macrophages were the main OPN sources in DIHS, SJS/TEN and EM‐DR patients. These data suggest that the OPN level can be used to evaluate the severity of inflammation in patients experiencing drug reactions.