Lichenoid mucocutaneous reactions associated with sintilimab therapy in a non-small cell lung adenocarcinoma patient: case report and review

Abstract

The immune checkpoint inhibitor (ICI), anti-programmed cell death receptor-1 (PD-1) antibody, has gained widespread approval for treating various malignancies. Among the immune-related adverse reactions (irAEs) during ICI treatment, the lichenoid reaction is noteworthy. Sintilimab, a new PD-1 inhibitor, has secured approval in China for treating refractory non-Hodgkin's lymphoma, and phase I/II clinical trials for other solid tumors are ongoing both domestically and abroad. This paper presents a case of a mucocutaneous lichenoid reaction associated with sintilimab therapy, its diagnosis, and management. Our study, using multiplex immunofluorescence staining, reveals localized infiltration of CD4⁺ and CD8⁺ T lymphocytes in the subepithelial lamina propria region with upregulated PD-1 expression, implying an association between PD-1 expression upregulation and lichenoid reactions provoked by PD-1 monoclonal antibody. We provide a summary of clinical characteristics and treatment guidelines for lichenoid reactions induced by ICIs from previous reports, highlighting the success of a combined therapeutic regimen of oral antihistamines and topical corticosteroids in controlling symptoms without interrupting ICI treatment.

Keywords: PD-1 inhibitor; Sintilimab Therapy; immune checkpoint inhibitors (ICIs); immune-related adverse events (irAEs); lichenoid reactions; mucocutaneous reactions; non-small cell lung adenocarcinoma.

FIGURE 1

Clinical examination and Intraoral examination (A–F). Irregular pink to purplish flat-topped papules and plaques with hyperpigmentation on the palms and dorsum of the hands and soles of the feet (G–L). Symmetrical papular white streaks with mild erosions and congestion on the oral mucosa and the inside of the upper and lower lips, and reticular white streaks consistent with Wickham’s streaks could be seen on the ventral part of the tongue and lips bilaterally.

FIGURE 2

Histopathological examination of buccal mucosa (A). Original magnification at ×10 Chronic inflammation; hyperkeratosis of epithelial surface layer; vacuolar degeneration and liquefaction degeneration of some basal cells; capillary proliferation and expansion of lamina propria, more eosinophils, neutrophils, lymphocytes, plasma cells infiltration; proliferation and degeneration of fibrous tissue (B). Original magnification at ×20. This panel highlights vacuolar and liquefaction degeneration of select basal cells, indicated by blue arrows. (C) Original magnification at ×40. The panel features extensive infiltration by eosinophils, neutrophils, lymphocytes, and plasma cells. Yellow arrow points to epithelial hyperkeratosis; the green arrow denotes eosinophils; the black arrow indicates neutrophils; the orange arrow designates lymphocytes; and the red arrow identifies plasma cells.

FIGURE 3

The multiplex immunofluorescence staining (A–C). The antigen distribution pattern observed in OLR. (D–F). The antigen distribution pattern observed in OLP. (G,H) Ten areas of equal size were randomly selected from each of the three groups for statistical analysis, including focal infiltration of inflammatory cells in OLR, scattered infiltration of inflammatory cells in OLR and OLP. (G): Comparison of the area% of PD-1 fluorescence-positive expression in OLR and OLP, p < 0.001. (H): Comparison of the integrated density of PD-1 fluorescence-positive expression in OLR and OLP, p <0.001 Note: (A–F) Staining using Luminlris™ HyperView multiplex immunostaining kit (IRISKit™MH010101). Primary antibodies were mouse anti-PD-1(ZSGB-BIO, ZM-0381), mouse anti-CD8(Immunoway, YM6938), and rabbit anti-CD4(HUABIO, ET1609-52).