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. 2024 Jan 13:15:157-164.
doi: 10.1016/j.jdin.2023.11.013. eCollection 2024 Jun.

Checkpoint inhibitor-induced lichen planus differs from spontaneous lichen planus on the clinical, histological, and gene expression level

Barbara Meier-Schiesser  1 , Christine Zecha  2 , Sarah Zierold  2 , Isabel Kolm  1 , Magdalena Röckel  3 , Waltraud Fröhlich  3 , Nora Mittag  2 , Christina Schmitt  2 , Joerg Kumbrink  4   5 , Jessica C Hassel  6 , Carola Berking  3 , Dorothee Nashan  7 , Lars Einar French  2   8 , Julio Vera-González  3 , Reinhard Dummer  1 , Katrin Kerl-French  2 , Lucie Heinzerling  2   3
Affiliations

Checkpoint inhibitor-induced lichen planus differs from spontaneous lichen planus on the clinical, histological, and gene expression level

Barbara Meier-Schiesser et al. JAAD Int. .

Abstract

Background: Although highly efficacious, immune checkpoint inhibitors induce a multitude of immune-related adverse events including lichenoid skin reactions (irLP) that are often therapy-resistant.

Objectives: To compare the clinical, histological, and transcriptional features of irLP with spontaneous lichen planus (LP).

Methods: Clinical and histological presentations of irLP and LP, as well as the gene expression profiles of irLP and LP lesional and healthy skin were assessed.

Results: irLP differed considerably from LP with regard to the distribution pattern of skin lesions with irLP appearing mostly in an exanthematous form, whereas lesions were more localized in the LP group. Histologically, dermal lymphocyte infiltration was significantly lower in irLP compared with LP, whereas lymphocyte exocytosis and apoptotic keratinocytes were significantly higher in irLP. Gene expression analysis revealed irLP to have a more inflammatory profile with elevated IFNG levels and a possible role of phagosome signaling compared with LP.

Limitations: The study is descriptive and necessitates further investigation with larger cohorts and broader analyses.

Conclusion: irLP differs from spontaneous LP on the clinical, histopathological, and gene expression level. The inflammatory gene signature in irLP suggests that topical JAK inhibitors could be an effective treatment, targeting local skin inflammation without systemic immunosuppression.

Keywords: cutaneous side effects; exanthematous; gene expression profiles; immune-related adverse events; inflammatory signatures.

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Conflict of interest statement

None disclosed.

Figures

Fig 1
Fig 1
Cutaneous manifestations of immune-related lichen planus (irLP) and spontaneous lichen planus (LP). A, Disseminated erosive lesions on the trunk and extremities of a patient with irLP. B, Polygonal papules on the inside of the lower portion of the arm and wrist of a patient with LP.
Fig 2
Fig 2
Histopathologic findings in immune-related lichen planus (LP) and spontaneous LP. Histology showing acanthosis, hypergranulosis, and vacuolar changes of the basal layer, several apoptotic keratinocytes in the basal and suprabasal layers of the epidermis and significant exocytosis of lymphocytes in the lower half of the epidermis in a representative case of immune-related lichen planus (irLP) (top left). Wedge-shaped hypergranulosis, “sawtooth”-like acanthosis, mild exocytosis of lymphocytes, few apoptotic keratinocytes, and a subepidermal dense band-like lymphocytic infiltrate with prominent pigment incontinence in a representative case of LP (bottom left). irLP (n = 8) and LP (n = 19) cases were evaluated regarding their lymphocytic infiltrate, lymphocyte exocytosis, apoptotic keratinocytes, vacuolization of basal keratinocytes, histiocytic, and eosinophil numbers. Grading 0 (absent) to 3 (strong presence) (right). (Hematoxylin-eosin stain [resolution: 96 dpi].)
Fig 3
Fig 3
Gene expression analysis reveals significantly upregulated immune pathways in immune-related lichen planus (irLP) compared with spontaneous lichen planus (LP). RNA was isolated from lesional skin of patients with irLP and LP. Representative heatmap of genes involved in phagosome signaling, showing upregulation of involved genes in irLP compared with LP lesional skin.
See this image and copyright information in PMC

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