Coexistence of lichenoid and psoriasiform eruptions following PD-1 blockade immunotherapy

Abstract

Dear Editor, Lichen planus (LP) and psoriasis are chronic inflammatory skin diseases characterized by aberrant keratinization and T cell-mediated autoimmunity. Although numerous cases of lichenoid or psoriasiform eruptions have been reported as immune-related adverse events (irAEs),1 their coexistence is extremely rare. Here, we report a unique case of cutaneous irAE in which both lichenoid and psoriasiform eruptions developed simultaneously following programmed cell death 1 (PD-1) blockade therapy. A 77-year-old Japanese man was diagnosed with advanced laryngeal cancer with lung metastasis and began treatment with pembrolizumab (200 mg every three weeks) eight months prior. After eleven treatment cycles, he developed skin eruptions on the extremities and trunk. Physical examination revealed flat-topped, polygonal, violaceous, scaly papules on the bilateral forearms and hands (Figure 1a, c) and red, scaly papules on the abdomen and lower limbs (Figure 1b, d). He exhibited no oral mucosal involvement. A skin biopsy from the hand lesions showed orthokeratosis, hyperkeratosis, hypergranulosis, dyskeratosis, basal liquefaction, and a lichenoid inflammatory infiltrate (Figure 1e, g). In contrast, a biopsy from the abdominal lesions revealed parakeratosis, hypogranulosis, and acanthosis with irregular elongation of the rete ridges (Figure 1f, h), consistent with diagnoses of lichenoid tissue reaction and psoriasiform dermatitis, respectively. The patient had no prior history of LP or psoriasis. Laboratory tests, including serologic tests for the hepatitis C virus and human immunodeficiency virus, were negative. He was not taking any other medications that might have triggered LP or psoriasis. Based on clinical, histopathological, and medication history findings, we diagnosed pembrolizumab-induced lichenoid and psoriasiform eruptions. Initial treatment with topical corticosteroids and vitamin D analogs over 4 months led to improvement of the skin lesions. However, a flare-up occurred, which was successfully managed with oral prednisolone (20 mg daily, tapered to discontinuation over 3 months), resulting in symptom resolution. LP and psoriasis share overlapping immunopathogenic pathways, including T cell infiltration and production of inflammatory cytokines (e.g., tumor necrosis factor-α and interferon-γ), which may be activated by immune checkpoint inhibitors (ICIs). Indeed, lichenoid and psoriasiform eruptions are more frequently reported in patients receiving PD-1/programmed cell death ligand 1 inhibitors than in those treated with cytotoxic T-lymphocyte antigen 4 inhibitors.1 Although such eruptions typically occur 3 to 12 weeks after ICI initiation,1 this case represents a rare example of late-onset cutaneous irAE. Both LP and psoriasis are associated with the Koebner phenomenon, which can be triggered by factors such as trauma, allergic/irritant reactions, drug exposure, dermatoses, and certain treatments.2 Several reports have documented a spontaneous co-occurrence of LP and psoriasis in a single patient.3-5 In a case report by Ujiie et al., LP and psoriasis developed on vitiliginous skin,5 suggesting that photodamage had a role in the manifestation of the Koebner phenomenon. Similarly, photodamage may have contributed to the distinct patterns observed in our patient, lichenoid eruption on sun-exposed areas and psoriasiform eruption on sun-protected areas. In summary, we describe a rare case of cutaneous irAE involving the simultaneous presentation of lichenoid and psoriasiform eruptions. We hope this report will aid in the broader understanding and clinical management of cutaneous irAEs. Figure Legends Figure 1. Clinical and pathological findings (a, c) Flat-topped, polygonal, violaceous, scaly papules on the forearm and hand. (b, d) Red, scaly papules on the abdomen. (e, g) Orthokeratotic hyperkeratosis, hypergranulosis, a band-like lymphocytic infiltrate in the upper dermis, and vacuolar degeneration along the dermoepidermal junction with apoptotic keratinocytes. (f, h) Parakeratosis, hypogranulosis, elongation of the rete ridges, and a perivascular inflammatory infiltrate in the upper dermis. Scale bars represent 100 μm (e, f) and 50 μm (g, h).