Lichen spinulosus in a patient undergoing Atezolizumab therapy for metastatic squamous cell lung carcinoma

Up to 40% of patients undergoing treatment with immune checkpoint inhibitors (ICIs) may experience cutaneous immune-related adverse events.1 Here, we present a case of a man who developed lichen spinulosus following treatment with Atezolizumab for metastatic squamous cell lung carcinoma. A 44-year-old patient presented at our Dermatology Department with a pruritic skin eruption that had developed during treatment with Atezolizumab, administered at the recommended dosage of 1200 mg intravenously every 3 weeks, for metastatic squamous cell lung carcinoma. Examination revealed numerous folliculocentric hyperkeratotic papules symmetrically affecting the scalp, upper arms and trunk, which were pruritic but not painful (Figure 1a–c). The lower limbs were also involved, though to a lesser extent, with sparse hyperkeratotic papules primarily on the thighs. Dermoscopy showed follicular plugs and hyperkeratosis (Figure 1d). Symptoms began 2 months after starting Atezolizumab and persisted for about a year, with no improvement from 10% Urea cream and Clobetasol propionate. A 4 mm punch biopsy from the back revealed epidermal thickening with orthokeratosis, keratinized follicular plugs, chronic inflammatory infiltrate with fibrosis, lymphocytic exocytosis, and atrophic sebaceous glands, which in some sections were completely absent (Figure 2a,b). The diagnosis of Lichen spinulosus (LS) was thus confirmed, and a treatment regimen with 25 mg of Acitretin was initiated. Significant improvement in itching and clinically visible lesions was observed within just 3 months. The therapeutic mechanism of immune checkpoint inhibitors primarily involves blocking PD-1/PDL1 and CTLA4, which stimulates the immune system to recognize and eliminate tumour cells. Over the past decade, the introduction of these therapies has revolutionized oncological treatments, witnessing an expanding range of indications and an increasing patient population benefiting from these interventions.2 Despite being such an important therapeutic innovation, the activation of the immune system comes at a cost, resulting in immune-related adverse events (irAEs) affecting various organs, notably the skin, where manifestations often occur earlier than other irAEs.2, 3 Regarding the pathogenetic mechanisms, three potential pathways have been proposed: the generation of autoreactive B and T cells during therapy, excessive production of proinflammatory cytokines, and antigen exposure following cytotoxic damage. The spectrum of skin reactions encompasses a wide array of autoinflammatory dermatoses, with maculopapular, lichenoid, and psoriasiform forms being the most frequent.1 Although some skin reactions correlate with enhanced anti-tumour responses, their prognostic significance remains unclear.4 LS usually affects children and young adults, presenting as folliculocentric papules on limbs and the chest. Severe LS in adults has been linked to systemic diseases like Crohn's disease and HIV, involving an exaggerated Th17-mediated response against hair follicular microorganisms such as Malassezia spp.5 During ICIs therapy, variations in the tumour microenvironment may drive CD4+ T cell differentiation toward Th17 subsets, accumulating around hair follicles and intensifying responses to Malassezia spp.5 Our patient's lower limb involvement, where Malassezia spp. is less prevalent, supports this hypothesis. Furthermore, in normal skin, the interaction between PD-1 on T-cells and PD-L1 on keratinocytes typically suppresses T-cell activation and prevents autoimmune mucocutaneous conditions. When this interaction is disrupted by PD-1 or PD-L1 inhibitors such as Atezolizumab, there is a loss of autoregulation, which may contribute to the process of lichenification leading to the onset LS.1, 6 Understanding the link between ICIs therapy and LS highlights the complex interaction between immunotherapy and dermatological manifestations. Further research is needed to elucidate underlying mechanisms and establish management strategies for cutaneous complications during ICIs treatment. The authors received no financial support for the research, authorship and/or publication of this article. All authors have contributed to the conception and design of this work, as well as acquisition, analysis, and interpretation of data. None declared. The patient in this manuscript has given written informed consent to the publication of his case details. Data sharing is not applicable to this article as no new data were created or analyzed in this study.