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A 66-year-old female patient presented with erythematous skin lesions and neuropathic pain on her lower back and left thigh. Initially, the patient was treated for herpes zoster, but her symptoms persisted and she developed leg paresis and hypesthesia. Further examination and testing revealed that the patient had early neuroborreliosis, a neurological manifestation of Lyme borreliosis. Treatment with antibiotics and analgesics led to significant improvement in the patient's symptoms. This case highlights the importance of considering neuroborreliosis in patients with unclear skin lesions and neurological symptoms. [Extracted from the article]

When deciding on systemic therapy for irAE psoriasis, it should be considered that TNF-alpha inhibitors might improve the response to treatment with ICI and thus the prognosis of the tumour disease. Immune checkpoint inhibitors (ICI) have become firmly established in the treatment of malignant melanoma (MM) and have significantly improved prognosis in advanced tumour stages.[[1]] Recently, the anti-programmed death 1 (PD-1) agent Pembrolizumab showed a significant reduction in the risk of disease recurrence for stage IIB or IIC MM.[2] As ICI interferes with immunoregulatory pathways by blocking checkpoints, non-specific activation of the immune system can result in the development of immune-related adverse events (irAE).[3] In patients receiving monotherapy with a PD-1 inhibitor, grade 3 or 4 irAEs occurred in 23% with nivolumab and in 16% with pembrolizumab.[[1]] The spectrum of cutaneous irAE is diverse and most commonly present as maculopapular exanthema with pruritus.[[3]] Another possible manifestation is psoriasis.[5] Treatment with biologics has been established in the therapy of severe psoriasis, one option being tumour necrosis factor (TNF)-alpha inhibitors.[6] Inflammatory signals such as TNF are essential factors that determine the aggressiveness of melanoma cells.[7] There is evidence that concomitant therapy with a TNF-alpha inhibitor may have positive effects on treatment response and thus tumour prognosis.[8] We report on a 67-year-old man with stage IIB MM. In the further course, the psoriasis was progressive; therefore, therapy with Nivolumab was terminated after six times at the patient's request. [Extracted from the article]

The microenvironment of malignant melanomas defines the properties of tumor blood vessels and regulates infiltration and vascular dissemination of immune and cancer cells, respectively. Previous research in other cancer entities suggested the complement system as an essential part of the tumor microenvironment. Here, we confirm activation of the complement system in samples of melanoma patients and murine melanomas. We identified the tumor endothelium as the starting point of the complement cascade. Generation of complement-derived C5a promoted the recruitment of neutrophils. Upon contact with the vascular endothelium, neutrophils were further activated by complement membrane attack complexes (MACs). MAC-activated neutrophils release neutrophil extracellular traps (NETs). Close to the blood vessel wall, NETs opened the endothelial barrier as indicated by an enhanced vascular leakage. This facilitated the entrance of melanoma cells into the circulation and their systemic spread. Depletion of neutrophils or lack of MAC formation in complement component 6 (C6)-deficient animals protected the vascular endothelium and prevented vascular intravasation of melanoma cells. Our data suggest that inhibition of MAC-mediated neutrophil activation is a potent strategy to abolish hematogenous dissemination in melanoma. [ABSTRACT FROM AUTHOR]