RESUMO
BACKGROUND: Rosacea is a chronic inflammatory skin disease with a pathophysiological mechanism that remains unclear. Recently, dysregulation of the sensory nerve system has been implicated in the development of this condition. OBJECTIVE: This study aimed to investigate the effect of capsaicin on neuroinflammatory mediators in rosacea. In addition, this study aimed to evaluate the attenuating effects of capsazepine, a transient receptor potential vanilloid type 1 (TRPV1) antagonist. METHODS: We obtained skin tissue from both rosacea patients and normal individuals for an in vivo study. In addition, normal human epidermal keratinocytes (NHEKs) were cultured, and treated with capsaicin and capsazepine for an in vitro study. Quantitative changes in neuroinflammatory mediators were evaluated by semi-quantitative reverse transcription-polymerase chain reaction (PCR), real-time PCR, enzyme-linked immunosorbent assay, and immunofluorescence staining. RESULTS: The data showed the increase of TRPV1, TRPV4, cathelicidin (LL37) and tumor necrosis factor-α (TNF-α) in skin tissue by real-time PCR. In addition, the data showed that cathelicidin (LL37), kallikrein-5 (KLK-5), TNF-α, vascular endothelial growth factor (VEGF), interleukin (IL)-1α, IL-1ß, IL-8, and protease-activated receptor 2 (PAR2) increased in capsaicin-treated NHEKs. Capsazepine attenuated the expression of TRPV1 and other mediators, except for IL-8, in capsaicin-treated NHEKs. CONCLUSION: We confirmed that TRPV1, TRPV4, cathelicidin (LL37) and TNF-α are increased in rosacea skin, and that capsaicin is associated with increase of neuroinflammatory mediators such as LL37, KLK-5, TNF-α, VEGF, IL-1α, IL-1ß, IL-8, and PAR2. Modulators or inhibitors of neuroinflammatory mediators including TRPV1 could be potential therapeutic option in the treatment of patients with rosacea.
RESUMO
Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) pathway have significantly improved outcomes for patients with a variety of malignancies, including non-small cell lung cancer (NSCLC). In contrast, the incidence of immune-related cutaneous adverse events such as vitiligo have been on the rise because of the increasing use of ICIs. Vitiligo-like depigmentation has been reported in only 2.0% to 8.3% of patients with melanoma and is considered a favorable prognostic factor. However, it has been rarely reported in patients with non-melanoma malignancies. We describe a case of vitiligo-like skin depigmentation after pembrolizumab use in a patient with stage IV NSCLC. Multiple ill-defined painless and non-pruritic depigmented patches appeared on the patient's hands, scrotum, and lower lip after five months of pembrolizumab. We continued treatment with pembrolizumab 2 mg/kg for 14 months with close monitoring of vitiligo lesions until the progression of brain metastasis, but the vitiligo-like depigmentation did not improve by the combined excimer laser and topical corticosteroid therapy. Clinicians should be aware that immune-related cutaneous adverse events such as vitiligo-like depigmentation are not limited to cases of melanoma but arise as a direct result of anti-PD-1 therapy.
