A case report of immune-mediated arthritis in a patient with cutaneous melanoma receiving checkpoint inhibition therapy.
- 作者列表："Papaxoinis G","Anastasopoulou A","Laskari K","Diamantopoulos P","Benopoulou O","Gogas H
INTRODUCTION:Immune checkpoint inhibitors (ICIs) represent an important advance in the treatment of melanoma. ICIs may induce autoimmune phenomena caused by concurrent activation of the immune system against normal cells. During the last years, cases of musculoskeletal side effects, especially immune-mediated arthritis (IA), have been increasingly reported. PATIENT CONCERNS:We present a 59-year-old woman, who was treated with pembrolizumab for a relapsed BRAF V600E mutated cutaneous malignant melanoma. The patient presented with right knee arthritis on week 30. DIAGNOSIS:The erythrocyte sedimentation rate and serum C-reactive protein levels were elevated, while rheumatoid factor and anti-cyclic citrullinated peptide antibodies were negative. Imaging confirmed the presence of fluid mainly in the suprapatellar bursa. Synovial fluid analysis revealed an inflammatory effusion, while other etiologies of inflammatory arthritis were excluded. INTERVENTIONS:Arthritis improved with an intra-articular injection of 8 mg dexamethasone. Twelve days later the arthritis relapsed in both knees, and although it was resistant to nonsteroidal anti-inflammatory treatment, it improved with systemic steroids. Tapering of methylprednisolone dose was feasible with the coadministration of leflunomide and subsequently hydroxychloroquine. OUTCOMES:Arthritis resolved and the patient is free of complications and disease activity 20 months after the initiation of the second line systemic treatment. CONCLUSIONS:We present an unusual case of IA associated with pembrolizumab treatment. The originality of the current report is based on the late occurrence, the monoarticular initial distribution, and uncommon location of IA at the knee.
简介: 免疫检查点抑制剂 (ICIs) 代表了黑色素瘤治疗的重要进展。ICIs可能诱导由同时激活免疫系统对抗正常细胞引起的自身免疫现象。在过去的几年里，肌肉骨骼副作用，特别是免疫介导性关节炎 (IA) 的病例越来越多地被报道。 患者担忧: 我们介绍了一位 59 岁的女性，她接受了pembrolizumab治疗复发性BRAF V600E突变的皮肤恶性黑色素瘤。患者于第 30 周出现右膝关节炎。 诊断: 红细胞沉降率和血清C反应蛋白水平升高，类风湿因子和抗环瓜氨酸肽抗体阴性。影像学证实主要在髌上囊存在液体。滑液分析发现炎性积液，而其他炎性关节炎的病因被排除。 干预: 关节内注射 8 mg地塞米松可改善关节炎。12 天后，关节炎在两个膝关节复发，虽然它对非甾体类抗炎治疗耐药，但用全身性类固醇改善。甲泼尼龙剂量逐渐减少与来氟米特和随后的羟氯喹联合给药是可行的。 结果: 在开始二线全身治疗 20 个月后，关节炎得到解决，患者没有并发症和疾病活动。 结论: 我们提出了一个罕见的IA与pembrolizumab治疗相关的病例。目前报告的独创性是基于IA在膝关节的晚期发生、单关节初始分布和不常见位置。
METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.
METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.