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Development of Acute Vogt-Koyanagi-Harada-like Syndrome during the Treatment Course with Vemurafenib for Metastatic Melanoma.


  • 影响因子:1.52
  • DOI:10.1080/09273948.2019.1597896
  • 作者列表:"Apivatthakakul A","Kunavisarut P","Rothova A","Pathanapitoon K
  • 发表时间:2020-04-02

:Purpose: To report on ocular Vogt-Koyanagi-Harada (VKH)-like syndrome under vemurafenib treatment for metastatic melanoma.Design: A case report.Method: Description of clinical and imaging manifestations including fundus photography, fluorescein, and indocyanine green angiography.Results: A 46-year-old Thai female was diagnosed with metastatic melanoma of the skin and had been treated with multiple surgical excisions, radiotherapy, and vemurafenib (initial dose 480 mg orally twice daily, subsequently increased to maximum dose of 960 mg twice daily). After 6 months of vemurafenib use, she complained of bilateral redness and photophobia and was diagnosed with bilateral anterior uveitis, which was topically treated. Two weeks later, her visual acuity (VA) sharply deteriorated to 20/80 and counting fingers. Ocular examination at that stage stronly resembled acute VKH disease. She exhibited intraocular inflammation, and her fundus examination revealed bilateral optic disc swelling and serous retinal detachment. Fluorescein angiogram showed disc leakage and multiple pinpoint hyperfluorescence leakage spots and indocyanine green demonstrated multiple hypofluorescent spots. Oral prednisolone 30 mg/day was commenced while vemurafenib medication was ceased. Three weeks later, her vision improved, and serous retinal detachment subsided. However, her cutaneous melanoma recurred.Conclusions: Vemurafenib, a potential adjunct treatment for metastatic melanoma, was complicated by the development of panuveitis, papillitis, and multiple serous detachments. These ocular symptoms were similar to the presentation of acute VKH syndrome.


目的: 报道vemurafenib治疗转移性黑色素瘤下的眼部Vogt-小柳原田 (VKH) 样综合征。设计: 病例报告。方法: 描述临床和影像学表现,包括眼底照相、荧光素和吲哚青绿血管造影。结果: 一名 46 岁的泰国女性被诊断为皮肤转移性黑色素瘤,并接受了多次手术切除,放射治疗和vemurafenib (初始剂量 480 mg口服,每日两次,随后增加至最大剂量 960 mg,每日两次)。使用vemurafenib 6 个月后,主诉双侧发红、畏光,诊断为双侧前葡萄膜炎,予以局部治疗。两周后,她的视力 (VA) 急剧恶化至 20/80,并计数手指。该阶段的眼部检查stronly类似于急性VKH病。她表现出眼内炎症,眼底检查发现双侧视盘肿胀和浆液性视网膜脱离。荧光素血管造影显示椎间盘渗漏和多个精确的超荧光渗漏点,吲哚青绿显示多个低荧光点。开始口服泼尼松龙 30 mg/天,同时停止vemurafenib药物治疗。三周后,她的视力改善,浆液性视网膜脱离消退。然而,她的皮肤黑色素瘤复发。结论: Vemurafenib是转移性黑色素瘤的潜在辅助治疗药物,并发全葡萄膜炎、乳头炎和多发性浆液性脱离。这些眼部症状与急性VKH综合征的表现相似。



作者列表:["Zhang B","Li L","Zhang N","Zhao M","Liu Y","Wei L","Ma L","Xu Z"]

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.

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作者列表:["Pham CT","Juhasz M","Sung CT","Mesinkovska NA"]

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.

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作者列表:["Lang UE","Love NR","Cheung C","McCalmont TH","Kim J"]

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.

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