Specificity of hand-foot skin reaction induced by multikinase inhibitors: clinical, histological and ultrasound characteristics

E. A. Shatokhina, S. Potkin, P. Malkov, L. Kruglova, A. Polonskaya
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Abstract

Background. Multikinase inhibitors of angiogenesis are currently the most effective group of drugs in target therapy for cancer. They are associated with a high prevalence of a specific cutaneous adverse reaction, which manifests as a hand-foot skin reaction (HFSR). This side effect is quite prominent in the majority of patients, usually graded as II–III degree, which leads to the dose reduction and even discontinuation of the drug. The study objective is to evaluate clinical, histological and ultrasound characteristics of a HFSR associated with MKI treatment, and to assess the influence of a HFSR on patient’s quality of life. Materials and methods. The study included 46 patients with HFSR, who were previously treated with sorafenib or lenvatinib. Clinical characteristics of HFSR, including severity grading, were evaluated. We also performed ultrasound and histological examinations and assess the Dermatology Life Quality Index. Results. Grade III HFSR was in 5 (10.86 %) patients, grade II – in 25 (54.35 %), and grade I – in 16 (34.79 %). Dermatology Life Quality Index depended on the HFSR severity, with the mean value 24.5 ± 2.4. Pathomorphological examination revealed irregular epidermal proliferation with hypertrophic psoriasiform acanthosis, minimal keratinocyte vacuolization, few apoptotic figures, dyskeratosis, hyperkeratosis and microvessel dilation in the papillary dermis. Ultrasound examination showed increased vascularization in papillary and reticular dermis in affected skin areas, which was more prominent in patients with severe degrees of HFSR. The pronounced enhancement of vascularization was detected in fragmented hypoechogenic sites along the border of papillary and reticular dermis and in similar sites along the border of dermis and hypodermis. Conclusion. The use of multikinase inhibitors leads to pronounced changes not only in the surface layers of the skin, but also in the dermis and subcutaneous fat, which significantly worsens the quality of life of patients. This indicates the need to search for pathogenetically based methods of treatment of HFSR and create practical guidelines for supportive treatment of patients with HFSR taking multikinase inhibitors.
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多激酶抑制剂诱导手足皮肤反应的特异性:临床、组织学和超声特征
背景。血管生成多激酶抑制剂是目前肿瘤靶向治疗中最有效的一类药物。它们与特定皮肤不良反应的高发率有关,表现为手足皮肤反应(HFSR)。这种副作用在大多数患者中相当突出,通常分级为II-III度,导致剂量减少甚至停药。本研究目的是评估与MKI治疗相关的HFSR的临床、组织学和超声特征,并评估HFSR对患者生活质量的影响。材料和方法。该研究包括46例HFSR患者,他们之前接受过索拉非尼或lenvatinib治疗。评估HFSR的临床特征,包括严重程度分级。我们还进行了超声和组织学检查,并评估皮肤生活质量指数。结果。III级HFSR 5例(10.86%),II级25例(54.35%),I级16例(34.79%)。皮肤病生活质量指数与手足口病严重程度有关,平均值为24.5±2.4。病理形态学检查显示不规则表皮增生伴增生性牛皮癣样棘层,角质细胞空泡化极少,少量凋亡,角化异常,角化过度,乳头状真皮微血管扩张。超声检查显示受累皮肤区乳头状和网状真皮层血管化增加,在严重程度的HFSR患者中更为突出。在沿乳头状和网状真皮边界的碎片状低回声区域以及沿真皮和真皮边界的类似区域检测到明显的血管化增强。结论。多激酶抑制剂的使用不仅会导致皮肤表层的明显变化,还会导致真皮层和皮下脂肪的明显变化,从而显著恶化患者的生活质量。这表明需要寻找基于病理的HFSR治疗方法,并为服用多激酶抑制剂的HFSR患者的支持性治疗制定实用指南。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Opuholi Golovy i Sei
Opuholi Golovy i Sei Medicine-Otorhinolaryngology
CiteScore
0.40
自引率
0.00%
发文量
43
审稿时长
8 weeks
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