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

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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