Abstract:

Zhu Huiling, Cheng Xiping, Huang Weining, Wang Xia, Wen Liuyan, Fan Hui, Zhang Yangbing, Zhang Dehua, He Jiaxi, Xiong Chunping, Han Jiande Department of Dermatology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China（Zhu HL, Cheng XP, Huang WN, Wang X, Wen LY, Fan H, Zhang YB, Xiong CP）; Department of Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China （Zhang DH）; Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China （He JX）; Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China （Han JD） Corresponding authors: Xiong Chunping, Email: xiongchunping2015@163.com; Han Jiande, Email: hanjd_gzb@21cn.net 【Abstract】 Objective To investigate the clinical features of cutaneous adverse reactions to tyrosine kinase inhibitors. Methods Thirty patients with cutaneous adverse reactions to tyrosine kinase inhibitors were enrolled from the First Affiliated Hospital of Guangzhou Medical University between January 2015 and December 2016, and their laboratory test results, histopathological findings and treatment response data were collected and analyzed retrospectively. Results Of the 30 patients, 15 presented with acneiform eruptions, 10 with eczematoid eruptions, 2 with morbilliform rashes, 1 with telangiectasia, 1 with hand-foot skin reaction, 9 with xerosis, 7 with nail changes and 4 with hair changes. A patient with grade 4 acneiform eruptions showed a markedly elevated alanine transaminase （ALT） level （315 U/L）. Mild ALT abnormalities （48.5 - 88.1 U/L） were found in 3 patients with grade 3 acneiform eruptions, 1 with grade 2 acneiform eruptions, 1 with grade 1 acneiform eruptions and 1 with eczematoid eruptions complicated by fever. Two patients with eczematoid eruptions and 1 with morbilliform rashes showed elevated proportions of peripheral blood eosinophils （0.057 - 0.303）. Pathological changes of the acneiform eruptions included hyperkeratosis and dilation of hair follicles and neutrophilic infiltration. Pathological manifestations of eczematoid eruptions included different degrees of spongiosis, thickened spinous layer, irregular elongation of rete ridges and liquefaction degeneration of basal cells in the epidermis, and perivascular infiltration of lymphocytes and eosinophils in the superficial dermis. Patients with grade 1 - 3 acneiform eruptions received oral minocycline for 6 weeks, skin lesions gradually regressed, but relapse occurred after the withdrawal. After withdrawal of targeted antineoplastic agents and 2-week treatment with systemic glucocorticoids, skin lesions gradually regressed in patients with grade 4 acneiform eruptions, those with eczematoid eruptions complicated by fever, and those with morbilliform rashes. Skin rashes also resolved in patients with mild morbilliform rashes and those with mild eczematoid eruptions after 2 weeks of treatment with antianaphylactic agents and topical glucocorticoids. Oral antibiotics were effective for the treatment of periungual erythematous swelling or granulomas. Conclusion Tyrosine kinase inhibitor-related cutaneous adverse reactions include a constellation of disorders, and hepatic function can be impaired.