Two Cases Of Targeted Drug-induced Pustular Neutrophilic Dermatosis And Review Of The Literature

Background: As tumor-targeted drugs are being developed and introduced,the reports of skin adverse reactions associated with them are increasing,and there have been a few reports in the literature that tumor-targeted drugs can cause neutrophilic dermatosis.Objective of the study: To analyze the clinical manifestations,pathological characteristics and treatment regression of neutrophilic dermatosis caused by tumor-targeting drugs,to provide clinicians with diagnostic and therapeutic references for timely diagnosis and treatment of the disease,and to improve the quality of patient survival.Methods: The medical history,clinical manifestations,adjuvant examinations,pathological findings and treatment regression of two patients with neutrophilic dermatosis caused by tumor-targeting drugs admitted to the Department of Dermatologyof Qingdao Municipal Hospital from January 2019 to December 2020 were retrospectively analyzed,and the patients were followed up.A review of the literatureon targeted drug-related neutrophilic dermatosis was conducted by searching CNKI,Wanfang,Pubmed and other databases,with emphasis on a retrospective analysis of a total of 14 cases with complete clinical data at home and abroad from 2003 to 2021,based on the Common Terminology Criteria for Adverse Events(CTCAE).Adverse Events CTCAE-Version 5.0)[1] to classify the patients’ rashes.Results: The summary results of 2 cases of neutrophilic dermatosis admitted to our dermatology department are as follows.The two patients were a 31-year-old male and a 55-year-old female,respectively.The male patient was taking dasatinib and ponatinib for chronic granulocytic leukaemia,and the female patient was taking trastuzumab and patsuzuximab for breast cancer after surgical treatment.Both patients had no previous history of similar disease,and both had a CTCAE rating of grade 2.The clinical presentation was mainly diffuse erythema,papules and pustules all over the body,with one case in the palmoplantar and genital areas Laboratory findings: one case showed elevated leukocytes,neutrophils and C-reactive protein,two cases had normal eosinophil counts and ratios,and both patients responded well to treatment with systemic glucocorticoids and hormone-like medications.A review of the foreign literature reported the following clinical information on 14 patients with neutrophilic dermatosis due to targeted drugs.Sex and age of onset: A total of 14 cases were included in this study,4 male patients and 10 female patients,with a male to female sex ratio of 1:2.5.The minimum age of onset was 48 years,the maximum age was 83 years,the median age was 62 years and the mean age was 63 years.Drug use history and latency: Among the 14 patients,2 used bortezomib,2usedsunitinib,2 used imatinib,2 used ponatinib,2 used ibrutinib,and each 1 used trastuzumab,dalafenib,verafenib and dasatinib.Among the patients with a clear time between first dose and onset,the longest latency period was 18 months and the shortest was 1 week,with a mean latency period of 19.3 weeks.Clinical manifestations: 6 of the 14 patients were diagnosed with Sweet’s syndrome,manifesting as oedematous erythema,papules,nodules and pustules with tenderness,4of which occurred on the trunk and extremities and 3 of which had a rash on the face.Two patients with gangrenous pyoderma presented with painfuloedematous erythema on the trunk and extremities,and one patient presented with joint pain;one patient presented with erythema and papules with pain and itching on the trunk of the neck after taking dasatinib,with recurrent disease.Histopathological examination: All 14 patients underwent pathological biopsy,of which8 cases showed diffuse neutrophil infiltration in the dermis,4 cases had edema in the dermal papillae,5 cases had neutrophil infiltration in the fatty lobular areas,2 cases showed granulomatous lipofuscinosis and 1 case showed superficial mononuclear cell infiltration in the dermis.Treatment: Of the included cases,9 received glucocorticoid systemic therapy,2 of which were treated with additional topical glucocorticoid cream with an efficiency of100%,1 patient received oral doxycycline to inhibit the inflammatory response and neutrophil chemotaxis with an efficiency of 100%,and 4 patients had their rash resolve spontaneously within a few months after reduction or discontinuation of the original targeted drug.Conclusion: 1.Pustular neutrophilic dermatosis(PND)is a rare adverse reaction associated with targeted drugs,with patients having a predominantly grade 1-2 rash rating.The clinical presentation is characterised by papules,pustules and nodules,usually on the trunk and extremities.The histopathological features of the rash are massive neutrophil accumulation inthe epidermis,dermis and subcutaneous fat layer,with or without perivascular inflammatory cell infiltration.Local and systemic application of glucocorticoids may have good efficacy,and the rash subsides in some patients after reducing the dose of targeted drugs or discontinuing them.