Dupilumab in the treatment of acquired perforating dermatosis induced by sorafenib

Dear Editor, Acquired perforating dermatosis (APD) is a disease group with pruritic keratotic papules and nodules with transepidermal elimination of dermal connective tissue materials such as collagen, elastic fibers, and keratin being a characteristic feature in histopathological analysis. Managing the disease can be challenging in some cases.[1] Here, we present the case of a female patient with APD who was using sorafenib for hepatocellular cancer treatment and was successfully treated with dupilumab. A 70-year-old female presented to our dermatology clinic with itchy lesions. Her medical history included type 2 diabetes mellitus, asthma, congestive heart failure, and hepatocellular cancer. The patient had been receiving sorafenib treatment for hepatocellular cancer for the past 7 months. Two weeks after starting sorafenib, the patient developed itchy lesions on her extremities, which spread to her entire body. Dermatological examination revealed widespread erythematous keratotic papules and nodules on the trunk and lower extremities [Figure 1a]. Histopathological examination of a punch biopsy taken from a nodule on the leg showed hyperkeratosis, acanthosis, a nodule-forming lesion just below the epidermis, with a cystic appearance and filled with elastic-collagen fiber bundles and necrotic debris. Elastic fibers were detected in the epidermis [Figure 1c and d]. Based on clinical examination and histopathological evaluation, a diagnosis of APD was made. In the patient with unresectable hepatocellular cancer, sorafenib treatment was continued by the oncology department. Considering that the patient’s complaints appeared 2 weeks after starting sorafenib, increased in complaints with repeated drug administration, and the Naranjo Adverse Reaction Score for sorafenib was 6 (5–8: Probable), it was concluded that APD had developed as a result of sorafenib use. Due to the patient’s comorbidities, treatment initially involved narrow-band UVB phototherapy (cumulative dose: 21.8 J/cm2) and clobetasol 17-propionate cream for 2 months. However, when the patient did not respond to this treatment, phototherapy was discontinued. Since there is literature suggesting that dupilumab is effective in treatment-resistant APD cases, dupilumab was initiated. The patient received an initial subcutaneous dose of 600 mg of dupilumab, followed by 300 mg every 2 weeks. The patient’s itching initially decreased with the treatment, and regression of the lesions was observed at the 3-month follow-up without any side effects [Figure 1b].Figure 1: (a) Diffuse erythematous keratotic papules and nodules on the patient’s lower extremities, (b) regressed appearance of the patient’s lesions with postinflammatory hyperpigmentation in the 3rd month of dupilumab treatment, (c) hyperkeratosis in the epidermis, acanthosis, a cystic lesion that forms a nodule just under the epidermis (star), filled with elastic-collagen fiber bundles and necrotic debris (H and E, ×4), (d) transepidermal elimination of elastic fibers (Elastin Van Gieson, ×20).APD can be caused by various factors, including medications, trauma, and infections.[1] Sorafenib has been associated with several dermatological side effects due to its effects on keratinocyte differentiation, and cases of sorafenib-induced APD have been reported.[2] In this case, APD was considered to be secondary to sorafenib use. Dupilumab is a monoclonal antibody that binds to the α-unit of the interleukin (IL)-4 receptor, reducing IL-4 and IL-13 levels. By decreasing itching and preventing microtrauma caused by scratching, dupilumab can have therapeutic effects on APD. In addition, Liu et al. found increased levels of T helper-2 (Th2) transcription factors and cytokines, such as GATA-3, IL-4, and IL-13, in APD biopsy materials, suggesting that APD is a Th2 pathway-mediated disease. These findings further support the potential role of dupilumab in managing APD.[3] Recent literature has reported cases of APD responding to dupilumab [Table 1].[3-8] For example, Alsebayel et al. observed a complete treatment response with dupilumab in an APD patient with Wilson disease.[4]Table 1: Acquired perforating dermatosis cases treated with dupilumab reported in the literatureTo the best of our knowledge, this is the first case of drug-induced APD successfully treated with dupilumab. Through this case, we aim to enhance understanding of cutaneous adverse reactions related to sorafenib and emphasize that dupilumab is a safe alternative treatment option for treatment-resistant APD cases, particularly in patients with comorbidities. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent form. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.