A Case of Multiple Recalcitrant Verruca Vulgaris Associated With Atopic Dermatitis Successfully Treated With Nemolizumab and Topical Imiquimod

Verruca vulgaris (VV), caused by human papillomavirus (HPV), is common in children but often becomes recalcitrant in patients with atopic dermatitis (AD) due to epidermal barrier dysfunction, altered cutaneous immunity, and chronic scratching [1]. In such patients, intensifying anti-inflammatory therapy may improve eczema but sometimes promotes viral persistence, whereas conventional wart treatment risks exacerbating dermatitis. We report a case in which nemolizumab combined with topical imiquimod enabled simultaneous control of AD and refractory VV. An 11-year-old boy had a two-year history of AD and multiple VV. Prior therapies—including topical salicylic acid, cryotherapy, and CO2 laser ablation—were unsuccessful. At a prior hospital, dupilumab improved eczema on the trunk and limbs but worsened periocular dermatitis, while severe pruritus persisted. Continuous scratching appeared to contribute to the widespread dissemination of VV to the forehead, periungual and subungual areas, genitalia, coccyx, and popliteal fossa. Because eczema improvement but viral lesions progressed, his condition was deemed refractory. At our institution, topical delgocitinib and difamilast ointments were introduced along with nemolizumab (30 mg every 4 weeks). This regimen led to rapidly alleviated pruritus and improved facial dermatitis. Concurrently with nemolizumab initiation, imiquimod 5% cream was applied three times weekly only to verruca lesions on the right popliteal fossa in an amount sufficient to gently rub into the lesion. After 2 weeks, regression was noted in VV on the forehead and fingers. Application was then extended to all lesions, and after 4 weeks, complete resolution was observed without exacerbation of AD (Figure 1). Imiquimod is a Toll-like receptor 7 agonist that activates both innate and adaptive immunity and promotes clearance of HPV-infected keratinocytes. Clinical reports have demonstrated the efficacy of imiquimod in recalcitrant VV [2, 3]. Nevertheless, in AD patients, imiquimod carries the risk of eczema aggravation due to enhanced inflammation. In this case, nemolizumab played a pivotal role in suppressing pruritus, thereby limiting scratching-induced autoinoculation of HPV. This created a therapeutic window in which topical imiquimod could exert its antiviral effect without triggering AD flares. The combination achieved simultaneous control of inflammation and viral infection, effectively overcoming the clinical dilemma in AD with disseminated VV. Previous reports have described the disappearance of verruca vulgaris after dupilumab therapy in AD patients [4, 5]. (One case was also treated with cimetidine and Candida antigen therapies [4]). These outcomes are thought to result indirectly from improved skin barrier function and normalization of the cutaneous immune milieu, rather than direct antiviral effects. However, our case illustrates that not all patients benefit in this manner. In this child, dupilumab improved eczema but did not adequately control pruritus or halt viral dissemination. Our experience suggests that in such cases, a combination of nemolizumab and topical imiquimod may represent a valuable therapeutic option. Nemolizumab addresses the behavioral and mechanical drivers of viral spread by reducing pruritus, while imiquimod directly enhances antiviral immunity. Together, these complementary mechanisms provide a novel strategy for managing complex cases of AD with refractory viral warts. Informed consent was obtained from the patient's parents for off-label treatment and for publication of this case report, including clinical data and images. According to the institutional policy of Hiroshima University Hospital, ethics committee approval is not required for individual off-label treatments supported by prior published case reports and conducted with parental consent.