Photodiagnosis and Photodynamic Therapy 32 (2020) 101979 Available online 28 August 2020 1572-1000/© 2020 Elsevier B.V. All rights reserved. Intralesional vitamin D3 versus new topical photodynamic therapy in recalcitrant palmoplanter warts Randomized comparative controlled study Nahla A. Ibrahim a , Doaa A. Abdel Fadeel b , Ahmed Sadek c , Maha Fadel b , Abeer Tawfk d, * a General Institute of Health Insurance Hospitals, Dermatology Unit, Nasr City Hospital, Cairo, Egypt b A Pharmaceutical Technology Unit, Department of Medical Applications of Laser, National Institute of Laser Enhanced Sciences, Cairo University, Egypt c Al-Haud Al-Marsoud Hospital, Cairo, Egypt d Dermatology unit, Department of Medical Applications of Lasers (MAL), National institute of Laser Enhanced Sciences, Cairo University, Giza, Egypt A R T I C L E INFO Keywords: Warts Vitamin D3 Photodynamic therapy Eosin Dermoscope ABSTRACT Background: Recalcitrant palmoplanter warts represent a therapeutic challenge. Side effects of local destructive methods necessitates the need for other less morbid modalities. Recently immunotherapy as well as light based devices and lasers have emerged as therapeutic approaches. Aim of the study: To compare between the safety and effcacy of intralesional vitamin D3 injection and photo- dynamic therapy (PDT) using eosin in treatment of recalcitrant palmoplanter warts. Patients and Methods: Prospective, randomized, controlled comparative study. Fifty -six patients with recalcitrant palmoplanter warts were randomly divided into 3 groups. Group A was injected with intralesional vitamin D3. Group B was subjected to PDT using eosin loaded in trasferosomes as a photosensitizer. Group C is the control group. Clinical improvement was assessed by photographic records and dermoscopic assessment, at baseline, before each session and after completion of treatment. Patients were followed up for 6 months after cure to detect recurrence. Results: Group A and B showed complete clearance in 88.89 % and 86.36 % respectively compared to 18.75 % in the control group. These results were statistically signifcant (P value<0.001). No side effects were reported except for pain during injection in group A. Conclusion: In the current study, both vitamin D3 and PDT using Eosin are safe, highly effective and well tolerated modalities in treatment of viral warts 1. Introduction Warts are common epidermal proliferations of the skin and mucous membrane caused by infection with human papilloma virus (HPV). Warts may undergo spontaneous resolution in some patients whereas, in others, they may show persistence and progression with distant spread, despite of the conventional therapy, hence becoming recalcitrant [1]. The treatment of warts with conventional local destructive therapies, including, cryotherapy, chemical cautery, electrocautery and laser vaporization is painful, expensive and time consuming. Moreover these modalities may be associated with scarring and frequent recurrences [1]. Besides, they don’t act systemically, so they are unsuitable for pa- tients with multiple and distant lesions. To overcome these problems, immunotherapy has been tried widely in the recent years [2]. The basic principle of the intralesional immunotherapy depends on its ability to employ the immune system to arise a delayed hypersensitivity response to HPV infected tissue with subsequent pro- duction of Th1 cytokines. This activates cytotoxic and natural killer cells leading to eradication of local and distant warts [3]. Therefore, different immunotherapeutic agents have been used including Candida albicans antigens, measles mumps rubella (MMR) vaccine, tuberculin (purifed protein derivative) and intralesional vitamin D3 (Vit-D3) [4]. The mechanism of action of Vit-D3 is through its ability to regulate epidermal cell proliferation and differentiation in addition to its immunomodulatory activities by modulation of cytokine production. These effects are mediated through Vit-D receptors (VDR) of the skin. Furthermore upregulation of skin VDR induces antimicrobial peptide expression [5]. Another alternative modality in treatment of recalcitrant warts is the off-label use of topical photodynamic therapy (PDT) [6]. Photodynamic therapy utilizes a photosensitizer (PS) and visible light in presence of * Corresponding author. Contents lists available at ScienceDirect Photodiagnosis and Photodynamic Therapy journal homepage: www.elsevier.com/locate/pdpdt https://doi.org/10.1016/j.pdpdt.2020.101979 Received 13 July 2020; Accepted 21 August 2020