The aim of the current work is to evaluate the efficacy and safety of intralesional combined Digoxin and furosemide versus intralesional 5-flurouracil in the treatment of plantar warts.

Warts are benign proliferations of skin and mucosa caused by the human papilloma virus (HPV). Currently, over 170 HPV types have been identified. Certain HPV types tend to infect skin at specific anatomical sites, such as palmoplantar warts, which are typically caused by serotypes 1, 2, and 4, however warts caused by any HPV type can occur at any site (Tulay & Serakinci, 2016).

Plantar warts most commonly present with pain that occur with activities that put pressure on the soles of the feet. They commonly affect plantar areas of increased pressure, such as the heels or metatarsal heads. On gross inspection, plantar warts may appear as a singular rough, flesh-colored to yellow or grey-brown, hyperkeratotic papule, or a thickened "cobblestoned" plaque, termed a mosaic wart, which consists of multiple plantar warts that have coalesced (Witchey et al., 2018).

There are several modalities for the treatment of warts including, cryotherapy, electrocoagulation, topical salicylic acid, topical 5-fluorouracil, intralesional immunotherapy, and laser surgery. All these treatment options can be painful, time-consuming, and/or expensive, and none is considered the gold standard (Latif et al., 2021).

K+ influx is essential for the replication of DNA viruses, such as HPV. Both digoxin, which is a cardiac glycoside, and furosemide, which is a loop diuretic, inhibit the K+ influx by interacting with cell membrane ion co-transporters (Na+/K+-ATPase and Na+-K+-2Cl-co-transporter-1). Therefore, it is hypothesized that these two compounds may be valuable in the treatment of HPV-induced warts. This new approach is called ionic contra-viral therapy (Rijsbergen et al., 2019). Intralesional injection of combined digoxin and furosemide was found to be safe and effective as a treatment option for multiple plantar warts (Fathy et al., 2021).

5-Fluorouracil (5-FU) is an antimetabolite that can be used alone or with other chemotherapeutic agents to treat solid tumors. It is one of the pyrimidine analogues. Due to its structure, 5-FU disrupts nucleoside metabolism and can be integrated into the single and double helix of RNA and DNA, respectively, causing cell cytotoxicity and death (Zoheir et al., 2022).

Intralesional 5-fluorouarcil has been found to be a highly effective, safe and cheap alternative in the treatment of warts, with a significantly good response in genital warts also (Kamal et al., 2108).

Inclusion Criteria:

• Patients with multiple plantar warts (≥ 3) will be included.

Exclusion Criteria:

• Patients under 18 years old or patients over 65 years old.
• Pregnancy or breast feeding.
• Patients received vaccination or any other treatment of warts during the last month.
• Patients with a known sensitivity to any of the investigational product ingredients.
• Patients with history of asthma, allergic skin disorders or convulsions.
• Patients with signs of any systemic or local inflammation or infection.
• Patients with any evidence of immunosuppression including HIV.
• History of cardiac diseases, relevant abnormal K level or ECG abnormalities for patients who will receive the combined digoxin and furosemide.