Needle-free injection of 5-fluorouracil suggests efficacy and tolerability in the treatment of palmoplantar warts: A randomized clinical trial

To the Editor: The treatment of palmoplantar warts remains a challenge because of pain and poor curative effect.1Hekmatjah J. Farshchian M. Grant-Kels J.M. Mehregan D. The status of treatment for plantar warts in 2021: No definitive advancements in decades for a common dermatology disease.Clin Dermatol. 2021; 39: 688-694https://doi.org/10.1016/j.clindermatol.2021.05.024Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Needle-free injections, through which the liquid is administered into the skin at high velocity, has proved to be efficient and painless in treating various dermatologic diseases, such as nonmelanoma skin cancer.2Han H.S. Hong J.Y. Kwon T.R. et al.Mechanism and clinical applications of needle-free injectors in dermatology: literature review.J Cosmet Dermatol. 2021; 20: 3793-3801https://doi.org/10.1111/jocd.14047Crossref PubMed Scopus (5) Google Scholar,3Zhao W. Wang J. Zhang Y. Zheng B. A retrospective study comparing different injection approaches of 5-aminolevulinic acid in patients with non-melanoma skin cancer.J Dermatolog Treat. 2022; 33: 1465-1472https://doi.org/10.1080/09546634.2020.1832186Crossref PubMed Scopus (1) Google Scholar We performed a randomized clinical trial to explore the efficacy and tolerability of needle-free injection of 5-fluorouracil (5-FU) versus cryosurgery therapy for the treatment of palmoplantar warts. Seventy-six patients aged between 10 and 75 years with palmoplantar warts were randomized in a 1:1 ratio to receive a needle-free injection of 5-FU or cryotherapy every 3 to 4 weeks for a maximum of 3 sessions (Supplementary Fig 1, available via Mendeley at https://data.mendeley.com/datasets/m47gy8g8cc/1). The severity of pain during the therapy was rated on the basis of a 0 to 10 ascending visual analog scale (0 = no pain; 10 = excruciating pain). Immediate and late adverse effects were evaluated after each treatment session. Warts were superficially pared to remove the associated callus without reaching the bleeding points before each treatment. Patients in the needle-free group were treated with intralesional injections of 5-FU with an injector (INJEX). An approximate 0.05- to 0.3-mL mixture of 5-FU (10 ml, 0.25g) and lidocaine (5 ml, 0.1g) was injected vertically into each wart. Participants in the cryotherapy group received 3 serial applications in which liquid nitrogen was applied with a spray during each session (Supplementary material II, available via Mendeley at https://data.mendeley.com/datasets/m47gy8g8cc/1). The warts were observed and detected by dermoscopy.4El Sayed M.H. Sayed F.S. Afify A.A. Intralesional zinc sulfate 2% vs intralesional vitamin D in plantar warts: a clinicodermoscopic study.Dermatol Ther. 2020; 33e13308https://doi.org/10.1111/dth.13308Crossref Scopus (14) Google Scholar Responses to treatment were classified as complete response (CR), partial response (PR; decreased area of warts was >50%), and no response (NR; decreased area of warts was <50%). Analysis was conducted using the SPSS software package. χ2 test and Mann-Whitney test were used as appropriate. P values of <.05 were considered significant. All patients completed the study. Baseline characteristics of the studied patients are shown in Table I.Table IBaseline characteristics of the studied patientsVariableNeedle-free group (N = 38)Cryosurgery group (N = 38)P valueNo.%No.%Age (y)Mean ± SD22.47 ± 10.91428.39 ± 10.300.017Median (Range)22 (10-48)28 (10-55)Sex Male2052.632258.645 Female1847.371642Number Single1847.371334.21.243 Multiple2052.632565.79M (Q1, Q3)2 (1, 4)2 (1, 5).454Median (Range)2 (1-7)2 (1-8)Duration (years)M (Q1, Q3)9 (4.75, 12)8 (6, 24).366Median (Range)9 (1-60)8 (1-60)Size (mm)N = 97N = 111 >102424.742522.52.707 <107375.268677.48Site Palm1313.402623.42.065 Plantar8486.608576.58M, Median; Q, quartile. Open table in a new tab M, Median; Q, quartile. In the needle-free injection group, 24 (63.16%) patients showed CR, 10 (26.32%) showed PR, and 4 (10.53%) showed NR. In the cryosurgery group, 8 (21.05%) patients had CR, 24 (63.16%) had PR, and 6 (15.79%) had NR (P < .001). The visual analog scale of the needle-free injection group ranged from 1 to 7, with a median of 3, whereas the median visual analog scale of cryotherapy was 6.5 (P < .001) (Table II; Supplementary Fig 1, available via Mendeley at https://data.mendeley.com/datasets/m47gy8g8cc/1).Table IITherapeutic response of patients and warts and the visual analog scale of studied patientsItemNeedle-free groupcryosurgery groupP valueNo.%No.%Therapeutic response of patientsPatient number3838 Complete2463.16821.05.001 Partial1026.322463.16 No response410.53615.79Therapeutic response of wartsWart number97111 Complete6870.104338.740 Partial2121.654641.44 No response88.252219.82The VAS of the patientsM (Q1, Q3)3 (2, 4)6.5 (5, 8)0Median (Range)3 (1-6)6.5 (2-9)M, Median; Q, quartile; VAS, visual analog scale. Open table in a new tab M, Median; Q, quartile; VAS, visual analog scale. Serious adverse effects were not observed in both groups. The most common adverse effect of the injector was a mild bruise immediately after injection caused by high pressure, which could be handled easily by some rest. On the other hand, intense pain and localized blisters were reported in most patients in the cryosurgery group. No recurrence of warts was reported during 6-month follow-up period in both groups. Our study suggests that needle-free injection of 5-FU is a promising therapy, especially for patients who are pain averse and needle phobic. The limitations of the study included small patient numbers and the inability to blind the participants. The response rate of needle-free injections of 5-FU was attractive, where 34 of 38 (89.5%) patients had CR or PR. To the best of our knowledge, this is the largest randomized clinical trial regarding the use of needle-free jet injection in warts. None disclosed.