Inclusion Criteria

Exclusion Criteria

Procedure

The patients received intralesional injections of vitamin D₃ at a concentration of 200,000 IU at the base of each wart, with a volume of 0.2 to 0.5 mL per wart. To minimize discomfort and ensure patient safety, a maximum of five warts were injected into in a single session. Treatments were spaced one month apart, with follow-up sessions scheduled as needed.

Response Assessment

The response to treatment was assessed after each session and classified into three groups:

Patients who achieved complete disappearance were followed up for a period of six months after the last injection by clinical and dermoscopic examinations to detect any signs of recurrence.

RESULTS

Fifty common, flat and palmoplantar warts of varying sizes were collected, in a total of 14 patients (5 children, 9 adults). The majority of the fifty warts were common warts (n = 25, 50%); the other forms included plantar warts (n = 15, 30%), periungual warts (n=9, 18%), and one flat wart (n = 1, 2%). The age range for both sexes fell between 8 and 45 years. The evolution of the warts varied from 6 months to 2 years with an average of one year.

Complete remission was observed in 25 lesions (50%), a partial response in 20 (40%), and no response in 5 (10%). The five children of different ages between 8 and 16 years who participated in this study with a total of 13 warts presented a complete remission, unlike the adults, whose responses were variable.

No recurrence was observed after the complete remission of the lesions. The number of intralesional injections varied from 2 to 5, with an interval of one month between sessions.

We compared patients with warts less than 5 mm in diameter to those with warts greater than 5 mm in diameter and found no difference in the therapeutic response.

Adverse effects were mainly significant pain during injection in all patients (100%). Intralesional injections of plantar warts were marked by slight edema that disappeared after one week (30%), with pain on pressure for four days after the procedure. One patient was left with an erythematous scar at the injection site. No signs of hypervitaminosis D or systemic side effects were observed. Table 1 and Figures 1–5 show the results.

Table 1: Intralesional treatment of warts: results and adverse effects observed.

	Figure 1: (a) Multiple common warts on the back of the hands before treatment. (b) Complete clearance after 2 injections.
	Figure 2: (a) Periungual warts before treatment. (b) Complete clearance after 3 injections.
	Figure 3: (a) Two warts on the back of the foot before treatment. (b) Complete clearance after 5 injections, with persistence of an erythematous scar.
	Figure 4: (a) Warts in the second toe and in the last intertoe space. (b) Complete clearance after 4 injections.
	Figure 5: (a) Subungual wart before treatment. (b) Complete clearance after 2 injections.

DISCUSSION

Our study differed from those reported in the literature by the concentration of vitamin D3 injected into the warts, which was 200,000 IU.

Raghukumar et al. included 60 patients with recalcitrant extragenital warts who received an injection of 0.2 to 0.5 mL of vitamin D 600,000 IU with an interval of three weeks between the injections. A complete response was observed in 90% of the patients, with a mean of 3.66 injections. Side effects were minimal. A recurrence was noted in two patients [6].

Haidar Al Sabak et al. used the same dosage of vitamin D3 600,000 IU for the treatment of 204 warts. They observed that 167 warts (81.9%) underwent complete disappearance, 23 warts (11.3%) had a partial response, and no response was observed in 14 warts (6.7%) [7]. The side effects were similar to our results.

Ibrahim et al. included 50 patients with common warts, who received an injection of 0.2 mL of vitamin D3 300,000 IU at the base of each wart. A complete response was observed in 40% of the patients, with the disappearance of distant warts in two patients [8].

The low percentage of a complete response in our patients, especially adults, could be explained by the low concentration of vitamin D3 of 200,000 IU, which is the maximum dose available in our country. However, in children, the favorable response may be explained by greater immune reactivity, shorter-lived warts, thinner skin, and therefore, good penetration of vitamin D3.

Since vitamin D3 has an immunomodulatory action, studies have compared its efficacy with other immunomodulatory agents [9,10,12]. Kavya et al. collected 42 patients with multiple warts. Intralesional injections of vitamin D3 (0.2 mL, 15 mg/mL) resulted in a complete response in 78.57% of the patients, with no reported adverse effects. They compared their results with other studies of injections of immunomodulatory agents and concluded that their results were superior to the results obtained with purified protein derivative (PPD), bleomycin, MMR (measles-mumps-rubella) vaccine, Candida albicans antigen, and Mycobacterium indicus pranii vaccine. The response with Mycobacterium w. vaccine was superior to vitamin D3, yet the number of sessions was higher with significant local and systemic side effects [9].

Ghada Fathi et al. included patients with recalcitrant multiple plantar warts and divided them into three groups: group 1 received vitamin D3 injection, group 2 received Candida antigen injection, and group 3 received saline injection. They obtained a better clinical response in group 1 [10].

Indeed, vitamin D controls cell proliferation and differentiation and has immunoregulatory activities. Its effects are mediated by the vitamin D receptor (VDR), present in keratinocytes, melanocytes, fibroblasts, and cells of the skin’s immune system. After vitamin D injection, it binds to its receptor (VDR) leading to an increase in the expression of Toll-like receptors (TLR) by macrophages. This leads to the expression of antimicrobial peptides and cathelicidins and an increase in VDR. This explains its ability to strengthen the immune system against the HPV virus [7,13,14]. An interesting observation was made by Tawfik et al., who took biopsies of warts and peripheral skin in 30 patients and demonstrated that VDR expression was significantly increased in warts with a significant difference [15]. This supports the effectiveness of using vitamin D in the treatment of warts; however, the higher the concentration, the better the efficacy rate.

Limitations of the Study

The study only included 14 patients and 50 warts, which may limit the generalizability of the results. A larger sample size is needed to validate the results and assess the effectiveness of intralesional vitamin D3 injections in different populations.

The lack of a control group makes it difficult to compare the efficacy of intralesional vitamin D3 injections with other treatment modalities.

CONCLUSION

Intralesional injection of vitamin D shows promise as an effective treatment for cutaneous warts, especially in pediatric patients who tend to respond better than adults. The immunomodulatory effects of vitamin D3 appear to improve the body’s ability to fight the virus. However, the low concentration of vitamin D3 may have reduced the effectiveness of the treatment, especially in adults.

To improve treatment outcomes, we suggest that using a higher concentration of vitamin D3 may provide a stronger immunological response. A higher dosage may increase the effectiveness of the treatment and reduce the number of injections required for the complete clearance of warts. It may also minimize patient discomfort, making the treatment more acceptable and less painful overall.

Statement of Human and Animal Rights

All the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 2008 revision of the Declaration of Helsinki of 1975.

Statement of Informed Consent

Informed consent for participation in this study was obtained from all patients.