Received: 27 September 2018 Revised: 18 February 2019 Accepted: 22 March 2019

DOI: 10.1111/dth.12882

THERAPEUTIC HOTLINE: SHORT PAPER

Effectiveness of intralesional vitamin D3 injection in the

treatment of common warts: Single-blinded placebo-controlled
study

Ibrahim M. Abdel Kareem | Ibrahim M. Ibrahim | Sameh F. F. Mohammed |

Ahmed Abo-Bakr Ahmed

Department of Dermatology and Venereology

Faculty of Medicine, Al- Azhar University, Abstract
Cairo, Egypt Warts are common viral infection of the skin, usually treated with destructive methods
Correspondence like electrocautery, cryotherapy or laser ablation. Topical vitamin D has been used to
Ibrahim M. Abdel Kareem, Department of treat warts with variable success is to evaluate the efficacy of intralesional vitamin D3
Dermatology and Venereology Faculty of
Medicine, Al-Azhar faculty of Medicine, Cairo, injection in the treatment of common warts. Fifty patients were divided into two
Egypt. groups: 30 patients as cases group who received intralesional injection of 0.2 mL of
Email: [email protected];
[email protected] vitamin D3 (300,000 IU) into the base of mother wart for two sessions and another
20 patients as a control group who were injected with normal saline solution. Stan-
dardized photographs were taken before the procedure, and 1 month and 3 months
after the procedure. The degree of the response was classified into complete, partial,
and no response. Complete clearance of the target injected warts occurred in 40% of
patients in cases group while it occurred only in 5% of patients in control group
(p ≤ .001) that was statistically significant. Intralesional injection of vitamin D3 may be
considered a good and safe modality for the treatment of common warts.

KEYWORDS
verruca, vitamin D, warts

1 | I N T RO D UC T I O N Vitamin D controls cell proliferation and differentiation and has

immunoregulatory activities. Its effects are mediated via the vitamin D
Warts are common viral infections of the skin and mucous mem- receptor (VDR), which is present in keratinocytes, melanocytes, fibro-
branes and are prevalent worldwide. Warts are caused by the human blasts, and immune system cells of the skin (Al Ghamdi & Khurram, 2011).
papilloma virus (Lynch, Cliffe, & Morris-Jones, 2014).
Two therapeutic options of warts are commonly used: the first is
2 | P A T I E N T S A N D M E T H O DS
the destructive method such as chemical cautery, cryotherapy, and
electrocautery, and the second is the immunotherapy, which is based The study was designed as a single blinded placebo controlled study
on the activation of the immune system (Vender, Bourcier, Bhatia, & and included 50 patients complaining of common warts, of both sexes
Lynde, 2013). Immunotherapy could lead to resolution without any and their age range was 12–50 years. Patients did not receive treat-
physical changes or scarring and in addition would augment the host ment for warts neither topical for 1 month nor systemic for 3 months
response against the causative agent (Sinha, Relhan, & Garg, 2015). before the procedure. We excluded patients with known allergy to
Topical vitamin D has been tried for treating warts with variable vitamin D, pregnant, lactating, and who suffered from chronic sys-
degree of success (Moscarelli et al., 2011). temic disease.

Dermatologic Therapy. 2019;32:e12882. wileyonlinelibrary.com/journal/dth © 2019 Wiley Periodicals, Inc. 1 of 3

https://doi.org/10.1111/dth.12882
2 of 3 KAREEM ET AL.

• Patients were divided into two groups: (cases group) 30 patients 4 | DISCUSSION
received intralesional injection with 0.2 mL of vitamin D3
(300,000 IU DEVIT-3, Deva, Turkey) into the base of mother wart The results of this present study are matching with Aktaş , Ergin,
for two sessions 1 month apart and (control group) 20 patients Demir, & Ekiz, 2016 who treated 20 patients with plantar warts only
were injected with normal saline by same regimen as a placebo. by intralesional vitamin D3 (300,000 IU/mL) injection and showed
Photographs were taken before injection then after 1 month and that 80% of their patients had complete resolution with neither recur-
3 months of injection. rence nor serious side effects. The percentage of patients with com-
• Treatment responses were divided into three, “no response,” plete clearance were higher than our study and this may be explained
“partial response,” and “complete response”. Of note, “no by the different anatomical site of wart and small sample size of
response” was defined as absolutely no improvement with injec- patients, also their study was not controlled.
tions, “partial response” as a noticeable improvement but not full Also, Raghukumar et al., 2017 treated 64 patients with intralesional
clearance, and “complete response” as total clearance of wart. vitamin D3 (600,000 IU/mL) injection with multiple sessions up to com-
Resolution of distant untreated warts was also assessed (Alikhan, plete clearance or maximum four sessions and showed that 90% of
Griffin, & Newman, 2016). patients showed complete clearance. In addition, 6.66% of patients
showed partial clearance and the average number of sessions
were 3.66.

2.1 | Statistical analysis These results support our assumption in our study but the differ-
ence in percentage of complete clearance may be due to the higher
Data were analyzed using the statistical package SPSS version concentration of vitamin D3, also the multiple sessions and this pre-
22 (international business machines corporation [IBM], NY). sent study ignored the side effects that may occur with high doses of
vitamin D3.
The effects of vitamin D injection in treating warts still not
3 | RESULTS completely understood; however, it acts through controlling cell pro-
liferation and differentiation via upregulation of vitamin D receptors
Patients in both groups were complaining of warts of different sites on keratinocytes and immune system cells of the skin that leads to
and numbers; they were mainly in hands, and of less than five. The the activation of toll like receptors of human macrophages and induc-
degree of response was evaluated in both groups, and it was complete tion of antimicrobial peptides' expression as thymic stromal,
clearance of the target wart in 40% of patients in cases group and lymphopiotin, and cathelecidin. It also reduces the synthesis of IL 1a
only in 5% of patients in control group. Partial response occurred in and IL6 resulting in decreased inflammation. (Moscarelli et al., 2011).
23.3% in patients in cases group; and there was no change in 36.7% In conclusion, vitamin D3 intralesional injection may be considered
of patients in cases group and 95% of patients in control group as a good modality to treat common warts with simple, safe, and effi-
(Figure 1). Therefore, the cases group improved significantly after the cient procedure.
intralesional injection of vitamin D3 with statistically significant differ-
ence (p value ≤ .001). Interestingly, two patients in cases group
showed complete clearance of distant warts those were not injected, 5 | RECOMMENDATIONS
and we did not notice this response in the control group (Table 1).
Some side effects occurred in cases group like itching, pain, or both Intralesional injection of Vitamin D3 may be considered as a good
and it occurred in 60% of cases group and only 20% in control group modality for the treatment of common warts. We recommend
with statistical significant difference (Table 2). Warts of less than increasing the number of sessions rather than increasing the dose.
1 year in duration and less than five improved significantly than Further studies may be needed to explore the actual mechanism of
others of longer duration and more in numbers. vitamin D3 on keratinocytes and viral warts. Follow up for longer

F I G U R E 1 Patient of cases group

received intralesional vitamin D3 injection
with complete response of the target and
some nontarget nearby warts
KAREEM ET AL. 3 of 3

TABLE 1 Therapeutic response in the studied groups

Cases (n = 30) Control (n = 20)

Improvement No. % No. % χ2 p

Target wart
MC
No response 11 36.7 19 95.0 17.384* p < .001*
Partial 7 23.3 0 0.0
Complete 12 40.0 1 5.0
Distant warts
FE
No response 28 93.3 20 100.0 1.389 p = .510
Partial 0 0.0 0 0.0
Complete 2 6.7 0 0.0

Note. χ2, p: χ2 and p values for Chi square test for comparing between the two groups; MCp, p value for Monte Carlo for Chi square test for comparing
between the two groups; FEp, p value for Fisher Exact for Chi square test for comparing between the two groups.
*: Statistically significant at p ≤ .05.

TABLE 2 Adverse effects in the studied groups

Cases (n = 30) Control (n = 20)

No. % No. % χ2 p
Side effects
Negative 12 40.0 16 80.0
7.792* .005*
Positive 18 60.0 4 20.0
Itching 8 44.4 0 0.0
MC
Pain 7 38.9 4 100.0 3.847 p = .156
Both 3 16.7 0 0.0

Note. χ , p: χ and p values for Chi square test for comparing between the two groups;
2 2 MC
p: p value for Monte Carlo for Chi square test for comparing
between the two groups.
*: Statistically significant at p ≤ .05.

periods may be required in further studies to detect the recurrence or Lynch, M. D., Cliffe, J., & Morris-Jones, R. (2014). Management of cutane-
the new growth. ous viral warts. The British Medical Journal, 348, g3339.
Moscarelli, L., Annunziata, F., Mjeshtri, A., Paudice, N., Tsalouchos, A.,
Zanazzi, M., & Bertoni, E. (2011). Successful treatment of refractory
wart with a topical activated vitamin D in a renal transplant recipient.
CONF LICT OF IN TE RE ST
Case Reports in Transplantation, 2011, 368623.
The authors have no conflict of interest to declare. Raghukumar, S., Ravikumar, B. C., Vinay, K. N., Suresh, M. R.,
Aggarwal, A., & Yashovardhana, D. P. (2017). Intralesional vitamin D3
injection in the treatment of recalcitrant warts: A novel proposition.
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