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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 25  |  Issue : 1  |  Page : 14-17

A comparative study of therapeutic efficacy of intralesional measles, mumps, and rubella vaccine and intralesional Vitamin D3 in the treatment of recurrent warts


Department of Dermatology, Venereology and Leprosy, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India

Date of Submission20-Aug-2020
Date of Acceptance23-Apr-2021
Date of Web Publication04-May-2021

Correspondence Address:
Dr. Manjunath Kadnur
Department of Dermatology, Venereology and Leprosy, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdds.jdds_89_20

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  Abstract 


Background: Recurrent or resistant warts may be due to defective cell-mediated immune response. Immunotherapy is directed at manipulating the immune system to achieve an anti-human papillomavirus immune reaction. Purpose: Our study compared the safety and efficacy of intralesional measles/mumps/rubella (MMR) vaccine to intralesional Vitamin D3 injection in recurrent warts. Methods: Sixty-six patients were divided into two groups of 33 each. In Group A and B, patients were injected with 0.5 ml of Vitamin D3 and 0.5 ml of MMR vaccine, respectively, intralesionally into the base of the largest wart every 2 weeks until complete clearance or for a maximum of 4 doses. The patients were evaluated for clinical improvement and any adverse effects. Results: Complete clearance of warts was noted in 52% (17) in Group A and in 70% (23) in Group B. Excellent to complete response was noted in 82% (27) in Group A and in 91% (30) in Group B. The clinical improvement noted with intralesional MMR vaccine was not statistically different than with intralesional Vitamin D3 (P > 0.05). Conclusion: Intralesional MMR and Vitamin D3 are promising options for recurrent warts.

Keywords: Immunotherapy, measles/mumps/rubella vaccine, Vitamin D3


How to cite this article:
Jartarkar SR, Kadnur M, Mamatha P, Mishra SS, Spoorthy B. A comparative study of therapeutic efficacy of intralesional measles, mumps, and rubella vaccine and intralesional Vitamin D3 in the treatment of recurrent warts. J Dermatol Dermatol Surg 2021;25:14-7

How to cite this URL:
Jartarkar SR, Kadnur M, Mamatha P, Mishra SS, Spoorthy B. A comparative study of therapeutic efficacy of intralesional measles, mumps, and rubella vaccine and intralesional Vitamin D3 in the treatment of recurrent warts. J Dermatol Dermatol Surg [serial online] 2021 [cited 2021 May 12];25:14-7. Available from: https://www.jddsjournal.org/text.asp?2021/25/1/14/315346




  Introduction Top


Warts, caused by human papillomavirus (HPV), are benign epidermal proliferations of skin and mucosa. There are several strains of the virus, a few of which are premalignant.[1] Although there are various cytodestructive and immunotherapeutic agents available, no single therapy is yet approved or 100% effective.[2] Cytodestructive therapeutic modalities are limited by pain, scarring, and frequent recurrence.[3] Higher chances of recurrence and cumbersome procedures make immunotherapy more popular, especially in the treatment of recurrent warts.[4] Recurrent or resistant warts may be associated with a defective cell-mediated immune response.[5]

Immunotherapy is directed at manipulating the immune system to achieve an anti-HPV immune reaction.[6] The response of warts to immunotherapy – including purified protein derivative, measles/mumps/rubella vaccine (MMR), candidal antigen, and Vitamin D3 – is variable, and selecting from the existing agents remains challenging. Both intralesional MMR and intralesional Vitamin D3 can be effective individually. However, there has been a paucity of studies comparing intralesional MMR with intralesional Vitamin D3 injection in the treatment of recurrent warts. The aim of our study is to compare the efficacy and safety of intralesional MMR and intralesional vitamin D3 injection in the treatment of recurrent warts.


  Methods Top


The present study was a prospective comparative interventional study carried out from May 2019 to May 2020 in the Outpatient Department of Dermatology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, after approval from the institutional ethical committee. The study included 66 patients of recurrent warts attending the outpatient department of our institute. The patients were randomly assigned into two groups of 33 each. Patients with single or multiple recurrent viral warts who were willing to give voluntary written consent to participate in the study were included. Exclusion criteria included age <12 years or >70 years, pregnant and lactating women, patients with keloidal tendency, anogenital warts, any evidence of immunosuppression, any systemic/local inflammation/infection/asthma/meningitis, and prior hypersensitivity to Vitamin D3, MMR vaccine, or any other drug.

Written informed consent was obtained from each patient willing to be included in the study. Age, sex, duration of disease, site of warts, number of warts, presence/absence of distant warts, and the prior treatment history were noted. Photographs were taken at the first visit and at each visit and after 3 months after the last injection.

In Group A, patients were injected with 0.5 ml of Vitamin D3 (6 lakh IU, 15 mg/ml) and in Group B, patients were injected with freeze-dried MMR vaccine after reconstitution with 0.5 ml of the provided diluent. The injections were given intralesionally into the base of the largest wart with an insulin syringe. The procedure was repeated every 2 weeks in a similar fashion until complete clearance or for a maximum of 4 doses. The patients were evaluated for clinical improvement and any adverse effects. The patients were followed up for 3 months after the last injection to detect any recurrences.

The efficacy assessment was done by photographs at baseline, before each session, and after 2 weeks of completion of the last injection and after 3 months. The clinical improvement was rated as complete clearance, excellent response, good response, or unsatisfactory response by the physician's global assessment using a visual analog scale score [Table 1] at each visit taking into account baseline clinical photographs.[7] After completion of treatment period, the patients were followed up every month for 3 months to detect any recurrences.
Table 1: Visual analog scale score

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The statistical analysis was done using SPSS version 21 (Statistical product and service solutions, IBM, Chicago, U.S). The statistical tests used in this study were independent sample t-test or Mann–Whitney U-test. P < 0.05 was considered statistically significant.


  Results Top


All 66 patients completed the study. The mean age of patients was 31 ± 9.2 in Group A and 27 ± 5.8 in Group B. The most common site of involvement was palmoplantar warts in both the groups followed by extremities. The most common type of wart was verruca vulgaris in both the groups followed by filiform warts and verruca plana. The number of warts ranged from 1 to 197 in Group A, the mean being 11. The number of warts ranged from 1 to 79 in Group B, the mean being 14. Duration of the warts ranged from 2 months to 4 years in Group A and 2 months to 6.5 years in Group B. Distant warts were present in 30% (10) in Group A and in 27% (9) in Group B. Most of our patients in 70% (23) in Group A and 67% (22) in Group B had undergone cytodestructive treatment in the form of electrosurgery prior to receiving immunotherapy.

In Group A, complete clearance of warts was noted in 52% (17), excellent response was noted in 30% (10), good response in 9.1% (3), and minimal response in 9.1% (3) of the patients [Figure 1]. In Group B, complete clearance of warts was noted in 70.% (23), excellent response in 21% (7), good response in 6.1% (2), and minimal response in 3.1% (1) of the patients [Table 2], [Graph 1] and [Figure 2]. The mean number of injections required for complete clearance of warts was 3.8 in Group A and 3.2 in Group B.
Figure 1: A 41-year-old with multiple warts over the dorsum of the feet after 4 injections of intralesional vitamin D3

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Figure 2: A 27-year-old male with multiple plantar warts after 3 sessions of intralesional measles/mumps/rubella vaccine

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Table 2: Clinical improvement noted in Group A and B

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In Group A, 60.6% of patients (20) had palmoplantar warts and 80% of them (16) showed complete to excellent response. In Group B, 69.6% of patients (23) had palmoplantar warts, of which 86.9% of patients (20) showed complete to excellent response [Graph 2] and [Graph 3].



Excellent to complete response was noted in 82% (27) in Group A and in 91% (30) in Group B, and this difference was not statistically significant with P > 0.05.

In Group A, pain during intralesional injection was the major complaint occurring in 26 (79%) out of 33 patients and persistent erythema was noted in 3 (9.1%) patients, which subsided within 1 week spontaneously [Table 3]. No recurrence was noted in either group after 3 months of completion of the treatment.
Table 3: Side effects noted in Group A (intralesional Vitamin D3)

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In Group B, pain during the injection was noted in 20 (61%) out of 33 patients, and flu-like symptoms were noted in 4 (12%) patients, which subsided within 2–3 days [Table 4]. No recurrence of warts was noted during the follow-up period in patients with complete clearance in either of the groups.
Table 4: Side effects noted in Group B (intralesional mumps and rubella)

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  Discussion Top


Local cytodestructive modalities have been commonly employed for the treatment of warts, but these methods are associated with destruction of the epidermis and a variable part of the dermis; scarring and recurrence may occur.[8] Immunotherapy has been employed due to the ability of the immune system to recognize viral antigens and clear the virus.[9],[10] When a viral antigen is injected, there is proliferation of peripheral blood mononuclear cells, promoting Th1 cytokine response, particularly interferon-gamma and interleukin (IL) 2 and 4. This leads to cytotoxic T-cell activation and also stimulates tumor necrosis factor (TNF) alpha and IL 1 release, helping in the eradication of HPV-infected cells.[9],[10]

Vitamin D3 controls cell proliferation and differentiation and has immunoregulatory activity. The effect of vitamin D3 on warts may relate to the regulation of epidermal cell proliferation and differentiation and to modulation of cytokine production. Upregulation of Vitamin D receptors (VDR) and Vitamin D1 hydroxylase genes following activation of toll-like receptor leads to induction of antimicrobial peptides.[11] This causes inhibition of IL-6, IL-8, TNF-α, and TNF-γ expression through the VDR pathway.[12]

Although the exact mechanism of these agents on warts remains to be elucidated, most of the agents aim at eliminating the virus by enhancing host cell-mediated immunity instead of just clearance of the skin lesions.[13] In our study, warts improved with both MMR vaccine and with Vitamin D3 treatment. No recurrence was noted at the end of 3 months of completion of treatment, which may represent long-term HPV-directed immunity and an advantage of immunotherapy.

In an open-label placebo-controlled study done by Nofal and Nofal to evaluate the efficacy and safety of MMR vaccine in common warts, 70 patients were treated with intralesional MMR vaccine for recalcitrant warts every 3 weeks for a maximum of 3 sessions and complete clearance was noted in 63% of the cases.[14] In a case-controlled study, 20 patients with common warts were treated with intralesional MMR vaccine, and complete response occurred in 65% of the patients.[1] In an open-label prospective study, 30 patients with extragenital warts were treated with intralesional MMR vaccine every 2 weeks for 3–5 times, and complete response was noted in 70% of the patients.[15] Other studies have reported response rates from 45% to 83% to intralesional Vitamin D3 and MMR.[5],[16]

No significant side effects were noted in our study in both the groups and this was in concordance with previous studies.[14],[16]

Limitations of our study were small sample size and short follow-up period of 3 months to detect any recurrences.


  Conclusion Top


Nevertheless, both intralesional MMR and Vitamin D3 seem to be promising, safe, and possibly cost-effective treatments for recurrent warts. With low cost, good tolerability, effect on both treated and distant warts, low recurrence rates, and excellent safety profile, immunotherapy may be a first-line therapy for multiple disseminated warts and second-line therapy for warts recalcitrant to standard therapies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Dhope A, Madke B, Singh AL. Effect of measles mumps rubella vaccine in treatment of common warts. Indian J Drugs Dermatol 2017;3:14-9.  Back to cited text no. 1
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Thappa DM, Chiramel MJ. Evolving role of immunotherapy in the treatment of refractory warts. Indian Dermatol Online J 2016;7:364-70.  Back to cited text no. 4
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Maheshwari DG, Sengar DS, Shrivastava DS. An open randomized comparative study of various intralesional immunotherapeutic agents in cutaneous warts. Int J Med Sci Clin Invention 2018;5:3852-9.  Back to cited text no. 5
    
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Bacelieri R, Johnson SM. Cutaneous warts: An evidence-based approach to therapy. Am Fam Physician 2005;72:647-52.  Back to cited text no. 6
    
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Gonçalves MA, Donadi EA. Immune cellular response to HPV: Current concepts. Braz J Infect Dis 2004;8:1-9.  Back to cited text no. 8
    
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Wananukul S, Chatproedprai S, Kittiratsacha P. Intralesional immunotherapy using tuberculin PPD in treatment of palmoplantar and periungual warts. Asian Biomed 2009;3:39-43.  Back to cited text no. 9
    
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Gupta S, Malhotra AK, Verma KK, Sharma VK. Intralesional immunotherapy with killed Mycobacterium w vaccine for the treatment of ano-genital warts: An open label pilot study. J Eur Acad Dermatol Venereol 2008;22:1089-93.  Back to cited text no. 10
    
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Aktaş H, Ergin C, Demir B, Ekiz Ö. Intralesional Vitamin D injection may be an effective treatment option for warts. J Cutan Med Surg 2016;20:118-22.  Back to cited text no. 11
    
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Ibrahim NA, Abdel Fadeel DA, Sadek A, Fadel M, Tawfik A. Intralesional vitamin D3 versus new topical photodynamic therapy in recalcitrant palmoplanter warts Randomized comparative controlled study. Photodiagnosis Photodyn Ther 2020;32:101979.  Back to cited text no. 12
    
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Salman S, Ahmed MS, Ibrahim AM, Mattar OM, El-Shirbiny H, Sarsik S, et al. Intralesional immunotherapy for the treatment of warts: A network meta-analysis. J Am Acad Dermatol 2019;80:922-30.e4.  Back to cited text no. 13
    
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Nofal A, Nofal E. Intralesional immunotherapy of common warts: Successful treatment with mumps, measles and rubella vaccine. J Eur Acad Dermatol Venereol 2010;24:1166-70.  Back to cited text no. 14
    
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Raju J, Ashwini VS, Nanjundaswamy BL, Raghavendra KR. Intralesional measles, mumps amd rubella vaccine – An effective therapeutic tool in the treatment of wart. J of Evidence Based Med Hlthcare 2015;50:8548-51.  Back to cited text no. 15
    
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Kavya M, Shashikumar BM, Harish MR, Shweta BP. Safety and efficacy of intralesional Vitamin D3 in cutaneous warts: An open uncontrolled trial. J Cutan Aesthet Surg 2017;10:90-4.  Back to cited text no. 16
[PUBMED]  [Full text]  


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