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ORIGINAL ARTICLE
Year : 2019  |  Volume : 20  |  Issue : 3  |  Page : 231-235

Evaluation of efficacy and safety of intralesional Measles-Mumps-Rubella virus vaccine for the treatment of common warts in children and adolescents


Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra (Tanda), Himachal Pradesh, India

Date of Web Publication28-Jun-2019

Correspondence Address:
Dr. Vikram K Mahajan
Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra (Tanda), - 176 001, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_106_18

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  Abstract 


Background: No single treatment for warts has proven 100% efficacy and most therapeutic modalities remain unsatisfactory. Immunotherapy with Measles-Mumps-Rubella (MMR) vaccine remains underevaluated, especially in children. Objective: To evaluate the efficacy and safety of intralesional MMR vaccine in the treatment of common warts in children. Materials and Methods: Fifty-five (36 boys and 19 girls) children aged 5–18 (mean ± standard deviation 12.8 ± 3.88) years with common warts received 0.25 ml of MMR vaccine injected intralesionally in the largest wart. The dose was repeated at 2-week interval until complete clearance or for a maximum of 5 doses. Thereafter, they were followed up once a month for 24-week study period. The response was evaluated as complete clearance (complete disappearance of the wart(s) including distant ones and appearance of normal skin), partial clearance (≤99% reduction in size and number including distant ones and few residual warts still visible), good response (some reduction in size only including that of distant ones but no decrease in number of warts), or poor response (no change in size and number). Results: Only 46 patients completed the study and 27 (58.7%) of them had complete clearance of warts, 9 (19.6%) showed partial clearance and 10 (21.3%) patients showed no response. In 15 of 27 patients complete clearance was achieved after 5 doses, 7 had complete clearance after 4 doses and 2 patients each showed complete clearance after 2 and 3 doses, respectively. Conclusion: Intralesional MMR vaccine immunotherapy appears promising, effective, and safe treatment for common warts in children with the advantage of single-lesion infiltration, and resolution without scarring or pigmentary changes commonly seen with destructive therapies. However, better designed larger controlled studies are warranted.

Keywords: Humanpapilloma virus, immunotherapy, verrucae, warts


How to cite this article:
Mahajan VK, Chauhan PS, Sharma A, Mehta KS, Rawat R, Sharma V. Evaluation of efficacy and safety of intralesional Measles-Mumps-Rubella virus vaccine for the treatment of common warts in children and adolescents. Indian J Paediatr Dermatol 2019;20:231-5

How to cite this URL:
Mahajan VK, Chauhan PS, Sharma A, Mehta KS, Rawat R, Sharma V. Evaluation of efficacy and safety of intralesional Measles-Mumps-Rubella virus vaccine for the treatment of common warts in children and adolescents. Indian J Paediatr Dermatol [serial online] 2019 [cited 2019 Nov 13];20:231-5. Available from: http://www.ijpd.in/text.asp?2019/20/3/231/261861




  Introduction Top


Common warts (Verruca vulgaris), caused by humanpapilloma virus (HPV) infection, are common and frequently occur in children and young adults. Although spontaneous regression may occur, warts that are resistant to treatment or present over palms, soles, or dorsal hands and feet for being painful or cosmetically disfiguring are most distressing for the affected person requiring active intervention. Conventionally, chemical cauterization with trichloroacetic acid, salicylic acid, podophyllin, or their destruction by surgical excision, electrocautery, laser ablation, cryosurgery, and photodynamic therapy has been used for their treatment. These are often painful, cause disfiguring scars, and remain unsuitable for children. Moreover, outcome of most therapies remain unpredictable. Thus, a treatment that is effective and safe especially in children remains highly desirable. Intralesional immunotherapy using intralesional interferons, viral/bacterial antigens, vaccines, or proinflammatory cytokines employs the ability of the immune system to recognize viral, bacterial or fungal antigens that induces a delayed-type hypersensitivity reaction not only to the antigen but also against the HPV, thereby increasing the ability of the immune system to recognize and clear HPV.[1] With increasing understanding of role played by cell-mediated immunity (CMI) in pathogenesis or persistence of HPV infection, treatment of warts with immunotherapeutic modalities (intralesional interferons, viral antigens, vaccines, proinflammatory cytokines) or immune boosters (oral levamisole, cimetidine, zinc sulfate or topical imiquimod, contact sensitizers) has been attempted with variable success.[2],[3],[4],[5],[6],[7],[8],[9] Autogenous vaccine, candida antigen, mumps antigen, trichophytin skin test antigen, tuberculin/purified protein derivative (PPD), bacillus Calmette–Guérin vaccine, Measles-Mumps-Rubella virus (MMR) vaccine, killed Mycobacterium w (Mycobacterium indicus pranii) vaccine have been used invariably to induce CMI for treating common warts.[8],[9],[10],[11] However, they mostly remain unevaluated in children. We studied the efficacy and safety of intralesional MMR vaccine in the treatment of common warts in children and adolescents.


  Materials and Methods Top


Fifty-five children/adolescents with clinically diagnosed common warts were enrolled after informed consent from parents/guardian. Demographic and clinical details for number, sites involved and size of warts were recorded and photographic records were made at baseline (before treatment) and subsequently at each follow-up visit. They were advised not to use any other wart treatment concurrently. Patients with apparent infection or immunosuppression, asthma, allergic disorders, meningitis or convulsions, or who had received treatment for warts in the preceding month were excluded.

The study was approved by Institutional Scientific Protocol Review Committee and Institutional Ethics Committee (Rgn no ECR/490/Inst/HP/ECR/490/Inst/HP/2013/RR-16) and registered with the Clinical Trials Registry of India (reference No. REF/2017/01/013135). Informed consent was obtained from all patients or their parents/guardians for being enrolled in the study and publication of data with the understanding that names and initials will not be disclosed and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2013.

Treatment protocol and outcome evaluation

Single-dose vial of freeze-dried MMR vaccine (Tresivac, marketed by Serum Institute of India Ltd, Mumbai, India) was reconstituted with 0.5 ml of provided diluent (distilled water for injection) as per manufacturer's instructions just before intralesional use. The reconstituted MMR vaccine 0.25 ml was injected in one largest wart using a 30G insulin syringe (one dose) and repeated at every 2-week interval until complete clearance or for a maximum of five doses. Any unused portion of reconstituted vaccine was discarded.

All treated children were evaluated by an independent blinded observer and by comparing clinical photographic records at each treatment session for decrease in size and number of warts and any immediate side effects, if any. Resolution of distant untreated warts was also assessed. The clinical improvement was rated by the patient/guardian and physician global assessment using Visual Analog Scale (VAS) score at each visit taking baseline clinical photograph as controls. The response was evaluated as complete clearance (VAS score 100, complete disappearance of the wart(s) including distant ones and appearance of normal skin), partial clearance (VAS score 75%–99%, ≤99% reduction in size and number including distant ones and few residual warts still visible), good response (VAS score 50%–75%), some reduction in size only including that of distant ones but no decrease in number of warts) or poor response (VAS score <50, no change in size and number) [Table 1]. After completion of treatment, the patients were followed up every month for 6 months for continuous clinical improvement, recurrences, or any late adverse effects and patient satisfaction level on Likert scale at the end of the study period [Table 1].
Table 1: Evaluation of clinical improvement and patient satisfaction level

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  Results and Observations Top


[Table 2] lists the baseline characteristics of the study participants. There were 36 boys and 19 girls (M: F = 1.8:1) aged 5–18 (mean ± standard deviation [SD] = 12.8 ± 3.88) years. The majority, 40 (77.7%) children were aged between 11 and 18 years. The duration of warts was 1 month to 72 (mean ± SD = 17.2 ± 16.66) months and the number varied from a solitary to >10 warts localized mainly over dorsal hands and feet, and soles (in 32 patients), periungual skin (in 3 patients), and multiple sites including hands and face in one child. No child had received any treatment for warts previously. Nine children did not follow-up at various stages of study and were excluded from final analysis. [Table 3] depicts therapeutic outcome; overall, in 46 children who completed the study warts showed complete clearance in 27 (58.7%) children and partial clearance occurred in 9 (19.6%) children during 24 weeks of study period. Complete clearance of warts occurred after five doses in 15 (32.6%) children and after 4 doses in 7 (15.2%) children. In 2 (4.3%) children each the complete clearance of warts occurred after 2 and 3 doses, respectively [Figure 1], [Figure 2], [Figure 3]. Only one (2.2%) child had complete clearance of warts after first dose itself and in 2 (4.4%) children warts completely cleared 8 weeks after 5th dose. No response was observed in 10 (21.7%) children, did not complete follow-up, and despite repeated counseling they/parents remained unsatisfied. All patients experienced mild-to-moderate injection site pain at the time of MMR vaccine injection that did not warrant discontinuation of treatment. There were no systemic adverse effects, scarring, or residual pigmentation. MMR vaccine injection for periungual warts did not adversely affect nail growth or caused onycholysis or nail dystrophy. No recurrence of warts was noted among cured at the end of the study period. All cured patients or their parents/guardians were very much satisfied (score of 5 on Likert scale) from treatment.
Table 2: Baseline characteristics of patients

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Table 3: Treatment outcome and follow-up for therapeutic outcome, recurrences and long-term adverse effects

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Figure 1: Common warts over dorsal hand before and after three treatment doses: The largest wart (encircled) was treated with intralesional measles-mumps-rubella virus vaccine. Complete clearance of treated and distant warts occurred after four doses

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Figure 2: Common warts over thumb and periungual skin before and after five treatment doses: The largest wart (encircled) was treated with intralesional measles-mumps-rubella virus vaccine. Complete clearance of treated and distant warts occurred after five doses

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Figure 3: Plantar warts before and after five treatment doses: The largest wart (encircled) was treated with intralesional measles-mumps-rubella virus vaccine. Clearance continued after completion of five doses and they resolved completely at end of study period

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  Discussion Top


The exact mechanism of effectiveness of intralesional injection of MMR vaccine or antigen in warts remains hypothetical. It is possible that it accelerates the clearance of virus and viral infected cells by stimulation of CMI and humoral immunity that is suggested to play a significant role in the pathogenesis and persistence of warts or perhaps the nonspecific inflammatory response to the antigens is the major mechanism of immunotherapy.[6],[7],[12],[13] The stimulated immune response subsequently clears all lesions on the body rather than only the locally treated lesions. With this understanding, the intralesional injection of MMR vaccine and antigens has been evaluated as a treatment option for common warts with cure in 81.4% patients as compared to 27.5% in placebo group by Nofal et al.[14] A significantly higher rate of complete response was found in target and distant warts with PPD (60% each) and MMR (80%, 40%, respectively) compared with controls (0%), with no significant difference between both treatments.[15] Warts decreased more than half in size in 51% of 136 patients and 26.5% had complete resolution in another study by Na et al.[13] Complete clearance of warts in our 27 (58.7%) and partial clearance in 9 (19.6%) children including those over dorsal hands and feet, soles or periungual skin occurred in this study with 1–5 injections of MMR vaccine in 0.25 ml/dose. Similarly, Nofal et al.[16] in a recent study also reported complete clearance in 63% but with 5 doses of 0.5 ml injected once in 2 weeks in to each wart up to five doses. On the other hand, Gamil et al.[17] found it effective in multiple plantar warts and reported complete resolution of 87% plantar warts in forty patients within three intralesional injections of 0.1 ml given once in 3 weeks. From clearance of distant warts even at less number of doses and continued clearance of warts in our two children even after the last dose, it seems that MMR vaccine could effectively stimulate CMI against common warts in some of the children with no recurrences in this study. Except for injection site pain and swelling lasting for a day, none of the studied subjects developed itching, erythema, or flu-like symptoms, the commonly reported adverse effects of MMR vaccine.[13],[16] However, unsatisfactory response in 21.7% children is perhaps from suboptimal dose of MMR vaccine used. On the other hand, injection site pain and poor therapeutic response in the short term were perhaps responsible for dissatisfaction and possible high drop out in this study.

Limitations

Small number of patients, lack of placebo or other therapeutic group for comparison, and short follow-up are some of the limitations of this study.


  Conclusion Top


Intralesional MMR vaccine immunotherapy appears effective, and safe treatment for common warts in children/adolescents with the advantage of single-lesion infiltration and resolution of even untreated distant warts, low recurrence, and without scarring or pigmentary changes commonly seen with destructive warts therapies. However, better designed, large studies with matched age and number of warts controls are highly desirable for making definite conclusions, especially in view of spontaneous regression of warts and for finding minimum effective dose, dosing schedule, and duration of the therapy that makes the treatment effective.

Declaration of patient consent

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

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Lichon V, Khachemoune A. Plantar warts: A focus on treatment modalities. Dermatol Nurs 2007;19:372-5.  Back to cited text no. 4
    
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Maronn M, Salm C, Lyon V, Galbraith S. One-year experience with Candida antigen immunotherapy for warts and molluscum. Pediatr Dermatol 2008;25:189-92.  Back to cited text no. 8
    
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Singh S, Chouhan K, Gupta S. Intralesional immunotherapy with killed Mycobacterium indicus pranii vaccine for the treatment of extensive cutaneous warts. Indian J Dermatol Venereol Leprol 2014;80:509-14.  Back to cited text no. 10
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Chauhan PS, Mahajan VK, Mehta KS, Rawat R, Sharma V. The efficacy and safety of intralesional immunotherapy with MMR (Measles, Mumps, Rubella virus) vaccine for the treatment of common warts in adults: Results of a pilot study. Indian Dermatol Online J 2019;10:19-26.  Back to cited text no. 11
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Zamanian A, Mobasher P, Jazi GA. Efficacy of intralesional injection of mumps-measles-rubella vaccine in patients with wart. Adv Biomed Res 2014;3:107.  Back to cited text no. 12
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Na CH, Choi H, Song SH, Kim MS, Shin BS. Two-year experience of using the measles, mumps and rubella vaccine as intralesional immunotherapy for warts. Clin Exp Dermatol 2014;39:583-9.  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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Shaheen MA, Salem SA, Fouad DA, El-Fatah AA. Intralesional tuberculin (PPD) versus measles, mumps, rubella (MMR) vaccine in treatment of multiple warts: A comparative clinical and immunological study. Dermatol Ther 2015;28:194-200.  Back to cited text no. 15
    
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Nofal A, Nofal E, Yosef A, Nofal H. Treatment of recalcitrant warts with intralesional measles, mumps, and rubella vaccine: A promising approach. Int J Dermatol 2015;54:667-71.  Back to cited text no. 16
    
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Gamil H, Elgharib I, Nofal A, Abd-Elaziz T. Intralesional immunotherapy of plantar warts: Report of a new antigen combination. J Am Acad Dermatol 2010;63:40-3.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
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