10.5826/dpc.1202a68
Introduction: Lately, immunotherapy has evolved as a safe and reliable management option for treatment of warts. Various immunogens among others in use include vaccines and antigens like purified Protein Derivative of Tuberculin (PPD) and mycobacterium w (Mw) or mycobacterium indicum prani vaccines.Objectives: The study was aimed to assess the effectiveness and safety profile of intralesional Mw vaccine against intralesional PPD for the management of multiple warts with assessment of the improvement in quality of life (QoL) using the Dermatology Life Quality Index questionnaire.Methods: Patients aged above 12 years with ≥2 warts were recruited for the study. These individuals were randomized into groups A and B, namely Mw vaccine (group A) and PPD Tuberculin (group B). At each visit, 0.1-0.2 ml of active antigen was infiltrated intralesionally into the largest/mother wart. The injections were repeated after every 4 weeks, for the next 12 weeks. QoL improvement was measured.Results: This intention to treat analysis was completed by 102 patients, of which 55 were in group A and 47 in group B. The rate of complete clearance was comparable in group A (76.3%) with the one in group B (65.9%, P = 0.064). Prior to treatment initiation, the most severely impacted domain of life by warts was ‘symptoms and feelings’. There was a statistically significant improvement in QoL at the end of the treatment ( P &lt;0.01).Conclusions: Mw vaccine holds leverage over PPD with a marginally higher rate of clearance and less adverse events for managing warts.
text/xml
2160-9381
1839
en
Rajesh Dutt Metha
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
warts
An intention-to-treat-analysis of the efficacy of immunotherapy using Mycobacterium w vaccine and Purified Protein Derivative of Tuberculin for warts with assessment of improvement in quality of life
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2022-05-02
2021-06-12
2022-05-02
2022-05-24
e2022068
Dermatol Pract Concept
Introduction: Lately, immunotherapy has evolved as a safe and reliable management option for treatment of warts. Various immunogens among others in use include vaccines and antigens like purified Protein Derivative of Tuberculin (PPD) and mycobacterium w (Mw) or mycobacterium indicum prani vaccines.Objectives: The study was aimed to assess the effectiveness and safety profile of intralesional Mw vaccine against intralesional PPD for the management of multiple warts with assessment of the improvement in quality of life (QoL) using the Dermatology Life Quality Index questionnaire.Methods: Patients aged above 12 years with ≥2 warts were recruited for the study. These individuals were randomized into groups A and B, namely Mw vaccine (group A) and PPD Tuberculin (group B). At each visit, 0.1-0.2 ml of active antigen was infiltrated intralesionally into the largest/mother wart. The injections were repeated after every 4 weeks, for the next 12 weeks. QoL improvement was measured.Results: This intention to treat analysis was completed by 102 patients, of which 55 were in group A and 47 in group B. The rate of complete clearance was comparable in group A (76.3%) with the one in group B (65.9%, P = 0.064). Prior to treatment initiation, the most severely impacted domain of life by warts was ‘symptoms and feelings’. There was a statistically significant improvement in QoL at the end of the treatment ( P &lt;0.01).Conclusions: Mw vaccine holds leverage over PPD with a marginally higher rate of clearance and less adverse events for managing warts.
Rajesh Dutt Metha
2022/05/02
10.5826/dpc.1202a68
e2022068
Department of Dermatology, Venereology and Leprosy, Sardar Patel Medical College, Bikaner, Rajasthan
2160-9381
warts
en
e2022068
Wananukul S, Chatproedprai S, Kittiratsacha P. Intralesional immunotherapy using tuberculin PPD in the treatment of palmoplantar and periungual warts. Asian Biomed. 2009;3:739-743. DOI: 10.5372/ABM.V3I6.279.
An intention-to-treat-analysis of the efficacy of immunotherapy using Mycobacterium w vaccine and Purified Protein Derivative of Tuberculin for warts with assessment of improvement in quality of life
https://dpcj.org/index.php/dpc/article/download/1839/1552
          An Intention-to-Treat-Analysis of the
   Efficacy of Immunotherapy Using Mycobacterium
      W Vaccine and Purified Protein Derivative of
         Tuberculin for Warts With Assessment
           of Improvement in Quality of Life
                          Alpana Mohta1, Manoj Kumar Sharma2, Pramila Kumari3,
                                Bhikam Chand Ghiya1, Rajesh Dutt Mehta1


1 Department of Dermatology, Venereology and Leprosy, Sardar Patel Medical College, Bikaner, Rajasthan, India
2 Department of Dermatology, Venereology and Leprosy, Jhalawar Medical College, Jhalawar, Rajasthan, India
3 Department of Dermatology, Venereology and Leprosy, Era’s medical college, Lucknow, Uttar Pradesh, India



Key words: warts, HPV, PPD tuberculin, immuvac vaccine, Mw vaccine, intralesional immunogens.
Citation: Mohta A, Sharma MK, Kumari P, Ghiya BC, Mehta RD. An intention-to-treat-analysis of the efficacy of immunotherapy using
mycobacterium w vaccine and purified protein derivative of tuberculin for warts with assessment of improvement in quality of life.
Dermatol Pract Concept. 2022;12(2):e2022068. DOI: https://doi.org/10.5826/dpc.1202a68
Accepted: September 29, 2021; Published: April 2022
Copyright: ©2022 Mohta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication
Corresponding author: Alpana Mohta, MBBS, MD, Senior Resident, Department of Dermatology, Venereology and Leprosy, Sardar Patel
Medical College, Bikaner, Rajasthan. Email: dralpanamohta10@gmail.com




  ABSTRACT             Introduction: Lately, immunotherapy has evolved as a safe and reliable management option for treatment
                       of warts. Various immunogens among others in use include vaccines and antigens like purified Protein
                       Derivative of Tuberculin (PPD) and mycobacterium w (Mw) or mycobacterium indicum prani vaccines.
                       Objectives: The study was aimed to assess the effectiveness and safety profile of intralesional Mw
                       vaccine against intralesional PPD for the management of multiple warts with assessment of the im-
                       provement in quality of life (QoL) using the Dermatology Life Quality Index questionnaire.
                       Methods: Patients aged above 12 years with ≥2 warts were recruited for the study. These individuals
                       were randomized into groups A and B, namely Mw vaccine (group A) and PPD Tuberculin (group B). At
                       each visit, 0.1-0.2 ml of active antigen was infiltrated intralesionally into the largest/mother wart. The
                       injections were repeated after every 4 weeks, for the next 12 weeks. QoL improvement was measured.
                       Results: This intention to treat analysis was completed by 102 patients, of which 55 were in group
                       A and 47 in group B. The rate of complete clearance was comparable in group A (76.3%) with the one
                       in group B (65.9%, P = 0.064). Prior to treatment initiation, the most severely impacted domain of life




Original Article | Dermatol Pract Concept. 2022;12(2):e2022068                                                                       1
                     by warts was ‘symptoms and feelings’. There was a statistically significant improvement in QoL at the
                     end of the treatment ( P <0.01).
                     Conclusion: Mw vaccine holds leverage over PPD with a marginally higher rate of clearance and less
                     adverse events for managing warts.



Introduction                                                      by asking them to choose a number from a simple random
                                                                  number table. However, since this study was done in an
Warts or verruca are benign tumors cause by the infection of      open-label setting, both the patients and the investigators
keratinocytes with the Human Papilloma Virus (HPV) [1].           were aware of the treatment being received. The study was
The prevalence rates of warts range from 3%-20%, with a           approved by our institutional ethical board (ethical approval
gradual increase in incidence rate from childhood to adoles-      number: F/SPMC/IERB/2158). Additionally, all the study
cence, followed by a rapid decline after the late 20s [2]. Even   participants gave their written informed consent to be re-
though in most of the cases these warts resolve on their own,     cruited in the study.
the patients often resort to various treatment options due to
their unsightly appearance, symptomatology and potentially        Inclusion criteria
contagious nature.                                                Individuals aged 12 years or above with 2 or more warts
    Traditionally, used destructive therapies for warts in-       were included in our study. Only patients with either previ-
clude surgical excision, cryotherapy, radiofrequency abla-        ously untreated warts, or those who had not received treat-
tion, electrical and chemical cauterization, etc. Bleomycin,      ment in the last 1 month were included.
salicylic acid, trichloroacetic acid, podophyllin, 5-fluoroura-
cil, imiquimod, are a few of the conventional pharmacolog-        Exclusion criteria
ical agents in use. Over the last few decades, even lasers and
                                                                  Immunocompromised and systemically ill patients, pregnant
photodynamic therapy have been employed to treat warts.
                                                                  or lactating women, and subjects with a history of any al-
Nevertheless, the usefulness of all these therapies is limited
                                                                  lergy or hypersensitivity reaction to any of the components
due to their absence of antiviral properties, high recurrence
                                                                  of BCG, PPD or Mw in the past were excluded from the trial.
rates, and the need to treat ever wart individually [2].
    Various intralesional antigens that have been utilized for
                                                                  Treatment protocol
warts, namely, Bacillus Calmette and Guerin (BCG) vaccine,
                                                                  The study participants were administered either of the 2
measles, mumps, and rubella (MMR) vaccine, Mycobacte-
                                                                  regimens depending upon their group. Additionally, the pa-
rium w (Mw) vaccine, skin test antigens like purified protein
                                                                  tients were advised against taking other alternative treat-
derivative of tuberculin (PPD), mumps, trichophyton, and
                                                                  ments during the study period until the end of the last
Candida with good success rates [3,4].
                                                                  follow-up visit.
                                                                     Individuals in group A were given with 0.1-0.2 ml of
Objectives                                                        intralesional Mw vaccine (IMMUVAC 0.6 ml - Inj., Cadila
                                                                  Pharmaceuticals Limited) using a 26 G needle into the base
This prospective, randomized open label study was aimed to        of the largest wart. Correspondingly, in group B, 0.1-0.2 mL
assess the effectiveness and safety profile of intralesional Mw   PPD Tuberculin (TUBERSOL® S1ml inj. Sanofi, containing
vaccine against intralesional PPD for the management of mul-      Five (5) tuberculin units per test dose of 0.1 mL) was injected
tiple warts and improvement in patients’ quality of life (QoL).   into the largest mother wart. The therapy was repeated ev-
                                                                  ery four weeks either until there was complete clearance in

Methods                                                           all the warts, or until 12 weeks (total 4 sessions), whichever
                                                                  happened first.
Study Design and Randomization
This was a prospective, parallel-group study conducted at         Follow-up and Treatment Response
the dermatology out-patient department of our tertiary care       After the last session (at week 12), monthly follow-up was
hospital. Patients with 2 or more extragenital warts were         done for the next 3 months. The treatment response was la-
evaluated and recruited for our study into two arms, namely       beled as follows: complete clearance (CC) with 100% clear-
group A (Mw vaccine) and group B (PPD tuberculin). De-            ance of all the warty tissue and reappearance of normal skin
mographic data and baseline parameters including number           markings, moderate clearance (MC) with 99%-25% re-
and site of warts were noted. The patients were randomized        duction in size or number of warts, and no clearance (NC),



2                                                                     Original Article | Dermatol Pract Concept. 2022;12(2):e2022068
with < 25% reduction in size/number. Immediate or delayed                a little - 1; a lot - 2; very much - 3. Total score interpreta-
adverse events were also noted at each visit. An additionally            tion was done as follows: 0-1 = no effect at all on patient’s
supplementary assessment to note any signs of recurrence and             life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very
delayed response was also done at 6 months after the last dose.          large effect, and 21-30 = exceedingly large effect. The DLQI
    The primary endpoint was CC of all warts at week 8 and               questionnaire was supplied to all the participants at week 0
week 12, which also included the warts that might have devel-            and week 24 and the improvement in QOL was noted by
oped appeared or developed recurrence during the treatment               comparing the scores.
period. Secondary endpoints included CC at week 24, recur-                   These questions (Q) were further divided into 6 domains
rence of warts at week 12 in the patients who had clearance              in accordance with the framework of Salah, ie symptoms
at week 4, and recurrence of warts at week 24 in the patients            and feelings accompanying the disease (Q1-Q2), impairment
who had clearance at week 12, and the side effect profile.               of daily activities (Q3-Q4), effects on leisure time (Q5-Q6),
    The analysis of both primary and secondary endpoints                 effect on work/school (Q7), interpersonal relations (Q8-Q9),
was done according to an intention-to-treat (ITT) model.                 and impact of treatment on QOL (Q10) [5].
Randomized patients who had received at least one treatment
session and returned back for at last 1 follow-up visit were             Statistical Tools
included. In cases any therapy-session/follow-up visit was               Statistical analysis was done using the Statistical Package for
missed, the analysis took the status of the last-observation-car-        the Social Sciences version 20. Paired and unpaired t-tests,
ried-forward (LOCF) in order to estimate any subsequent ob-              Chi-square test and Z scores were calculate wherever nec-
servation points. This ITT model presumed that if a patient              essary. Categorical and continuous variables were presented
with warts CC was lost to follow-up, then he did not develop             as absolute numbers, percentages, mean, and standard devi-
any new warts or experience any recurrence. Similarly, those             ation (SD). A p value of ≤0.05 was considered to be statisti-
patients who had partial or no clearance at the last visit, did          cally significant.
not experience clearance in warts once lost to follow-up.

                                                                         Results
Dermatology Life Quality Index (DLQI)
questionnaire                                                            This intention to treat analysis included 120 subjects ran-
Along with the clinical response, the treatment outcome was              domized into 2 groups with 60 patients per group. The demo-
also measured by comparing the change in the score of the hindi          graphic and clinical data of both groups were comparable.
validated version of the DLQI questionnaire at first session             While 45 patients were treatment naïve, 75 had received 1 or
(week 0), and at the end of the last follow-up visit (week 24).          more treatments in the past with treatment failure or relapse.
The questionnaire had 10 questions, each having a maximum                The mean duration of warts in both groups was comparable
score of 3 (total score 30). Every question had the following            (Table 1). The study was completed by 102 patients (55 in
possible scores: not at all or not relevant or unanswered- 0;            group A and 47 in group B) (Figure 1). The overall number


                                     Table 1. Baseline demographic data of patients
                                 Group A (Mw vaccine)                 Group B (PPD tuberculin)
                                        N=55                                   N=47                                  P value
 Age Distribution in Years
 Range                      12-55 yrs                            12-60 yrs                                 0.09
 Mean ± SD                  23.5 ± 8.4 yrs                       26.9 ± 11.7 yrs
 Gender Distribution
 Male                       38                                   33                                        0.91
 Female                     17                                   14
 Male:female                2.2:1                                2.3:1
 DURATION OF WARTS (IN MONTHS)
 Mean ± SD                  7.12 ± 4.01                          8.71 ± 5.13                               0.08
 Mean Number of Warts ± Sd
                            12.01 ± 6.19                         10.77 ± 7.32                              0.35
 Inference: Both the groups had comparable for baseline demographics
PPD = Purified Protein Derivative of Tuberculin ; Mw = Mycobacterium w vaccine; SD = standard deviation



Original Article | Dermatol Pract Concept. 2022;12(2):e2022068                                                                        3
of patients with CC in all warts (according to ITT) was 42                              clearance (MC and NC) had 17.26 warts. There was also a
and 31, in group A and B respectively during the final assess-                          significant difference in the mean duration of warts between
ment done on at week 24 (figure 3,4,5,6) (Table 2). Between                             patients who responded and those who didn’t respond to the
the 2 groups, the difference in the clearance rate of all warts                         therapy. The combined mean duration of warts in patients
            st    nd        rd                 th
at week at 1 , 2 , 3 and 4 dose was not statistically signif-                           from both groups with CC was 7.21 months, and that of
icant (Figure 2). Similarly, while comparing the response in                            patients with MC/NC was 9.47 months (P = 0.02).
only injected warts, the rate of CC was 85.45% (N = 47) and                                   Assessment of secondary outcomes revealed a compara-
76.59% ( N = 36), respectively. The mean number of injec-                               ble adverse reactions profile in both groups. The side effect
tions required for CC in group A were 2.38, while in group                              event profile of our patients was excellent with transient in-
B this value was 2.56. None of the patients experienced re-                             jection site pain and erythema being the most common ad-
currence during the ensuing follow-up period.                                           verse events. Other rare side effects included transient fever,
    During the analysis of the impact of other factors on treat-                        injection site nodule formation and transient urticaria.
ment response, we discovered that the mean number of warts                                    While analyzing the DLQI questionnaire, the most se-
had a significant influence on the rate of clearance (P <0.01).                         verely affected domains were symptoms and feelings accom-
Patients with CC from both groups combined had 9.13 mean                                panying the disease (Q1 and Q2), and the inconvenience
number of warts. Meanwhile, those with moderate to no                                   experienced by patients while seeking treatment (Q10). The




                                                                      ASSESSMENT FOR ELIGIBILITY
                                                                              (N=120)


                                                                       TREATMENT NAΪVE (N=45)
                                                                      PREVIOUSLY TREATED (N=75)




                       EXCLUDED FROM                                                     ANALYSED (N=102)
                                                                         GROUP A                                     GROUP B
                       ANALYSIS (N=18)
                                                                   MW VACCINE (N=55)                          PPD TUBERCULIN (N=47)

                     1. REFUSED TO
                   PARTICIPATE (N=11)
                                                                ATTRITION AFTER 2ND DOSE (N=7)              ATTRITION AFTER 2ND DOSE (N=8)


                   2. DROP OUTS AFTER
                       1ST DOSE (N=7)                           ATTRITION AFTER 3RD DOSE (N=9)                 ATTRITION AFTER 3RD (N=6)



                 Figure 1. Patient selection, follow-up and attrition in an intention-to-treat analysis. PPD = Purified Protein
                 Derivative of Tuberculin ; Mw = Mycobacterium w vaccine




                                                               CUMULATIVE RATE OF COMPLETE CLEARANCE
                  45
                                                                                                                                 42
                  40

                  35                                                                                         36
                                                    GROUP A (MW VACCINE)
                        NUMBER OF PATIENTS




                  30                                                                                                             31
                                                    GROUP B (PPD TUBERCULIN)
                  25
                                                                                         24
                  20
                                                                                                              18
                  15

                  10                                                                     11
                                                                     8
                   5
                                                0                    3
                   0                               0
                                             BASELINE        AFTER 1ST DOSE    AFTER 2ND DOSE       AFTER 3RD DOSE      AFTER 4TH DOSE

                 Figure 2. Cumulative response rate between the 2 groups.



4                                                                                             Original Article | Dermatol Pract Concept. 2022;12(2):e2022068
                Figure 3. (A) Multiple interdigital warts at baseline. (B) Complete resolution after 4 doses of Mw vaccine.




Figure 4. (A) Multiple myrmecia wart at baseline. (B) Complete resolution after 4 doses of Mw vaccine.




                  Figure 5. (A) Multiple interdigital warts at baseline (B) Complete resolution after 2 doses of PPD tuberculin.



Original Article | Dermatol Pract Concept. 2022;12(2):e2022068                                                                     5
                Figure 6. (A) Plantar warts at baseline. (B) Complete resolution after 4 doses of PPD tuberculin


                          Table 2. Rate of clinical response in an intention to treat analysis
                                                                       CLEARANCE RATE IN WARTS
                                          GROUP A (Mw) N=55                 GROUP B (PPD) N=47               X2 value       P value
 COMPLETE CLEARANCE                             42 (76.3%)                        31 (65.9%)
 PARTIAL CLEARANCE                               9 (16.4%)                         5 (10.6%)                   5.47          0.064
 MINIMAL / NO CLEARANCE                           4 (7.3%)                        11 (23.4%)
PPD = Purified Protein Derivative of Tuberculin; Mw = Mycobacterium w vaccine


mean DLQI score of patients in group A and B at week 0                [10-12]. While PPD was first used by Kus et al for manage-
was 8.03 ± 1.03 SD and 7.96 ± 1.53 SD, respectively, which            ment of warts with a success rate of only 29% [13]. Other
improved to 2.14 ± 0.77 SD and 2.71 ± 1.02 SD at week 24,             studies have demonstrated 46% to 96% clearance rate
respectively (P <0.01).                                               [14-16].
                                                                          We found minimal recurrence rate in our study during

Discussion                                                            the ensuing 6 months follow-up period. The rate of reduc-
                                                                      tion in warts was also significant and statistically compa-
The Mw vaccine is based on a cultivable non-pathogenic my-            rable between the 2 groups, however, there was a higher
cobacterium known as the mycobacterium inducus pranii,                clearance rate in patients treated with Mw vaccine. The side
which was developed at the All India Institute of Medical             effect profile was also better with Mw. Serious side effects
Sciences in the 1970s. After more than 36 years of being              like injection site granuloma, atypical mycobacterial infec-
tested rigorously, the vaccine was approved for the preven-           tion and generalized urticarial rash were seen only in PPD
tion of leprosy in 2019 [6]. PPD, on the other hand, is a             group. Also, the Mw group responded faster to the given
skin antigen used for determining an immune response to               treatment than PPD group.
tuberculosis [7]. These immunotherapeutic agents work on                  Interestingly, there was only a marginal difference in the
the principle of eliciting a Th1 mediated immune response             response rate between injected and distant warts, reinforcing
with the production of high levels of of IL-2, IL-5, and IFN-γ.       our hypothesis that both Mw vaccine and PPD tuberculin
    The role of Mw for management of warts was noted for              could be effective even if injected intramuscularly.
the first time by Gupta et al in genital warts with an impres-            One thought-provoking observation in our study was
sive success rate of 89% [8]. Later Meena et al observed its          the delayed and sustained response in warts. At least 3 pa-
favorable response in multiple cutaneous warts with 83%               tients in group A and 4 in group B who only had partial
CC rates [9]. Various authors in the past have reported the           clearance after the last injection, developed CC in all their
effectiveness of Mw in warts to range from 55% to 93%                 warts at the end of the follow up period. It can, therefore,



6                                                                          Original Article | Dermatol Pract Concept. 2022;12(2):e2022068
be concluded that in some cases both immunogens might                         Comparative Study. J Cutan Med Surg. 2016;20(2):123-129. DOI:
impart a slowly developing but long-term immunity. So,                        10.1177/1203475415616962. PMID: 26553733.
                                                                         5.   Salah E. Impact of multiple extragenital warts on quality of life
the dermatologists must counsel their patients that they
                                                                              in immune-competent Egyptian adults: a comparative cross-sec-
must wait for at least 3 months to let the immunotherapy
                                                                              tional study. Clin Cosmet Investig Dermatol. 2018;11:289-295.
work. It was our observation that there was a dramatic                        DOI: 10.2147/CCID.S165908. PMID: 29928139. PMCID:
improvement in patients’ QoL following the completion                         PMC6001836.
of treatment. Fifty-three (96.3%) subjects in group A and                6.   Talwar GP, Gupta JC, Mustafa AS, et al. Development of a
44 (93.6%) in group B were satisfied with their treatment.                    potent invigorator of immune responses endowed with both
                                                                              preventive and therapeutic properties. Biologics. 2017;11:55-
The most significant improvement was seen in the domain
                                                                              63. DOI: 10.2147/BTT.S128308. PMID: 28496303. PMCID:
of ‘symptoms and feelings’. A majority of patients also re-
                                                                              PMC5422320.
ported a noteworthy improvement in their interpersonal                   7.   Amirnia M, Khodaeiani E, Fouladi DF, Masoudnia S. Intrale-
relationships.                                                                sional immunotherapy with tuberculin purified protein derivative
    Limitations of our study included a short follow-up pe-                   (PPD) in recalcitrant wart: A randomized, placebo-controlled,
riod, small sample size, no analysis of genital warts, absence                double-blind clinical trial including an extra group of candidates
                                                                              for cryotherapy. J Dermatolog Treat. 2016;27(2):173-178. DOI:
of a control group, and no analysis of immunological pa-
                                                                              10.3109/09546634.2015.1078871. PMID: 26295565.
rameters. Another major limitation included the fact that we
                                                                         8.   Gupta S, Malhotra AK, Verma KK, Sharma VK. Intralesional
couldn’t perform any HPV tests, and therefore, we couldn’t                    immunotherapy with killed Mycobacterium w vaccine for the
evaluate the response according to HPV subtypes. The ex-                      treatment of ano-genital warts: an open label pilot study. J
trapolated results of the patients lost at follow-up in our ITT               Eur Acad Dermatol Venereol. 2008;22(9):1089-1093. DOI:
model also posed a significant limitation.                                    10.1111/j.1468-3083.2008.02719.x. PMID: 18484970.
                                                                         9. Meena JK, Malhotra AK, Mathur DK, Mathur DC. Intralesional
                                                                            immunotherapy with Mycobacterium w vaccine in patients

Conclusion                                                                  with multiple cutaneous warts: uncontrolled open study. JAMA
                                                                            Dermatol. 2013;149(2):237-239. DOI: 10.1001/jamaderma-
                                                                            tol.2013.866. PMID: 23426493.
We found PPD and Mw to be effective in the management of
                                                                        10. Chandra S, Sil A, Datta A, Pal S, Das NK. A double-blind, ran-
extragenital warts. Both immunogens have a good safety pro-
                                                                            domized controlled trial to compare the effectiveness and safety
file and lead to a significant improvement in patients’ QoL.                of purified protein derivative of tuberculin antigen with Myco-
    Informed Consent: The authors certify that they have                    bacterium w vaccine in the treatment of multiple viral warts.
obtained all appropriate patient consent forms. In the form                 Indian J Dermatol Venereol Leprol. 2019;85:355-66. DOI:
the patient(s) has/have given his/her/their consent for his/                10.4103/ijdvl.IJDVL_549_18. PMID: 31172979.
                                                                        11. Singh S, Chouhan K, Gupta S. Intralesional immunotherapy with
her/their images and other clinical information to be re-
                                                                            killed Mycobacterium indicus pranii vaccine for the treatment of
ported in the journal. The patients understand that their
                                                                            extensive cutaneous warts. Indian J Dermatol Venereol Leprol.
names and initials will not be published, and due efforts                   2014;80(6):509-514. DOI: 10.4103/0378-6323.144145. PMID:
will be made to conceal their identity, but anonymity cannot                25382507.
be guaranteed.                                                          12. Garg S, Baveja S. Intralesional immunotherapy for difficult to
                                                                            treat warts with Mycobacterium w vaccine. J Cutan Aesthet
                                                                            Surg. 2014;7(4):203-208. DOI: 10.4103/0974-2077.150740.
References                                                                  PMID: 25722598. PMCID: PMC4338463.
                                                                        13. Kus S, Ergun T, Gun D, Akin O. Intralesional tuberculin for
 1. Forman D, de Martel C, Lacey CJ, et al. Global burden of hu-            treatment of refractory warts. J Eur Acad Dermatol Venereol.
    man papillomavirus and related diseases. Vaccine. 2012;30               2005;19:515-516. DOI: 10.1111/j.1468-3083.2004.01176.x.
    Suppl 5:F12-F23. DOI: 10.1016/j.vaccine.2012.07.055. PMID:              PMID: 15987315.
    23199955.                                                           14. Nimbalkar A, Pande S, Sharma R, Borkar M. Tuberculin pu-
 2. Sterling JC, Handfield-Jones S, Hudson PM; British Association          rified protein derivative immunotherapy in the treatment of
    of Dermatologists. Guidelines for the management of cutaneous           viral warts. Indian J Drugs Dermatol. 2016;2:19-23. DOI:
    warts. Br J Dermatol. 2001;144(1):4-11. doi: 10.1046/j.1365-            10.4103/2455-3972.184103
    2133.2001.04066.x. PMID: 11167676.                                  15. Saoji V, Lade NR, Gadegone R, Bhat A. Immunotherapy using
 3. Salman S, Ahmed MS, Ibrahim AM, et al. Intralesional immu-              purified protein derivative in the treatment of warts: An open un-
    notherapy for the treatment of warts: A network meta-analysis.          controlled trial. Indian J Dermatol Venereol Leprol. 2016;82:42-
    J Am Acad Dermatol. 2019;80 (4):922-930.e4. doi: 10.1016/j.             46. DOI: 10.4103/0378-6323.171650. PMID: 26728809.
    jaad.2018.07.003. PMID: 30003983.                                   16. Wananukul S, Chatproedprai S, Kittiratsacha P. Intralesional im-
 4. Dhakar AK, Dogra S, Vinay K, Sarangal R, Kanwar AJ, Singh MP. In-       munotherapy using tuberculin PPD in the treatment of palmo-
    tralesional Mycobacterium w Vaccine Versus Cryotherapy in Treat-        plantar and periungual warts. Asian Biomed. 2009;3:739–743.
    ment of Refractory Extragenital Warts: A Randomized, Open-Label,        DOI: 10.5372/ABM.V3I6.279.




Original Article | Dermatol Pract Concept. 2022;12(2):e2022068                                                                                7
