Journal of Dermatological Treatment

ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: https://www.tandfonline.com/loi/ijdt20

A comparative study of topical cantharidin and

intralesional PPD to treat molluscum contagiosum

Fathia M. Khattab & Mohamed M. Nasr

To cite this article: Fathia M. Khattab & Mohamed M. Nasr (2019): A comparative study of topical
cantharidin and intralesional PPD to treat molluscum contagiosum, Journal of Dermatological
Treatment, DOI: 10.1080/09546634.2019.1657226

To link to this article: https://doi.org/10.1080/09546634.2019.1657226

Accepted author version posted online: 16

Aug 2019.
Published online: 29 Aug 2019.

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JOURNAL OF DERMATOLOGICAL TREATMENT
https://doi.org/10.1080/09546634.2019.1657226

ARTICLE

A comparative study of topical cantharidin and intralesional PPD to treat

molluscum contagiosum
Fathia M. Khattab and Mohamed M. Nasr
Dermatology, Venereology and Andrology and Departments, Faculty of Medicine, Zagazig University, Zagazig, Egypt

ABSTRACT ARTICLE HISTORY

Background: The immune system plays an important part in the clearance of molluscum contagiosum Received 23 June 2019
(MC) and, therefore, there has lately been a trend in using immunotherapy in MC therapy. Tuberculin- Accepted 13 August 2019
purified protein derivatives (PPDs) and topical cantharidin have not earlier been compared with their Published online 26 August
effectiveness in therapy 2019
Aim: The aim of this research was to determine the effectiveness and security of intralesional immuno- KEYWORDS
therapy in the therapy of MC with tuberculin PPD versus topical cantharidin Immunotherapy; intrale-
Patients and methods: Twenty patients with various MC lesions received topical cantharidin as control sional; tuberculin-purified
(group A) and 20 MC patients received intralesional tuberculin PPD following prior intradermal immunity protein derivative;
tests (group B). molluscum contagiosum;
Results: Complete clearance of lesions was detected in 90.0% of patients in the cantharidin group; the topical cantharidin
partial response was detected in10.0% of the patients. However, in the PPD group, 85% of the patients
showed a complete response and 15% showed a partial response, with no significant difference in the
clinical response between the two groups. Mild side effects were detected.
Conclusion: The results suggest that intralesional PPD and topical cantharidin 0.7% are effective and safe
treatment modalities, but benefits of intralesional PPD is being a simple, effective and safe treatment
with tolerable pain and can be an alternative treatment for multiple resistant types.

Introduction provides extensive control of viral proliferation and eventually

Molluscum contagiosum is a skin or sometimes mucous mem-
brane viral infection. It is triggered by a molluscum contagiosum
virus (MCV) called a DNA poxvirus (1). There is no reservoir of ani-
mals in the virus (infecting only humans). There are four types of
MCV, MCV-1 to -4; the most common is MCV-1, and MCV-2 is gen-
erally seen in adults (2).
MC’s current methods of therapy include curettage, cryosur-
gery, laser therapy, and multiple topical agents such as tretinoin,
imiquimod, and cantharidin. However, these techniques are often
traumatic and hard to respond to patients with multiple
lesions (3).
In disease resolution, the cell-mediated immune system plays a
significant role. Although most lesions spontaneously disappear
within 6 to 18 months, therapy in most patients is needed
because of the psychological impact of extensive lesions (4).
Cantharidine, a topical vesicant extracted from blister beetle
(Lytta vesicatoria), is a frequently used therapy for MC (5,6). Its
action mechanism includes the activation or release of epidermal
serine proteases leading to tonofilament detachment, which
causes intraepidermal blistering and inflammation, promoting the
shedding of infected keratinocyte and viral clearing. MC (7,8).
Since cell-mediated immunity plays a part in the pathogenesis
of MC, intralesional immunotherapy with measles, mumps, and
rubella or Candida vaccine has lately been suggested (9). The
immune system mounts an immune response not only to the pro-
tein contents of the vaccine but also to the MC virus, which
destroys all body lesions (10).
Intralesional PPD immunotherapy has been discovered to be a
simple and efficient method of therapy for the therapy of viral
warts; a skin immune response can cause warts enhancement and
or clearance, often with anatomically separate lesions other than
those injected (11). The aim of this study was to evaluate the effi-
cacy and safety of intralesional PPD in the treatment of MC as
compared to that of topical cantharidin.
Subject and methods
This randomized controlled clinical trial, the untreated distant MC
of the same patients a control, included 40 patients with MC
chosen from the University of Zagazig’s Department of
Dermatology and Venereology Outpatient Clinic Hospitals during
the period from June 2018 and June 2019 and endorsed by the
Faculty of Medicine. They were 19 males, with 21 women ranging
from 3 to 40 years of age. Written informed consent was obtained
from each patient who meets the inclusion criteria.
Patients clinically diagnosed with MC, aged between 3 and 40
with a positive tuberculin test or a previous history of BCG vaccin-
ation are inclusion criteria. Pregnant and lactating women,
patients with keloidal skin tendency, immunosuppressed people,
patients with fever or signs of any systemic or local inflammation
or infection, patients with any other therapy in the last 3 months
prior to enrollment, previous history of asthma, allergic skin

CONTACT Fathia M. Khattab fathiakhattab@yahoo.com Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Zagazig
University, Egypt
ß 2019 Taylor & Francis Group, LLC
2 F. M. KHATTAB AND M. M. NASR

illnesses, meningitis or seizures and Genital MC were excluded Statistical analysis

from the research.
Data were analyzed using SPSS, version 20.0 (SPSS Inc., Chicago,
Illinois, USA). The frequencies, percentages and the mean ± SD
were computed.w2-test was used to comparing qualitative varia-
Study design bles. Mann–Whitney test was used as a test of significance to
Each subject was subject to full history including prior MC treat- compare quantitative data between groups. The 5% level was
ment, full general examination and skin examination for MC chosen as the level of significance and 95% confidence interval.
lesions, including location, size, amount and length of lesions.
Group A (control group): This group included 20 patients with Results
MC; Cantharidine crystals (Pharmacy Compounding Centers of
America, Houston, TX) were ready to create a 0.7% solution for Group A: It included 20 MC patients subjected to topical applica-
tion of 0.7% Cantharidine solution. 13 patients were males
topical administration in acetone, hydroxy propyl cellulose and
(65.0%) and seven patients were females (35.0%). Their ages
flexible collodion under the rules of USP 795 (Town Total
ranged from 3 to 30 years with a mean of 8.75 ± 6.4 years. The
Compounding Center, Melville, NY). Cantharidine (0.7% concentra-
duration of the disease ranged from 1 to 4 months with a mean
tion) applies to cotton-swab wooden end lesions and the sur-
of 1.6 ± 0.8 months (Table 1).
rounding skin is sparing. Then washed off in 4 h and left without
Eleven patients had lesions on the face and neck (55.0%). Nine
occlusion. For up to six visits, patients were treated every 2 weeks.
patients had lesions on other sites (45.0%). 14 patients had few
Group B: Only 20 patients who were injected Received an IL
MC lesions (
10 lesions) while 6 patients had multiple lesions
injection of tuberculin PPD at a dose of 10 IU (0.1 ml) with an
>10 lesion (Table 2).
insulin syringe in the largest lesion at a regular interval of 2 weeks
Group B: It included 20 MC patients subjected to intralesional
for up to six injections or less in cases of a complete lesion clear-
injection of tuberculin PPD. Ten patients were males (50%) and
ance used as a 2 ml tuberculin PPD (Mantoux test), an intradermal
Ten patients were females (50%) and their ages ranged from 3 to
test produced by Vacsera Company, Cairo, Egypt. The product 40 years with a mean of 13 ± 9.3 years. The duration of the disease
was placed in the dark except when doses between 2 and 81 C ranged from 1 to 6 months with a mean of 3 ± 1.9 months
(10) are effectively removed from the vial (9). The expiry date of a (Table 3).
tuberculin PPD vial is 1 month from the date it was opened (11). Nine patients had lesions on face and neck (45.0%) and eleven
To verify current immunity, patients received 0.1 ml of PPD patients had lesions on other sites (55.0%). Ten patients had few
antigen intradermal injection on the volar aspect of the left shoul- lesions (
10 lesions) while ten patients had multiple lesions <10
der and patients with erythema and a diameter of at least 5 mm lesions (Table 2).
within 48–72 h were chosen for the PPD group (12). For six con- In this study, no statistically significant difference was
secutive treatments, injections were made into the largest lesion detected between the two groups as regards clinical response. In
each other week. The size of each patient’s test reaction deter- group (A) 18 patients (90.0%) showed a complete response to
mined the volume of PPD antigen for intralesional injection using topical Cantharidine therapy after three to eight weeks of treat-
the method described by Wananukul et al. (13). The test was read ment while two patients (10.0%) showed a partial response to
after 48–72 h, and induration with or without erythema showed topical Cantharidine therapy after treatment (Figure 1). While in
sensitivity. When the induration was about 5 mm in diameter, we the group (B) 17 patients (85%) showed a complete response
regarded the experiment positive. The dose of PPD injected for
therapy was 0.3 ml if 5–9 mm induration, 0.2 ml if >9–15 mm Table 1. Comparison between studied groups as regard demographic data.
induration, and 0.1 ml tuberculin if >15 mm induration. Patients Cantharidin PPD
who were not reactive to the test were excluded from the study. group group
Total No ¼ 20 No ¼ 20
Dermographic number
data 40 No. % No. % Test p-value
Evaluation and follow up
Sex
At the end of the 2nd, 4th, 6th and 8th weeks, all patients were Male 19 13 65.0 10 50 0.13a .72
examined. Depending on clinical and photographic evaluations, Female 21 7 35.0 10 50 NS
the clinical reaction to therapy was assessed on each visit; com- Age (years)
X̅ ± SD 8.75 ± 6.4 13 ± 9.3
plete lesion disappearance, a decline in the number of lesions. Range 3–30 5–37 1.78b .08
The evaluation was done by photographing patients with a 16.2- Median 7 9.5 NS
megapixel Sony DSC-WX50 digital camera (Sony, Tokyo, Japan) Duration of the disease (month)
before therapy and 2 weeks after each session and up to 6 months X̅ ±SD 2.3 ± 1.4 3 ± 1.9 .24
per month. Range 1–5 1–6 1.1 NS
Median 1.0 2.5
Immediate and late negative implications such as pain, ery-
Site of lesions
thema, induration, edema, hyperpigmentation, and hypopigmen- Face 13 7 35.0 6 30.0 0.58a .44 NS
tation were evaluated. Before and after therapy, photos were Neck 7 4 20.0 3 15.0 0.0a 1.0 NS
taken for lesions. When all lesions completely disappeared, the Chest 5 2 10.0 3 15.0 0.0a 1.0 NS
patients were regarded as respondents. The patients were Abdomen 2 0 0.0 2 10.0 0.53a .46 NS
Lower limb 5 3 15.0 2 10.0 0.0a 1.0 NS
regarded as non-respondent if there was no change. If the num- Upper limb 4 2 10.0 2 10.0 0.0a 1.0 NS
ber of lesions decreased, the patients were regarded to be partial a
Chi-square test.
respondents. Follow up was done for patients with complete b
Independent samples Student’s T-test.
response for 6 months to detect any recurrence. NS: non-significant.
 JOURNAL OF DERMATOLOGICAL TREATMENT 3

Table 2. Comparison between two studied groups as regard the relation

between complete response and other parameters.
Cantharidin group PPD group
No ¼ 18 No ¼ 17
Dermographic
data No % No % X2 p-value
Age(years)

10 16 88.8 14 82.3 0.03 .86 N.S
>10 2 11.2 3 17.7
Duration(months)

3 13 72.2 13 76.4 1.42 .23 N.S
>3 5 27.8 4 23.6
Site of lesions
Face and neck 14 77.6 15 88.2 0.13 .71 N.S
Other 4 22.4 2 11.8
No. of lesions

10 15 83.3 14 82.3 2.37 .12 N.S
>10 3 16.7 3 17.7
NS: non-significant; X2: Chi-square test.

Table 3. Comparison between two studied groups as regard clinical response

to therapy.
Cantharidin Group PPD Group Figure 1. A case of MC showing complete response after topical Cantharidin .7%
No ¼ 20 No ¼ 20 for eight week.
Clinical Response No. % No. % X2 p-value
Complete response 18 90.0 17 85.0 0.21 .65 N.S
Partial response 2 10.0 3 15.0
NS: non-significant; X2: Chi-square test.

after 2 to 8 weeks (a mean of 4 injections with PPD vaccine), while

two patients (15%) showed a partial response at end of therapy
(five intralesional injections with PPD vaccine) (Figure 2; Table 3).
In this study, no statistically significant difference was detected
between the two groups as regards demographic data. There is
no statistically significant difference between the two groups as
regards the relation between a complete response and other
parameters (age, duration, site, and a number of lesions)
(Table 2).
In this study, the adverse effects were tolerated by most
patients. In group (A) blistering was reported in (10.0%), hyperpig-
mentation in (10.0%) and burning sensations in (25%).
In group (B) pain at the site of injection was the main side
effect reported in all cases (100%) also erythema and edema were
Figure 2. A case of MC showing complete response after five intralesional injec-
observed in (15.0%) and one case reported anaphylaxis (5.0%). A tions of PPD.
statistically significant difference was detected between the two
groups as regards burning sensation in the group (A) but not in
the group (B). Topical cantharidin is a commonly used treatment for verruca
A highly statistically significant difference was detected vulgaris and MC. In a 2009 survey of pediatric dermatologists,
between the two groups as regards pain at the site of injection in approximately 99% of those polled had previously used topical
the group (B) but not in the group (A). cantharidin, with 92% reporting subjective satisfaction with its
results (6).
Discussion Satisfaction with cantharidin therapy was high, especially in
molluscum contagiosum. Pain (7–85.7%), blistering (10–100%),
MC’s current methods of treatment include curettage, cryosurgery, and hyper-/hypopigmentation (1.8–53.3%) were the most com-
laser therapy, and multiple topical agents such as tretinoin, imi- monly occurring adverse effects with cantharidin treatment (5).
quimod, and cantharidin. There are no FDA approved specific Silverberg et al. (1) revealed that, after administration of topical
treatments for molluscum contagiosum infection in immunocom- cantharidine, over 90% of pediatric respondents with MC in a
petent individuals yet (1). Up to our knowledge, this study is the retrospective cohort had experienced full lesion clearance with no
first trial for the treatment of MC using PPD vaccine. significant adverse side effects and 95% parental satisfaction. In a
Topical application of cantharidine, a blister beetle-derived 2009 retrospective study by Cathcart et al. (6) Ninety-six percent
vesicant, has a lengthy history of being used mainly to treat cuta- of respondents showed enhancement in MC lesions. A prospect-
neous molluscum contagiosum. It has been used in various con- ive study of multiple MC treatments showed 60% patient/parent
centrations, 0.7%, and, 9%, to treat MC (2). satisfaction with cantharidine use; writers supported cantharidine
4 F. M. KHATTAB AND M. M. NASR
as a fast, a nontraumatic alternative for the office-based sup-
plier (8).
Compared to these previous research, Coloe Dosal et al. (6)
proposed that performing cantharidine therapy over 2 months
was not significantly better than performing placebo in the first
reported placebo-controlled prospective trial.
Furthermore, Osier and Eichenfield (14) indicate that confound-
ers may have influenced the research by Coloe Dosal et al. (6),
including a longer average period of MC pretreatment in the pla-
cebo arm and a greater percentage of dry skin respondents in the
therapy arm.
Immunotherapy with MMR vaccine and Candida antigen has
been suggested for the treatment of MC as cell-mediated immun-
ity plays a role in its pathogenesis. Intralesional immunotherapy
using measles, mumps, and rubella (MMR) vaccine has been
recently suggested as an effective treatment modality for MC (10).
Intralesional immunotherapy’s mechanism of action is still
obscure. It proposed that the immune system mounts an immune
response that provides extensive viral proliferation control and
eventually destroys all body lesions (9).
Tuberculin-purified protein derivatives are nonpathogenic,
quickly increasing, atypical Mycobacterium belonging to Runyon
Class IV was first created in India. It was endorsed in India as an
immunotherapy complement to multi-drug leprosy treatment
(12). It is highly antigenic and produces cytokine (IL-2, IFN-g) (15).
PPD wart immunotherapy recorded by Amirnia et al. (16) in
which 77.1% clearance was recorded in recalcitrant warts, and
studies by Saoji et al. (17) (with 76% clearance of flight, prevalent
warts and plantar warts), Abd-Elazeim et al. (18) (with 75% clear-
ance in recalcitrant common warts), Eassa et al. (19) (47.5% clear-
ance in remote genital warts following weekly intradermal PPD
injection in forearms) and Lahti and Hannuksela (20) (57% full
clearance of common warts following topical use of tuberculin
PPD jelly). However, this study’s reaction rate was smaller than
that recorded by Wananukul et al. (13) (with full clearance in 93%
of target warts and 87% of remote warts) and Abo Elela et al. (21)
(with 94.1% clearance of target plantar warts after IL
PPD injection).
In this study, no statistically significant difference was detected
between the two groups as regards clinical response.
In group (A)18 patients (90.0%) showed a complete response
to therapy and two patients (10.0%) showed a partial response
within a period of treatment ranged from 3 to 8 weeks with no
recurrence in (16 cases) (80.0%) while recurrence in 20.0% (4
cases) after 6 months.
In group (B) 17 patients (85%) showed complete response and
3 patients (15%) showed partial response with no recurrence in
fifteen patients (75%) and five patients (25%) reported recurrence
after 6 months. All patients suffered from pain during injection.
In this study, the adverse effects were tolerated by most
patients. In group (A) blisters were reported (20.0%), hyperpig-
mentation in (10.0%) and burning sensations in (25%). In group
(B) pain at the site of injection was the main side effect reported
in all cases (100%) also erythema and edema were observed in
(10.0%) and one case reported anaphylaxis (5.00%).
Conclusion
Both topically and intralesionally, cantharidin 0.7% and PPD
are reliable, less costly modalities with equal effectiveness for
non-genital MC. Topical cantharidin 0.7% efficient, painless and
noninvasive because of its keratolytic impact and daily application
in the home.
PPD intralesional immunotherapy is an efficient technique,
especially in uncooperative patients for generalized non-genital
MC lesions. It has the advantage of elevated tolerability without
scarring and injection in one or two lesions, not in all lesions.
Disclosure statement
No potential conflict of interest was reported by the authors.
ORCID
Fathia M. Khattab http://orcid.org/0000-0002-2600-4021
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