Evidence - Based Case Report

Efficacy and safety of 5% imiquimod cream compared to 10% KOH

solution for adult molluscum contagiosum
Marsha Bianti, Agung Muhammad Rheza, Aninda Marina, Rizka Farah Hilma
Sarah Mahri, Teffy Nuary, Rahadi Rihatmadja
Department of Dermatology and Venereology Universitas Indonesia,
dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia

Email: marsha.bianti@gmail.com

Abstract
Background: Molluscum contagiosum (MC) is a benign infection caused by the Molluscipox virus that most
often affects children and sexually active adolescents. Various topical therapeutic options are available,
however, no single intervention is convincingly effective. Potassium hydroxide (KOH) solution is widely used
but its usefulness is hampered with adverse effects. Newer preparation, 5% imiquimod cream seems to be
as, if not more, effective. However, it is not legally available yet in Indonesia.
Aim: To assess the efficacy and safety of 5% imiquimod cream in treating adult molluscum contagiosum.
Methods: Literature search was done through Pubmed, EBSCO, dan Cochrane databases. Inclusion criteria
included articles in English, available in free full text and matched with the clinical question as well as
providing the clinical outcome of papules clearance within 12 weeks.
Results: There were three articles found to be related to the clinical question and they were critically
appraised for their validity, importance, and applicability.
Conclusion: Only two studies were valid and further assessed for their importance and applicability. In
regards to importance, imiquimod has fewer side effects than KOH, yet it was not constantly shown to be
superior to KOH in curing MC lesions. We conclude that KOH solution is the preferred treatment of MC in
adults.

Keywords: imiquimod, KOH, molluscum contagiosum, safety, efficacy

Background
Molluscum contagiosum (MC) is a benign viral
infection that often affects children, sexually active
adolescents, and the immunocompromised of all
ages.1 It is a self-limiting epidermal papular
condition caused by the Molluscipox virus.
Although it is self-limiting and may resolve
spontaneously, it is somewhat troublesome to
patients. First, the lesions are cosmetically
unattractive. Secondly, even though most of MC
cases are asymptomatic, pruritus is sometimes
significant, particularly in those with underlying
atopic dermatitis. Lastly, it may persist for months
to years and recurrencences are common.
MC is characterized by smooth, dome-shaped,
discrete, opalescent papules with a central core;
some develops surrounded areas of scales and
erythema (molluscum dermatitis).2 It is a sexually
transmitted diseases in adults. The prevalence of
MC has risen significantly in the past decades.
This appears to be parallel to the overall increase
of other sexually transmitted diseases and HIV
infection.2 Assessment for risk and benefits for
MC therapy is important. In immunocompetent
individual, lesion will generally resolve without
complication.
Many modalities have been used but sound
scientific evidences supporting them is lacking.3
Topical therapeutic modalities include topical
cantharidin, retinoid creams, imiquimod cream,
salicylic acid, trichloroacetic acid, KOH solution,
cidofovir, silver nitrate paste and tape stripping.
Imiquimod and KOH were considered common for

J Gen Proced Dermatol Venereol Indones. 2019:3(2);18-23. 19

treating MC. A Cochrane Database analysis in
2009 regarding treatments for MC found no single
intervention was convincingly effective.3 Newer
Cochrane review that had been published after we
corroborated the question concluded similarly.4
Case Illustration
A 26-year-old male came to our clinic with a
complaint of whitish papules with central
umbilication around genital area for 2 months
duration. He also complained of mild itch. There
was history of promiscuity, but his HIV screening
test was non-reactive. Dermoscopic examination
revealed white-yellowish area consistent with MC
He asked for effective and safe medication and
refused manual extraction procedure. He
preferred not to be treated with KOH because his
partner had received such treatment and
experienced side effects. The doctor thinks that
5% imiquimod cream is a good alternative, but
unsure if it is as effective with fewer side effects
than the widely available preparation.
Clinical Question
Is 5% imiquimod cream more effective and safer
than 10% KOH solution in clearing molluscum
contagiosum papules in adults?
P : adults with molluscum contagiosum
I : 5% imiquimod cream
C : 10% KOH solution
O : complete clearance of papules
Clinical question type: therapy
Are the valid results of this randomised trial important?
Table 1. Clearing of Lesions
RRR
CER EER CER-EER
CER
Seo et 3/13= 0,23 6/14= 0,43 0,23-0,43
al. 0,23
= -0,87
Chatra 3/20 = 0,15 10/20 = 0,5 0,15-0,5
et al. 0,15
= -2,3
CER: Control Event Rate, EER: Experimental Event Rate, RRR: Relative Risk Reduction, ARR: Absolute
Risk Reduction, ARI: Absolute Risk Increase, NNT: Number Needed to Treat
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Methods
Literature search through Pubmed, EBSCO, dan
Cochrane was done on April 6th 2017 using
keywords ‘molluscum contagiosum’ AND
‘imiquimod’ AND ‘KOH’ OR ‘potassium hydroxide’
AND ‘treatm ent’. Inclusion criteria were articles in
English, available in free full text and matched
with our clinical question. The desired outcome
was complete clearing of papules in 12 weeks
clinically. (Appendix 1)
Results
Selection
Seven articles were obtained from literature
searching. First selection was based on
title/abstract, with elimination of same articles.
The remaining was re-assessed based on
inclusion criteria. Three articles were suitable for
our EBCR clinical question and were critically
appraised using CEBM critical appraisal
worksheet. (www.cebm.net/critical-appraisal/).
Critical Appraisal
Three relevant studies by Seo et al., Chatra et al.,
and Metkar et al. were critically appraised for their
validity, importance, and applicability.
Comparisons of the studies were summarized
below (Table 1, Table 2 and Table 3).
It is important to note that all the studies lack of
validity. Randomization was not concealed and
clinicians were not blind to treatment. Two studies
found that the use of imiquimod will increase the
risk of failure (ARI 20% and 30%, respectively).
ARR NNT
CER-EER 1/ARR
0,23-0,43= 1/0,2 = 5
0,2 (20%)  ARI
0,15-0,5= 0,35 (35%) 1/0,35 = 2,85 ~ 3
 ARI
19
Table 2. Side Effect

CER EER RRR ARR NNT

CER-EER/ CER CER-EER 1/ARR
Seo et al. 6/14 = 0.43 6/13= 0.46 0.43-0.46 0.43-0.46 = 0.03 1/0.03 = 33.33 ~
0.43 (3%)  ARI 33
= -0.69
Chatra et 10/20 = 0.5 4/20 = 0.2 0.5-0.2 0.5-0.2= 0.3 1/0.3 = 3.33 ~ 3
al. 0.5 (30%)  ARR
= 0.6 (60%)
CER: Control Event Rate, EER: Experimental Event Rate, RRR: Relative Risk Reduction, ARR: Absolute
Risk Reduction, ARI: Absolute Risk Increase, NNT: Number Needed to Treat

Can you apply this valid, important evidence about therapy in caring for your patient?

Table 3. Critical Appraisal

Seo et al. Chatra et al.

Do these results apply to your patient?
Is your patient so different from No
those in the study that its results
cannot apply?
Is the treatment feasible in your No, due to availability
setting?
What are your patient’s potential benefits and harms from the therapy?
Benefits: none
Harms:
- based on absolute risk
calculation, there was no
superiority of using
imiquimod (ARI 20%).
- Imiquimod proved to have
slightly more side effects
(ARI 3%)
Are your patient’s values and preferences satisfied by the regimen and its consequences?
Do your patient and you have a Yes
clear assessment of their values and
preferences?
Are they met by this regimen and its No
consequences?
Quite, in the scenario the
patient was adult
No
Benefits:
- Imiquimod prove to be
safer than KOH (ARR
30%).
Harms:
- In terms of clearing of
lesion, imiquimod was not
convincingly superior to
KOH. (ARI 35%).
Yes
No

Study by Chatra et al. pointed that imiquimod was Result

somewhat safer (NNT 3). However, Seo et al.
found that imiquimod might cause more side
effects.5
Three articles were obtained from literature
searching, two of them were randomized
controlled trial (Seo et al. and Chatra et al.),
whereas one was nonrandomized comparative
study (Metkar et al.) therefore, it was not valid and
no longer assessed for importance and
applicability.5-7
In Seo study, 30 subjects were divided into two
study groups.5 Out of 30 patients, 3 patients were
noncompliant and did not follow up, thus only 27
were analyzed based on per protocol analysis.

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Results showed there was no significant
difference between MC treatment using 5%
imiquimod cream and 10% KOH solution at 12
weeks of observation. Complete clearance of
lesions was found only in 57% patients treated
with imiquimod, while in patients treated with KOH
had 77% rate of clearance. The reduction in
number of lesions at the end of week 12 was
statistically significant in each group (p < 0.05).
However, comparison of the number of the lesions
between two groups was not statistically
different (p = 0.413). The incidence rate of side
effects in imiquimod group was slightly higher
than KOH group (46% vs 42%). The side
effects were observed on the sites of application
and they included erythema, ulceration, scaling,
and hyperpigmentation. However, it was transient
and tolerable.
Chatra study recruited 40 pediatric patients.6 This
study showed statistically significant results where
KOH was more effective than imiquimod in
treating MC at the end of 12 weeks (p = 0.019).
Imiquimod group showed complete clearance in
50% patients, while KOH group demonstrated
similar outcome in 85% patients. Out of 20
patients who received KOH solution, 10 (50%)
showed adverse effects, whereas of the 20
patients who received imiquimod, it was only in 4
subjects (20%). The result was significant
statistically with p =0.18. The side effects
observed after treatment with KOH were
pigmentary disturbance and burning sensation.
Discussion
Publication of studies involving imiquimod and
KOH were apparently lacking, therefore any
conclusion of superior efficacy of one group over
another can not be over emphasized. Two out of
three studies selected for this paper were
randomized controlled trial studies but neither
were blinded. Blinding could not be done because
of difference in the mode of application; imiquimod
was applied directly on the lesion, while KOH was
applied with cotton swab or toothpick. This could
lead to bias in the results. Study by Metkar, was
not randomized, therefore its validity was not
appraised.7
All studies have comparable sample size, ranging
from 20 to 40 subjects. This number was too small
for a clinical trial and might not represent the
target population. In most studies, the setting was
not clearly defined. Only study by Metkar stated
J Gen Proced Dermatol Venereol Indones. 2019:3(2);18-23.
dermatology department in tertiary care center as
the clinical setting.7 The age of the subjects
ranged from 1-36 years (Seo et al.)5, 1-18 years
(Chatra et al.)6, and 1-40 years (Metkar et al.)7.
Only the second study singled out subjects in the
pediatric population, while in the first and third the
age was more diverse. These differences were
not considered serious problem because MC is
one of the most common cutaneous viral infection
that can be found both in children or adult.
From all studies, both imiquimod and KOH have
good efficacy in clearing the lesions. Marked
superiority was found only in one study (Chatra et
al.), while the other showed only marginal results,
even the p values were not significant (p > 0.05).
In terms of safety, most studies showed KOH to
have more adverse effect than imiquimod. One
study showed imiquimod has more adverse
effects slightly than KOH (46% vs 42%). Yet,
adverse effects of KOH were transient and
tolerable. Therefore, no specific recommendation
is available for adult with MC, but due to price and
availability, KOH seems to be more superior. In
pediatric patients, these adverse effects of KOH
were less tolerable because of the child pain
threshold is relatively low. Thus, the use of
imiquimod is more recommended for children with
MC, despite the fact that imiquimod is more
expensive and not well distributed.
Conclusion
Based on critical appraisal, only two studies were
valid and further assessed for their importance
and applicability. In regard to importance,
imiquimod has fewer side effects than KOH, yet it
was not constantly shown to be superior to KOH
in curing MC lesions. We conclude that KOH
solution is the preferred treatment of MC in adults.
References
1. Nguyen HP, Franz E, Stiegel KR, Hsu S,
Tyring SK. Treatment of molluscum
contagiosum in adult, pediatric, and
immunodeficient populations. J Cutan Med
Surg. 2014;18:299-306.
2. Piggott C, Friedlander SF, Tom W. Poxvirus
Infections. In: Goldsmith LA, Kats SI,
Gilchrest BA, Paller AS, Leffell DJ, Wolff K.
(Eds.) Fitzpatrick’s dermatology in general
medicine. New York: McGraw-Hill. 2012;
2:2417-20.
3. Van der Wouden JC, van der Sande R, van
Suijlekom-Smit LW, Berger M, Butler CC,
21
 Koning S. Interventions for cutaneous
molluscum contagiosum. Cochrane
Database Syst Rev. 2009;4:CD004767.
4. Van der Wouden JC, van der Sande R,
Kruithof EJ, Sollie A, van Suijlekom-Smit LW,
Koning S. Interventions for cutaneous
molluscum contagiosum (Review). Cochrane
Database Syst Rev. 2017;5:CD004767.
5. Seo SH, Chin HW, Jeong DW, Sung HW. An
open, randomized, comparative clinical and
histological study of imiquimod 5% cream vs.
10% potassium hydroxide solution in the
treatment of molluscum contagiosum. Ann
Dermato. 2010;22:156-62
6. Chatra N, Sukumar D, Bhat RM, et al. A
comparative study of 10% KOH solution and
5% imiquimod cream for the treatment of
Molluscum contangiosum in the pediatric
age. Indian Dermatol Online J. 2015;6:75-80
7. Metkar A, Pande S, Khopkar U. An open,
non-randomized, comparative study of
imiquimod 5% cream vs. 10% potassium
hydroxide solution in the treatment of
molluscum contagiosum. Indian J Dermatol
Venereol Leprol. 2008;74:614-8

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 Appendix 1. Literature Searching Strategy

A A A
Molluscum O Potassium
N N N
contagiosum Imiquimod KOH R Hydroxide Treatment
D D D

Pubmed EBSCO Cochrane

*Searching time:
April 6th 2017,
3 3 1 15.00 PM

Filter for same articles

Screening through title and abstract Inclusion criteria:

- Articles that matched
with clinical question
3 - Available in free full
text
- Written in English
language
Metkar, et al (2008)
Seo, et al (2010)
Chatra, et al (2015)

Reading the full text** **Reading time:

April 6th-8th 2017

Critical appraisal of 3 articles

J Gen Proced Dermatol Venereol Indones. 2019:3(2);18-23. 23