Received: 6 May 2020 Revised: 4 July 2020 Accepted: 8 July 2020

DOI: 10.1111/dth.14034

REVIEW ARTICLE

Treatment of cutaneous viral warts in children: A review

Karina Ruth Soenjoyo1 | Brandon Wen Bing Chua2 | Lynette Wei Yi Wee3 |
Mark Jean Aan Koh3 | Seng Bin Ang1,3,4

1
Duke-NUS Medical School, Singapore,
Singapore Abstract
2
Department of Pharmacy, KK Women's and Viral warts or verruca are very common skin infections in children. Although benign,
Children's Hospital, Singapore, Singapore
lesions can be extensive, painful, bleed, or lead to cosmetic disfigurement. Although
3
Dermatology Service, KK Women's and
Children's Hospital, Singapore, Singapore spontaneous resolution can occur, parents often bring their children for treatment,
4
Family Medicine Service, KK Women's and especially when they are symptomatic. Many publications have assessed the efficacy
Children's Hospital, Singapore, Singapore
and safety of treatment of warts in adults. However, treatment in children can be
Correspondence challenging due to their immune responses and lower threshold for pain. We review
Lynette Wei Yi Wee, Dermatology Service, KK
the current literature on the methods, efficacy, and side effect profile of common
Women's & Children's Hospital, 100 Bukit
Timah Road, Singapore 229899, Singapore. treatment modalities for cutaneous viral warts in children. There is evidence that sali-
Email: lynette.wee.w.y@singhealth.com.sg
cylic acid and cryotherapy are effective, and although cryotherapy is more effective,
there is a higher risk of side effects such as pain and blistering. Combination treat-
ment with salicylic acid and cryotherapy may reduce these side effects. Although
there is limited data, other treatment options such as cantharidin, immunotherapy
and other mechanical therapies, for example, carbon dioxide lasers, may also be con-
sidered, especially for recalcitrant lesions.

KEYWORDS

children, cryotherapy, salicylic acid, verruca, viral warts

1 | I N T RO DU CT I O N Destructive treatment methods may not be suitable for children, due

Viral warts or verruca are common, benign skin growths caused by
human papilloma virus (HPV). They are ubiquitous in the general pop-
ulation, but are more prevalent in children, affecting up to one third of
school-going children.1-3Approximately two-thirds of lesions can
resolve spontaneously within 2 years without treatment.4 Indications
for treatment include pain, discomfort, recurrent bleeding and
cosmesis.5 Early treatment is also important for epidemiological con-
trol and to prevent spread to close contacts.6 However, there is no
consensus on the most efficacious and safest treatment option in
children.
Two systematic reviews, published in 2002 and 2012, reviewing
studies in both adults and children, concluded that only salicylic acid
(SA) showed a modest therapeutic effect.1,7 Both reviews found that
trials comparing cryotherapy with placebo has shown no significant
difference in efficacy, similar for trials comparing cryotherapy with
salicylic acid. Side effects were not compared in both reviews.
to their lower threshold for pain and discomfort. Our review aims to
assess and discuss the efficacy and safety of various treatment modal-
ities for cutaneous viral warts in children based on the existing
literature.
2 | METHODS
We performed a literature search on PubMed, Embase, and Web of
Science from February 2019 to June 2020. The studies included were
published from 1961 to 2020. The inclusion criteria included studies
of any treatment for viral warts that involved only children and ado-
lescents (0–21 years) or studies that performed separate analyses for
children and adults. The exclusion criteria were studies that included
immunocompromised patients and anogenital warts, as management
can be different. We also excluded letters, case reports, case series,
studies with unavailable abstracts or full texts, and studies not

Dermatologic Therapy. 2020;e14034. wileyonlinelibrary.com/journal/dth © 2020 Wiley Periodicals LLC. 1 of 10

https://doi.org/10.1111/dth.14034
2 of 10 SOENJOYO ET AL.

TABLE 1 Data from (mainly paediatric) studies on the treatment modalities of non-genital warts in children

Methods Efficacy Side effect Tips

No intervention • Watchful • Clearance rates: 5.8% 6 wks— • Nil. • Good for
observation and 63.6% at 2 yr.9-17 uncomplicated warts.
reassurance. • Caregivers should be
counselled that it will
take time.
Cryotherapy • Most commonly • Clearance rates: 51.6% over 13 • Pain and blistering.24,26 • Cotton wool application
liquid nitrogen wks—68.2% over 3 • To reduce the discomfort, is preferred for
therapy with spray mo.9,14,17,24-27 may try “sensitive areas” such
gun technique or • Clearance rates of plantar warts  topical anesthetic (eg, as the face or in
cotton wool is generally lower than warts at EMLA cream), 29 younger children.19,20
application.18,19 other sites.9,27  distraction techniques, • Paring before
• 2-3 weekly  use of SA between cryotherapy is
treatments cryotherapy recommended for
• 1-2 freeze-thaw sessions.30 hyperkeratotic plantar
cycles/session. or palmar warts.28
• 5-10 seconds of
freezing/cycle.19-23
Salicylic acid (SA) • Topical SA can be Clearance rates of SA monotherapy • Skin irritation. • Useful for home
monotherapy bought over the • Skinrythema pain.34 treatment.
and combination counter and • 18% at 6 mo to close to 100% at • Blistering.34 • Compliance may affect
therapies applied twice daily. 2 yr.9,11,14,17Clearance rates of SA • Salicylicism (if applied to efficacy and should be
• SA is often combination therapies wide surface areas). emphasized.
combined with • SA and glycolic acid: 100% over 8
other therapies wks.31
such as • SA and fluorouracil: 20.0%.17
5-fluorouracil, • SA and lactic acid: 58.8%-75%
lactic acid, glycolic over 18 mo.32
acid, podophyllin/ • SA-podophyllin-catharidin: 66.9%
cantharidin, over 1 yr and 86.5% over 40
cryotherapy, and mo.33,34
imiquimod. • SA and cryotherapy: 57.6% over
13 wks and 91.3% over
4.5 yr.24,35
• SA and imiquimod: 81.1% over
3 mo.27
Other topical Formalin with or Clearance rates: • Pain and blistering .24 • There is paucity of data
therapies without curettage, • Formalin with or without • Stinging orsoreness .39 on efficacy and safety.
nitric-zinc complex curettage: 99%.36 • Use with caution.
solution, pyruvic • Nitric-zinc complex solution:
acid, promicid gel 83.9% at 6 mo.37
with or without • Pyruvic acid: 81.8% at 29 mo.38
occlusion, • Promicid gel under occlusion:
monochloroacetic 78.3% at 17 wks.39
acid (MCA), silver • Promicid gel without occlusion:
nitrate, retinoids, 73.3% at 17 wks.39
Adapalene gel, • MCA: 59.3% at 13 wks.24
cantharidin. • Silver nitrate: 56.3% at 60 mo.12
• Retinoids: 50,0%, 84.6% at 12
wks, and 42.9% at 2 yr.13,14,17
• Adapalene gel: 100.0% at 75 d.26
• Cantharidin: 22.2%.17
Immunotherapy Topical DPCP, topical Clearance rates: • Moderate erythema. • Recommended for
SADBE, topical • Topical DPCP: 88.3%.40 • Side effect profiles were recalcitrant or extensive
imiquimod, topical • SADBE: 31.8% over 2 yr and missing in many studies. warts.
BCG, intralesional 57.6% over 3 mo.14,42 • Less readily available in
candida, • Topical imiquimod: 77.6% over 2 most pediatric or
intralesional MMR yr and 25.0%.14,17 dermatology clinics.
vaccine oral • Topical BCG: 59.5% over 6 • Weigh the risks and
cimetidine, and oral wks.41 benefits before using.
zinc sulfate.
SOENJOYO ET AL. 3 of 10

TABLE 1 (Continued)

Methods Efficacy Side effect Tips

• Intralesional candida: 70.9% over
5 yr and 87.3% over 1 yr.43,44
• Intralesional MMR: 27.6% over 2
yr and 89.9% over 6 mo.8,45
• Oral cimetidine (dose: 25-40
mg/kg/day): 87%.46,47
• Oral zinc sulfate: 68.2% at 1 mo,
86.4% at 2 mo.48
Mechanical/ Curettage, Clearance rates: • Pain is commonly • Duct tape monotherapy
destructive electrocautery, CO2 • Curettage: 55.6% over 2 yr and reported. or in combination with
therapy laser, pulsed dye 63.7%.14,36 • Pain, erythema, and topical SA or
laser, long-pulsed • Electrocautery: 27.3% over 2 yr transient cryotherapy is safe and
Nd:YAG laser and 72.7%.14,17 hyperpigmentation may useful for younger
superficial • CO2 laser: 57.1% over 10 mo.49 be seen with conventional patients.
radiotherapy, • Pulsed dye laser: 35.0% over 2 yr or daylight photodynamic • Other mechanical
conventional and 32.1% over 20 mo.14,50 therapy. therapies are often not
photodynamic • Long-pulsed Nd:YAG laser: readily available and
therapy, daylight 100.0% over 12 wks (three laser should be carefully
photodynamic treatments).52 considered before use.
therapy, and duct • Superficial radiotherapy:
tape. 95.7%.51
• Conventional photodynamic
therapy: 73.3%.53
• Daylight photodynamic therapy:
80.0%.53
• Duct tape: 16.0% over 6 wks and
66.7% over 2 yr.10,14
Alternative Homeopathy, Clearance rates: • NIL • Limited data available.
therapies relaxation mental • Homeopathy: 30.0% at 8 wks
imagery, transfer and 42.9% at 5 mo.15,54
factor therapy. • Relaxation mental imagery:
50.0% at 18 mo.11
• Transfer factor therapy: 33.3% at
7 wks for transfer factor
therapy.16

Abbreviations: BCG, bacillus calmette-guerin; DPCP, diphenylcyclopropenone; EMLA, eutectic mixture of local anesthetics; MMR, measles, mumps, and
rubella; SA, salicylic acid; SADBE, squaric acid dibutylester.

published in the English language. Data extracted from the studies
included the study design, participant characteristics, types of inter-
vention, clearance rates, time to clearance, and side effects.
3 | RESULTS
option in children with uncomplicated warts or who are unable to tol-
erate the side effects of treatment, especially pain. However, care-
givers have to be advised on the length of time required for self-
resolution, as well as the risk of autoinoculation to other body sites
and spread to close contacts while awaiting resolution.

Table 1 provides a summary of all treatment modalities. Details of all
included studies can be found in Table 2.
3.1 | No intervention
Cutaneous viral warts can undergo spontaneous resolution if left
untreated, especially in immunocompetent children.8 However, this
may take up to a few years. Assessing the reported clearance rates in
placebo groups of studies, rates of clearance can range from 5.8% at
9-17
6 weeks to 63.6% at 2 years. Watchful non-intervention is a viable
3.2 | Cryotherapy
Liquid nitrogen, at −196 C, is the most common agent used for cryo-
therapy. Techniques may differ in the methods of application, dura-
tion of treatment, and frequency of treatment. Spray gun technique
and cotton wool application are the most common methods of appli-
cation. Two studies have shown that both methods are equally effec-
tive.18,19 Cotton wool application is especially useful for more
“sensitive areas” such as the face or in younger children who may not
tolerate the pain from the use of spray guns.19,20 Warts are usually
frozen until a 1 to 2 mm ice halo forms around the target area.
4 of 10
Although some guidelines recommend 5 to 30 seconds of application,
the ice halo can usually be achieved typically after 5 to 10 seconds of
20
cryotherapy in children, who may not tolerate longer applications.
study has shown that a 10 second freeze results in better clearance
21
than treating till there is a halo of ice around the wart. After the ice
halo thaws, typically after 15 to 30 seconds, cryotherapy can be re-
applied. A study has shown that a second freeze-thaw cycle can
increase the cure rates for plantar warts but not for palmar warts.22
The recommended interval between each session is 2 to 3 weeks.23
Reported clearance rates with cryotherapy range from 51.6% over
9,14,17,24-27
13 weeks to 68.2% over 3 months. Cryotherapy has been
shown to be significantly more efficacious than salicylic acid in some
studies.9,24 Due to warts being thicker on the soles, as well as the per-
sistent friction from footwear, the rates for clearance of plantar warts
9,27
is generally lower and slower than warts at other sites. Paring
hyperkeratotic warts, especially palmar or plantar warts, using a surgi-
cal blade is recommended before application of cryotherapy, to
increase the efficacy of treatment.28 Interestingly, a study using an
N2O gas operated machine for 1 to 2 minutes, applied once every
fortnight reported a clearance rate of 100.0% over 75 days for eight
patients.26
The most common side effects of cryotherapy are pain and
24,26
blistering. Pain most often occurs during application of the cryo-
therapy but can also occur minutes to hours after application.
Methods to reduce pain and discomfort from cryotherapy include
the use of a topical anesthetic (eg, EMLA cream) prior to cryother-
apy29 or distraction techniques (eg, games or videos on mobile
devices) during the session.30 Interestingly, in one study, the addi-
tion of SA in between the cryotherapy treatment sessions decreased
the incidence of pain and blistering but marginally increased the risk
24
of irritation.
3.3 | Salicylic acid (SA) monotherapy and
combination therapies
Salicylic acid (SA) is a keratolytic agent used in the treatment of vari-
ous dermatological conditions. It is a useful topical for home treat-
ment of cutaneous warts. There are many different preparations and
concentrations of SA. Over the counter SA products usually contain
20% to 30% SA. The recommended use is once to twice daily. Over-
night occlusion with duct tape after application is often recommended
by pediatric dermatologists. Reported clearance rates of warts treated
with SA ranges from 18% in 6 months to close to 100% at
2 years.9,11,14,17 One paper reported compliance rates to application
of SA at 70%.11 Practically, patients and caregivers need to be advised
that response to SA is slow and may take several months of
treatment.
Salicylic acid is also combined with other keratolytics in some
topical preparations, for example, SA with 5-fluorouracil, SA with
lactic acid and SA with glycolic acid. Of the studies describing the
use of these combination topical therapies, SA and glycolic acid
appears to be the most efficacious with clearance rate of 100% over
SOENJOYO ET AL.
8 weeks.31 SA and 5-fluorouracil had a clearance rate of only 20%
for 5 patients over an unspecified duration.17 SA and lactic acid had
A a clearance rate of 58.8% to 75% over 18 months with twice daily
application.11,32
Multi-modality treatment with SA and other treatments can also
increase efficacy, for example, SA combined with podophyllin and
cantharidin, SA with cryotherapy and SA with imiquimod. Clearance
rates were 66.9% over 1 year and 86.5% over 40 months for SA-
podophyllin-cantharidin combination therapy, 57.6% over 13 weeks
and 91.3% over 4.5 years for SA and cryotherapy, and 81.1% over
3 months for SA and imiquimod.24,27,33-35
Skin irritation is a reported complication of SA treatment, how-
ever, there are no studies reporting the incidence, especially in the
pediatric population. No other significant side effects were
reported in the studies. If skin irritation occurs, patients and care-
givers should be advised to stop treatment for a few days and to
re-start after the irritation resolves. Rarely, if signs of secondary
infection are seen, topical or oral antibiotics may be required. There
is also a small risk of salicylic acid toxicity, marked by tinnitus, nau-
sea, and vomiting, particularly if applied more extensively. Twenty
percent of patients on SA and glycolic acid experienced side effects
including irritation and erythema.31 For patients on SA-podophyl-
lin-cantharidin therapy, 23.5% experienced pain and 88.0% experi-
enced blistering. 34 No side effects have been reported for other
combination therapies.
3.4 | Other topical therapies
There is limited data on the efficacy and safety of other topical thera-
pies for the treatment of warts in children. Reported clearance rates
were 99% for formalin with or without curettage, 83.9% for nitric-zinc
complex solution, 81.8% for pyruvic acid, 78.3% for promicid gel
under occlusion, 73.3% for promicid gel without occlusion, 59.3% for
monochloroacetic acid (MCA), 56.3% for silver nitrate, 42.9% to 100%
for retinoids (including adapalene) and 22.2% for cantharidin
12-14,17,24,26,33,36-39
Side effects reported in some of the studies
included pain (75.8%) and blistering (36.7%) with MCA24 and pain,
stinging or soreness with promicid gel (33.9%).39 No side effects were
reported in studies for nitric-zinc complex solution or adapalene
gel.26,37
3.5 | Immunotherapy
Immunotherapy employs the use of substances to stimulate or sup-
press the immune system to treat certain diseases. Various forms of
immunotherapy have been used in the treatment of viral warts, which
include both topical and intralesional preparations. Topically applied
immunotherapy that have been used to treat warts include dip-
henylcyclopropenone (DPCP), squaric acid dibutylester (SADBE),
imiquimod and bacillus calmette-guerin (BCG). Intralesional immuno-
therapy include candida, MMR (measles, mumps, rubella) vaccine,
TABLE 2 Details of included studies
Period of Age range Number of
Author Study design follow-up (years) children Type of wart Interventions Clearance rates, fraction (percentage)
25
Larsen et al 1996 Prospective, 3 mo 0-18 27 All Cryotherapy Cryotherapy: 15/22 (68.2)
randomized cohort
SOENJOYO ET AL.

study
Bruggink et al 20109 Randomized controlled 13 wks 4-12 105 Common and Cryotherapy, salicylic acid, Cryotherapy: 16/31 (51.6), 95% CI
trial plantar placebo (35-68)%
Salicylic acid: 15/36 (41.7), 95% CI
(27-58)%
Placebo: 11/38 (28.9), 95% CI (17–45)%
Bruggink et al 201524 Randomized controlled 13 wks 4-12 185 All Cryotherapy, monochloroacetic Cryotherapy: 20/35 (57.1), 95% CI
trial acid, salicylic acid (41-72)%
+ cryotherapy Monochloroacetic acid: 54/91 (59.3)
Salicylic acid + cryotherapy: 34/59
(57.6), 95% CI (45-69)%
Stefanaki et al 201527 Randomized controlled 3 mo 2-12 86 All Cryotherapy, salicylic acid Cryotherapy: 33/49 (67.3)
trial + imiquimod Salicylic acid + Imiquimod: 30/37 (81.1)
Gupta et al 201526 Randomized controlled 75 da 13-18 11 Plantar Cryotherapy, adapalene gel Cryotherapy: 8/8 (100.0)
trial Adapalene gel: 3/3 (100.0)
Felt et al 199811 Randomized controlled 18 mo 6-12 Not mentioned All Salicylic acid, relaxation mental Placebo: NA (25.0)
trial imagery, placebo Salicylic acid: NA (58.8)
Relaxation mental imagery: NA (50.0)
Van Brederode et al Retrospective study 4.5 yearsa 4-15 46 Plantar Saliylic acid + cryotherapy Salicylic acid + cryotherapy: 42/46 (91.3)
200135
Coskey 198433 Prospective cohort 1 year 2-16 121 All 30% salicylic acid + 5% Salicylic acid + podophyllin + catharidin:
study podophyllin + 1% catharidin 81/121 (66.9)
Nguyen 201934 Retrospective study 40 mo <18 52 All 30% Salicylic acid + 2% Salicylic acid + podophyllin + catharidin:
(survey-based) podophyllin + 1% 45/52 (86.5)
cantharidin
Khattar et al 200732 Randomized controlled 12 wks 13-18 6 All Salicylic acid + lactic acid, Zinc Salicylic acid + lactic acid: 3/4 (75.0)
trial oxide Zinc oxide: 1/2 (50.0)
Rodriguez-Cerdeira et al Prospective study, 8 wks 7-16 20 All Salicylic acid + glycolic acid, Salicylic acid + glycolic acid: 20/20
201131 non-blinded, non- glycolic acid (100.0)
randomized study
Giacaman et al 201937 Prospective cohort 6 mo 4–16 12 Common and Nitric-zinc complex solution Nitric-zinc complex solution: 10/12
study periungual (83.9)
Yazar et al 199412 Randomized controlled 60 moa 4-18 29 Common Silver nitrate, placebo Silver nitrate: 9/16 (56.3)
trial Placebo: 3/13 (23.1)
Halasz 199838 Retrospective medical 29 moa 0-16 11 All Pyruvic acid (with or without Pyruvic acid: 9/11 (81.8)
chart review 5-fluorouracil
Kubeyinje 199613 Prospective, 12 wks 5-14 51 Plane 0.05% tretinoin cream, placebo 0.05% tretinoin cream: 22/26 (84.6)
randomized study Placebo: 8/25 (32.0)
Veien et al 199139 Randomized controlled 17 wks <14 Not mentioned Plantar Promicid gel, promicid gel Promicid gel: NA (73.3)
trial + occlussive Promicid gel + occlusive: NA (78.3)
Salem et al 201341 Randomized controlled 6 wks 3-14 37 All Topical Bacillus Calmette- Topical BCG: 22/37 (59.5)
trial Guerin (BCG)
Silverberg et al 200042 Retrospective study 3 mo 3-17 59 All SADBE: 34/59 (57.6)
5 of 10

(Continues)
TABLE 2 (Continued)
6 of 10

Period of Age range Number of

Author Study design follow-up (years) children Type of wart Interventions Clearance rates, fraction (percentage)
Squaric acid dibutylester
(SADBE)

Suh et al 201440 Prospective Not mentioned <10 79 All Diphenylcyclopropenone DPCP: 158/179 (88.3)
uncontrolled open- (DPCP)
label study
Maronn et al 200843 Retrospective chart 1 year 1.5-15 55 All Intralesional Candida Intralesional candida: 48/55 (87.3)
review
Muñoz Garza et al Retrospective chart 5 years 3-18 220 All, recalcitrant Intralesional Candida Intralesional candida: 156/220 (70.9)
201544 review
Na et al 20148 Retrospective study 2 years 0-10 29 All Intralesional measles, mumps Intralesional MMR: 8/29 (27.6)
and rubella (MMR)
Zamanian et al 201445 Randomized controlled 6 mo 0-20 18 All Intralesional MMR Intralesional MMR: 8/9 (89.9)
trial, double-blinded Placebo: 2/9 (22.2)
Yilmaz et al 199646 Randomized controlled 3 mo 4-16 32 All, multiple Cimetidine Cimetidine: 9/17 (52.9)
trial, double-blinded Placebo: 8/15 (53.3)
Gooptu et al 200047 Open label study 3 mo 0-16 16 All, recalcitrant Cimetidine Cimetidine: 9/16 (56.3)
Yaghoobi et al 200948 Randomized controlled 2 mo 8-21 22 All, recalcitrant, Oral zinc sulfate Oral zinc sulfate at 1 mo: 15/22 (68.2)
trial multiple Oral zinc sulfate at 2 mo: 19/22 (86.4)
Vickers 196136 Retrospective study Not mentioned 0-17 446 All Formalin, formalin + curettage, Curettage: 5/9 (55.6)
curettage Formalin: 222/223 (99.6)
Formalin + curettage: 120/121 (99.2)
De haen et al 200610 Randomized controlled 6 wks 4-12 103 All Duct tape, placebo Duct tape: 8/51 (16.0)
trial Placebo: 3/52 (5.8)
Park et al 200750 Prospective, non- 20 moa 2-12 56 All Pulsed dye laser Pulsed dye laser: 18/56 (32.1)
blinded, non-
randomized study
Lim et al 199249 Retrospective study 10 mo 8-18 7 Periungual Carbon dioxide (CO2) laser CO2 laser: 4/7 (57.1)
Alshami et al 201652 Prospective study 12 wks 1-12 89 Deep palmoplantar, Long-pulsed 1064 nm Nd:YAG Nd:YAG laser at 3 laser treatments (12
recalcitrant laser wks): 89/89 (100.0)
Macht et al 197751 Retrospective study Not mentioned <12 167 All Superficial radiotherapy Superficial radiotherapy: 159/167 (95.7)
Borgia et al 202053 Prospective study 24 wks 4-17 30 Facial, plane, Conventional photodynamic Conventional photodynamic therapy:
multiple therapy vs daylight 11/15 (73.3)
photodynamic therapy Daylight photodynamic therapy: 12/15
(80.0)
Kuwabara et al 201514 Retrospective medical 2 yearsb 0-17 617 All Salicylic acid, cryotherapy, Cryotherapy: 70/115 (60.9)
chart review tretinoids, imiquimod, Curettage: 5/9 (55.6)
squaric acid dibutylester Duct tape: 54/81 (66.7)
(SADBE), curretage, duct Electrocautery: 3/11 (27.3)
tape, electrocautery, pulsed Imiquimod: 121/156 (77.6)
dye laser, placebo Pulsed dye laser: 7/20 (35.0)
Retinoid: 6/14 (42.9)
SADBE: 7/22 (31.8)
Salicylic acid: 131/178 (73.6)
Placebo: 7/11 (63.6)
SOENJOYO ET AL.
 SOENJOYO ET AL. 7 of 10

tuberculin purified protein derivative (PPD) and BCG vaccine. These

Salicylic acid + 5-Fluorouracil: 1/5 (20.0)

Clearance rates, fraction (percentage)
treatments are thought to stimulate the cellular immune system to

Transfer factor therapy: 4/12 (33.3)

increase recognition and clearance of HPV. Clearance rates vary
between the different modalities and many studies have small num-
Cryotherapy: 129/267 (48.3)

Electrocautery: 8/11 (72.7)

bers of children. For the topical immunotherapies, clearance rates

Homeopathy: 9/30 (30.0)

Salicylic acid: 3/13 (23.1)

Homeopathy: 3/7 (42.9)

Cantharidin: 2/9 (22.2)
Cimetidine: 2/5 (40.0)

Imiquimod: 1/4 (25.0) were 88.3% for DPCP, 59.5% for BCG, 51.3% for imiquimod, 44.7%

Placebo: 7/30 (23.3)

Placebo: 4/16 (25.0)

Retinoid: 1/2 (50.0)

Placebo: 3/7 (42.9)

for SADBE.14,17,40-42 For the intralesional immunotherapies, clearance

Placebo: 0/2 (0)

rates were 70.9% to 87.3% for candida and 27.6% to 89.9% for
MMR.8,43-45 Studies for intralesional tuberculin PPD and BCG have
been done mainly in adults with no pediatric data. Many studies also
did not report on the side-effects of treatment. One patient described
moderate erythema after imiquimod 5% cream.27 Importantly, many
0.025% tretinoin, cimetidine,
+ 5-Fluorouracil, cantharidin,

imiquimod, electrocautery,

of these modalities are less readily available in most pediatric or der-

Salicylic acid, salicylic acid

cryotherapy, placebo

Transfer factor therapy

matology clinics. Some, like MMR and candida require intralesional
Homeopathy, placebo

administration which may be too painful for use in pediatric patients.

However, as the therapeutic effects of immunotherapy can occur at
Interventions

Homeopathy

distant sites from the area injected, it may be useful for older children
and adolescents with extensive warts where the antigen can be
injected only to the largest lesions. This may lead to better compliance
compared to destructive therapies which needs to be applied on all
warts for effects to occur. Consideration for their use in children
Type of wart

needs to be carefully discussed with parents and caregivers, especially

Common

Common

on the benefits and risks. In general, they should only be rec-

ommended for recalcitrant or problematic warts and should only be
All

All

administered by physicians well-versed in their use.

Cimetidine, an H2-receptor antagonist with immunomodula-
7
60

28
318

tory effects have been used for the treatment of warts in children
Number of

in a handful of studies. Cure rates for oral cimetidine after 2 to

children

3 months of treatment ranged from 52.9% to 56.3% at doses rang-

ing from 25 to 40 mg/kg/day in 3 to 4 divided doses. No significant
side effects have been reported in these studies. 46,47Oral zinc sul-
Different for each participant, but the author used 2 years as cutoff for clearance rate.

fate is also postulated to have immunomodulatory effects, as zinc is

Age range
(years)

a micronutrient necessary for normal immune cell function. Oral

<12

6-12

6-18
11-18

zinc sulfate therapy has reported clearance rate of 68.2% at

1 month and 86.4% at 2 months for children with recalcitrant and
multiple warts.48 Response to treatment corresponded with a rise
Different for each participant, but longest duration mentioned above.
Not mentioned

in serum zinc levels. There were no adverse effects reported.

follow-up
Period of

8 wks

7 wks
5 mo

Abbreviations: CI, confidence interval; NA, not applicable.

3.6 | Mechanical destructive therapies

Randomized controlled

Randomized controlled

Randomized controlled
trial, double blinded
Retrospective study

Apart from cryotherapy, other mechanical therapies that have been

studied for the treatment of cutaneous warts in children include
Study design

curettage, electrocautery, carbon dioxide (CO2) laser, pulsed dye laser,

trial

trial

and superficial radiotherapy. The clearance rates were 59.7% for

curettage, 50% for electrocautery, 57.1% for CO2 laser, 33.6% for
(Continued)

pulsed dye laser, 100.0% for long-pulsed 1064 nm Nd:YAG laser,

95.7% for superficial radiotherapy, 73.3% for conventional photody-
Stevens et al 197516
Tenzel et al 196915
17

Kainz et al 199654
Theng et al 2004

namic therapy and 80.0% for daylight photodynamic ther-

apy.14,17,36,49-53 Pain is the most common side-effect of these
TABLE 2

treatment modalities and may not suitable for use in younger patients.
Author

Transient mild hyperpigmentation and erythema may also be seen

with both conventional and daylight photodynamic therapy.
b
a
8 of 10 SOENJOYO ET AL.

Consideration for their use in children needs to be carefully discussed
with parents and caregivers, especially on the benefits and risks. In
general, they should only be recommended for recalcitrant or exten-
sive warts and should only be administered by physicians well-versed
in their use.
A simple and painless treatment is overnight occlusion of warts
with duct tape. Reported clearance rates in two studies were 16.0%
over 6 weeks and 66.7% over 2 years.10,14 Side effects are minimal
and minor.
3.7 | Alternative therapies
Alternative therapies that have been described in the literature for
the treatment of warts in children. However, these are small stud-
ies with less than 30 participants, and conclusions cannot be
drawn on their effectiveness or safety in children. These alterna-
tive therapies include homeopathy, relaxation mental imagery, and
11,15,16,54
transfer factor therapy. The reported clearance rate for
these treatments range from 30.0% at 8 weeks to 50.0% at
18 months.
Physicians should continuously monitor for response of warts after
starting treatment. Considerations for recalcitrant warts include inade-
quate treatment, wrong diagnosis, and immunocompromised state.
Differential diagnoses of viral warts in children include callosities,
epidermal nevi, porokeratosis, fibrokeratomas and other benign or
malignant tumors. If immunodeficiency is suspected, screening
investigations include complete blood counts with white cell differential
counts, complement levels, immunoglobulin levels, and human immuno-
deficiency virus HIV serology. Onward referral to an immunologist may
be required.
4 | CONC LU SION
Cutaneous warts are common in children and adolescents, and
may cause problems such as pain, discomfort and bleeding.
Figure 1 provides a recommended therapeutic algorithm for the
treatment of cutaneous warts in children and adolescents.
Although spontaneous resolution can occur, many parents or
caregivers will bring their children for treatment. Salicylic acid
and cryotherapy are the most commonly studied treatments and
are both effective, relatively safe and readily available. Cryother-
apy may be more efficacious than salicylic acid, but with higher
risks of pain and blistering. In younger children, salicylic acid
would be a more acceptable option. Combination therapies may
also be considered for better cure rates. For more extensive or
difficult to treat warts, other treatment modalities, for example,
immunotherapy and mechanical therapies, may be considered.
However, the data on efficacy and safety in children is not as
well established and should only be considered when other ther-
apies have failed. We recommend further randomized trials to
evaluate these treatment modalities, comparing with the more
established options of cryotherapy and salicylic acid.

Viral Wart

Palmoplantar Non- Palmoplantar

< 7 years or ≥ 7 years or

uncooperative cooperative • Observe
• SA monotherapy
• SA combination topicals

Fails
• Observe • Cryotherapy
• SA ± occlusion Fails ± paring
(duct tape) ± SA • Cryotherapy
• SA combination ± occlusion (duct tape) ± SA
topicals • SA combination topicals

Fails
Fails
• Lasers
• Lasers • Immunotherapy
• Immunotherapy (topical or intralesional)
(topical or intralesional)
SA: Salicyclic acid

FIGURE 1 Therapeutic algorithm for cutaneous warts in children and adolescents. SA, salicyclic acid
SOENJOYO ET AL. 9 of 10

ORCID 18. Bleiker TO, Bourke JF, Lear J. A comparison of cryogun versus cotton
Karina Ruth Soenjoyo https://orcid.org/0000-0002-4587-6060 buds for the treatment of warts. Br J Dermatol. 1997;137(Suppl. 50):
26 (Abstract).
Lynette Wei Yi Wee https://orcid.org/0000-0002-5395-0734
19. Ahmed I, Agarwal S, Ilchyshyn A, Charles-Holmes S, Berth-Jones J.
Mark Jean Aan Koh https://orcid.org/0000-0002-4136-4105 Liquid nitrogen cryotherapy of common warts: Cryo-spray vs. cotton
wool bud. Br J Dermatol. 2001;144(5):1006-1009. https://doi.org/10.
RE FE R ENC E S 1046/j.1365-2133.2001.04190.x.
20. Sterling JC, Handfield-Jones S, Hudson PM. Guidelines for the man-
1. Kwok CSG, S.; Bennett, C.; Holland, R.; Abbott, R. Topical treatments
agement of cutaneous warts. Br J Dermatol. 2001;144(1):4-11.
for cutaneous warts. Cochrane Database Syst Rev 2012;(9):Cd001781.
https://doi.org/10.1046/j.1365-2133.2001.04066.x.
doi:https://doi.org/10.1002/14651858.CD001781.pub3
21. Connolly M, Bazmi K, O'Connell M, Lyons JF, Bourke JF. Cryotherapy
2. De Koning MNCQ, D K, Bruggink SC, et al. High prevalence of cuta-
of viral warts: A sustained 10-s freeze is more effective than the tra-
neous warts in elementary school children and the ubiquitous pres-
ditional method. Br J Dermatol. 2001;145(4):554-557. https://doi.
ence of wart-associated human papillomavirus on clinically normal
org/10.1046/j.1365-2133.2001.04449.x.
skin. Br J Dermatol. 2015;172(1):196-201. https://doi.org/10.1111/
22. Berth-Jones J, Bourke J, Eglitis H, et al. Value of a second freeze-
bjd.13216.
thaw cycle in cryotherapy of common warts. Br J Dermatol. 1994;131
3. Van Haalen FMB, C S, Gussekloo J, Assendelft WJJ, Eekhof JAH.
(6):883-886. https://doi.org/10.1111/j.1365-2133.1994.tb08594.x.
Warts in primary schoolchildren: Prevalence and relation with envi-
23. Bunney MH, Nolan MW, Williams DA. An assessment of methods of
ronmental factors. Br J Dermatol. 2009;161(1):148-152. https://doi.
treating viral warts by comparative treatment trials based on a stan-
org/10.1111/j.1365-2133.2009.09160.x.
dard design. Br J Dermatol. 1976;94(6):667-679. https://doi.org/10.
4. Lynch MD, Cliffe J, Morris-Jones R. Management of cutaneous viral
1111/j.1365-2133.1976.tb05167.x.
warts. Br Med J. 2014;348:g3339. https://doi.org/10.1136/bmj.g3339.
24. Bruggink SC, Gussekloo J, Egberts PF, et al. Monochloroacetic acid
5. Bruggink SC, Eekhof JAH, Egberts PF, van Blijswijk SCE,
application is an effective alternative to cryotherapy for common and
Assendelft WJJ, Gussekloo J. Natural course of cutaneous warts
plantar warts in primary care: A randomized controlled trial. J Investig
among primary school children: a prospective cohort study. Ann Fam
Dermatol. 2015;135(5):1261-1267. https://doi.org/10.1038/jid.
Med. 2013;11(5):437-441. https://doi.org/10.1370/afm.1508.
2015.1.
6. Steele K, Irwin WG. Liquid nitrogen and salicylic/lactic acid paint in
25. Larsen PØ, Laurberg G. Cryotherapy of viral warts. J Dermatol Treat.
the treatment of cutaneous warts in general practice. J R Coll Gen
1996;7(1):29-31. https://doi.org/10.3109/09546639609086866.
Pract. 1988;38(311):256-258.
26. Gupta R, Gupta S. Topical adapalene in the treatment of plantar
7. Gibbs S, Harvey I, Sterling J, Stark R. Local treatments for cutaneous
warts; randomized comparative open trial in comparison with cryo-
warts: systematic review. BMJ. 2002;325(7362):461.
therapy. Indian J Dermatol. 2015;60(1):102. https://doi.org/10.4103/
8. Na CH, Choi H, Song SH, Kim MS, Shin BS. Two-year experience of
0019-5154.147835.
using the measles, mumps and rubella vaccine as intralesional immu-
27. Stefanaki C, Lagogiani I, Kouris A, Kontochristopoulos G, Antoniou C,
notherapy for warts. Clin Exp Dermatol. 2014;39(5):583-589. https://
Katsarou A. Cryotherapy versus imiquimod 5% cream combined with
doi.org/10.1111/ced.12369.
a keratolytic lotion in cutaneous warts in children: A randomized
9. Bruggink SC, Gussekloo J, Berger MY, et al. Cryotherapy with liquid
study. J Dermatol Treat. 2016;27(1):80-82. https://doi.org/10.3109/
nitrogen versus topical salicylic acid application for cutaneous warts
09546634.2015.1034079.
in primary care: Randomized controlled trial. CMAJ. 2010;182(15):
28. Scheinfeld NS. Treatment of verruca vulgaris. Skinmed. 2006;5(1):
1624-1630. https://doi.org/10.1503/cmaj.092194.
37-38.
10. De Haen M, Spigt MG, Van Uden CJT, Van Neer P, Feron FJM,
29. Gupta AK, Koren G, Shear NH. A double-blind, randomized, placebo-
Knottnerus A. Efficacy of duct tape vs placebo in the treatment of
controlled trial of eutectic lidocaine/prilocaine cream 5% (EMLA) for
verruca vulgaris (warts) in primary school children. Arch Pediatr
analgesia prior to cryotherapy of warts in children and adults. Pediatr
Adolesc Med. 2006;160(11):1121-1125. https://doi.org/10.1001/
Dermatol. 1998;15(2):129-133. https://doi.org/10.1046/j.1525-
archpedi.160.11.1121.
1470.1998.1998015129.x.
11. Felt BT, Hall H, Olness K, et al. Wart regression in children: Compari-
30. Tey HL, Tan EST, Tan FGC, Tan KL, Lim ISH, Tan ASL. Reducing anxi-
son of relaxation-imagery to topical treatment and equal time inter-
ety levels in preschool children undergoing cryotherapy for cutaneous
ventions. Am J Clin Hypn. 1998;41(2):130-138.
viral warts: Use of a portable video player. Arch Dermatol. 2012;148
12. Yazar S, Basaran E. Efficacy of silver nitrate pencils in the treatment
(9):1001-1004. https://doi.org/10.1001/archdermatol.2012.1656.
of common warts. J Dermatol. 1994;21(5):329-333. https://doi.org/
31. Rodríguez-Cerdeira C, Sánchez-Blanco E. Glycolic acid 15% plus sali-
10.1111/j.1346-8138.1994.tb01748.x.
cylic acid 2%: A new therapeutic pearl for facial flat warts. J Clin
13. Kubeyinje EP. Evaluation of the efficacy and safety of 0.05% tretinoin
Aesthet Dermatol. 2011;4(9):62-64.
cream in the treatment of plane warts in Arab children. J Dermatol Treat.
32. Khattar JA, Musharrafieh UM, Tamim H, Hamadeh GN. Topical zinc
1996;7(1):21-22. https://doi.org/10.3109/09546639609086864.
oxide vs. salicylic acid-lactic acid combination in the treatment of
14. Kuwabara AM, Rainer BM, Basdag H, Cohen BA. Children with warts:
warts. Int J Dermatol. 2007;46(4):427-430. https://doi.org/10.1111/j.
a retrospective study in an outpatient setting. Pediatr Dermatol. 2015;
1365-4632.2006.03138.x.
32(5):679-683. https://doi.org/10.1111/pde.12584.
33. Coskey RJ. Treatment of plantar warts in children with a salicylic
15. Tenzel JH, Taylor RL. An evaluation of hypnosis and suggestion as
acid-podophyllin-cantharidin product. Pediatr Dermatol. 1984;2(1):71-
treatment for warts. Psychosomatics. 1969;10(4):252-257. https://
73. https://doi.org/10.1111/j.1525-1470.1984.tb00446.x.
doi.org/10.1016/S0033-3182(69)71737-6.
34. Nguyen AL, Quint KD, Bouwes Bavinck JN, Erceg A, de Kort WJA,
16. Stevens DA, Ferrington RA, Merigan TC, Marinkovich VA. Random-
Körver JEM. Real-life treatment of cutaneous warts with cantharidin
ized trial of transfer factor treatment of human warts. Clin Exp
podophyllin salicylic acid solution. Dermatol Ther. 2019;32(6):e13143.
Immunol. 1975;21(3):520-524.
https://doi.org/10.1111/dth.13143.
17. Theng TSC, Goh BK, Chong WS, Chan YC, Giam YC. Viral warts in
35. van Brederode RL, Engel ED. Combined cryotherapy/70% salicylic acid
children seen at a Tertiary Referral Centre. Ann Acad Med Singapore.
treatment for plantar verrucae. J Foot Ankle Surg. 2001;40(1):36-41.
2004;33(1):53-56.
10 of 10
36. Vickers CF. Treatment of plantar warts in children. Br Med J. 1961;2
(525):743. https://doi.org/10.1136/bmj.2.5254.743.
37. Giacaman A, Granger C, Aladren S, et al. Use of topical nitric-zinc
complex solution to treat palmoplantar and periungual warts in a
pediatric population. Dermatol Ther. 2019;9:755-760. https://doi.org/
10.1007/s13555-019-00330-5.
38. Halasz CL. Treatment of warts with topical pyruvic acid: with and
without added 5-fluorouracil. Cutis. 1998;62(6):283-285.
39. Veien NK, Madsen SM, Avrach W, et al. The treatment of plantar
warts with a keratolytic agent and occlusion. J Dermatol Treat. 1991;2
(2):59-61. https://doi.org/10.3109/09546639109086776.
40. Suh DW, Lew BL, Sim WY. Investigations of the efficacy of dip-
henylcyclopropenone immunotherapy for the treatment of warts. Int
J Dermatol. 2014;53(12):e567-e571. https://doi.org/10.1111/ijd.
12688.
41. Salem A, Nofal A, Hosny D. Treatment of common and plane warts in
children with topical viable bacillus calmette-guerin. Pediatr Dermatol.
2013;30(1):60-63. https://doi.org/10.1111/j.1525-1470.2012.
01848.x.
42. Silverberg NB, Lim JK, Paller AS, Mancini AJ. Squaric acid immuno-
therapy for warts in children. J Am Acad Dermatol. 2000;42(5 I):
803-808.
43. Maronn M, Salm C, Lyon V, Galbraith S. One-year experience with
candida antigen immunotherapy for warts and molluscum. Pediatr
Dermatol. 2008;25(2):189-192. https://doi.org/10.1111/j.1525-
1470.2008.00630.x.
44. Muñoz Garza FZ, Roé Crespo E, Torres Pradilla M, et al. Intralesional
candida antigen immunotherapy for the treatment of recalcitrant and
multiple warts in children. Pediatr Dermatol. 2015;32(6):797-801.
https://doi.org/10.1111/pde.12667.
45. 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. https://doi.org/10.4103/2277-9175.129701.
46. Yilmaz E, Alpsoy E, Basaran E. Cimetidine therapy for warts: a
placebo-controlled, double-blind study. J Am Acad Dermatol. 1996;34
(6):1005-1007. https://doi.org/10.1016/S0190-9622(96)90279-0.
SOENJOYO ET AL.
47. Gooptu C, Higgins CR, James MP. Treatment of viral warts with
cimetidine: an open-label study. Clin Exp Dermatol. 2000;25(3):183-
185. https://doi.org/10.1046/j.1365-2230.2000.00608.x.
48. Yaghoobi R, Sadighha A, Baktash D. Evaluation of oral zinc sulfate
effect on recalcitrant multiple viral warts: A randomized placebo-
controlled clinical trial. J Am Acad Dermatol. 2009;60(4):706-708.
https://doi.org/10.1016/j.jaad.2008.09.010.
49. Lim JT, Goh CL. Carbon dioxide laser treatment of periungual and
subungual viral warts. Australas J Dermatol. 1992;33(2):87-91.
50. Park HS, Kim JW, Jang SJ, Choi JC. Pulsed dye laser therapy for pedi-
atric warts. Pediatr Dermatol. 2007;24(2):177-181. https://doi.org/10.
1111/j.1525-1470.2007.00370.x.
51. Macht SH, Cordero JM. Superficial radiotherapy of warts: results of
treating 531 warts. Radiology. 1977;122(1):231-232. https://doi.org/
10.1148/122.1.231.
52. Alshami MA, Mohana MJ. Novel treatment approach for deep pal-
moplantar warts using long-pulsed 1064-nm Nd:YAG laser and a
moisturizing cream without prior paring of the wart surface. Photo-
med Laser Surg. 2016;34(10):448-455.
53. Borgia F, Giuffrida R, Coppola M, et al. Efficacy and safety of conven-
tional versus daylight photodynamic therapy in children affected by
multiple facial flat warts. Photodiagn Photodyn Ther. 2020;31:101819.
https://doi.org/10.1016/j.pdpdt.2020.101819.
54. Kainz JT, Kozel G, Haidvogl M, Smolle J. Homoeopathic versus pla-
cebo therapy of children with warts on the hands: a randomized,
double-blind clinical trial. Dermatology. 1996;193(4):318-320. https://
doi.org/10.1159/000246277.
How to cite this article: Soenjoyo KR, Chua BWB, Wee LWY,
Koh MJA, Ang SB. Treatment of cutaneous viral warts in
children: A review. Dermatologic Therapy. 2020;e14034.
https://doi.org/10.1111/dth.14034