DOI: https://doi.org/10.

53350/pjmhs20221612512

ORIGINAL ARTICLE
Efficacy of Topical 1% Adapalene Versus Cryotherapy in Treatment of
Plantar Warts
ARIFULLAH MAJ1, MUHAMMAD ADEEL SIDDIQUE2, LT. COL. MAJID HUSSAIN3
1
TMO Dermatology, Combined Military Hospital, Abbottabad
2,3
Dermatology, Combined Military Hospital, Abbottabad
Correspondence author: Arifullah, Maj, Email: drarifullah123@gmail.com, Cell: 03202233240

ABSTRACT
Background: Warts are spiny, rough papules or nodules that can be found anywhere on skin. They are caused by human
papilloma virus (HPV) infection. There are over 100 HPV types documented. Approximately 6% of children and 2% of adults
consult the doctor for wart. The aim of the current study was To compare the efficacy of topical Adapalene gel 0.1% under
occlusion with cryotherapy in the treatment of plantar wart
Methodology: It was Randomized control trial carried out at the Department of Dermatology, Combined Military Hospital,
Abbottabad, Pakistan, from Feb 2022 to July 2022. A total of 60 Patients coming to hospital with complaints of plantar warts
were randomized into two equal groups of 30 patients. Patients reporting on odd serial number were allocated to group A,
treated with application of topical 1% adapalene gel overnight on daily basis under occlusion, while patients reporting on even
serial number were allocated to group B, treated with cryotherapy for two freeze thaw cycles, done with liquid nitrogen at -
196°C temperature using direct application by a dipstick. The primary outcome was to measure the complete resolution of
warts after 8 weeks from start of treatment.
Results: Age range in this study was from 18 to 45 years with mean age of 32.366±8.61 years, while duration of disease was
from 2 to 12 weeks with mean duration of 6.433±2.90 weeks. After 8 weeks of treatment, 27 patients (90%) in group-A, while 20
patients (66.66%) in group-B achieved complete resolution of warts (p-value 0.028).
Practical implication: In the practical implications of this study, while comparing topical adapalene versus cryotherapy in trials,
an important fact is that cryotherapy is done under supervision by the physician on fortnightly basis while adapalene is applied
under occlusion by patients themselves daily at home, so, a major advantage of use of adapalene gel is also its simplicity and
convenience of use. Another advantage to the patient is in shape of painless application at home compared to the cryotherapy.
However, one disadvantage with adapalene gel is that it has to be used under occlusion by plastic sheet on daily basis which
may feel messy to some patients
Conclusion: Topical 0.1 % adapalene was more effective than cryotherapy in the treatment of plantar warts.
Keyword: Human papillomavirus, Plantar warts, Adapalene, Cryotherapy.

INTRODUCTION keratinocytes encircled by koilocytosis indicates the cell damage

Plantar Warts which are also called verruca, papilloma or verruca by the virus. (5)
pedis are commonly found skin conditions reported in both adults As per reports, 35% of total cutaneous warts are plantar
and children. Warts appear as rough, spiny papules found warts. (5) Among these warts 30% are reported to be spontaneously
anywhere on the skin. Human papilloma virus (HPV), which is a cleared but the remaining ones cause pain, irritation and are also
DNA virus, is responsible for the infection that causes these warts. unappealing cosmetically. (6)
The documented types of HPV are more than 100. The subtypes The treatments suggested for plantar warts include
of HPV that typically causes warts on the skins of hands and feet cryotherapy, salicylic acid, bleomycin, cantharidin, intralesional
include 1, 2, 4, 27 and 57. The inoculation of a keratinocyte is immunotherapy and laser. Unfortunately, none of these have
result of an epidermal abrasion as well as transient impairment of proven to be vastly effective in all types of patients. (7,8)
immune system.(1) Estimated annual incidence of plantar warts is Destruction of the affected cells of epidermis through burning
14%.(2) Consultation for warts is approximately 2% by the adults it chemically or damaging it by using physical pressure is the idea
while 6% for the children. behind most of above suggested treatments. In this process
Clinical appearance of warts varies and depends on the HPV damage of healthy surrounding tissues causes pain in most of the
type involved and the site of appearance of warts. Although patients.(8,9) On the other hand this planned cell damage don’t
benign, plantar warts can cause discomfort and pain. As reported destroy the virus in the cells of perilesional tissues resulting in
in some studies, the response to the treatment of plantar warts and failure of treatment and recurrence of warts.(8) It is reported that 2%
natural course may be influenced by the type of HPV involved.(3,4) of the population again goes for medical consultation after
The plantar warts appear clinically as well-confined lesions along suffering from pain, limitation of their activities, prevention of
with overlying hyperkeratosis. While debridement done with infection and aesthetics.(2,8,10)
hyperkeratosis, bleeding is commonly visible along with the Among the above-mentioned therapies, cryotherapy is the
pinpointed skin lines interruption. When ambulated directly with first line therapy selected by most clinicians performed by applying
pressure, warts are mostly pain full. Nails may also become liquid nitrogen directly on the warts.(11) For this purpose liquid
dystrophic if involved in lesions of warts.(5) Existence of HPV is nitrogen having a boiling point of -195.6°C is used. Cotton bud or a
common on fomites. They also exist on common showers of cryospray is used for application. The protocols of this treatment
swimming pools having abrasive surfaces which become high risk vary, however, therapy is repeated after every two weeks till the
places to nurture the virus and cause epidermal erosion. (6) Virus wart is cleared. (12) The therapy is based on producing a localized
easily lives over longer periods at low temperatures and comes freezing by applying liquid nitrogen followed by slow thawing that
into contact from inert cold objects. The entry of virus is made result in destruction of the tissues infected by virus. This method
through small crakes in the skin. Keratinocytes thus become therefore does not directly kills the virus. (13,14) Rapid application is
infected leading to hyperplasia of epidermal cells that appears one of the advantage of cryotherapy and it is also proven cost-
clinically as exophytic lesion. Replication of the basal cell is effective.(12) The commonly found side effects are irritation, pain,
encouraged by the virus. Granular and prickle cell layers goes scar formation bruising and dyspigmentation. Delayed healing
through hyperplasia besides the papillae arching up the and chances of relapses also accounts for possible disadvantages.
(12,15)
vasculature upwards into the wart. Eccentric nucleus of the

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 A. Maj, M. A. Siddique, Lt. Col. M. Hussain

Cryotherapies that have newly become available and are RESULTS

over-the-counter are not as cold as liquid nitrogen. These also Age range in this study was from 18 to 45 years with mean age of
possess the same types of side effects including pain, 32.366±8.61 years, while duration of disease was from 2 to 12
hypopigmentation and a “ring wart” (a Koebner response). The weeks with mean duration of 6.433±2.90 weeks. Mean age and
cure rate mentioned in literature varies from 39 to 92%, which duration of disease in group-A and group-B are shown in Table-I.
might be due to difference in using techniques. Aggressive
technique of usage may give better outcomes but may also be with Table-1: Mean±SD of patients according to age and duration of disease in
increased adverse effects.(16) both groups. n=60
In order to avoid these side effects and disadvantages, Demographics Group-A Group-B
alternative treatment options are tried in many studies. Adapalene Mean±SD Mean±SD
is a good choice among these which is a synthetic naphthoic acid (n=30) (n=30)
derivative. Being a third generation topical retinoid, it is able to Age (years) 32.2±8.60 32.533±8.77
Duration of Disease (weeks) 6.366±2.95 6.5±2.89
reverse keratinization as well as the affinity for retinoic acid
receptors, found in the epidermis. Available as 0.1% aqueous gel,
adapalene has anti-inflammatory action, modulates cell Frequency and percentage of male gender was dominant in
differentiation and inhibits cell proliferation. both groups as shown in Table- II.
Few studies with small number of patients have proven
Table-2: Frequency and percentage of patients as per gender in both
efficacy of topical adapalene for treatment of plantar warts in past groups. n=60
years. A study on 10 patients, done in 2011, with topical adapalene Gender Group-A Group-B
has shown complete disappearance of the lesions in an average of n=30 n=30
39 ± 15.07 days. (11) n (%) n (%)
Another study by same investigator , done in 50 patients Male 17 (56.66%) 16 (53.33%)
have shown to clear plantar warts earlier than cryotherapy Female 13 (43.33%) 14 (46.66%)
treatment.(13) A study done in Pakistan, published in 2020, has Total 30 (100%) 30 (100%)
shown that 1% adapalene and cryotherapy were equal in efficacy
in treating plantar warts.(17) Hence our study intended to compare The residential status of patients as being urban or rural is
the efficacy of topical 1% adapalene versus conventional therapy given in Table-III.
like cryotherapy in treatment of plantar warts to so that an
alternative can be suggested on the basis of more results for Table-3: Residential status of both groups. n=60
patients suffering from this ailment. Residential Status Group-A Group-B
n=30 n=30
n (%) n (%)
METHODOLOGY Urban 14 (46.66%) 17 (56.66%)
This randomized control study was conducted at the Department of Rural 16 (53.33%) 13 (43.33%)
Dermatology, Combined Military Hospital, Abbottabad, Pakistan, Total 30 (100%) 30 (100%)
from Feb 2022 to July 2022. A total of 60 patients coming to
hospital with complaints of having 1-3 plantar warts were After 8 weeks of initiating the treatment, treatment in group-A
randomized into two equal groups of 30 patients. Patients enrolled was significantly more effective in complete resolution of plantar
for the study on odd serial number were allocated to group-A, warts than treatment in group-B as shown in Table-IV.
treated with application of topical 1% adapalene gel overnight on
daily basis under occlusion with polythene sheet wrap and Table-4: Efficacy of treatment after 8 weeks of treatment in both groups.
advised for fortnightly follow up. While patients on enrolled for the Group-A Group-B p-value
study on even serial number were allocated to group-B for n=30 n=30
cryotherapy treatment for two freeze thaw cycles, done with liquid Efficacy n (%) n (%)
Yes 27 (90.00%) 20 (66.66%) 0.028
nitrogen at -196°C temperature using direct application by a
No 3 (10.00%) 10 (33.33%)
dipstick, conducted by paramedics under the supervision of the
Total 30 (100%) 30 (100%)
researcher of the study.
Fortnightly follow up was advised so that procedure can be
repeated if needed, assessed through the re appearance of skin DISCUSSION
texture. Depending upon the anatomical location and patient’s sensitivity,
The primary outcome was to measure the proportion of plantar warts can be either painful or non-painful. Presence of
patients with completely cleared warts on physical examination plantar warts on pressure-bearing areas such as the feet leads to
after 8 weeks from start of treatment. The thick skin areas were physical morbidity but it’s psychological as well. A therapy that is
pared before going through the treatment procedure in both the painless, resolves the lesions and leaves no scars in 1 to 3 visits
groups. can be taken as ideal.
Pregnancy, any systematic illness, patients on As in plantar warts, there are interruption of skin lines that is
immunosuppressive therapy, patients presenting with mosaic visible with naked eye and enhanced by viewing through
warts, those who had used any treatment of their plantar warts dermatoscope, reappearance of these skin lines throughout these
during last 4 weeks were excluded. Any patient who lost follow up lesions help the clinicians to evaluate the resolution of the wart.(16)
was also excluded. The modalities that are available for the treatment of plantar
Data was analyzed using SPSS version 26. The quantitative warts include physical destruction like cryotherapy, chemical
variables like age and duration of disease were calculated by destruction like salicylic acid and immunomodulator therapy like
taking means and standard deviation. The qualitative variables like retinoids.(14) The most conventional among these is the
gender and efficacy were calculated by frequencies and cryotherapy where liquid Nitrogen having a boiling point of -
percentages. Efficacy in two groups was compared by chi-square 195.6°C is used for this purpose. Kwock et al shared in their
test, where p-value of ≤0.05 was considered significant. results that the results of cryotherapy are comparable with the
Written consent was obtained from all the patients. results obtained with salicylic acid, which can be declared as gold
Ethical Approval: Permission for conducting study was taken standard modality.(15)
from ethical committee of Combined Military Hospital, Abbot Abad, Bruggink et al. shared the results of their study where they
Pakistan. found that cryotherapy when compared to salicylic acid is more
effective only in common warts but not for plantar warts. (18)

P J M H S Vol. 16, No. 12, December, 2022 513

Efficacy of Topical 1% Adapalene Versus Cryotherapy in Treatment of Plantar Warts

Cryotherapy is mostly painful. It does not work through killing It is suggested to conduct further studies with more number
the virus directly rather lead to a cell-mediated response via local of patients to confirm more advantages of using topical 0.1%
inflammation. There are new easily available cryotherapies, which adapalene gel under occlusion in treatment of plantar warts.
are not as cold as was the liquid nitrogen, but they also have
disadvantages in the shape of pain, hypopigmentation, a ring wart, CONCLUSION
blistering or a circular resurgence of the plantar wart (called This study has concluded that topical 0.1 % adapalene is more
Koebner response). Cure rates for cryotherapy is reported from effective than cryotherapy in the treatment of plantar warts. It is
39% to 92%, the difference is because of using different easy to use with at home administration so offer better patient
techniques described in literature.(16) compliance.
Keeping in view the above mentioned side effects, better Conflict of Interest: None.
alternative have been studied and used for treating plantar warts, Acknowledgements: The services of paramedic staff of the
an important one among these are retinoids. Among retinoids, department for data collection, performa filling and patient
adapalene is the one most commonly employed. With the use of education for application of treatment are acknowledged.
0.1% topical adapalene under occlusion, Gupta et al, reported that
39 ± 15.07 days was the total time taken for complete clearance of
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