Received: 8 June 2021 Revised: 21 July 2021 Accepted: 31 July 2021

DOI: 10.1111/dth.15083

ORIGINAL ARTICLE

Efficacy and safety of cryotherapy, electrodesiccation, CO2

laser, and Er:YAG laser in the treatment of seborrheic keratosis

Shirin Zaresharifi1,2 | Reza M. Robati1,3 | Sahar Dadkhahfar1 |

4 5
Mohammad-Mehdi Forouzanfar | Nooshin Zaresharifi

1
Skin Research Center, Shahid Beheshti
University of Medical Sciences, Tehran, Iran
2
School of Medicine, Shahid Beheshti
University of Medical Sciences, Tehran, Iran
3
Department of Dermatology, Loghman Hakim
Hospital, Shahid Beheshti University of
Medical Sciences, Tehran, Iran
4
Department of Emergency Medicine,
Shohada Tajrish Hospital, Shahid Beheshti
University of Medical Sciences, Tehran, Iran
5
Department of Pathology, Tehran University
of Medical Sciences, Tehran, Iran
Correspondence
Reza M Robati MD, Skin Research Center,
Shahid Beheshti University of Medical
Sciences, Tehran, Iran.
Email: rezarobati@sbmu.ac.ir
Abstract
Seborrheic keratosis (SK) is a common benign skin epidermal lesion. Different treat-
ment modalities have been proposed for this lesion. This study aimed to compare the
efficacy and safety of electrodesiccation, cryotherapy, CO2 laser, and Er:YAG laser in
the treatment of SK. The study was carried out on 30 patients each with four similar
facial SKs. Each lesion was assigned to be treated with cryotherapy, electrodesicca-
tion, CO2 laser, and Er:YAG laser in a random fashion. Therapeutic results were eval-
uated 8 weeks after the interventions through clinical and dermatoscopic
assessment. Treatment improvement criteria for each lesion included the texture of
the lesion, severity of the pigmentation, and an overall assessment of the healing.
The severity of burning, pain, erythema, and the duration of the erythema after the
procedures were documented. A survey of the patients' satisfaction with the treat-
ments was also performed. In the assessment of overall lesion healing by two derma-
tologists, the improvement rate was significantly higher in the CO2, Er:YAG lasers
and electrodesiccation group compared to the cryotherapy (p < 0.001). However, the
CO2 and Er:YAG laser and the electrodesiccation groups showed no significant dif-
ference (p > 0.05). Moreover, no significant difference was observed in post-
treatment pigmentation and texture between the groups (p > 0.05). The pain and
burning severity after the interventions were negligible in all four groups. Prolonged
erythema was not observed in any of the cases; however, the duration of erythema
in the Er:YAG laser group was significantly longer (p < 0.001). Patient satisfaction in
the cryotherapy group was significantly lower than the other three groups
(p < 0.001). The efficacy of treatment and patient satisfaction rate is highly compara-
ble between electrodesiccation, CO2 laser, and Er:YAG laser but significantly higher
than cryotherapy.

KEYWORDS
CO2 laser, cryotherapy, electrodesiccation, Er:YAG laser, seborrheic keratosis

1 | I N T RO DU CT I O N are usually multiple lesions.1 The most common sites of involvement

include the head and neck area followed by the trunk, and limbs.2
Seborrheic keratosis (SK) is one of the most common benign skin Patients usually seek treatment for SKs due to cosmetic issues,
lesions in outpatient dermatology visits, affecting over 83 million peo- irritation of the lesions, or any concern about the malignancy.3 Abla-
ple in the United States. Their prevalence increases by age and there tion and minimally invasive surgery remain the most preferred

Dermatologic Therapy. 2021;e15083. wileyonlinelibrary.com/journal/dth © 2021 Wiley Periodicals LLC. 1 of 7

https://doi.org/10.1111/dth.15083
2 of 7
modalities for the treatment of SK. Cryotherpy is a common method
in the treatment of SKs. However, regarding its risk of scarring and
dyspigmentation, it is sometimes less preferable by some experts.
Electrodesiccation and laser radiation including CO2 and Er:YAG
lasers are other available treatments.1
CO2 laser with a wavelength of 10,600 nm is widely used in the
4
treatment of cutaneous lesions and skin resurfacing. Although CO2 laser
is safe, some patients may experience adverse effects including scarring,
hyperpigmentation, hypopigmentation, and infections.5 Er:YAG laser with
a wavelength of 2940 nm is another widely practiced laser in dermatol-
ogy used for purposes such as ablation of benign epidermal lesions,
improving skin pigmentation and scars. The Er:YAG laser has a lower
absorption depth than the CO2 laser. Its complications are usually mini-
mal and include dyspigmentation and bleeding.6–8 According to the publi-
shed literature, laser ablation of the SK lesions has shown comparable
and effective results compared to cryotherapy but with lower complica-
tions; however, the findings are limited and further studies are necessary.
To the best of our knowledge, limited studies are available in the
literature about the evaluation and comparison of the treatment
modalities commonly used for the resolution of SKs. The present
study aimed to compare the therapeutic outcomes and patients' satis-
faction with electrodesiccation, cryotherapy, CO2 laser, and Er:YAG
laser in the treatment of SKs.
2 | P A T I E NT S A N D M E TH O D S
This clinical trial was conducted on patients with SK lesions who vis-
ited our dermatology clinic in Shohada-e Tajrish Hospital from
December 2018 to June 2020. This study was approved by the ethics
committee or our center (IR.SBMU.SRC.REC.1398.003) and was per-
formed according to the principles of the Declaration of Helsinki.
Written informed consent was signed by all volunteers after a thor-
ough explanation of all the procedures and possible complications.
The protocol was also approved by the Iranian Registry of Clinical Tri-
als (IRCT20141228020468N5).
Forty-two volunteers with multiple facial SKs lesions were
included in the study. Four lesions with similar characteristics regard-
ing their size and pigmentation were selected on each patient's face.
Each lesion was randomly assigned to a group of cryotherapy, electro-
desiccation, CO2 laser, and Er:YAG laser treatments in a 1:1:1:1 ratio.
Inclusion criteria were patients 35–85 years of age, and at least four
pigmented SK lesions with similar size and characteristics on the face.
Exclusion criteria were history of keloid formation, coagulation disorder
or the use of drugs involved in coagulation, uncontrolled diabetes,
uncontrolled hypertension, active infection in the area, unwillingness or
inability to seek follow-ups at the scheduled time, history of inherited or
acquired connective tissue disease, sensitivity to lidocaine or tetracaine,
cryoglobulinemia, cold urticaria, and cold intolerance.
Concerning the beginning of the COVID-19 pandemic, the patients
were all contacted and asked about their symptoms including burning,
pain, and erythema by phone during the first week and at the end of the
second week postprocedure to reduce their visits in the clinic. Eight
ZARESHARIFI ET AL.
weeks after the treatment session, the patients were requested to visit
the clinic for further evaluation and dermatoscopy of the lesions.
Lesions were photographed at the baseline and 8 weeks
postprocedure with a digital camera in a room with constant light.
Dermoscopy using FotoFinder digital dermoscopy (at 20 fold magnifi-
cation) was also performed for each lesion (FotoFinder®TeachScreen
Systems software GmbH; Bad Birnbach, Germany). Photographs of
the lesions were analyzed and assessed by two board-certified derma-
tologists in a blinded fashion.
We evaluated the pigmentation and texture alterations as well as
overall improvement in each lesion. Evaluation criteria included lesion
color which was scored from 5 (most hypopigmented) to +5 (most
hyperpigmented); lesion texture scale, scored from zero (most ele-
vated) to 10 (flat); and also an overall lesion improvement score
ranged from zero (unchanged) to 10 (normal-appearing skin). All the
scores were in an ordinal fashion. Two weeks after the treatment ses-
sion patients were contacted and asked to rate the severity of pain,
burning, and erythema based on a 10-point ordinal scale for each
lesion, and the results were documented. The severity of these symp-
toms ranged from zero (no symptom) to 10 (the most extreme). Dura-
tion of the symptoms was also documented regarding the number of
days they lasted.
2.1 | Settings of the interventions and
technical data
Cryotherapy was performed with direct application of the liquid nitro-
gen by the open spray method for 10 seconds as a single freeze–thaw
cycle. Local anesthesia was induced with the injection of 0.2–0.5 cc
lidocaine 2% 15 min before the interventions for Er:YAG laser, CO2
laser, and electrodesiccation. The Er:YAG laser (Lotus II; Laseroptek
Co., Ltd., Sungnam, Gyenggido, Korea) was used with a zoom hand-
piece, short pulse (350 μs) mode, a spot size of 4 mm, the fluence of
5.662 J/cm2, pulse energy of 400 mJ, and a repetition rate of 3–5 Hz.
CO2 laser (MIXEL; Hironic Co., Ltd., Sungnam, Korea) was used with
the surgical mode, the fluence of 2.5 J/ cm2, pulse duration of 0.4 sec-
onds, frequency 2.5 Hz, and a spot size 4 mm. The electrodesiccation
was performed by the mode of biterminal using a monopolar fine-
tipped electrode. The electrosurgical generator unit (MEG1, Kavandish
System, Tehran, Iran) was set to a low setting (3–5 watts).
The clinical endpoint of treatment was crusting and removal of
the lesion with the lowest possible energy. The crust was then wiped
off with saline-soaked gauze. After the procedure, the lesions were
covered with zinc oxide cream and dressing. Patients were instructed
about postprocedure wound care, reapplication of zinc oxide oint-
ment, and sun protection.
2.2 | Statistical analysis
Data were analyzed by using SPSS Statistics for Windows, Version
24.0 (IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY:
ZARESHARIFI ET AL. 3 of 7

IBM Corp). Quantitative data were expressed with a mean (±SD) and and other groups (p < 0.001). Erythema duration was less than
qualitative data with percentages. Friedman's test was used for com- 2 weeks in all groups. Erythema duration was longer (about 2–4 days)
parisons. Findings are significant with p < 0.05. in the Er:YAG comparing to other groups (p < 0.001) (Table 2).

3 | RESULTS 3.3 | Patient satisfaction

A total of 42 patients enrolled to participate in this study and under-
went randomization for therapeutic interventions. Thirty patients with
Fitzpatrick skin phenotype of II to IV have completed the trial. Twelve
patients were lost to follow-up, mainly due to the restrictions in the
COVID-19 pandemic. The mean age was 61.8 ± 1.3 years. The mini-
mum and the maximum were 45 and 82 years, respectively. 21 (70%)
participants were male and 9 (30%) were female.
The mean patient satisfaction scores ranged from 8 to 9.5 indicating
that all interventions were acceptable by the patients, with no notice-
able discomfort. However, the mean satisfaction score in cryotherapy
was significantly lower than the other three groups (p < 0.001). The
patient satisfaction score difference between the other three groups
was not statistically significant (Table 3).

3.1 | Lesion texture, pigmentation, and overall
improvement score
After treatments, almost all lesions were flat. A score of 10 or close to
10 indicates that the lesions were well aligned with the healthy skin
around them. The groups were not significantly different regarding
their texture (p = 0.9) (Table 1).
The mean pigmentation score of the lesions for all groups was close
to zero indicating that the treatment site had the same color as the sur-
rounding skin or was slightly more hypopigmented. The four groups
were not significantly different in this regard (p = 0.8) (Table 1).
The overall improvement score of lesions in the cryotherapy
group was 8.3 ± 1.2; however; it was more than nine in all other
groups (Table 1). In the intergroup comparison, the mean score of the
overall improvement of lesions in the cryotherapy group was signifi-
cantly lower than the other three groups (p < 0.001) (Figures 1, 2).
3.2 | Pain, burning, and erythema
There was no significant difference between the groups in terms of
pain and burning sensation, and in all cases, it was close to zero
(p > 0.05) (Table 2). The pain and burning sensation if present were
mild and lasted only a few hours postprocedure.
Erythema severity showed a difference among the groups
(Table 2). This difference was only significant between Er:YAG laser
T A B L E 1 Lesion texture, pigmentation, and overall improvement
score after 8 weeks
Groups (n = 30) Texture Color Overall healing
4 | DI SCU SSION
There are some comparative studies upon the efficacy of cryotherapy,
electrodesiccation, CO2, or Er:YAG lasers in the treatment of different
skin lesions such as actinic keratosis, cherry angiomas, and solar
lentigo.9–11 Our study aimed to compare the efficacy and safety of
electrodesiccation, cryotherapy, CO2, and Er:YAG lasers in the treat-
ment of SK lesions. However, few studies compared the efficacy and
safety of these therapeutic options in the treatment of SK. To the best
of our knowledge, this is a distinctive study upon the comparison of
all these four therapeutic interventions both clinically and by
dermoscopy in the treatment of SK.
Based on the currently available literature, most comparison
results were in line with our present study. In a study by Ali et al.,
comparing CO2 laser and electrodesiccation on SK lesions, all lesions
were resolved completely with no significant difference in the aes-
thetic outcome; the risk of complications was also statistically similar
between the two methods.12 Gruel et al. investigated the effect of Er:
YAG laser and cryotherapy in SK treatment on 42 patients. After the
first session of treatment, 100% of lesions healed with Er:YAG laser
and 68% with cryotherapy, which showed a significant difference.
The rate of hyperpigmentation was lower in the former group.13 In a
study by Wood et al., cryotherapy was significantly preferred over
curettage by both physicians and patients due to less hypopigmented
scarring and postoperative wound care.14 In the study of Ethington
et al., both electrodesiccation and cryotherapy showed similar efficacy
in the treatment of SK lesions and there was no significant difference
in the terms of patient satisfaction; there was a nominal but not statis-
tically significant difference in the posttreatment hyperpigmentation
favoring cryosurgery over electrodesiccation group.15
According to the currently available literature and the present
study, all four treatment methods are largely comparable in efficacy

CO2 laser 10 ± 0 0.2 ± 0.7 9.4 ± 0.9 and safety; however; there is a slight difference in the posttreatment
complications and cosmetic results.12,15
Electrodesiccation 10 ± 0 0.1 ± 0.7 9.2 ± 1
Up to 80% of people with SK lesions, particularly women, have
Cryotherapy 9.8 ± 0.6 0.03 ± 1.4 8.3 ± 1.2
a significant desire for SK removal. Concerns about the possible
Er:YAG laser 10 ± 0 0.3 ± 1 9.3 ± 1.1
posttherapeutic complications including postinflammatory dyspigmen-
p value 0.9 0.8 <0.001
tation and scaring are the major setbacks of treatment.16
4 of 7 ZARESHARIFI ET AL.

F I G U R E 1 The clinical images of the lesions at the baseline (A) 2 weeks (B) and 8 weeks (C) after the cryotherapy (1), CO2 laser (2), Er:YAG
laser (3) and electrodesiccation (4)

Posttreatment dyspigmentation is potentially more important for interventions.17 Fortunately, in the present study, the texture of the
CO2 lasers than Er:YAG due to the greater depth of thermal damage. lesions treated with all the modalities was highly comparable to the
Scarring is another potential complication in all investigated healthy surrounding skin. This finding is consistent with other studies
ZARESHARIFI ET AL.
F I G U R E 2 The dermoscopic images of the
lesions at the baseline (A) and 8 weeks after the
cryotherapy (1), CO2 laser (2), Er:YAG laser (3) and
electrodesiccation (4)
on Er:YAG, CO2 lasers, electrodesiccation, and cryosurgery in SK
treatment.12–14 The development of persistent erythema after these
interventions is another important complication. In the present study,
the lesions in all four groups developed transient erythema after the
interventions, which faded in 1–2 weeks. The duration of erythema
was about 2–4 days longer in the Er:YAG laser compared to other
5 of 7
groups. Skin phenotype and depth of tissue damage are major factors
contributing to prolonged erythema. In addition, long-term erythema
increases the risk of postinflammatory hyperpigmentation.12,18 Similar
to the present study, no persistent erythema was reported in the
available literature. As SKs are benign epidermal lesions and superfi-
cial, low energy ablation is the optimal route of the treatment.12–14
6 of 7 ZARESHARIFI ET AL.

T A B L E 2 Severity of pain, burning,

Groups (N = 30) Pain Burning Erythema Duration of erythema
erythema and duration of erythema after
CO2 laser 0.03 ± 0.2 0.03 ± 0.2 2.8 ± 1.3 9.6 ± 3.3 interventions
Electrodesiccation 0.03 ± 0.2 0.1 ± 0.4 2.3 ± 1.4 8.4 ± 3.9
Cryotherapy 0.03 ± 0.2 0.2 ± 0.6 2.5 ± 1.4 7.8 ± 4.9
Er:YAG laser 0.07 ± 0.4 0.1 ± 0.4 3.1 ± 1.4 11.9 ± 4.7
p-value 0.4 0.2 <0.001 <0.001

TABLE 3 Patients' satisfaction score Sahar Dadkhahfar: Performed the dermoscopic assessments,
acquired the data and wrote the manuscript.
Groups (n = 30) Mean SD Min Max p value
Mohammad-Mehdi Forouzanfar: Contributed to manuscript prep-
CO2 laser 9.4 1.9 7 10 <0.001
aration and editing.
Electrodesiccation 9.5 1.9 7 10
Nooshin Zaresharifi: Acquired the data and wrote the manuscript.
Cryotherapy 8 2 6 10
All authors contributed sufficiently and met the criteria for
Er:YAG laser 9.1 2.6 6 10
authorship.

DATA AVAILABILITY STAT EMEN T

The primary limitations of this study were the restricted num-
ber of participants and follow-up sessions mainly due to the social
effect of the COVID-19 pandemic. Moreover, only the patients
with facial pigmented SKs were included in our study. The out-
come may vary in non-pigmented or extra facial lesions. Further
studies with larger sample sizes, including lesions with other prop-
erties and locations, could be beneficial to elucidate any difference
in the efficacy and safety of different modalities in the treat-
ment of SK.
In summary, the efficacy of treatment and patient satisfaction
rate was highly comparable with electrodesiccation, CO2 laser, and
Er:YAG laser but significantly higher than cryotherapy. Moreover, all
four methods showed acceptable clinical efficacy in the treatment of
SK lesions with no major or persistent side effects. Therefore, less
expensive and more available therapeutic methods including electro-
desiccation and cryosurgery could be considered as an appropriate
and highly efficient alternative to laser therapies particularly in
patients with multiple SK lesions to get the best outcome and
decrease their expenses.
ACKNOWLEDGMENTS
This paper has been extracted from the dermatology residency thesis
written by Dr. Shirin Zare-Sharifi in School of Medicine, Shahid
Beheshti University of Medical Sciences, Tehran, Iran (registration no
98.177).
CONF LICT OF IN TE RE ST
The authors declare there is no potential conflict of interest.
AUTHOR CONTRIBUTIONS
Shirin Zaresharifi: Designed this project, acquired the data and wrote
the manuscript.
Reza M Robati: Designed and supervised all aspect of the project,
served as the corresponding author and wrote and edited the
manuscript.
The data that support the findings of this study are available on
request from the corresponding author. The data are not publicly
available due to privacy or ethical restrictions.
OR CID
Shirin Zaresharifi https://orcid.org/0000-0003-4002-6953
Reza M. Robati https://orcid.org/0000-0002-7947-8642
Sahar Dadkhahfar https://orcid.org/0000-0003-4058-2562
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