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CLINICAL MANAGEMENT RECOMMENDATION 
 

 

Clinical Management of Actinic Keratosis: Review and Update 
 

Haowei Han, DO1, Daniela K. Berman, AA2, Brian Berman MD, PhD1, 3  
 
1 Center for Clinical and Cosmetic Research, Miami, FL 
2 University of California Berkeley Plant Gene Expression Center, University of California, Berkeley, Berkeley, CA 
3 Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, FL  
 

 

 
 

 
 
Actinic keratosis (AK), also known as senile 
keratosis or solar keratosis, was first 
described by Dubreuilh in 1826.1 Later in 
1958, Pinkus renamed this lesion as actinic 
keratoses.1 2 AK literally means thickened, 
scaly growth caused by electromagnetic 
radiation.3 It commonly presents as ill-
bordered macules, papules or plaques, 
maybe covered with dry scales or showing 
varying degree of hyperkeratosis. The color 
of AK ranges from pink to erythematous to 
brownish, in cases of pigmented AK. AK 
frequently locates at the sun exposed area, 
and sometimes, they are better pinpointed by 
palpation than visualization.4 In majority of 
the cases, AK are asymptomatic albeit some 
patients may report burning or pruritus 
sensation.1 5 The key risk factor for 
developing AK is cumulative sun exposure.6 
An epidemiology study in Turkey with 54,786 
patients from outpatient dermatology clinic 
found that the AK prevalence was 4.61% for 

patients between 60 and 69 years old, 9.38% 
for patients between 70 and 79 years old, and 
14.57% for patients ≥80 years old. AK 
prevalence was 2.50% across all age 
groups.5 The author concluded that AK 
prevalence was higher in patients >60 years 
of age and most commonly in patients >80 
years of age. Furthermore, AK was more 
prevalent in males and in patients with 
Fitzpatrick skin types 2 and 3.5 Another 
epidemiology study in Netherlands examined 
various risk factors and revealed that male 
sex, the age of 70 years or older, Glogau 
scale 3 and 4, and the tendency to develop 
sunburn were significantly associated with 
the development AK.7   
 
On dermoscopic examination, non-
pigmented facial AKs typically manifests as a 
“strawberry pattern” which entails an 
erythematous vessel pseudo network, 
prominent follicular openings, and a 
surrounding white halo.4 A few histological 
and clinical subtypes of AK were described in 
the literature, for instance, hypertrophic, 

ABSTRACT 

Actinic keratosis is commonly seen in dermatology clinics. Age and chronic sun exposure are the 
essential risk factors for its pathogenesis. It is regarded as a premalignant lesion; hence, aggressive 
treatment is warranted. Abundant research has been published about overall management, however, 
extensive knowledge about actinic keratosis prevention, the cost, safety profile, and mechanisms of the 
existing therapeutics are pivotal in optimal clinical care. In this review article, we hereby present several 
commonly used approaches in office settings and the current guidelines. Finally, we will discuss the 
limitations of the available clinical evidence.  

 

INTRODUCTION 

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atrophic, AK with cutaneous horn, 
pigmented, actinic cheilitis, acantholytic, and 
hyperplastic.3 8 A common histological 
feature is atypical keratinocytic proliferation 
confined in the epidermis.3 It is regarded as 
the spectrum along the continuum to 
squamous cell carcinoma (SCC).9 Although 
the rate for individual AK to progress into 
SCC is low, but 82.4% of SCCs were 
developed from AK directly or from tissue that 
is adjacent to AK lesions.10 AK is principally 
caused by sun exposure, or ultraviolet B (UV-
B) radiation (wavelength 290–320 
nanometer). Particularly, UV-B induces the 
formation of thymine dimer in DNA structures 
which leads to mutations in the telomerase 
gene and p53 gene, the tumor suppressor 
gene. Telomerase is the key enzyme to 
regulate cellular death. Increase in 
telomerase activity delays the programmed 
cell death and keeps cells immortal or keep 
proliferating unstoppably. Neoplastic 
keratinocytes, which are seen in over 90% of 
invasive SCC, are also frequently present in 
AKs.11 12 P53 gene is located on 
chromosome 17p13 and normally arrest the 
cell cycle and allow the repair of damaged 
DNA. Dysregulation of p53 pathways results 
in the uncontrolled growth and proliferation of 
damaged keratinocytes, and potentially 
neoplastic cells. This is suggested to be an 
early phase in SCC carcinogenesis, so that 
cancer can start to prosper and progress.12 A 
prospective large population study in 
California followed patients with and without 
AK (served as the control group) for 10 years 
and found the annual risk of acquiring SCC 
for AK group was 1.92% compared to 0.83% 
for the control group. At the final 10 years end 
of study time point, the incidence of SCC was 
17.1% in AK group while the incidence of 
SCC was 5.7% among control patients.6 With 
that being said, the early detection and 
treatment, patient education, and sun 
protection are critical for the overall 
management as well as efforts to decrease 

the healthcare burden. In this article, we 
herein present some approaches to prevent 
and manage AK based on the available 
literature and our own clinical experience. 
 

 
 
Inarguably, sun protection is the most 
paramount approach to prevent not only AK 
but skin cancers as well. This conclusion was 
well established by several clinical trials.13 14 
The American Academy of Dermatology 
(AAD) website recommends patients avoid 
tanning beds and protect themselves by 
applying broad spectrum sunscreen daily 
with a SPF (sun protection factor) of 30 or 
higher. It also emphasizes the cruciality of 
routine self-body skin check and 
dermatologist visits.15 
 
Studies have further investigated topical 
chemoprevention for AK. A randomized, 
placebo-controlled trial with 283 individuals 
showed that topical application of 5-
fluorouracil at the face and ears resulted 41% 
fewer new lesions at 24 months compared to 
placebo group.16 A similar study was reported 
with over 900 participants. Patients were 
instructed to apply either 5% fluorouracil 
cream or placebo on the face or ears twice 
daily for up to 4 weeks. The treatment group 
had fewer non-hypertrophic AK lesions at 6-
month and 42-month follow-up visits. 
Reciprocally, the number of hypertrophic AK 
didn’t differ significantly in both groups at 42-
month.17 A pooled analysis of two trials 
compared long term efficacy of imiquimod 
5% cream and diclofenac 3% gel. The 
investigators observed superior result with 
imiquimod, 5% cream in multiple parameters, 
less percentage of histological changes to 
grade III AK or even SCC, greater time for 
neoplastic changes to occur, less proportion 
with malignant transformation into invasive 
SCC, and lower AK recurrence rate.18  

PREVENTION 

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AK is often recognized as a field disease 
rather than a single clinically apparent lesion. 
The theory, field cancerization, contemplates 
that the skin proximal to AK lesions also 
carries a higher risk of malignancy due to 
shared chronic solar radiation.19 Therefore, 
field treatments are commonly applied. It not 
only tackles the clinically perceptible lesions, 
but also the subclinical ones that may 
potentially progress into AK or even SCC.20 
Cryotherapy is commonly used when there 
are only a handful of visible or palpable 
lesions. Field treatment targets a certain 
anatomical region, including topical 
imiquimod, 5-fluorouracil (5FU), and 
photodynamic therapy (PDT). The commonly 
used monotherapies are listed in Table 1. 
The treatment regimen for United States 
Food and Drug Administration (FDA) 
approved field therapies were listed in Figure 
1.  
 
Single Lesion 
 
Liquid Nitrogen Cryotherapy 
 
Cryotherapy, the mainstay treatment for AK, 
is fast, inexpensive and can be easily done in 
the office setting. Either direct spray or probe 
may be used to deliver liquid nitrogen. The 
freezing time ranges from 5 to 10 seconds, 
and the “ice ball” should extend at least 1 
millimeter beyond the clinical margin of AK. 
Depending on the degree of hyperkeratosis, 
multiple freeze-thaw cycles may be required. 
Cryotherapy causes local tissue damage and 
heals by secondary intention.21 With that  
being said, cryotherapy often leads to 
transient patient discomfort. Other side 
effects may be seen in certain individuals, for 
instance, hypopigmentation, scaring, and 

prolong wound healing, thus, patient 
education and wound care instructions need 
to be provided for desired clinical 
outcomes.21  
 
Field Treatment 
 
Imiquimod 
 
Imiquimod is an immune response modifier 
that belongs to the imidazoquinolines drug 
class and upregulates several key cytokines. 
It binds to the Toll-like receptor 7 and 
releases interferon-alpha, which leads to 
activation of the T helper type 1 (Th1) 
response. It has both anti-viral and anti-
tumoral effects.22 23 In sum, imiquimod comes 
with three different concentrations and is only 
approved for immunocompetent individuals. 
The efficacy and the safety profile of 
imiquimod was well illustrated in several 
randomized Phase III clinical trials and meta-
analyses.24 25 26 27 23 The most common side 
effects were treatment site reactions, such as 
erythema, ulceration, blistering, erosion, 
edema and influenza like symptoms.4 28 
Many of the side effects were well tolerated 
and short-lived. Interestingly, case study has 
tried to apply 5% cream imiquimod on human 
skin to an area over 300 square centimeters 
(cm2), suggesting a more efficient use of this 
medication.29 
 
Tirbanibulin  
 
Tirbanibulin works by inhibiting tubulin 
polymerization and upregulating p53 
expression. It also arrests rapidly dividing 
cells at the interphase Gap 2 and mitosis, 
subsequently induces apoptosis.30 In 2020, 
FDA licensed topical tirbanibulin 1% ointment 
as a field treatment of AK to up 25 cm2 
contiguous area of the face or scalp.31 The 
clinical data of tirbanibulin was found on two

CLINICAL MANAGEMENT 

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Figure 1. FDA-approved, topical field therapies and total applications 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



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Table 1. Commonly used monotherapies for single AK or field treatment (5-FU: 5 fluorouracil; ALA: 5-
aminolevulinic acid; FDA: Food and Drug Administration; MOA: mechanism of action, PDT: photodynamic therapy; 
RCT: randomized clinical trials, SE: side effects,)4 21 22 30 34 37 48 46 51  
 

Treatment  
 

MOA Side Effects Clinical evidence FDA indication Treatment 
regimen 

Single lesion 

Liquid Nitrogen 
Cryotherapy 

Damage the tissue 
and re-epithelialize 

Patient discomfort, 
hypopigmentation, 

scarring, and 
prolong wound 
healing. 

Few meta-analysis 
and systematic 

review 

Not available 
information 

Freeze the 
clinically visible AK 

for 5-10 seconds 
per cycle. and the 
“ice ball” should 

extend at least 1 
millimeter beyond 
the margin of AK. 

Multiple freeze-
thaw cycles may 
be required for 

thick lesions. 
Wound care 
instruction will be 

provided to the 
patient. 

Field treatment 

imiquimod 2.5% 
cream 

Upregulate 
immune response 

Treatment site 
reactions 

(erythema, 
ulceration, 
pruritus, blistering, 

erosion, edema), 
influenza like 
symptoms 

several Phase III 
RCTs and meta-

analysis.  

AK on the face or 
scalp in 

immunocompetent 
adults 

Once per day 
overnight for about 

8 hours X 2 weeks 
--> 2 weeks of 
treatment free 

period --> 2 weeks 
of treatment. 

imiquimod 3.75% 

cream 

AK on the face or 

scalp in 
immunocompetent 
adults 

Once per day 

overnight for about 
8 hours X 2 weeks 
--> 2 weeks of 

treatment free 
period --> 2 weeks 
of treatment. 

Imiquimod 5% 
cream 

non-
hyperkeratotic, 

non-hypertrophic 
AK on the face or 
scalp in 

immunocompetent 
adults 

One 
application/day, 

2times/week X 16 
weeks, maximum 
area of 25 cm2 per 

application 

5-FU (varying 

concentration from 
0.5% to 5%) 
cream or solution  

inhibiting DNA and 

RNA replication 
and increase 
expression of p53 

Treatment site 

reactions 

several Phase III 

RCTs and meta-
analysis.  

Topical treatment 

of multiple AK 

Apply cream or 

solution twice daily 
for 2-4 weeks. 

Conventional PDT 
(10% 5-
aminolevulinic 

acid/methyl 
aminolevulinate + 
red light/blue light) 

Photosensitizer is 
activated by light 
source and 

generates reactive 
oxygen species 
(ROS), which 

causes selective 
cellular damage 

Treatment site 
reactions, itchy, 
edema, post-

inflammatory 
pigment changes. 

Multiple RCTs 10% ALA gel + red 
light: single or field 
AK on the scalp 

and face 
 

Photosensitizer 
application -> 
incubation time of 

several hours -> 
exposure to light 
source. Patients 

are educated for 
sun protection for 
several days after 

PDT. 
 

BF-200 ALA PDT Stabilize ALA and 
increase 
epidermal 

penetration.  

Multiple Phase III 
RCTs 

Europe: facial and 
non-facial AK  
United States: 

mild-moderate AK 
on face/scalp 

Day Light PDT 

(DL-PDT) 

Same as 

conventional PDT  

Less pain and 

inflammation than 
conventional PDT 

Multiple RCTs Not available Photosensitizer 

and sunscreen 
without physical 

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blocker were 
applied topically-

>outdoor for 2 
hours-> stay 
indoor for the rest 

of the day.  

Tirbanibulin 1% 

ointment 

Inhibit tubulin 

polymerization and 
upregulate P53 
expression 

Treatment site 

reactions, pain, 
pruritus 

Two identically-

designed, phase 
III RCTs 

AK to up 25 cm2 

contiguous area of 
the face or scalp 

One packet (2.5 

mg tirbanibulin in 
250 mg) once /day 
for 5 consecutive 
days 

Topical diclofenac 
3% in 2.5% 

hyaluronic acid 
(DFC/HA) 

Inhibits the 
cyclooxygenase-1 

and 
cyclooxygenase-2 
and decreases 

arachidonic acid 
(AA) byproduct 

Pruritus, contact 
dermatitis, dry 

skin. 
Milder 
inflammatory 

response than 5-
FU.  

Several Phase III 
RCTs and meta-

analysis 

AK Topically apply 
twice/day for 60-

90 days 

Ingenol Mebutate 

(IMB) (0.015% gel 
and 0.05% gel) 

Disruption of 

plasma membrane 
and mitochondria. 
It also triggers 

cytotoxic reaction 

Pain, 

hypopigmentation. 

Several Phase III 

RCTs 

United States: AK  0.015% gel: once 

daily 3 days on 
face or scalp 
 

0.05% gel: once 
daily for 2 days on 
the truck or 

extremities.  
 
Treatment area 

should be less or 
equal to 25 cm2 

 

identically-designed phase III randomized 
clinical trials. In these trials, LSR(local skin 
reaction) scores were recorded from baseline 
to day 57.30 The LSR score composed of six 
components: erythema, flaking/scaling, 
crusting, swelling, vesiculation/pustulation, 
and erosion/ulceration. Each parameter was 
evaluated by a 0-3 scoring system, the sum 
of all parameters was calculated as the LSR 
score. Significantly higher complete 
clearance (CC, 100% reduction in lesion 
counts at day 57) and partial clearance rate 
(75% reduction in lesion counts at day 57) 
were observed in the treatment group than 
placebo group. The patients who achieved 
CC also had a recurrence rate of 47% at 1 
year follow up. The most common adverse 
effects were treatment site pain and pruritus, 
which regressed spontaneously. No one had 
exited the study due to any adverse event.30 
Nevertheless, case studies have 
demonstrated successful topical application 
of more than 25 cm2 on human skin, 
potentially making tirbanibulin more cost-
effective.31  

Two post-hoc analyses of the two Phase III 
tirbanibulin trials were reported. One 
compiled the LSR score from baseline to day 
57 in 174 patients in the treatment group who 
achieved CC. 26.5% of patients (46 out of 
174) had LSR ≤3 and 70.2% patients had 
LSR ≤5. The conclusion further supported 
that tirbanibulin is well tolerated by study 
patients.32 Another one examined several 
factors and found AK on the face and fewer 
lesions at baseline were indicator for 
treatment success whereas Fitzpatrick skin 
type, body-mass index (BMI), and prior AK 
therapies were not associated to desired 
clinical outcome.33 Overall, the advantage of 
tirbanibulin is relatively short treatment 
course and the ease to apply the medication 
at home, and high patient compliance, 
however, the price may be a concern.  
 
5-Fluorouracil (5-FU) 
 
Systemic fluorouracil has been used to cure 
various malignancies for decades.34 Its 
underlying mechanism involves inhibiting 

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thymidylate synthetase and other key steps 
in DNA and RNA replication, as well as 
increasing the expression of p53.34 
Capecitabine is an oral prodrug converted to 
fluorouracil via a 3-step enzymatic process, 
ultimately by thymidine phosphorylase, an 
enzyme often overexpressed in cancerous 
cells. 15 high-risk solid organ transplant 
recipients (>2 new non-melanoma skin 
cancers in the past 6 months or >10 new AKs 
in the past 12 months) received low dose oral 
capecitabine (1g/m2 twice daily for 14 days 
and off treatment for 7 days per 21 days 
treatment cycle). Their mean incidence rate 
of AKs was 4.77 per month before treatment 
and 2.32 per month during treatment.35 
Topical fluorouracil comes with varying doses 
and vehicles. The most common side effects 
were local inflammatory reactions, such as 
erythema, blistering, erosions.36  
 
Photodynamic therapy (PDT) 
 
The protocol of PDT starts with topically 
applying a photosensitizer, typically 5-
aminolevulinic acid (ALA) or methyl 
aminolevulinate (MAL) over the treatment 
area, proceed by an incubation period of 
several hours, and finally exposing to a light 
source. The photosensitizer has a high 
affinity for rapidly proliferating cells and 
pilosebaceous units. It acts as a prodrug and 
is converted to reactive oxygen species 
(ROS) when exposing to light with 
appropriate wavelength (470-700 nm), finally 
causes cytotoxic damages.37 38  
 
Although the efficacy, safety profile, and 
excellent cosmetic result of PDT were 
demonstrated in multiple randomized clinical 
trials, the reported protocols were non-
uniformed, with heterogeneities in length of 
incubation period, photosensitizer 
concentrations, setting of the illuminator, 
whether an assistive laser was used, and etc. 
Classically, 10% ALA gel and red light 

illuminator was approved by the FDA. A split 
face of 40 patients with 4-8 AK lesions 
underwent application of either 10% or 20% 
ALA gel followed by 1000 second blue light 
illumination revealed both regimens were 
equally effectively, but the 20% ALA gel 
application had a more robust local 
inflammatory reaction.39 
 
The most common side effects of PDT were 
treatment site pain, inflammation, and 
burning, especially after sunlight exposure. 
Many innovative PDT approaches aimed to 
mitigate treatment related pain. Martin 
documented a novel PDT intervention on the 
face that consisted of a 15 minutes 
incubation period of ALA followed by 60 
minutes of blue light. This novel intervention 
also had an equivalent efficacy with the 
conventional PDT with minimal pain and 
discomfort.40 Similarly, another split 
face/scalp study compared conventional ALA 
PDT protocol (incubate for 1 hour and blue 
light for 1000 second) versus modified 
protocol (blue light immediately following ALA 
application). Consequently, all patients in the 
modified protocol group reported significantly 
less pain than the control group and the 
efficacy were similar in both groups.41 
Another evolutionary modality is the daylight 
PDT (DL-PDT). A photosensitizer, typically 
ALA, as well as a sunscreen without physical 
blocker of ultraviolet light (titanium oxide or 
zinc oxide) were applied topically followed by 
exposing the patient to sunlight for two hours. 
Afterwards, patients are instructed to remove 
the excessive photosensitizer and stay 
indoors for the rest of the day. DL-PDT can 
be done anytime of the year in countries that 
are south to latitude 45° north, which 
encompasses most of Europe and the United 
States, South America, and Australia. 
Optional outdoor temperature should be 
more than 10°C, otherwise, it would be too 
cold for the elderly patients. Besides almost 
pain free, other advantage of DL-PDT are the 

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affordability and simplicity to perform in office 
setting.42 Several studies had proved that DL-
PDT are equally efficacious with conventional 
PDT. 43 44 One of the drawback of DL-PDT is 
the uncontrollability of natural weather, 
alternative light emitting sources, such as 
lamp illuminator, were also discussed to 
solve this problem.45  
 
Another creative modification is the nano-
sized emulsion integrated 7.8% ALA gel, 
namely BF-200 ALA, that stabilizes the ALA 
molecule and augments epidermal 
penetration. It is marketed for AK in facial and 
non-facial regions in Europe. Conversely, it is 
only authorized for managing AK on the face 
in the United States.46 47 
 
Topical Diclofenac (DFC)  
 
Topical diclofenac is a non-steroidal anti-
inflammatory drug (NSAID), which inhibits 
the cyclooxygenase-1 and cyclooxygenase-2 
and decreasing arachidonic acid (AA) 
byproduct. The AA byproduct are thought be 
to the culprit of tumorigenesis.48 A bilateral 
comparison study of DFC and 5-FU showed 
that DFC had a milder inflammatory reaction 
despite longer treatment course.49  
 
Ingenol mebutate (IMB) 
 
IMB incites local necrosis via disruption of the 
mitochondria and cellular plasma membrane. 
It also trigger cytotoxic reactions to specific 
tumor cells.50 51 It is only authorized to use in 
the United States, but not in European 
countries due to reported higher risk of non-
melanoma skin cancer (NMSC) in IMB 
compared to imiquimod cream during the 
post-marketing surveillance.52 

 
Comparison of Various Treatment 
Options 
 

Direct comparison of distinct modalities is 
scarce. A prospective trial in Netherlands 
aimed to evaluate the efficacy of four field 
treatments (5% 5-FU cream, 5% imiquimod 
cream, MAL PDT, and 0.015% IMB gel) for 
AK enrolled 624 patients who were randomly 
treated with either approach. At the 1-year 
end of treatment, the success rates were: 5-
FU (74.7%), imiquimod (53.9%), MAL PDT 
(37.7%), and IMB (28.9%). The treatment 
compliance rates were: IMB (98.7%), MAL 
PDT (96.8%), 5-FU (88.7%), and imiquimod 
(88.2%). Good to excellent aesthetic 
outcome rates were: MAL PDT (96.6%), IMB 
(95.1%), 5-FU (90.3%), and imiquimod 
(89.7%).53 
 
A few meta-analyses and systematic 
literature review have compared the relative 
efficacy of the existing options. The first one, 
published in 2012, convinced that PDT is 
superior to cryotherapy in terms of efficacy 
and cosmetic results when targeting a single 
lesion. Additionally, DFC, 5-FU, imiquimod, 
and IMB were equally efficacious in 
managing AK field.24 
 
In 2013, Gupta and colleagues ranked the 
following approaches from highest to lowest 
based on reported clearance rates: 5-FU, 
ALA PDT (which is equivalent to imiquimod, 
IMB, and MAL PDT), cryotherapy, DFC/ 
Hyaluronic acid, and finally placebo. 
Conversely, other factors needs to be 
evaluated when judging the most suitable 
option for the patient.54 Another meta-
analysis published in 2014 examined 10 
modalities and concluded that treatments 
with the relatively highest efficacy were: BF-
200 ALA PDT , followed by imiquimod 5% for 
16-week, ALA PDT, and 5-FU 0.5%.55 
 
A retrospective chart review scrutinized the 
rate of invasive SCC incidences after more 
than 1 year of initial AK field treatment. The 
study emphasized that imiquimod was 

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equivalent to 5-FU in preventing SCC 
development; both therapeutics were 
superior to ALA PDT. However, this study 
didn’t account for the treatment compliance 
and anatomical location. For patients who 
had multiple regimens for their AK, the 
investigators assigned them based on the 
first treatment they have received which may 
potentially neglected issues such as 
treatment crossover.10 
 

 
 
A consensus was reached among several 
international experts in 2015 regarding 
clinical diagnosis and management of AK. In 
this consensus, patients were classified into 
four categories: I. 1-5 clinical AK lesions per 
field; II. 6 or more AK lesions per field; III. 6 
or more AK lesions with the addition of 
chronic actinic damage and hyperkeratosis 
per field; and finally, IV. 
immunocompromised patients with any 
degree of AK severity. First, sun protection is 
recommended for all patients. Secondly, 
cryotherapy is strongly recommended for 
single AKs (category I). 0.5% 5-FU, 3.75% 
imiquimod, IMB (0.015% gel and 0.05% gel), 
ALA PDT, and MAL PDT were strongly 
recommended for patients in category II and 
III.  For patients in category IV, none of the 
approaches was highly recommended. 
Cryotherapy, curettage, 5% 5-FU, 5% 
imiquimod, ALA PDT, MAL PDT were weakly 
recommended depending on case-to-case 
scenario.56   
 
The most recent AAD AK diagnosis and 
management guidelines strongly 
recommended sun protection, 5-FU, 
imiquimod, cryotherapy, and tirbanibulin, 
which benefits clearly outweigh the risks. 
Remarkably, the experts firmly believed that 
the actual therapeutic effect of tirbanibulin 
was close to the reported therapeutic effect. 

Other options, DFC, ALA red light PDT, ALA 
blue light PDT, DL PDT should be employed 
in certain conditions as the benefits finely 
balance with risks.57 
 

 
 
The limitations of the available clinical 
evidence were the meager of long-term 
follow up data and effective armamentarium 
for immunocompromised patients and non-
facial AK. We necessitate more research in 
those aspects to further assist our 
management and comprehension of AK, and 
even SCC.  
 

 
 
Actinic keratosis usually occurs at sun-
exposed areas. Although the risk for 
individual AK progressing into SCC is low, 
the majority of SCC arise from AK. Its 
pathogenesis involves the UV-B induced 
thymine dimer formation, mutation of tumor 
suppressor genes, disruption of cell cycle, 
and finally, the proliferation of neoplastic 
keratinocytes. Treatment of AK can be 
categorized by single lesion or field 
treatment. The theory of field cancerization 
suggests that skin tissue proximal AK lesions 
also have a higher risk of progression, thus, 
field treatments are more commonly used. 
Sun protection is crucial for all patients. 
Liquid nitrogen cryotherapy is the mainstay 
treatment for single AK, while PDT, topical 
imiquimod, and fluorouracil are commonly 
used as field treatment. Tirbanibulin, recently 
approved by the FDA, was endorsed as a 
highly effective option per consensus 
guidelines. Ultimately, more studies 
concerning long term recurrence rate, 
suitable approaches for 
immunocompromised patients and non-facial 
AK are mandated. 
 

CONCENSUS GUIDELINES 

LIMITATIONS 

CONCLUSION 

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(c) 2022 THE AUTHORS. Published by the National Society for Cutaneous Medicine. 283 

Conflict of Interest Disclosures: HH & DKB: None 
BB: Biofrontera, Advisory Board & Investigator; SUN 
Pharmaceuticals, Inc Advisory Board & Consultant; 
LEO Pharma, US Speaker, Advisory Board & 
Investigator; Almirall LLC, Consultant, Speaker; PHD 
Biosciences, Consultant 
 
Funding: None 
 
Corresponding Author: 
Brian Berman, MD, PhD 
Center for Clinical and Cosmetic Research 
2925 Aventura Boulevard, Suite 205 
Aventura, FL 33180 
Email: bbmdphd@gmail.com 

 
 
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July 2022     Volume 6 Issue 4 
 

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