ArticlePDF Available

Actinic keratosis prevention – A double-blind, half-face interventional study with a topical treatment

  • Private Office , Milan, Italy
  • Giuliani, Milan, Italy
  • International Hair Research Foundation

Abstract and Figures

Actinic keratosis (AK) is a chronic and recurrent disease and in this double-blind, half face, placebo controlled study we attempt to examine the efficacy of a topical treatment containing 2,4,6-octatrienoic acid and anthraquinone knipholone for the prevention of new AK lesion formations. New lesion onset was detected with methyl-5-aminolevulinic acid and Wood’s lamp after 6 months of treatment (T1) and 12 months after treatment end (T2). Absence of new lesion at T1, was 86.11% in active treatment side while 77.78% in placebo side. At T2 the percentage was higher in skin treated with active product (83.33% of subjects) compared to placebo (63.89% of subjects).Taking into consideration the number of new lesions during the study period, at T1 the new AK lesions were not statistically significantly influenced by the treatments, while at T2, AK lesions were detected in 30.55% of placebo-treated area while in the contralateral part the lesions were 13.89%. The reduction induced by active treatment was statistically significant.The product containing 2,4,6-octatrienoicienoic acid and anthraquinone knipholone is effective in reducing new AK lesion formation in subjects with a history of AKs.
Content may be subject to copyright. Journal of Solid Tumors 2019, Vol. 9, No. 1
Actinic keratosis prevention A double-blind,
half-face interventional study with a topical treatment
Elisabetta Sorbellini1, Barbara Marzani2, Daniela Pinto2, Fabio Rinaldi1
1International Hair Research Foundation, Milan, Italy
2Giuliani S.p.A. R&D, Milan, Italy
Received: September 19, 2018 Accepted: November 18, 2018 Online Published: November 29, 2018
DOI: 10.5430/jst.v9n1p1 URL:
Actinic keratosis (AK) is a chronic and recurrent disease and in this double-blind, half-face, placebo controlled study we attempted
to examine the efficacy of a topical treatment containing 2,4,6-octatrienoic acid and anthraquinone knipholone for the prevention
of new AK lesion formations. New lesion onset was detected with methyl-5-aminolevulinic acid and Wood’s lamp after 6 months
of treatment (T1) and 12 months after treatment end (T2). Absence of new lesion at T1, was 86.11% in active treatment side
while 77.78% in placebo side. At T2 the percentage was higher in skin treated with active product (83.33%) compared to placebo
(63.89%). Taking into consideration the number of new lesions during the study period, at T1 the new AK lesions were not
statistically significantly influenced by the treatments, while at T2, AK lesions were detected in 30.55% of placebo-treated area
while in the contralateral part the lesions were 13.89%. The reduction induced by active treatment was statistically significant.
The product containing 2,4,6-octatrienoic acid and anthraquinone knipholone is effective in reducing new AK lesion formation in
subjects with a history of AKs.
Key Words: Actinic keratosis prevention, Actinic keratosis lesion onset, 2,4,6-octatrienoic acid, Anthraquinone knipholone
Actinic keratosis (AK) is the most common diagnosed in
the outpatient setting
and the most common in situ can-
cerous skin lesion
characterized by intraepithelial atypical
proliferations of keratinocytes.[3]
Clinically, the lesions are presented as erythematous or flesh-
colored, multiple, palpable macules, papule or plaques with
a size from few millimeters to > 2 cm.
[4, 5]
and verrucous keratotic lesions could constitute other less
reported clinical presentations.
Mainly, AK lesions are
asymptomatic, but some subjects report discomfort, such as
burning sensation or itch.[6]
AK lesions can be classified, based on their appearances as
atrophic, hypertrophic, pigmented, proliferative, lichenoid,
acantholytic or Bowenoid.
One of the major concern about
this pathology is that any single AK lesion can evolve in in-
vasive squamous cell carcinoma (SCC) and it is not possible
to foresee the specific lesion progression. The situation is
further complicated by spontaneous remission or stabiliza-
tion. From an epidemiological point of view, data underline
AK prevalence in fair-skinned subjects and in high-level sun
exposure body areas. Even if probably underestimated, the
incidence of AK is reported to be 16%-25% in USA, while
> 20% in Europe.[8]
Studies of AK prevalence in Europe are limited, currently
few data ara available on Spain, Germany, Netherlands. Only
Correspondence: Fabio Rinaldi; Email:; Address: International Hair Research Foundation, Milan, Italy.
Published by Sciedu Press 1 Journal of Solid Tumors 2019, Vol. 9, No. 1
two studies are available on Italian population where the
prevalence rates vary greatly. The first one reported an AK
prevalence of 1.4% with a higher incidence in Sicily and
while the second one, hospital-based, reported a
prevalence of 27.4% in dermatology outpatients.[10]
Since skin area affected by AK is the chronically sun-exposed
area, chronic long-term solar radiation exposure represents
the major AK risk factor.
Other reported risk factors are
specific phenotypic characteristics such as Fitzpatrick skin
types I-III, photodamages (i.e. facial wrinkles), age and the
number of hours spent in the sun.
The last factor has
also a strong impact on public health for outdoor workers due
to their great occupational UV exposure. As a consequence,
some Countries are working on to find and adopt strategies
for decrease the potential incidence of this occupational dis-
Cumulative UV radiation induces DNA damage in ker-
atinocyte creating genetically unstable cells, inactivating
functional repair genes, such as p53, and inducing oxidative
stress through the reactive oxygen species (ROS) production.
UV-damages not only can give rise to AK, but represent also
the common risk factor in progression of AK to SCC.
Although this risk is considered relatively low and uncertain,
the range is up to 0.53% in subjects with a history of non-
melanoma skin cancer, while the rate of lesion regression
after one year is 15%-63% and the recurrence rate of lesions
between 15%-53%.[16]
AK-derived photodamage can be extended from the le-
sional area to surrounded zone affected by subclinical al-
The concept of “field cancerization” describes
the area of molecular alterations observed in a chronical
photodamage skin with several foci of non-melanocytic cu-
taneous neoplasm.
All stages of AK progression can be
present: from UV-damage keratinocytes, subclinical lesions
(non-visible, non-palpable), early or late clinical lesions, and
eventually SCCs.
After the surgery for the primary AK
lesion, the imperative clinical action is addressed to treat
the entire field cancerization in order to reduce the lesion
recurrences and prevent new lesion development.
effective field-directed therapeutic options are available but
the side effects, such as inflammation risk, scarring, dyschro-
mia can potentially decrease patient treatment adherence.
As a consequence, there is a growing need for novel preven-
tive strategies.The aim of this clinical study was to evalu-
ate the efficacy and tolerability of a topical cosmetic treat-
ment containing 2,4,6-octatrienoic acid and anthraquinone
knipholone in the prevention of new AK lesion onset. Le-
sions were monitored by means of fluorescence diagnosis
by coupling topical application of methyl ester of aminole-
vulinic acid (MAL) to Wood’s UV lamp with the aim to
detect occult areas of abnormal skin.
[3, 19, 20]
Previous pre-
clinical studies reported the capacity of 2,4,6-octatrienoic
acid to counteract photo-senescence in human fibroblast,
increasing the biological antioxidant potential and the ex-
pression and activity of antioxidant enzyme catalase.
Moreover, in UV-irradiated normal human keratinocytes
2,4,6-octatrienoic acid showed a protective effect against
UVA and UVB-induced damage and induction of DNA repair
Anthraquinone knipholone from Bulbine
frutescens extract is also included in the topical formulation
as a selective inhibitor of leukotriene metabolism activated
by UV damage.[22]
The study has been conducted according to the principles of
the Declaration of Helsinki and was performed in Milan on
subjects residing in Lombardy region, Italy.
2.1 Study population
Eligibility criteria for study participation included: male and
females 50 to 75 years of age with Fitzpatrick skin types I–III,
skin photodamage grade >3
with at least 1 treated AK
lesion in the past in sun-exposed area (scalp, face, decolletè)
but the absence of AK lesions at the study inclusion.
Subjects were excluded from the study if within the six
months before they received treatment interfering with the
evaluations: facial chemical peel, or any other resurfacing
procedure, botulinum toxin, facial fillers, immunosuppres-
sive or immunomodulation agents, oral retinoids. Subjects
were instructed to self-apply 1/day the 2 products on the half
face, not to use any facial products nor procedures during the
2.2 Study design
In this double-blind placebo controlled trial, 36 eligible sub-
jects applied the active product (2,4,6-octatrienoic acid, an-
thraquinone knipholone and excipients) to one-half of their
face and placebo (excipients) to the opposite side, once daily
for six months.
Subjects were asked to continue their normal life style during
the study including the sun protection habits, and in case of
sun, exposition to report any sun burn or erythema event.
Moreover, during the study, a commercial sunscreen (Licht-
ena R
Dermosolari SPF 50+) was provided to all subjects.
Investigator assessments of new pre-cancerous lesions and
tolerance were conducted at Baseline (T0), after 6 months
of treatment (T1) and 12 months after treatment end (follow
up, T2). Digital photographs of the left and right sides, der-
2ISSN 1925-4067 E-ISSN 1925-4075 Journal of Solid Tumors 2019, Vol. 9, No. 1
matoscopic evaluation of the whole face were also taken at
all visits.
All subjects underwent diagnosis with photodynamic technic
with methyl-5-aminolevulinic acid (MAL) and Wood’s lamp.
MAL 5% was topically applied in occlusion condition for
30 minutes (modified by Cubeddu et al., 1999).
the use of Wood’s ultraviolet lamp permits the detection of
cutaneous lesions as pink fluorescence in the presence of
activated protoporphyrin IX from MAL. Prior treatment, the
patient skin photodamage and absence of pre-cancerous le-
sions were assessed by the examining physicians. Each side
was assessed separately.
2.3 Study endpoints
2.3.1 Efficacy
Investigator evaluations for the presence and new forma-
tion of pre-cancerous lesion on the left and right sides were
graded separately. The pre-cancerous lesions were graded us-
ing a noninvasive fluorescence diagnosis by means of MAL
5% and Wood’s lamp.[19]
2.3.2 Safety
Tolerance was assessed by investigators at T1 and T2 by
objective irritation parameters (including erythema, edema,
and scaling) on a four-point scale where 0 = none, 1 = mild,
2 = moderate, and 3 = severe; and the reporting of adverse
2.3.3 Statistical analysis
All values were expressed as mean
standard error of mean
(SEM). Results were checked for normal distribution using
Shapiro-Wilk test before further analyses. Statistical differ-
ences between groups were carried out by Welch’s
using GraphPad Prism version 7.00 for Windows (GraphPad
Software, La Jolla California USA,
–values equal to or less than .05 were considered signifi-
36 subjects were enrolled in the study, 14 men and 22 women
(38.9% and 61.1%, respectively). The mean age was 61
years (see Table 1).
Table 1. Age and gender distribution in patients
Gender N Mean age (SEM)
Female 22 61.64 (6.40)
Male 14 61.57 (6.06)
All subjects concluded the study and no side effect was re-
ported by the patient or by physician evaluation by means of
objective irritation parameters.
After 6 months of treatment (T1), the clinical benefit, rep-
resented by absence of new lesion, in area treated with ac-
tive product was 86.11% (90.91% women and 78.57% men)
while the placebo side, the clearance was 77.78% (77.27% of
women and 71.43% of men). At follow-up, 12 months after
end of treatment (T2), the frequency of sustained cleared
lesions was higher in skin area treated with active product
(83.33% of subjects, 90.91% women and 71.43% men) com-
pared to placebo effect (63.89% of subject, 68.18% of women
and 57.14% of men) (see Table 2).
Table 2. Clinical benefit during the study period
Clearance rate
Sustained clearance rate
T1 T2
Active side
Men 78.57 71.43
Women 90.91 90.91
Total 86.11 83.33
Placebo side
Men 71.43 57.14
Women 77.27 68.18
Total 77.78 63.89
In particular, as regard the appearance of new lesions, after
6 months of treatment (T1), new AK lesions were present
in 25% of area treated with placebo (4 men and 5 women)
while, 13.89% in the face zone treated with active product
(3 men and 2 women). At T1 the mean (
SEM) number of
new AK lesion was not statistically significantly influenced
by the treatments. At T2, after 12 months from treatment end,
AK lesions were detected in 30.55% of placebo-treated side
(in 5 men and 6 women) while 13.89% in the contralateral
treated side (in 3 men and 2 women) (see Table 3).
Table 3. New lesion in the face area treated with active
product and contralateral part treated with placebo
Subjects with new lesion (number)
T1 T2
Active side
Men 3 3
Women 2 2
Total (%) 13.89 13.89
Placebo side
Men 4 5
Women 5 6
Total (%) 25 30.55
Published by Sciedu Press 3 Journal of Solid Tumors 2019, Vol. 9, No. 1
The AK mean (
SEM) number measured during the follow-
up in placebo area shown the disease progression, while
active treatment induced a statistically significant reduction
in the new AK formation (p< .05, see Figure 1).
Figure 1. Mean ±SEM of AK lesion detected at T1 (6
months of treatment) and T2 (12 months after the treatment
end) in 36 subjects treated half face with placebo and
contralateral half face with active product. p< .05 active
treatment vs. placebo treatment.
AK is extremely frequent in dermatological clinical prac-
tice. AK treatment needs to reduce the risks of progression,
but complete lesion clearance is rarely achieved in real-life
Because of its chronicity, AK presents a high
recurrence rate despite the previous treatment received.
Recurrence of lesions was reported in 65% of subjects 1 year
after 5-Fluorouracil (5-FU) treatment;
a range from 17.4
to 39% of recurrence 1 year after Imiquimod treatment;
[25, 26]
while 54%-56% in Ingenol mebutate treated patients, after 1
In any case, field-directed treatments are essential to address
subclinical damage and reduce AK recurrence rates and po-
tentially reduce the risk of SCC development.[28–31]
The AK development is due to damages from chronic sun
exposure and because of its potential progression to invasive
squamous cell carcinoma, treatment and preventive measures
are required.
Some efforts have been done to prevent AK lesions and pro-
gression, the use of sunscreen is one of this measure. In a
randomized controlled trial, it was evaluated the regular use
of sunscreen and the new keratosis appearances in Australian
subjects during summer. The data showed that regular use
of sunscreen prevents the formation of new keratosis and
accelerate the remission of present lesions.
Another study
confirmed that regular application of sunscreen delays the
new lesion formation.[33]
However, sunscreen seems not able to reduce the BCCs
so many other attempts are made for an alter-
native form of chemoprevention. Sunscreen use and patient
education are the first line prevention strategy, but not the
only. An interesting study was conducted by Elments and
in which the drug Celecoxib, an inhibitor of
was effective in SCC prevention, but not
in the modulation of new AK formation.
The Italian studies
[9, 10]
were preparatory for our investiga-
tion and in particular to subject selection: we decided to limit
our patient inclusion to a single Italian region, Lombardy, in
order to have a more homogeneous population in terms of
habits, general sun irradiation and lifestyles.
Due to the formulation characteristic, cosmetics can be used
in the management of AK lesions, i.e. the unappealing aspect
of the AK lesions can be improved by cosmetic emollients
with an effect on patient comfort by means of skin dryness
and roughness reduction.[36]
The cosmetic for its intrinsic nature is more easy to use: not
particular recommendations or indications are needed. Sun-
screen use is recommended by different Guidelines for the
AK prevention and management, but often the real consumer
use condition makes the photoprotection inefficacy due to:
the low amount product applied (with a significative reduc-
tion in sun protection, up to 25% of labeled SPF),
and low
compliance to this type of cosmetics.
in vivo
assays demonstrated the capacity of 2,4,6-
octatrienoic acid to protect and counteract UV-induced DNA
damage. Pre- or post-treatment with 2,4,6-octatrienoic acid
accelerate DNA repair decreasing cyclobutane-pyrimidine
dimers, 7,8-dihydro-8-oxoguanine, and levels of phosphory-
lated histone H2A.X, associated with the amount of DNA
double-strand breaks by UV radiation.[38]
The performed study shows that the use of a topical formu-
lation containing 2,4,6-octatrienoic acid and anthraquinone
knipholone for 12 months could help the reduction of new
AK lesions formation, decreasing also skin photo-aging in
treated subjects.
As a chronic disease, AK treatment need a long-term dis-
ease control and prevention. It is of primary importance to
find new products to delay the recurrence and new lesion
formation in the skin sun damaged areas.
In this double-blind trial, the product containing 2,4,6-
octatrienoic acid and anthraquinone knipholone is effective
in reducing new AK lesion formation in subjects with a his-
tory of AKs in “real life condition”.
4ISSN 1925-4067 E-ISSN 1925-4075 Journal of Solid Tumors 2019, Vol. 9, No. 1
Further studies with longer follow up are necessary to con-
firm treatment prolonged efficacy.
Therefore, based on our experience, secondary prevention
by a cosmetic product should be extended in dermatological
practice to minimized the photo-induced skin damage and to
prevent recurrence in patients with a history of AK.
Patient regular monitoring, with at least a yearly consulta-
tion, can be performed by means of fluorescent detection by
Wood’s lamp and MAL (5%), an essential noninvasive diag-
nostic tool. This method is extremely helpful in permitting
the detection of otherwise occult areas of abnormal skin with
the advantage of
in vivo
tissue examination reducing the
biopsy need and it is well accepted by patients.
R.F. serves as a consultant for Giuliani S.p.A. P.D. and M.B.
are employed by Giuliani S.p.A.
Bickers DR, Lim HW, Margolis D, et al. American Academy of
Dermatology Association; Society for Investigative Dermatology.
The burden of skin diseases: 2004 a joint project of the American
Academy of Dermatology Association and the Society for Investiga-
tive Dermatology. J Am Acad Dermatol. 2006 Sep; 55(3): 490-500.
Casari A, Chester J, Pellacani G. Actinic Keratosis and Non-Invasive
Diagnostic Techniques: An Update. Biomedicines. 2018; 6(1): E8.
Jetter N, Chandan N, Wang S, et al. Field Cancerization Therapies
for Management of Actinic Keratosis: A Narrative Review. Am J
Clin Dermatol. 2018 Mar; 26.
007/s40257-018- 0348-7
Siegel JA, Korgavkar K, Weinstock MA. Current perspective on ac-
tinic keratosis: A review. Br J Dermatol. 2017 Aug; 177(2): 350-358.
Salasche SJ. Epidemiology of actinic keratoses and squamous cell
carcinoma. J Am Acad Dermatol. 2000 Jan; 42(1): 4-7.
Rosen T, Lebwohl MG. Prevalence and awareness of actinic kerato-
sis: barriers and opportunities. J Am Acad Dermatol. 2013 Jan; 68(1
Suppl 1): S2-9.
Peris K, Calzavara-Pinton PG, Neri L, et al. Italian expert consen-
sus for the management of actinic keratosis in immunocompetent
patients. J Eur Acad Dermatol Venereol. 2016 Jul; 30(7): 1077-84.
Dodds A, Chia A, Shumack S. Actinic keratosis: rationale and
management. Dermatol Ther (Heidelb). 2014 Jun; 4(1): 11-31. 0049-y
Naldi L, Chatenoud L, Piccitto R, et al. Prevalence of Actinic Ker-
atoses Italian Study (PraKtis) Group. Prevalence of actinic keratoses
and associated factors in a representative sample of the Italian adult
population: Results from the Prevalence of Actinic Keratoses Ital-
ian Study, 2003-2004. Arch Dermatol. 2006 Jun; 142(6): 722-6.
Fargnoli MC, Altomare G, Benati E, et al. Prevalence and risk factors
of actinic keratosis in patients attending Italian dermatology clinics.
Eur J Dermatol. 2017 Dec; 27(6): 599-608.
Berman B, Cockerell CJ. Pathobiology of actinic keratosis:
ultraviolet-dependent keratinocyte proliferation. J Am Acad Der-
matol. 2013 Jan; 68(1 Suppl 1): S10-9.
Kennedy C, Bajdik CD, Willemze R, et al. Leiden Skin Cancer Study.
The influence of painful sunburns and lifetime sun exposure on the
risk of actinic keratoses, seborrheic warts, melanocytic nevi, atypical
nevi, and skin cancer. J Invest Dermatol. 2003 Jun; 120(6): 1087-93.
Traianou A, Ulrich M, Apalla Z, et al. Risk factors for actinic kerato-
sis in eight European centres: a case-control study. Br J Dermatol.
2012 Aug; 167(Suppl 2): 36-42.
Krutmann J, Berking C, Berneburg M, et al. New Strategies in the
Prevention of Actinic Keratosis: A Critical Review. Skin Pharmacol
Physiol. 2015; 28(6): 281-9.
Emmert S, Schön MP, Haenssle HA. Molecular biology of basal and
squamous cell carcinomas. Adv Exp Med Biol. 2014; 810: 234-52. 4939-0437-2_13
Werner RN, Sammain A, Erdmann R, et al. The natural history of
actinic keratosis: A systematic review. Br J Dermatol. 2013 Sep;
169(3): 502-18.
[17] Malvehy J. A new vision of actinic keratosis beyond visible clinical
lesions. J Eur Acad Dermatol Venereol. 2015 Jan; 29(Suppl 1): 3-8.
Torezan LA, Festa-Neto C. Cutaneous field cancerization: Clini-
cal, histopathological and therapeutic aspects. An Bras Dermatol.
2013 Sep-Oct; 88(5): 775-86.
Cubeddu R, Pifferi A, Taroni P, et al. Fluorescence Lifetime Imaging:
An Application to the Detection of Skin Tumors IEEE. Journal of
Selected Topics in Quantum Electronics. 1999 Jul/Aug; 5(4): 923-29.
Sanmartin O, Guillen C. Images in clinical medicine. Fluorescence
diagnosis of subclinical actinic keratoses. N Engl J Med. 2008 May;
358(19): e21.
Briganti S, Flori E, Bellei B, et al. Modulation of PPAR
new insights in a stress induced premature senescence model. PLoS
One. 2014 Aug; 9(8): e104045.
Wube AA, Bucar F, Asres K, et al. A selective inhibitor of leukotriene
metabolism. Phytomedicine. 2006 Jun; 13(6): 452-6.
Glogau RG. Aesthetic and anatomic analysis of the aging skin. Semin
Cutan Med Surg. 1996 Sep; 15(3): 134-8.
Krawtchenko N, Roewert-Huber J, Ulrich M, et al. A randomised
study of topical 5% imiquimod vs. topical 5-fluorouracil vs.
cryosurgery in immunocompetent patients with actinic keratoses:
a comparison of clinical and histological outcomes including 1-
year follow-up. Br J Dermatol. 2007 Dec; 157(Suppl 2): 34-40.
Published by Sciedu Press 5 Journal of Solid Tumors 2019, Vol. 9, No. 1
Lebwohl M, Dinehart S, Whiting D, et al. Imiquimod 5% cream
for the treatment of actinic keratosis: results from two phase III,
randomized, double-blind, parallel group, vehicle-controlled tri-
als. J Am Acad Dermatol. 2004 May; 50(5): 714-21.
Lebwohl M, Swanson N, Anderson LL, et al. Ingenol mebutate gel
for actinic keratosis. N Engl J Med. 2012 Mar; 366(11): 1010-9.
Ulrich M, Lange-Asschenfeldt S, Rowert-Huber J. Effects of ingenol
mebutate 0.05% gel for the treatment of actinic field cancerization
including subclinical actinic keratoses assessment by reflectance
confocal microscopy. Br J Dermatol. 2014; 171(Suppl 4): 1-76.
Cantisani C, De Gado F, Ulrich M, et al. Actinic keratosis: Review
of the literature and new patents. Recent Pat Inflamm Allergy Drug
Discov. 2013 May; 7(2): 168-75.
Ulrich M, Alarcon I, Malvehy J, et al. In vivo reflectance confocal
microscopy characterization of field-directed 5-fluorouracil 0.5%/sali-
cylic acid 10% in actinic keratosis. Dermatology. 2015; 230: 193-198.
Cantisani C, Paolino G, Corsetti P, et al. Evaluation of Ingenol mebu-
tate efficacy for the treatment of actinic keratosis with Antera 3D
camera. Eur Rev Med Pharmacol Sci. 2015; 19: 92-97.
Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by
regular sunscreen use. N Engl J Med. 1993 Oct; 329(16): 1147-51.
Darlington S, Williams G, Neale R, et al. A randomized controlled
trial to assess sunscreen application and beta carotene supplementa-
tion in the prevention of solar keratoses. Arch Dermatol. 2003 Apr;
139(4): 451-5.
Green A, Williams G, Neale R, et al. Daily sunscreen application
and betacarotene supplementation in prevention of basal-cell and
squamous-cell carcinomas of the skin: a randomised controlled trial.
Lancet. 1999 Aug; 354(9180): 723-9. Erratum in: Lancet 1999 Sep
18; 354(9183): 1038.
Elmets CA, Viner JL, Pentland AP, et al. Chemoprevention of non-
melanoma skin cancer with celecoxib: A randomized, double-blind,
placebo-controlled trial. J Natl Cancer Inst. 2010 Dec; 102(24): 1835-
Dréno B, Amici JM, Basset-Seguin N, et al. Management of ac-
tinic keratosis: A practical report and treatment algorithm from
expert clinicians. J Eur Acad Dermatol Venereol. 2014
Sep; 28(9): 1141-9.
Neale R, Williams G, Green A. Application patterns among partici-
pants randomized to daily sunscreen use in a skin cancer prevention
trial. Arch Dermatol. 2002 Oct; 138(10): 1319-25.
Dirschka T, Gupta G, Micali G, et al. Real-world approach to ac-
tinic keratosis management: Practical treatment algorithm for office-
based dermatology. J Dermatolog Treat. 2017 Aug; 28(5): 431-442.
Flori E, Mastrofrancesco A, Kovacs D, et al. The activation of
by 2,4,6-Octatrienoic acid protects human keratinocytes
from UVR-induced damages. Sci Rep. 2017 Aug; 7(1): 9241. 09578-3
6ISSN 1925-4067 E-ISSN 1925-4075
ResearchGate has not been able to resolve any citations for this publication.
Full-text available
Actinic keratosis represents the earliest manifestation of non-melanoma skin cancer. Because of their risk of progression to invasive squamous cell carcinoma, an earlier diagnosis and treatment are mandatory. Their diagnosis sometimes could represent a challenge even for expert dermatologists. Dermoscopy, confocal laser microscopy and optical coherence tomography could help clinicians in diagnosis.
Full-text available
Actinic keratosis (AK) is a common keratinocyte intra-epidermal neoplasia. To assess AK prevalence and potential risk factors in patients attending Italian general dermatology clinics. This retrospective study was conducted on clinical data from consecutive white outpatients aged ≥30 years, attending 24 general dermatology clinics between December 2014 and February 2015. AK prevalence (entire population) and multivariate risk factor analysis (patients with current/previous AK and complete data) are presented. AK prevalence in 7,284 patients was 27.4% (95% CI: 26.4-28.4%); 34.3% in men and 20.0% in women (p<0.001). Independent AK risk factors in 4,604 patients were: age (OR: 4.8 [95% CI: 3.5-6.5] for 46-60 years, increasing with older age to OR: 41.5 [95% CI: 29.5-58.2] for >70 years), history of other non-melanoma skin cancers (OR: 2.7 [2.2-3.3]), residence in southern Italy/Sardinia (OR: 2.6 [2.1-3.0]), working outdoors >6 hours/day (OR: 1.9 [1.4-2.4]), male gender (OR: 1.7 [1.4-2.0]), facial solar lentigos (OR: 1.6 [1.4-1.9]), light hair colour (OR: 1.5 [1.2-1.8]), prolonged outdoor recreational activities (OR: 1.4 [1.2-1.7]), light eye colour (OR: 1.3 [1.1-1.6]), skin type I/II (OR: 1.3 [1.1-1.6]), and alcohol consumption (OR: 1.2 [1.0-3.3]). BMI ≥25.0 (OR: 0.6 [0.5-0.7]), regular sunscreen use (OR: 0.7 [0.6-0.8]), and a lower level of education (OR: 0.8 [0.7-1.0]) were independent protective factors. AK prevalence was high in Italian dermatology outpatients. We confirm several well-known AK risk factors and reveal possible novel risk and protective factors. Our results may inform on the design and implementation of AK screening and educational programmes.
Full-text available
Increasing attention is addressed to identify products able to enhance skin photoprotection and to prevent skin carcinogenesis. Several studies have demonstrated that the α-melanocyte stimulating hormone (αMSH), acting on a functional MC1R, provides a photoprotective effect by inducing pigmentation, antioxidants and DNA repair. We discovered a link between αMSH and the nuclear receptor Peroxisome Proliferator-Activated Receptor-γ (PPARγ), suggesting that some of the αMSH protective effects may be dependent on PPARγ transcriptional activity. Moreover, we demonstrated that the activation of PPARγ by the parrodiene 2,4,6-octatrienoic acid (Octa) induces melanogenesis and antioxidant defence in human melanocytes and counteracts senescence-like phenotype in human fibroblasts. In this study, we demonstrate that the activation of PPARγ by Octa exerts a protective effect against UVA- and UVB-induced damage on normal human keratinocytes (NHKs), the major target cells of UV radiation. Octa promotes the antioxidant defence, augments DNA repair and reduces the induction of proteins involved in UV-induced DNA damage response. Our results contribute to deepen the analysis of the αMSH/PPARγ connection and suggest perspectives for the development of new molecules and formulations able to prevent cutaneous UV damage by acting on the different skin cell populations through PPARγ activation.
Actinic keratoses (AKs) are atypical, precancerous proliferations of keratinocytes that develop because of chronic exposure to ultraviolet (UV) radiation. Treatment of AK can be lesion-directed or field-directed. Field cancerization theory postulates that the skin surrounding AK is also at increased risk for possible malignant transformation since it has been exposed to the same chronic UV light. Field-directed therapies thus have the potential to address subclinical damage, reduce AK recurrence rates, and potentially reduce the risk of squamous cell carcinoma (SCC) development. Published clinical studies have found lesion clearance rates ranging from 81 to 91% for photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL). Clinical studies have also been published on various topical treatments. Complete clinical clearance (CCC) was significantly higher in patients treated with a combination of 5-fluorouracil and salicylic acid (5-FU–SA) than in the vehicle group across multiple studies, and CCC ranged between 46 and 48% following treatment with imiquimod. Additionally, treatment with diclofenac sodium (DFS) found reduction in lesion sizes to range from 67 to 75%. Reported results have been similar for another non-steroidal anti-inflammatory drug (NSAID), piroxicam, which has more cyclooxygenase (COX)-1 activity than DFS. Active treatments with ingenol mebutate were also significantly more effective than vehicle at clearing AK lesions. All treatments resulted in mild, localized skin reactions. PDT using conventional light sources was associated with increased severity of pain and/or discomfort, while PDT using daylight as the light source was associated with less pain and occasionally no pain at all. Though no widely accepted algorithm for the treatment of AKs exists, field-directed therapy can be particularly useful for treating photo-exposed areas containing multiple AKs. Additional research with more direct comparisons between these field-directed therapies will help clinicians determine the best therapeutic approach. Here, we provide a balanced and comprehensive narrative review of the literature, considering both light-based and topical therapies with a focus on their field-therapy aspects, and propose a therapeutic algorithm for selecting an appropriate treatment in the clinical setting.
Actinic keratosis (AK) is a chronic skin disease in which multiple clinical and subclinical lesions co-exist across large areas of sun-exposed skin, resulting in field cancerisation. Lesions require treatment because of their potential to transform into invasive squamous cell carcinoma. This article aims to provide office-based dermatologists and general practitioners with simple guidance on AK treatment in daily clinical practice to supplement existing evidence-based guidelines. Novel aspects of the proposed treatment algorithm include differentiating patients according to whether they have isolated scattered lesions, lesions clustered in small areas or large affected fields without reference to specific absolute numbers of lesions. Recognising that complete lesion clearance is rarely achieved in real-life practice and that AK is a chronic disease, the suggested treatment goals are to reduce the number of lesions, to achieve long-term disease control and to prevent disease progression to invasive squamous cell carcinoma. In the clinical setting, physicians should select AK treatments based on local availability, and the presentation and needs of their patients. The proposed AK treatment algorithm is easy-to-use and has high practical relevance for real-life, office-based dermatology.
Actinic keratoses (AKs) are common, with prevalence in the U.S.A. estimated at almost 40 million in 2004 and annual costs of > $1 billion (U.S.D.). However, there is no universally accepted definition of AK and thus it is difficult to identify reliably. AKs are lesions of epidermal keratinocytic dysplasia that result from chronic sun exposure and have the ability to progress to invasive squamous cell carcinoma (SCC), but clinicians disagree about whether AKs are premalignant lesions, superficial SCCin situ or epiphenomena of chronically sun-damaged skin. Yearly AK to SCC progression rates of 0·6% were reported in an elderly population with multiple prior keratinocyte carcinomas (KCs); and rates of spontaneous AK regression have been reported to be > 50%, but regressed lesions often reappear. As AKs have both cosmetic consequences and potential for malignant transformation, there are multiple reasons for treatment. There is no current agreement on the most efficacious treatment, but 5-fluorouracil has been shown to both prevent and treat AKs, and imiquimod and photodynamic therapy may have the best cosmetic outcomes. AKs may be treated to improve appearance and relieve symptoms, but the keratinocytic dysplasia that gives rise to malignancy, and sometimes appears as an AK, may be what actually threatens patient health. Thus, treatments should aim to decrease the risk of KC or facilitate KC diagnosis by reducing the potential for misidentification created when a KC appears in a field of AKs. Improved agreement among clinicians on AK definition may improve management.
Actinic keratosis (AK) is a common skin disease which can potentially progress to invasive squamous cell carcinoma (iSCC). Given that mortality rates and health-care cost associated with iSCC are substantial, the management of AK represents an important public health issue. Several effective lesion-directed and field-directed treatments are available. Ablative procedures (e.g. cryosurgery, excision, laser ablation, curettage alone or with electrodessication) are considered cost-effective options for solitary lesions. Field-directed therapies (e.g. Ingenol Mebutate, imiquimod, PDT, 5-Fluorouracile, diclofenac 3%, 5-FU + Salicylic acid) can be used over large epidermal surfaces and are directed to treat both individual visible lesions and cancerization fields. In order to provide guidance for management choice in clinical practice, several guidelines concerning the diagnosis and treatment of AK have been published in the past decade. However, the introduction of novel therapeutic options requires continuous updates of recommendations and adaptation to national contexts. The present review summarizes the existing evidence and reports the results of a consensus workshop on the management of AK.
Actinic keratosis (AK) or lesions of epidermal dysplasia occurring in skin chronically exposed to solar radiation is very prevalent in lighter skin persons, with chronic long-term sun exposure being the major risk factor. With an aging population it is expected that the prevalence of AK will further increase. AK can progress to nonmelanoma skin cancer (NMSC) and is a public health concern. Six leading dermatologists with expertise in AK and NMSC from Germany met to discuss the nature of the disease and the prevention and treatment strategies available to dermatologists today. While cosmetic sunscreen products form an essential element of sun protection strategies, they are not adequate when damage has already been inflicted. Newly developed products of the medical device category offer DNA repair function paired with high sun protection factor (SPF) UV protection. An adjuvant treatment algorithm for various risk levels of AK was developed. For patients with low and moderate risk, sunscreen only is recommended. For patient groups with high and very high risk, a very high photoprotection and photorepair action (DNA repair enzymes) in medical device products all year round is recommended. © 2015 S. Karger AG, Basel.
Actinic keratoses (AKs) are common skin lesions that appear after long-term exposure to ultraviolet radiation. The presence of AKs is associated with an increased risk for development of nonmelanoma skin cancer. AKs vary widely in clinical and histologic presentation, which contributes to inadequate identification and presents challenges for consensus classification. Clinically adequate reduction in AK prevalence requires a multifaceted approach. There is a reasonable need to increase awareness and knowledge about AK, including symptoms, prevention, and associated risk of nonmelanoma skin cancer, especially among the public at large. Safe and effective treatment strategies are needed to optimize clearance of AKs, ideally to prevent progression to invasive cutaneous neoplasia.