Case Report
Open Access
A Case of Actinic Keratosis of the Scalp (Re)Treated With
Ingenol Mebutate 150 Mcg/G.
M Mazzeo, A Dattola, R Saraceno, L Bianchi
Department of Dermatology University of Rome "Tor Vergata", Rome, Italy
*Corresponding author: Annunziata Dattola, Md university Of Rome "Tor Vergata, Department Of Dermatology Policlinico Tor Vergata Viale
Oxford, Rome, Italy , 81 00133, Tel. +390620902743; Fax +390620902742; E-mail:
@
Received: July 11, 2016; Accepted: July 25, 2016; Published: August 05, 2016
Citation: Mazzeo M, Dattola A, Saraceno R, Bianchi L (2016) A Case of Actinic Keratosis of the Scalp (Re)Treated With Ingenol
Mebutate 150 Mcg/G. Clin Res Dermatol Open Access 3(5): 1-2. DOI: http://dx.doi.org/10.15226/2378-1726/3/5/00142
Abstract
Actinic keratosis (AK) is a cutaneous intraepithelialneoplasma
appearing within areas referred as 'fields of cancerization'caused by
sun damage progresses to Squamous Cell Carcinoma (SCC). Ingenolmebutate
gel is a new effective topical therapy for AK, used once daily
for 2 or 3 days depending on the location of lesions. We report a case
of patients with multiple AK of the scalp treated for two times with
ingenolmebutate 150 mcg/g gel.
Keywords: Actinic keratosis; Scalp; Sun Damage; Ingenolmebutate;
Keywords: Actinic keratosis; Scalp; Sun Damage; Ingenolmebutate;
Introduction
Actinic keratosis or solar keratosis is a common skin lesion
caused by sun damage that progresses to squamous cell carcinoma
(SCC) [1]. Risk factors for the development of actinic keratosis
include fair skin or light pigmentation, Caucasian individuals,
freckles, light coloured eyes (blue or green), blonde or red hair,
male gender, older age, severe baldness, skin wrinkling, and
increased sun exposure due to outdoor occupation/activities. In
particular, long-term exposure to ultraviolet light is considered
to be a risk factor [2]. For these reasons, lesions are primarily
found on sun-exposed areas such as the face, ears, and hands.
Clinically, lesions appear scaly, flat, or elevated and may range
in colour from red to brown. Actinic keratosisis usually the
first lesion in a disease continuum that progresses to invasive
SCC. Today, many authors consider actinic keratoses to be real
SCCs rather than simple precancerous lesions [1-2]. The risk
of transformation is enhanced in patients with increased solar
damage, immune suppression, and those of advanced age.
Disease progression depends on a number of clinical features
such as lesion size, the amount of ulceration, bleeding and in
duration, enlargement in diameter, and erythema. Studies have
shown that patients with actinic keratosis that have an increased
risk of malignancy show lesions that are in durated, inflamed,
large (diameter greater than 1cm), rapidly enlarging, bleeding,
erythematous, and ulcerated. Ingenolmebutate is an active
compound found in the sap of the Euphorbia peplums plant that
is known for its dermatological uses, including the treatment of
cancerous lesions [3]. This medication treats actinic keratosis lesions by rapidly inducing cell death. The exact mechanism by
which this occurs is unknown; however, it is thought that the
active ingredient has pleiotropic effects that inhibit tumour cell
growth or induce tumour cell death via multiple mechanisms.
This may include an immune-mediated response such as protein
kinase C or neutrophil activation. These inflammatory responses
may also contribute to the wound-healing properties of the
drug. The application of the gel results in the rapid destruction
of actinic keratosis lesions. The results of two clinical studies
of the biological effects of ingenolmebutate have shown that
topical administration induces epidermal necrosis and a deep
inflammatory response both in the epidermis and in the upper
part of the dermis of the treated skin, with a predominance of
infiltration of T cells, neutrophils, and macrophages. The necrosis
of the dermis, however, is rarely observed [4]. The efficacy and
safety of Picato 150 mg/g, administered on the face and scalp
for 3 consecutive days, have been studied in two clinical studies (double-blind, vehicle-controlled) comprising 547 patients (277
in the drug group and 270 in the vehicle group) [5]. Patients were
followed for 8 weeks during which they returned for clinical and
safety monitoring. Efficacy, measured as the complete and partial
clinical cure rate and median percentage reduction, was assessed
on day 57. The results were as follows: 42.2% of patients treated
with the drug (n=277) obtained a complete clinical cure rate,
while 63.9% achieved partial clinical healing. Further, 3.7% of
all patients treated with the vehicle (n=270) achieved complete
clinical recovery, while 7.4% of patients treated only with the
vehicle achieved partial clinical recovery. In the double-blind,
placebo-controlled vehicle, up to two cycles of treatment with
Picato 150 mg/g were administered to 450 patients with four
to eight actinic keratoses in a 25 cm2 area on the face or scalp.
The patients in which a first cycle of treatment did not lead to the
complete healing of all actinic keratoses in the area of treatment
after 8 weeks were randomised for a further cycle of treatment
with Picato or with the vehicle. Patients in which the first cycle
of treatment led to full recovery were evaluated at 26 and 44
weeks and randomised for a second course of treatment if they
had relapsed in the field. In all patients, efficacy was evaluated at
8 weeks after randomisation. The results were read at 8 and 12
weeks after randomisation: of all patients treated with the drug,
47% showed the resolution of lesions by the 8th control week, while 18% were resolved by the 12th week. Ingenolmebutate is
formulated in two different formulations: a 150 mcg/g gel and a
500 mcg/g gel. The former is used to treat localised lesions on the
face and scalp, while the second is used to treat actinic keratoses
localised on the rest of the body. The formulation also changes
the administration time, which is3 consecutive days applying
the medication once a day in the first case, while 2 days with
daily application in the second case [6]. Ingenolmebutate offers
some important advantages, including shorter therapy duration
than other drugs, faster healing than rivals on the market, and a
favourable side effects profile.
Case Report
Two months ago, a 74-year-old patient, pho type II, came
under our observation at the Department of Dermatology of
the University of Rome Tor Vergata. The patient had been
chronically exposed to sources of ultraviolet rays throughout life.
He showed no significant comorbidities despite an SCC located
on the scalp completely being excised 2 years earlier with the
endorsement of a skin graft removed from the right forearm.
Despite the patient receiving numerous recommendations
during these two years, he did not use any photo protection,
being exposed quietly to important sources of solar radiation.
During the first visit, the patient presented more than 15 actinic
keratoses scattered on a cancerous field spread across the entire
scalp (FIG.1). In particular, two of these injuries caught our
attention because of their hyperkeratinisation and infiltration,
fearing that it may instead be two real SCCs, as it is difficult to
distinguish actinic keratosis from SCC. Despite our concern, we
Figure 1&2
considered it suitable to proceed to therapy owing to the future
possibility of surgical intervention on a much cleaner area than
before. However, an ultrasound of the lymphnode stations and
a TC total body excluded a systemic dissemination. Given the
important hyperkeratinisation of the lesions, we proceeded with
topical therapy based on salicylic acid (20% for 10 days). We
then proceeded with an application of the drug for 3 consecutive
evenings, as it gives technical indications. However, given the size
of the picture, we treated again the patient's. Further, instead of
stopping at a single cycle, we used two cycles with a short break
of 10 days between one application and another. In the first
inspection, carried out 10 days after the first 3-day cycle, we
observed a major improvement; in part, however, this masked
the underlying erythema caused by the therapy. In the second
inspection carried out 10 days after the second cycle (36 days
from the first evaluation), we observed a complete resolution
of the picture (FIG 2). With the exception of a slight hyperaemia
immediately following the drug application, we observed no
significant side effects.
Conclusion
This case has shown the efficacy and safety of retreatment with
ingenolmebutate with clearance of AK lesions present on the
scalp. Our experiences adds that ingenol mebutate can be used
for field treatment of AK, with a high sustained clearance rate,
shorter duration of use and faster resolution of lesions.
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