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SHORT COMMUNICATION
Pulse–Daylight–Photodynamic Therapy in Combination with Corticosteroid and Brimonidine
Tartrate for Multiple Actinic Keratoses: A Randomized Clinical Trial
Stine Regin WIEGELL 1 , Urs Broby JOHANSEN 2 and Hans Christian WULF 1
Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, and 2 Clinic
of Dermatology, Karlslunde, Denmark. E-mail: [email protected]
1
Accepted Sep 23, 2018, E-published Sep 24, 2018
The introduction of daylight-mediated photodynamic
therapy (d-PDT) has resulted in pain-free field treatment
of multiple actinic keratoses (AK) of the face and scalp
(1). Erythema and crusting may be less pronounced after
d-PDT compared with conventional PDT (c-PDT) using
red light (2, 3). During PDT of multiple AK of the face
and scalp, patients are affected by inflammation, which
may cause absence from work or social activities. In a
recent study we introduced the concept of pulse-PDT, in
which methyl aminolevulinate (MAL) cream is applied
for only 30 min under occlusion and then removed to
ensure selective accumulation of the photosensitizer pro-
toporphyrin IX (PpIX) in the mitochondria and cytosol of
the diseased cells (4). The study showed that the use of
pulse-PDT could reduce erythema after PDT of multiple
AK on the face and scalp (4). The use of a super-potent
corticosteroid before and just after pulse-PDT further
reduced erythema.
The objective of this randomized study was to eva-
luate whether the combination of pulse-corticosteroid-
daylight-PDT (PS-d-PDT) would result in less post-PDT
erythema than d-PDT without affecting the efficacy of
the treatment of multiple AK on the face and scalp. A
further aim was to clarify whether the use of brimonidine
tartrate (BT), a selective α 2 -adrenergic receptor agonist,
could result in a further short-term reduction in PDT-
induced erythema.
MATERIALS AND METHODS
Twenty-five male patients with a total of 823 AK were included in
the study. AK on the face or scalp were marked in 2 symmetrical
squared areas and randomized to d-PDT or PS-d-PDT, respectively.
After lesion counting and mapping, a sunscreen (Actinica ® SPF
50+, Galderma, Uppsala, Sweden) was applied. Following lesion
preparation with a curette, MAL cream (Metvix ® , Galderma) was
applied to both treatment areas without occlusion. After 30 min, the
MAL cream was removed in the area randomized to PS-d-PDT and
super-potent glucocorticosteroid (Dermovat ® , GlaxoSmithKline,
Broendby Denmark) was applied. The MAL was not removed
from the d-PDT until after daylight exposure. Patients exposed
themselves continuously to daylight for 2 h, after which they stayed
indoors for the remainder of the day. Erythema was evaluated 24
h after PDT, at which time BT gel was applied in both treatment
areas, and erythema was re-evaluated 30 min later. Erythema was
measured using a skin reflectance meter (Optimize Scientific 558;
Chromo-Light, Vedbaek, Denmark) (5) and evaluated visually
by the investigator using a 4-point scale. Patients scored the pain
using a numerical scale (0–10) in both areas every 30 min during
daylight exposure.
doi: 10.2340/00015555-3049
Acta Derm Venereol 2019; 99: 242–243
The study was approved by the ethics committee of Region
Hovedstaden (H-4-2011-151). Statistical analyses were performed
with GraphPad Prism ® (GraphPad Software Inc., USA). Wilcoxon
matched-pairs signed rank test was used to compare paired data
and for correlations Spearman R correlation was used. A p-value
< 0.05 was considered significant.
RESULTS
No difference was found between the 2 treatment areas
in baseline characteristics, such as lesion count and ery
thema. Ninety percent of the lesions were grade I AK.
One patient was excluded from the BT part of the study
due to treatment with MAO-inhibitors.
The visually evaluated erythema one day after treat-
ment was less in areas treated with PS-d-PDT compared
with d-PDT (p = 0.0032).
Measured erythema was significantly increased
the day after both treatments compared with baseline
(p < 0.0001). Median erythema was significantly higher
in the d-PDT areas than in the PS-d-PDT areas the day
after treatment (p = 0.028) (Table I).
The use of BT on the treated areas 1 day after treatment
significantly reduced erythema (p < 0.0001) (Table I).
BT removed PDT-induced erythema as no significant
difference was found between erythema before PDT
and after BT in either d-PDT or PS-d-PDT treated areas
(p = 0.77 and p = 0.27, respectively). Both treatments
were almost pain-free, with a median maximal pain score
of 1 (p = 0.81). No significant difference in efficacy was
found between the 2 treatment areas (p = 0.42) (Table I).
At 3-month follow-up a mean of 1.4 new AK had
developed in the d-PDT-treated areas, compared with
2.6 new AK in the PS-d-PDT-treated areas ( p = 0.012).
Lesion response rate was not associated with increased
erythema ( p = 0.51 and p = 0.78).
Table I. Erythema and number of actinic keratosis before and after
treatment in both areas
d-PDT
Median (IQR)
Erythema
Baseline
24 h after PDT
24 h after PDT and BT
Actinic keratosis
Baseline
3-month lesion response rate (%)
PS-d-PDT
Median (IQR)
p-
value
39.9 (35.2–43.9) 38.6 (33.1–41.9) 0.32
47.8 (41.1–51.0) 44.6 (41.0–48.3) 0.0028
42.4 (36.2–45.6) 37.8 (33.6–42.0) 0.015
15 (13–20)
14 (12–21)
0.59
75.8 (64.7–86.7) 80.0 (66.7–87.5) 0.42
PDT: photodynamic therapy; BT: brimonidine tartrate; d-PDT: daylight-PDT; PS-
d-PDT: pulse-steroid-daylight-PDT; IQR: interquartile range.
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Journal Compilation © 2019 Acta Dermato-Venereologica.