Biomedical Engineering Reference
In-Depth Information
different from the IPL-alone group, suggesting that 30 minutes
is not suffi cient incubation time before PDT in acne patients.
It should be noted that prolonged incubation time did not
result in more adverse effects than in the short incubation
time group.
Another study by Hörtfel and colleagues (229) aimed to
determine the optimal light dose for effective PDT treatment of
acne and mechanism of action. Fifteen patients with mild-to-
severe acne were treated with 20% ALA cream occluded for
3 hours followed by illumination with red light (635 nm).
A light dose of 30 J/cm
2
was used on the left cheek and
50 J/cm
2
on the right cheek. At 10 weeks of clinical follow-up,
the authors found that the improvement of lesions was the
same for the two light doses and no signifi cant reduction in
P. acnes
or sebum excretion was found at any time after PDT.
Therefore, the authors theorize that other mechanisms of
actions should be considered such as effect on infi ltrating
infl ammatory cells around the acne lesion or decrease of follic-
ular obstruction by affecting keratinocyte shedding and hyper-
keratosis as suggested by Hongcharu and colleagues (211).
A recent study conducted by Yin and colleagues (230) com-
pared the effi cacy and safety of different ALA concentrations
in 180 Chinese patients. Patients received four sessions
(10 days apart) using different concentrations (5%, 10%, 15%,
and 20%) of ALA (1.5 hour occlusion) on one side and pla-
cebo on the other side as control followed by irradiation with
red light (633 ± 3 nm, 126 J/cm
2
). The authors found a signifi -
cant statistical difference among the four groups with different
ALA concentrations, with a clear positive correlation between
global improvement scores and ALA concentration. However,
there was no statistical difference in clinical outcomes between
15% and 20% ALA at 12 weeks of follow-up or more. Regard-
ing side effects, particularly hyperpigmentation was positively
correlated to the ALA concentration. Therefore, the authors
suggest that 10% and 15% ALA for 1.5 hours and red light
source should provide ideal treatment for moderate-to-severe
acne in patients with Fitzpatrick skin type III and IV.
Photodynamic Therapy with Pulsed Dye Lasers
A randomized controlled trial conducted by Hædersdal and col-
leagues (223) compared MAL-Long-pulsed dye laser (LPDL) to
LPDL alone in 15 patients treated with three sessions at 2 week
intervals. Twelve patients completed the study and were found to
present signifi cantly greater reduction in infl ammatory lesions
on the MAL-LPDL side versus the LPDL-alone side (80% vs.
67%, respectively) at 12 weeks after the fi nal treatment.
Alexiades-Armenakas (224) treated 14 patients with 20%
ALA with 45 minutes incubation time followed by activation
with LPDL (595 nm, 7-7.5 J/cm
2
, 10 ms, 10 mm spot size).
Patients received 1-6 monthly treatments and were main-
tained on topical regimen. Complete clearance was achieved in
100% (14/14 patients) with a mean of 2.9 treatments required
to achieve complete clearance for a mean follow-up time of
6.4 months. Moreover, a reduction in the erythema in ery-
thematous acne scars was observed.
PDT with Red Light Sources
The studies (78,211,225) investigating red light have demon-
strated an overall range of 20-69% reduction of acne lesions.
Hong and Lee (225) performed a split-face study in eight patients
comparing the use of red light (630 ± 63 nm, 30 mW/cm
2
, and
18 J/cm
2
) plus 20% ALA incubated for 4 hours to red light alone.
Six months after one treatment, the authors reported a 41.9%
reduction in infl ammatory lesions on the red light plus ALA side
and a 15.4% reduction on the red light side alone. Hörtfelt and
colleagues (226) compared MAL-pretreated red light (3 hours
occlusion, 635 nm, and 37 J/cm
2
) therapy to red light treatment
alone in 27 patients. After two treatment sessions, the authors
found 54% and 20% reductions in infl ammatory lesion on the
red light plus MAL side and red light alone side, respectively. The
improvement observed in the placebo/red light side was attrib-
uted to activation of endogenous porphyrins leading to photoin-
activation of
P. acnes
.
Wiegell and Wulf (227) conducted a randomized controlled
investigator-blinded study with 15 patients to compare the
effi cacy and tolerability of ALA-PDT versus MAL-PDT. MAL
and ALA were applied to each half of the face for 3 hours, fol-
lowed by illumination with red light (635 nm, 34 mW/cm
2
,
37 J/cm
2
). Thirteen patients completed the study and pre-
sented at 12 weeks follow-up similar response rates for the two
treatment regimens (59% reductions in infl ammatory lesions).
The two treatments were equally painful during illumination
but ALA-PDT resulted in more prolonged and severe adverse
effects after treatment. A previous study by Wiegell and Wulf
(228) had treated 21 patients with two MAL-PDT sessions at
2-week intervals. Approximately 2 g of MAL cream was applied
to the face and occluded for 3 hours followed by illumination
with red light (635 nm, 37 J/cm
2
). After 12 weeks, there was a
reduction of infl ammatory lesions of 68% in the PDT group
versus 0% in the control group (who received no treatment). It
should be noted that seven patients were unable to undergo
the second treatment due to side effects.
Adverse Reactions and Summary of Findings
for ALA- and MAL-PDT for Acne Vulgaris
Both ALA and MAL have shown effective with PDT for the
treatment of acne. The most prevalent side effects reported in
the studies were erythema, edema, and pain at the time of the
treatment. Other adverse reactions reported include crusting
(214,215), photosensitivity following posttreatment sun expo-
sure (214,224), pustular eruptions (223,228), and postinfl am-
matory hyperpigmentation (219,221).
In conclusion, PDT has shown safety and effi cacy in the
treatment of infl ammatory acne vulgaris with many effective
light sources and photosensitizers. Unfortunately, PDT has
been limited by the fact that both the cost of the medicine and
the cost of the laser or light procedure must be borne by the
patient. Clinicians should use topical PDT in the treatment of
acne particularly for those patients who are refractory to stan-
dard therapy, who have been on numerous medical therapies
in the past and who are looking for clinical results to occur at
a faster time interval. Further studies are warranted to estab-
lish consensus for optimal photosensitizer, ideal concentra-
tion, incubation time, activating light source, and frequency
of treatment.
clinical technique
Our treatment protocol using ALA-PDT for acne vulgaris
involves the same steps described above for AKs and photo-
rejuvenation except that we use longer incubation times
