ORIGINAL ARTICLE

Non-invasive diagnostic evaluation of phototherapeutic effects of red

light phototherapy of acne vulgaris
Cristina Zane, Rossana Capezzera, Alessandra Pedretti, Elena Facchinetti & Piergiacomo Calzavara-Pinton
Department of Dermatology, University of Brescia, Brescia, Italy

Summary

Key words:
acne vulgaris; non-invasive diagnostic
techniques; phototherapy; Propionibacterium
acnes; visible light
Correspondence:
Prof. Piergiacomo Calzavara-Pinton, Department of
Dermatology, University of Brescia, P.zale Spedali
Civili no.1, 25123 Brescia, Italy.
e-mail: calzavar@med.unibs.it,
dermobrescia@spedalicivili.brescia.it
Accepted for publication:
26 March 2008
Conflicts of interest:
None declared.
Background: During the past few years, various phototherapeutic protocols with full-
spectrum visible light or selected wavebands have been investigated in the treatment of
acne vulgaris with variable results.
Methods: Fifteen women suffering from moderate acne vulgaris of the face were exposed to
20 J/cm2 of broad-band red (l: 600–750 nm) light twice weekly for 4 weeks. In addition,
with the aim to improve the present knowledge of the mechanisms of action of
phototherapy, we measured skin sebum, pH, hydration and trans-epidermal water loss
(TEWL). Lesions of the trunk were not irradiated and served as controls.
Results: A significant improvement of acne lesions and a significant decrease of skin sebum
excretion and TEWL of the face were registered at the end of the therapy and at the 3-month
follow-up visit. The results could be related to a reduced follicular colonization of
Propionibacterium acnes, in that it was lethally damaged by photoactivated endogenous
porphyrins.
Conclusion: The present findings seem to indicate that red light phototherapy may represent
an effective, well-tolerated, safe, simple and inexpensive treatment option for moderate acne
vulgaris.

A cne vulgaris is the most common skin disorder during

adolescence (1).
Clinical presentation is polymorphic combining non-
inflammatory comedos and inflammatory lesions, e.g. papules,
pustules, nodules and cysts. In most cases it is mild and transitory,
but sometimes it causes severe disfigurement, permanent scars
and depression, and persists in adulthood age.
A wide array of topical and systemic therapies, e.g. antibiotics,
keratolytics, anti-androgens and vitamin A analogues, are
available. However, they may be only partially and temporarily
effective, poorly tolerated and even toxic after prolonged use. In
addition, clinical improvement may be slow.
Therefore, efforts for the development of new therapeutic
approaches are continuous.
Recently, phototherapy using full-spectrum visible light or
selected wavebands (green, violet, blue and combined blue and
red wavebands) proved effective, although a comparison of
results is not feasible because studies differed in emission
spectra and light doses as well as the total number and
frequency of exposures (2–7). In addition, action mechanisms
still remain to be clarified.
In the present study, we investigated the clinical effects of
repeated exposures to low doses of broad-band red light in the
treatment of moderate acne vulgaris and we used non-invasive
diagnostic techniques for the measurements of skin sebum, pH,
trans-epidermal water loss (TEWL), as well as hydration of the
stratum corneum in order to clarify the biological mechanisms of
this phototherapy (8).
Materials and methods
Patients
Fifteen women (mean age 22.4 years, range 17–29) with
moderate comedonic, papular and pustular acne of the face and
trunk were enrolled. The study was approved by the local ethics
committee and all patients signed an informed consent.
Exclusion criteria were tan, exposures to sunlight or tanning
booths, skin phototypes V or VI, photosensitivity disorders,
pregnancy, lactation and use of any topical or systemic treatment
(including oral contraceptives) for acne in the past 3 months.
The severity of acne of different areas of the face and trunk was
scored according to the Global Acne Grading System (GAGS) (9).
With this system, the presence, if any, of comedos, papules,
pustules and nodules in all affected skin areas is scored, in order
of severity on a 0–4 scale and then each value is multiplied by a
correction factor that is 2 for the forehead, right and left cheek,

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 Non-invasive evaluation of acne vulgaris

and 1 for nose and chin (9). The factor rate for each location was
determined according to the surface area as well as the
distribution and density of the pilo-sebaceous units of the
region (9). For the purposes of the present investigation, unlike
the original GAGS method, the scores of the areas of the face and
the scores of the chest and upper back were summed separately
and referred to as GAGSface and GAGStrunk.
Treatment protocol
Red light (range of emission 600–750 nm) was delivered by a
high-pressure metal halide lamp equipped with cut-off filters
(PDT 1200; Waldmann Medical Division, Villingen-Schwenningen,
Germany). Light doses were measured with a Macam SR 9910
spectroradiometer (Macam Photometrics, Livingston, UK).
The face was exposed twice weekly for 4 weeks to a fixed light
dose of 20 J/cm2. Irradiance at the skin level was 20 mW/cm2 at
a distance of the lamp of 40 cm from the skin and the exposure
time was 8 min. During exposures, the eyes were protected with
plastic goggles. Lesions of the chest and upper back were not
irradiated and served as untreated controls.
At baseline (t0), at the end of the therapy (t1) and at the 3-
month follow-up visit (t2), digital photographs were taken
under standardized conditions of illumination and were
evaluated by two blinded observers (C.Z. and P.C.P.).
During the study period, patients were asked not to change the
frequency of washing and their cleansing agent. They were
allowed to use a topical emollient base cream occasionally, if
needed. However, its regular use was not allowed.
The study was performed during winter months in order to
minimize the influence of exposure to natural sunlight.
Results
All patients completed the trial. At the end of the treatment, they
exhibited a reduction of both comedos and inflammatory lesions
(papules and pustules) of the face, with a statistically significant
(P o 0.05) decrease of the median GAGSface from 16.0 (IQR
15.0; 18.5) to 8.0 (IQR 6.5–14.5) (Table 1, Figs 1 and 2). At the
3-month follow-up visit, the improvement of the score was
retained (median: 8.0; IQR 6.0–14.0) with P o 0.05 in
comparison with baseline.
Untreated lesions of the chest and upper back did not improve
at the end of the therapy and follow up in comparison with
baseline (Table 1).
Treatments were well tolerated without relevant acute adverse
effects. All patients had a mild burning sensation and redness of
the face that spontaneously disappeared within 5 min. Scarring or
pigmentary changes were not registered.
At the end of the treatment, patients also showed a significant
decrease (P o 0.05) of skin sebum (from 132.7  19.9 mg/cm2
at baseline to 74.6  21.0 mg/cm2) and TEWL (from 20.3  7.7
to 9.1  2.6 g/m2 h) levels (Table 2). Changes remained
substantially similar at follow-up: skin sebum was 75.6  23.8
mg/cm2 and TEWL was 8.8  2.5 mg/cm2 (in both cases, P o 0.05
in comparison with the baseline).
The values of corneometry and skin pH of the face remained
unchanged at the end of the treatment and at the 3-month
follow-up visit when compared with baseline (Table 2).
Measurements of surface lipids, water content of the horny
layer, pH and water barrier function of the untreated skin of the
trunk did not show changes after 1 and 3 months from baseline.
Table 1. Variation of the modified clinical score (GAGS) at baseline (t0),
after 4 weeks (t1) and at follow-up (t2)

Face Trunk
Biophysical measurements
Patients t0 t1 t2 t0 t1 t2
TEWL was measured with the Tewameter TM 210, the water
content of the horny layer with the Corneometer CM 820, the 1 14 5 5 9 9 9
2 16 7 7 6 6 6
skin surface lipids with the Sebumeter SM 810 PC and the skin pH 3 20 13 11 6 6 3
with the Skin pH-Meter PH 900 (all from Courage and Khazaka 4 20 15 14 6 3 3
GmbH, Koln, Germany). Measurements were taken according to 5 14 8 8 3 3 6
established methods (10–12). The values for the face and trunk 6 16 6 5 3 3 3
represent the average of two measurements taken on the forehead 7 15 8 8 6 3 6
8 17 13 12 6 6 6
and chin as well as upper back and presternal skin, respectively. 9 15 3 3 6 9 6
Measurements were taken exactly on the same skin area at each 10 22 20 19 9 6 9
visit in order to avoid possible intraindividual variations of 11 17 14 14 6 6 6
biophysical parameters (13). 12 15 7 7 3 6 6
13 16 3 2 3 3 3
14 19 15 14 6 6 3
15 18 15 14 6 6 6
Statistical analysis Median 16 8 8‰ 6 6 6‰‰
IQR 15; 18.5 6.5; 14.5 6; 14 4.5; 6 3; 6 3; 6
Data are given as mean  standard deviation (m  SD) or median
Significant difference in comparison with t0 (P o 0.05).
and interquartile range (IQR), when appropriate.
‰
Clinical scores were compared with a non-parametric Non-significant difference in comparison with t1.
Non-significant difference in comparison with t0.
statistical test, the Wilcoxon test. Instrumental measurements ‰‰
Non-significant difference in comparison with t0 and t1.
were compared with a parametric test, the paired Student t-test.
GAGS, Global Acne Grading System; IQR, interquartile range.
Significance was defined as P o 0.05.

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Zane et al.

Discussion

In the present investigation, phototherapy with low-dose broad-

band red light improved inflammatory lesions, i.e. papules and
pustules, as well as non-inflammatory comedos with a sustained
improvement at the 3-month follow-up visit. The therapeutic
effect was limited to the exposed skin of the face, whereas
untreated acne lesions of the trunk did not show changes.
Exposures were well tolerated and patients experienced only a
mild and transitory burning sensation. The hazard of long-term
toxicity, namely skin cancer and photoaging, is unknown but it
seems unlikely on the basis of the present knowledge of the
biological effects of visible light in the skin.
The action mechanisms are still unclear but the present
instrumental findings may help in clarifying them.
The clinical improvement was accompanied by a significant
decrease of both sebum excretion and TEWL, which are
enhanced in acne (14). The reduced sebum excretion could be
related to a reduced follicular colonization by P. acnes that
constitutively synthesizes and accumulates intracellular
Fig. 1. Acne lesions before red light phototherapy (t0). porphyrins, namely coproporphyrin III, which can cause lethal
damage on photoactivation with red light (8, 15).
As a consequence, its influence on sebocyte viability and
differentiation is likely to decrease, leading to a reduced sebum
excretion (16).
A direct modulation of the biological activity and/or a lethal
photodamage of the sebaceous cells could also be possible
explanations for the reduced sebum excretion. However, this
appears unlikely as sebocytes accumulate constitutively only a
negligible amount of intracellular porphyrins and free
porphyrins are not present in the lipid droplets they secrete (17).
The reduction of the follicular colonization of P. acnes can also
explain the decrease of TEWL, as it would lead to a decrease in
the synthesis and excretion of various cytokines and chemokines
that induce the hyperkeratosis of the follicular epithelium (14,
16). This change leads to decreased amounts of ceramides in the
stratum corneum, and therefore to the impairment of the water
barrier function (14). Furthermore, the reduced colonization by
P. acnes causes a decrease of the synthesis and excretion in the
sebaceous duct of the extracellular lipase that hydrolyzes
triglycerides of the sebum to both glycerol and free fatty acids
with an additional comedogenic activity (1).
The reduced colonization of P. acnes can also represent the key
Fig. 2. The same patient after red light phototherapy (t1). biological event leading to the reduction of inflammation that we
observed clinically. Indeed, P. acnes produces and releases several
pro-inflammatory substances, including lipases, proteases,
Table 2. Variation of biophysical parameters (means  SD) at baseline hyaluronidases and chemotactic factors, which have a role in the
(t0), after 4 weeks (t1) and at follow-up (t2) development and maintenance of the local inflammatory
response (16). In addition, P. acnes induces production of an
t0 t1 t2
array of pro-inflammatory cytokines by keratinocytes and
Sebum (mg/cm ) 2
132.7  19.9 74.6  21.0 75.6  23.8 monocytes (18).
Skin pH (pH units) 5.8  0.6 5.7  0.4 5.7  0.5
Besides effects on P. acnes, red light is known to have a direct
Corneometry 71.5  7.6 69.7  6.8 69.3  6.6
(corneometry units) anti-inflammatory activity by targeting macrophages and other
TEWL (g/m2 h) 20.3  7.7 9.1  2.6 8.8  2.5 dermal cell populations. The following intracellular molecular
P o 0.05 in comparison with baseline. effects reduce both the production and the release of pro-
inflammatory cytokines and growth factors (19, 20). In

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addition, red light has a stimulatory effect on the proliferation
and activity of fibroblasts, leading to a reshaping of the
extracellular matrix (19, 20).
The other parameters that we measured, i.e. stratum corneum
hydration and skin pH, are usually normal in acne patients (21)
and did not change after phototherapy. These findings suggest
that the epidermis is not damaged by red light phototherapy.
The use of ultraviolet A (UVA) and various visible wavebands
for the treatment of acne vulgaris was reported previously. UVA
(wavelength range: 320–400 nm) light has a strong sensitizing
activity on P. acnes and anti-inflammatory activities as well (3, 22).
However, the hazard of sunburn and uneven pigmentation as
well as possible long-term adverse effects such as photoaging and
skin tumors limit its clinical use.
White (400–700 nm) (2), blue (440–495 nm) (2, 4), green
(495–558 nm) (3) and violet (380–440 nm) (3) wavebands as
well as a combination of red (640–750 nm) and blue
(440–495 nm) lights (2, 6, 7) have also been used. All studies
reported some improvement, but the comparison of results is not
feasible because of the differences in dosage, light spectra and
treatment protocols. In the present investigation, we used red
light because it offers the therapeutic advantage of deep
penetration into the skin, thus targeting the whole sebaceous
gland, including the infra-infundibular part, where P. acnes
proliferates and accumulates, and the upper dermis (23).
However, high light dosages, and therefore relatively prolonged
exposure times, are needed because the Q band of porphyrin
activation at 632 nm is 10–20-folds smaller than the peak in the
Soret band (2).
In the last few years, a variety of lasers have also been reported
to be useful in the treatment of acne vulgaris (24–26). A review
of these studies is beyond the scope of the present paper and can
be found in the literature (see, for e.g. (5)).
However, we emphasize that action mechanisms are quite
different because, unlike phototherapy with selected wavebands
of incoherent visible light, most laser systems work by destroying
not only the P. acnes bacteria but also the sebaceous glands.
Furthermore, possible advantages of laser therapy over
phototherapy with incoherent visible lamps have not been
demonstrated with comparative clinical trials up till now.
In conclusion, we believe that phototherapy with red light as
well as with other visible wavebands represents a safe and
effective non-invasive treatment option for acne vulgaris. Its use
could be particularly valuable when standard therapies prove to
be not or poorly effective, not or poorly tolerated or
contraindicated. In addition, treatment protocols combining
phototherapy with standard topical and oral treatments could
provide for a synergic or an additive therapeutic activity.
However, there is a clear need for randomized, blinded studies
with a prolonged follow-up.
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