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Dermatologic Therapy, Vol. 18, 2005, 253 –266                                        Copyright © Blackwell Publishing, Inc., 2005
Printed in the United States · All rights reserved
                                                                                               DERMATOLOGIC THERAPY
                                                                                                      ISSN 1396-0296




                             Optical treatments for acne
Blackwell Publishing, Ltd.




E. VICTOR ROSS
Dermatology Department, Naval Medical Center, San Diego, California



ABSTRACT: Light-based treatments for acne are becoming increasingly commonplace in dermatol-
ogy. This article reviews various light approaches in acne therapy. Methods are discussed from an
anatomical and a functional perspective. The emphasis is on the practicality of treatment as well as
the pros and cons of various devices. Also, a review of the recent literature is presented. The article is
intended to give the reader a panoramic view of this still-young and developing area. Most likely,
light-based acne treatment will receive more popularity as dermatologists learn how to integrate this
type of therapy within the context of more established drug agents.

KEYWORDS: acne, laser, light, treatment




Introduction                                                         Although there have been many studies, most
                                                                  investigations of light treatment of acne are sub-
The use of light in acne is not new. Full-spectrum                optimal. Typical study deficiencies are the lack of
sunlight has long been reported to be beneficial                   a split-face design, lack of long follow-up periods,
for acne, and office-based ultraviolet radiation was               no controls, and too few subjects. Also, there are
once used by dermatologists. The present article                  often no identifiable microscopic changes imme-
present a brief overview of acne treatment with                   diately after treatment, so that mechanisms for
electromagnetic devices. Both visible and infrared                improvement are not clear. The intrinsic volatility
light-based modalities, as well as radiofrequency                 of acne in any patient is often underemphasized,
devices, will be covered.                                         and the Federal Drug Administration (FDA)
   One could argue that all acne can be improved                  threshold for clearance of devices is often lower
without the use of electromagnetic waves. How-                    than that required for drug approval.
ever, as Cunliffe recently suggested (1), despite the
smorgasbord of available drug agents light-based
technologies may fill a current void within the                    Anatomy
treatment spectrum in a potentially “medication-
sparing” role.                                                    Light-based acne treatment starts with an under-
   Over the past few years there has been an                      standing of its pathophysiology. The sebaceous
outpouring of support for new and creative non-                   follicle is the site of lesion development. The most
pharmacological approaches to acne treatment (2).                 superficial portion of the sebaceous follicle, the
Antibiotic resistance, the adverse effects of topical             acroinfundibulum, shows a similar anatomy and
and systemic anti-acne medications, and improved                  keratinization as the adjacent epidermis (FIG. 1).
technologies have created a “buzz” for alternative                Deposition of epidermal melanin, as seen in open
acne treatments. However, not everyone is on the                  comedones (blackheads) and the addition of cera-
light bandwagon, and the cost of these therapies                  mides to sebum, occurs here. Melanin is also found
might always limit their use as a first-line approach              in the acroinfundibulum but not the lower parts of
(3).                                                              the follicle (with the exception of the hair shaft).
                                                                     The infrainfundibulum is located deeper in the
                                                                  infundibulum approximately 200 µm below the
Address correspondence and reprint requests to: E. Victor Ross,   surface. It keratinizes, but with a thin horny layer
Dermatology Department, Naval Medical Center San Diego,           with corneocytes that are frail and imperfect.
34800 Bob Wilson Drive, San Diego, CA 92134, or email:            This is the site of initial comedogenesis resulting
evross@nmcsd.med.navy.mil.                                        from increased proliferation and accumulation of




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                                                             “Hyperfunctioning” sebaceous glands are one of
                                                          the main contributors to acne. In an acne subject,
                                                          sebaceous glands and the entire sebaceous follicle
                                                          are much larger than in non-acne subjects (5). Their
                                                          miniaturization results in a marked decrease in acne
                                                          lesions counts and severity. Any long-term acne
                                                          cures most likely require their participation.


                                                          Basis for treatment
                                                          One can photochemically and/or thermally or
                                                          possibly even photoimmunologically interrupt
                                                          acne’s pathogenesis. Potential targets are the
                                                                                                .
                                                          infundibulum, sebaceous gland, P acnes, and any
                                                          of the components of the sebaceous follicle that
                                                          might modulate the inflammatory response.
                                                          Rather than considering individual acne lesions
                                                          as targets in light-based therapy, a more rational
                                                          approach should be directed toward prevention of
                                                          new lesions. Even with a severe acne outbreak,
                                                          lesional involvement comprises less than 1% of
                                                          the surface area of the face.
FIG. 1. Photomicrograph of sebaceous follicle in             As FIG. 1 shows, there are multiple targets for
acne-rosacea patient. Bar = 100 µm. As Plewig and         laser acne treatment. Some of the therapies are
Kligman (4) point out, this is where the “drama of acne   based on selective photothermolysis (SPT), whereas
is performed”.                                            others are based on generalized water heating
                                                          (FIG. 2). There is no unique chromophore for acne
                                                          lesions, although the abundance of sebum, bacteria,
sloughed follicular keratinocytes mixed with sebum.       and the hypervascularity of inflamed areas make
Plewig and Kligman (4) note that the infundibulum         for potential selective acne lesion and/or sebaceous
is a critical site in the development of acne. In the     follicle damage in the skin.
infrainfundibulum, the various Propionibacterium             When planning treatment approaches, one
species act on triglycerides and release their cyto-      should consider the behavior of light in the skin.
kines. Changes in infundibular keratinization, and        Light is either absorbed or scattered. The wavelength-
inflammation follow their release.                         specific depth of penetration (so-called optical
   The worms of oily material that are extruded           penetration depth) is defined as the depth at which
with a comedo extractor are almost pure colonies          light is attenuated to 37% of its incident intensity. Its
of Propionibacterium acnes. Most of the reddish-          value is experimentally determined and/or predicted
orange fluorescence seen on the face under 365-nm          by models. As an example, consider a sebaceous
light is the result of the coproporphyrin III pro-        gland located about 1 mm below the surface. The
duced by these anaerobic bacteria. The fluorescence        red light would be predicted to be attenuated to
is proportional to the quantity of Propionibacterium.     about 20% of the surface fluence, whereas the blue
Other components of the normal flora include               light intensity would have decayed to almost zero.
Staphylococcus epidermidis, Demodex, and yeasts.          Even though blue light is 40 times as potent in
   Inferiorly, the infrainfundibulum splits into          porphyrin excitation, so little blue light is available
numerous sebaceous ducts that provide commu-              at the sebaceous gland that red light would be
nication between the lobules of sebaceous glands          predicted to show a more robust photodynamic
and the infundibulum. Finally, the hair shaft itself      therapy (PDT) effect (FIG. 3). Still, some blue light
extends through the sebaceous follicle and is             (but less than 1% of its surface intensity) will reach
characterized by an intermediate morphology               the deeper parts of the sebaceous follicle. Indeed,
between a vellus hair and a terminal hair shaft.          because of the exponential nature of light attenu-
The miniature hair shaft contains melanin, which          ation in tissue, one cannot dismiss the role of blue
may be subject to both photothermal and photo-            light deep in the skin. Even a small dose of these
chemical effects.                                         “ultrapotent” photons can have a biological effect.


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                                                           and epidermis. Exposure may lead to increased
                                                           epidermal cell turnover and a mild desquamative
                                                                                                 .
                                                           effect. Also, superficially located P acnes will be
                                                           susceptible to both PDT and non-PDT bactericidal
                                                           effects of UVA (7). The exact chromophore for
                                                           UVA light is unknown.
                                                              Violet and blue light will penetrate deeper (90–
                                                           150 µm) than UVA light, but most of this wave-
                                                           length range is confined to the epidermis. It follows
                                                           that even with aminolevulinic acid (ALA) application
                                                           and preferential accumulation of ALA and proto-
                                                           porphyrine IX (PpIX) production in the sebaceous
                                                           gland (vide infra), it is unlikely that significant
                                                           amounts of light will reach deeper glands. On the
                                                           other hand, light will activate PpIX in the epidermis
                                                           and acroinfundibulum, resulting in damage to
                                                                                         .
                                                           these areas. Also, some P acnes will be killed.
                                                           There might also be an exfoliative effect with or
                                                           without ALA with this approach.
                                                              Green, yellow, and red light penetrate deeply
                                                           enough (280, 450, and 550 µm, respectively) to
                                                                                         .
                                                           have a primary effect on P acnes in the infundi-
                                                           bulum. With increasing power densities (beyond
FIG. 2. Photomicrograph of same acne-rosacea               200 mW/cm2), there is also direct heating of the
patient. Text boxes denote most likely anatomical          epidermis, blood vessels, and possibly even the
targets for various wavelengths of light. Depth of ALA     miniature pigmented hair shaft associated with
effect will scale with incubation time. Nd:YAG, RF, and    sebaceous follicles. One would expect some light
deeply penetrating halogen lamps will “start” heating      to reach the sebaceous gland, where after ALA
near the base of this sebaceous follicle.                  application, PpIX is formed.
                                                              Near infrared (NIR) light: the 1064-nm laser has
                                                           a unique place in the absorption spectrum of major
                                                           skin chromophores. There is some melanin and
                                                           HgB absorption. With pulse stacking and higher
                                                           fluences, water will also be heated such that tissue
                                                           damage can extend several mm in to the dermis.
                                                           With typical safe fluences (i.e., 10–50 J/cm2 for ms
                                                           pulse width domains), one would expect only
                                                           modest heating of the sebaceous gland, and the
                                                           gland is heated only because it is embedded in the
                                                           larger volume of heated tissue water. Severe damage
                                                           to the gland in this setting (without selective fat
                                                           heating) would cause considerable pain or possibly
                                                           full thickness dermal necrosis and scarring.
FIG. 3. Predicted PDT effect based on model for blue
and red lights as function of depth (courtesy of Gregory      Mid-infared lasers (MIR). These lasers can be
Altshuler PhD, Palomar Medical Technologies,               configured to heat different subsurface “slabs” of
Burlington, MA). Note that blue light yields very little   skin, depending on the cooling type, wavelength,
PDT activity at 1- and 1.5-mm deep in the skin.            pulse duration, and fluence. Water is the chro-
                                                           mophore. For example, the 1450-nm laser equipped
                                                           with cryogen spray cooling (DCD) heats from
   We now examine a range of wavelengths and               about 200–500 µm below the surface. The 1320-nm
the relative depths of action within the context of        laser heats a somewhat larger and deeper volume
their chromophores. We start anatomically with             because of a lower absorption coefficient. In corre-
ultraviolet A (UVA) light (6). Because of rapid            lating the anatomy of acne with the depth of MIR
attenuation as a result of scattering, UVA exposure        laser presentation, the present authors have observed
alone likely only affects the upper infundibulum           microscopic damage of superficially located




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FIG. 4. PpIX absorption curve with some specific pumping available wavelengths (from DUSA educational
presentation CD).


(200–600 µm) glands with the 1450-nm laser. How-         and specific visible light wavelengths, intercellular
ever, in human skin this was only observed with          porphyrins kill bacteria through membrane
high fluences. Most likely we are only mildly (and        damage. The PDT effect is the result of singlet O2
not irreparably) heating the sebaceous gland with        formation and has been demonstrated in vitro.
available settings with these devices. According         However, the efficiency of bacterial killing with
to the sebaceous gland absorption spectrum, there        endogenous porphyrins is low, and consecutive
is no selectivity for sebum over water in this range     in vitro illuminations were required to reduce
(1320 –1540 nm). It follows that sebaceous glands        viability by four or five orders of magnitude (8).
are damaged only if and because they are embedded        However, when supplied with ALA (a prodrug that
within the volume of tissue water heated.                                 .
                                                         creates PpIX), P acnes produces more porphyrins
   If one were to design a light source for selective    than it produces naturally, and the bacteria are
sebaceous gland heating, it would emit around 1.2        inactivated by several orders of magnitude more
or 1.7 µm. However, even for these wavelengths,          than without ALA (8).
the ratio between water and sebum absorption                The sebaceous gland is sterile. Therefore, pho-
coefficients is still small. On the other hand, because   tochemical damage to the gland itself requires an
the sebaceous gland should cool more slowly              exogenous porphyrin (or a prodrug such as ALA).
than the surrounding skin, one might be able to          Any blue, red, or green color light source alone might
optimize parameters for selective destruction of         result in the death of P. acnes but should not
the gland.                                               cause significant sebaceous gland damage.
   Light-based therapies can also be examined from          Johnsson (9) found that the extruded contents
a mechanistic viewpoint. Four broad approaches           of the sebaceous follicle yielded a spectrum with
are addressed.                                           an excitation peak ranging from 381 to 405 nm. This
                                                         finding supports violet-blue light as an excellent color
                                                                            .
                                                         range for killing P acnes. Less absorptive “Q bands”
Approaches to light-based therapies                      are other logical pumping wavelengths. They are
                                                         504, 576, and 538, and 630 nm (FIG. 4). Kjeldstad
                                                         (10) determined the action spectrum for P. acnes
Photochemical tissue interactions (without an
                                                         killing in the UVA and blue light regions. He found
exogenous photosensitizer)
                                                         that shorter wavelengths were more efficient
Photochemical treatment of acne using endogenous         than longer wavelengths. The exception was in the
                        .
porphyrins is based on P acnes photoinactivation.        range of 400 to 420 nm, where the action spectrum
Propionibacterium acnes produces coproporphy-            showed a relative peak (but not as high as for UV).
rins and protoporphyrins. With activation by UVA         Kjeldstad showed that the mechanisms of P. acnes


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sensitivity to near UV (320–400 nm) and blue light         acne improvement. The total light dose in the
(415 nm) were different; porphyrin sensitization           larger group was 650 J/cm2. Interestingly, improve-
accompanied by singlet O2 was the most important           ment did not increase between 10 and 20 treat-
mechanism with blue light. UVA inactivation on             ments. Also, the lower-dose group showed better
the other hand was felt to be related to alternative       improvement. In the present study, subjects were
inactivation mechanisms (11).                              not followed after the last treatment. In addition to
   Konig (12) found that with irradiation of follicular    decreased acne lesion numbers, they also found
extrusions with 407-nm light, there was photo-             decreased pilosebaceous fluorescence (18).
bleaching (degradation of the sensitizer) and                 In another study (19), 107 patients were rando-
production of photoproducts. The main photopro-            mized into four treatment groups: blue light, blue-
ducts were photophotoporhyrins with a maximum              red light, cool white light, and benzoyl peroxide.
absorption of 670 nm. It follows that with irradiation     Treatment sessions lasted 15 minutes, and the
of acne lesions, the areas will become increasingly        cumulative doses over 12 weeks of daily treatments
sensitive to longer wavelengths of light. However,         were 320 J/cm2 for the blue light and 202 J/cm2 for
there should be little PDT activity beyond 670 nm,         the red light. White light was used as a control. Over-
so that PDT action will not occur with near-infrared       all, the blue-red light combination was superior,
(NIR) and mid-infrared (MIR) exposures.                    showing 75% reduction in inflammatory lesions
   What follows is a brief summary of each device          after 12 weeks. The blue light and benzoyl peroxide
and how these devices might reduce acne severity.          produced similar improvement of about 60% after
This article starts with wavelength ranges and             12 weeks. Low-output white light (a room light “con-
proceeds to discuss individual devices and studies.        trol”) was associated with a 25% decrease in counts.
   Ultraviolet B (UVB) and UVA lights, despite the            In another study (25), patients were treated three
belief of most teenagers, have been shown to have          times a week for a total of 20 sessions. Treatments
no long-term efficacy in acne (at least not better          required about 20 minutes. Three types of light
than what might be expected from topical remedies          were used: 1) “full spectrum,” a mix of UVA, violet
and even placebo effects). UVA is the least benefi-         and green light; 2) “violet light,” a mix of UVA
cial (13). However, UV light may have some anti-           and violet light with a small contribution of green
inflammatory effect in acne, and 70% of patients            light; and 3) “green light,” a mix of mostly green
believe sunlight to be beneficial in acne (probably         light with a small contribution of violet light. The
as a result of acute effects of drying the skin) (5).      investigators observed a final reduction of acne seve-
Even though the action spectrum favors shorter             rity of 14%, 30%, and 22% at the end of 20 sessions
                     .
wavelengths for P acnes killing (i.e., UV versus blue      with full spectrum, violet, and green light, respec-
light), visible light penetrates better and, unlike UVA,   tively. Overall, the violet light group did best, but the
is not carcinogenic. Also, long-term exposure to           differences were not significant. As in most studies,
UVA light enlarges sebaceous glands (14).                  the light effects were primarily on inflammatory
   Blue-violet light continuous wave (CW) sources          lesions, with little effect on comedones and papules.
have been extensively studied in acne. These devices       They suggested, like others, that light treatment
emit light in the mW/cm2 range, use exposure               might be best combined with a topical keratolytic.
times of 10–20 minutes, and are painless so long              Kawada et al. (17) treated 30 patients using a
as exogenous photosensitizers (PS) are not used.           blue light source (metal halide source, clear light,
In this application, endogenous porphyrins (pro-           Lumenis), which has a peak emission between 407
duced as byproducts of P acnes metabolism) are
                              .                            and 420 nm. The irradiance was 90 mW/cm2, with
excited, and singlet oxygen is formed. Overall, acne       two treatments per week for up to 5 weeks. There was
clearance during treatment has been variable, and          an overall 55% reduction in the number of lesions
the relapse rate with endogenous porphyrin-based           (all types). Seventy-seven percent of the patients
treatment (with power densities of < 100 mW/cm2)           either “improved” or “markedly improved,” with 20%
appears to be high after cessation of therapy. A           either worsened or remained unchanged. One month
sampling of studies is presented (8,15–27).                after the final treatment, most of the improvement
   In one study, 34 patients were treated with a           was sustained. The only side effect was dryness.
blue-light device. Patients were divided into two             Gold et al. (28) recently compared treatment with
groups (based on high versus low dose) and treated         1% topical clindamycin b.i.d. versus blue light
with a high-energy high-pressure blue light (400–          irradiation for 16 minutes and 40 seconds (twice a
420 nm). They found that after 10 of 20 treatments         week for 4 weeks). Patients were randomized into
(10 minutes a day at approximately 55 mW/cm2, four         either treatment arm. Thirty-four patients were
times a week for 5 weeks) there was “very good”            enrolled, and 25 completed the study. The average




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decrease in number of inflammatory lesions after        is, singlet O2 production by long light exposures results
clindamycin was 14%, whereas at the 4-week post-             .
                                                       in P acnes killing. The irradiances are insufficient
treatment evaluation, the blue light group showed      to achieve significant temperature elevations in or
a 36% mean reduction in papules and pustules.          around the acne lesion or normal skin. The following
   Tzung et al. (29) examined the role of blue         studies involve irradiances and fluences where there
light in acne. They treated 31 patients and used       is at least a slight temperature elevation as well as
a 420-nm light source (F-36 W/Blue V, Waldmann         a possible PDT-mediated antibacterial effect.
Germany). They did not provide the irradiance but
noted that the total dose was 40 J/cm2. Patients       PDL. Seaton et al. (35) examined the effects of low-
were treated twice a week for 4 weeks. Only one        fluence PDL treatment (585 nm, 1.5 or 3 J/cm2,
side of the face was treated. They found that the      one pass, one treatment session) with a follow-up
treated side was much improved (about 52% reduc-       of 12 weeks. They found that acne severity improved
tion in lesion counts) at the end of the eight         markedly versus controls (53% lesion count decreases
sessions. The mean improvement was only 10%            in treatment areas versus only 9% in controls).
on the control side. Using a Wood’s light, they did    There was no difference between the high- and
not find a correlation between pretreatment fluo-        low-fluence groups. They postulated that the laser
rescence intensity and treatment efficacy. Also, a      might directly kill bacteria and also alter the
treatment effect was not correlated to a fluores-       immunological response to the bacteria. In a com-
cence intensity change. The authors concluded that     mentary accompanying the article, Webster (36)
the mechanism of blue light action is unknown.         noted that acne improved but that the patients
   A recent study (30) examined the role of 420-nm     did not become “acne free.” He related the success
CW light in acne management. In this study, 28         to a level encountered with benzoyl peroxide. He
patients were treated at up to 200 mW/cm2 for          also suggested that the laser might somehow alter
15 minutes twice a week for 4 weeks (eight total       the comedonal environment or follicular wall
treatments). Clinical improvement was 65% at the       maturation. Although low-fluence PDL will also
end of the sessions. The authors found P acnes in
                                           .           transiently heat microvessels, it is unknown what
21–28 cases via polymerase chain reaction (PCR)        role, if any, this plays in acne treatment. Recently
prior to therapy, however, only one of those cases     Orringer et al. (37) reported their research using
failed to show P acnes after treatment. Electron
                 .                                     a low-fluence PDL with a slightly different pulse
microscopy (EM) performed in 8/28 patients             profile and wavelength than Seaton et al. (35). They
showed P acnes in only one case – the authors were
          .                                            were unable to achieve significant lesion reduction
unsure how to reconcile this data with the PCR data.   in their split-face study. Chu (senior author in the
                                                       Seaton study) responded that the poor results in
                                                       this study might be the result of the wavelength
Interventions where photochemical and
                                                       difference, total numbers of pulse, high number
photothermal treatments might play a role
                                                       of dropouts, or failure to account for the possibility
The visible light devices cited previously work ex-    that laser-induced soluble factors might mitigate
clusively through photochemical mechanisms. That       acne of the untreated side (38). Chu recently



  A note regarding pulsed light sources and PDT. Short pulses are in conflict with one condition that
  optimizes PDT, that is, long application times and low power densities that allow for oxygen avail-
  ability and therefore enhanced singlet O2 formation. In two articles (31,32) it has been shown that
  lower irradiances demonstrate a more robust PDT effect. Although pulsed light sources have been
  shown to be equivalent to CW sources in some experiments, the PDT effect was only equivalent
  if the average irradiances were similar. Theoretically, it has been shown that very high irradiances
  are necessary to diminish the effects of PDT. Most pulsed light sources in dermatology are below
  the saturation threshold (4 × 108 W/m2) (33). In defense of pulsed-light PDT, Karrer (34) used a
  pulsed dye laser (1.5 ms) and found that ALA-PDL worked for actinic keratoses almost as well as
  incoherent light. All of these suggest that an optimal pulsed light therapy for acne (at least, with
  PDT as a mechanism) might require multiple passes with blue, green, yellow, and red light. The
  interval between passes should be designed such that the average irradiance is similar to that of CW
  devices with similar emission spectra.




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FIG. 5. Patient (a) before and (b) 3 weeks after final of four treatments with IPL (without ALA) (525–1200 nm,
8 J/cm2, two passes, 60 ms, 2-week interval between sessions). Improvement was modest, and relapse occurred
within 3 additional weeks.


presented his work in London, showing an up-            bands (vide supra), a second mechanism might
regulation in TGF beta following low fluence PDL         be photoactivation and singlet O2 creation.
treatment (N-lite). The resulting reduction in infla-       In another scenario, lesser settings are used with
mmation was thought to be to the result of soluble      multiple pulsing. In this second application type,
cytokines and an alteration in T cell function.         lower settings presumably change the ratio in favor
                                                        of photochemical over photothermal mechanisms.
Intense pulse light. Most devices emit in the 500–      There are newer pulsed light sources that use low
1200 nm range, with the greatest portion of the         energies and a spectrum that allows for consider-
spectrum in the 530–700 range. Intense pulsed           able violet-blue and/or green-yellow-red light.
light (IPL) has been used in two scenarios, with the    These handpieces are able to pump most, if not
first using settings normally used for rosacea and       all, of the absorption bands for PpIX. For example,
photorejuvenation. These settings, with or without      the present author has used an IPL emitting mostly
ALA, are able to achieve sufficient heating of telan-    green-yellow light (Lux G, 525–1200 nm, Palomar
giectasia and pigment dyschromias to diminish           Medilux, Palomar, Burlington, MA) or mostly
their appearance. Published studies of IPL with         violet-blue light violet (Lux V, 400–700 nm and 870–
“high” fluences (without ALA) have shown (39–41)         1200 nm) in weekly treatments (up to four) without
a reduction in redness and acneform papules. In         ALA. In this split-face study comprising four weekly
the present author’s own experience with traditional    treatments, patients were randomized into the
IPL treatments, a reduction in redness associated       “green-yellow” light or “violet” light groups. Both
with acne/rosacea has been observed, and patients       groups showed about 85% inflammatory lesion
have remarked that they observe fewer lesions in        reduction during treatment (FIG. 5a,b). The control
the postoperative period. In this first “high-setting”   sides improved by about 30%. However, within 3–
scenario, two potential mechanisms might be             8 weeks after the final treatment, the acne counts
operative. One is temperature elevation in the          began to return to baseline level. There was a
hyperemic acne lesions as well as at the dermal–        slight warm sensation during IPL treatments,
epidermal (DE) junction. Because of potential           indicating at least a mild thermal effect. However,
“pumping” of endogenous porphyrins in the Q-            no obvious thermal side effects were observed




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(i.e., microcrusting). Dierickx (42) used the same       laser alone showed more post-treatment flares,
system with both violet and green light hand-            decreased clearance, and faster relapses than in
pieces and found significant clearing of lesions          other arms of her trial where lasers were used in
(after up to five treatments over 5–15 weeks).            tandem with topical and oral medicines. Combi-
Follow-up to 3–6 months resulted in only a partial       nation treatment resulted in more rapid and
return of lesion counts in some patients.                sustained improvement (46).
    Another flash lamp device (Clear touch, Radiancy)
uses low fluence green-yellow light (about 7–9 J/cm2
with a 30-ms pulse) for P acnes killing and a “heat”
                             .                           Exogenous photosensitizer-assisted
pulse to “reduce inflammation.” A recent study of         PDT
50 patients showed 50% reduction in inflamed
lesions at the end of the study. Full faces were
                                                         ALA PDT
treated and compared to controls in a crossover
design. There were two treatments per week over          The preferential accumulation of ALA and subse-
4 weeks. Only mild transient erythema was                quent PpIX production in sebaceous glands has
noted as a side effect. No discomfort was observed       been shown (47,48) regardless of administration
(43).                                                    route (49,50). However, the selectivity and accu-
    The role of Demodex in the pathogenesis of           mulation in the glands will depend on the vehicle
acne remains controversial. However, Demodex             and application time. Most likely at least 3–4 hours
can be selectively coagulated via IPL (44). Although     will be required for significant accumulation in the
chitin is known to denature at relatively low tem-       gland itself. When light is delivered to ALA-treated
peratures, it is likely that the chitin wall contains    skin, PpIX is excited to a triplet state, indirectly
some melanin that may serve as a chromophore             creating singlet O2. ALA has been used with CW
as well (personal communication, Dr Karl J. Kramer,      light sources for a broad array of skin maladies,
Insect Cuticle Biochemist, Grain Marketing and           including acne. More recently, ALA is being pro-
Production Research Center, Kansas State Univer-         moted as a “booster” for IPL and PDL. The working
sity, April 27, 2004). It follows that primary heating   theory is that the combination of ALA and photo-
of the mites might contribute to the success of IPL      rejuvenation settings with PDL and IPL can achieve
treatments.                                              acne clearance, whereas simultaneously reducing
                                                         brown and red dyschromias. Three treatment
KTP laser. Based on pulse length, pulse structure,       sessions are typically advised at 4-week intervals.
and overall blood and pigment heating, the               ALA is applied for 1–2 hours after which light is
potassium titanyl phosphate (KTP) laser mimics           applied. Whereas there is evidence that this approach
the typical green-yellow (GY) IPL output. In a           reduces acne lesions, and it is possible that ALA
study of 11 patients with acne vulgaris, subjects        plays a role, the likelihood that the pulsed light
were treated in a split-face trial. Four treatments      source results in large amounts of immediate
were delivered over 2 weeks. Using fluences of            singlet O2 formation is small. It is more likely
7–9 J/cm2, a 4-mm spot, and contact cooling (6–          that that IPL-PDL reduces redness through well-
10 passes, cumulative fluence of 20–50 J/cm2),            established photothermal mechanisms or that
acne clearing was 36% on the treated side 1 month        there might be some synergy between PDT and
after the last treatment versus a 2% increase on         photothermal action (51).
the control (cooling only) side (45). Presumably,           PDT effects can be observed with pulsed light
heating of the vasculature as well as potential          (33). However, only moments of sun exposure will
photochemical effects are active with this approach.     create more singlet O2 than the 5–30 J/cm2 of
The present author has found, however, that in           pulsed green-yellow light (10). This will be truer if
patients with severe active rosacea, flares can           the pulsed light exposure occurs early after ALA
result from treatment fluences that are sufficient         application (before there is time for sufficient PpIX
to immediately show telangiectasia clearance.            production). No study thus far has shown micro-
Lesser fluences are more likely to show improve-          scopic evidence of selective sebaceous gland
ment without an immediate post-treatment flare.           damage after short contact (0–2 hours) ALA pulsed
Lee reported treatment of 25 patients with a KTP         light PDT.
laser alone. Using multiple passes with a fluence            Goldman and Boyce treated 22 patients in a study
per pass of 6–12 J/cm2 and contact cooling, she          with the 417-nm BLU-U light (DUSA Pharmaceu-
observed clearing of 60–70% after six treatments.        ticals) at 10 mW/cm2. They treated one group of
However, she reported that patients treated with         patients for 6 minutes without ALA (two treatments,


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1 week apart, with follow-up after 2 more weeks).         of the PpIX formation will be in the infundibulum
In the second group, they applied ALA for 15 minutes      and upper epidermis. On the other hand, with longer
and then treated with the light (two treatments           times and frequent wiping of the surface, one might
2 weeks apart – evaluation after 2 weeks more).           achieve preferential penetration into the sebaceous
Overall, they found a 25% reduction in acne sever-        follicle without epidermal compromise (54).
ity in the first group and 32% in group 2. There              Unlike the aforementioned studies, some inves-
was no pain. Some patients did report a sunburn           tigators have used more traditional PDT scenarios
reaction from inadvertent outdoor exposure (52).          (longer ALA application times, more deeply pene-
   Taub (39) recently reported her experience with        trating light, and lower average irradiances). For
ALA in the treatment of acne. She looked at 18            example, Itoh (55) used an excimer pumped dye
patients and applied ALA for 15–30 minutes after          laser (635 nm) and showed long-term remission in
an acetone scrub. She used either an IPL or BLU-U         facial acne after 20% ALA application (for 4 hours).
(or both). There were two to four treatments over 4–      Using the laser at 5 J/cm2, he showed complete
8 weeks. Twelve of 18 patients reported “improve-         remission in acne 8 months after one treatment.
ment.” Four of the patients reported an over 6-month      Another study of 13 patients, Itoh found good
remission in their acne. Taub was unable to deter-        improvement in acne after ALA application fol-
mine whether IPL or BluU achieved the best results.       lowed by irradiation with a halogen source (600–
   Gold et al. (53) treated 20 patients with one treat-   700 nm) (56).
ment per week for 4 weeks with final evaluations              More recently, Taylor and Prokopenko (57)
at 4 and 12 weeks after the final treatment. They          reported their work with ALA in acne. They used
applied ALA for 1 hour prior to activation with an        a red light (OmniLux Red, PhotoTherapeutics,
IPL. Of the 15 patients who completed the study,          Boldmere, UK) in a single treatment. The fluence
20% did not respond. Of the 12 patients with              ranged from 14 to 97 J/cm2 with this continuous
improvement, there was a mean 72% in reduction            wave 633-nm source. They found > 50% improve-
papular lesions.                                          ment in 7/10 patients after 3 months. Many of the
   There have been other novel approaches with            patients showed crusting and some patients showed
ALA-assisted treatment of acne. In a recent clinical      an acute acne flare a few days after treatment.
round table discussion, a list of options was pro-           Recently, Pollock et al. (58) examined the possi-
posed for acne and rosacea treatment (54). Among          ble mechanisms of action of ALA-PDT in acne.
them were PDL and ALA, IPL and ALA, and BLU-              They treated the back of 10 patients weekly for
U and ALA. Most of these approaches combine               3 weeks with ALA, light alone, or the combination
short contact (30 minutes to an hour) with ALA            at different sites. The ALA was applied for 3 hours
(Levulan, DUSA) followed by light exposures with          in a cream base and red light at 635 nm was deliv-
one of the aforementioned devices. In most cases,         ered at 25 mW/cm2 (CW), for a total dose of 15 J/
physicians will use similar settings as they would        cm2. They looked at sebum, acne lesion counts,
without ALA. Some will reduce the setting by 10–                 .
                                                          and P acnes counts. They found decreases in acne
20% to allow for the more robust reaction observed        counts 3 weeks after the final treatment. However,
after ALA. Some typical parameters are outlined in        they could not confirm the mode of action, as there
succeeding discussions: (a) PDL: 7 J/cm2, 6–10 ms,        were no changes in sebum excretion or P acnes.
10 mm spot 30/20 DCD, 595 nm, 3 J/cm2, 10 mm,             numbers.
10 ms, 30/30 DCD; (b) PDL: 40 ms, 12 mm, 595 nm,             Only one photochemically based acne study
6 J/cm2, three passes (18 J/cm2 total fluence); (c) IPL    has shown microscopic damage to the sebaceous
(Quantum, Lumenis): 2.4–2.4 ms, 10 ms delay,              glands (48). In that, the investigators treated 22
550 filter, 24–27 J/cm2.                                   patients on the back. Twenty percent ALA was
   Most of these treatments are performed monthly         applied 3 hours prior to irradiation with a CW
for 3 months. One concern by all of the panelists         broadband source (550–700 nm) for a total light
in the round table was the need for sun protection        dose of 150 J/cm2 per treatment. They examined
after treatment. Many physicians are advocating           fluorescence, sebum output, lesion counts, and
48 hours of sun avoidance/protection after the            histology. They noted an acute eruption of inflam-
procedure. It is clear that the use of ALA will expand    matory papules within 3–4 days after treatment
in acne treatment. In the future we may see various       that lasted up to 4 weeks. By 4 weeks, the lesions
application times, vehicles, and light sources. Pre-      began to improve, and most importantly, they
sently, a challenge is to achieve preferential accu-      identified sebaceous gland damage up to 20
mulation of ALA in the sebaceous gland versus the         weeks after treatment when there were multiple
epidermis. With short contact times (< 2 hours), most     treatment sessions (one per week for 4 weeks).




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Control sites showed no change. In all treatment       Mid-IR lasers. These wavelengths (1320, 1450, and
groups the sebum output was reduced. Fluores-          1540 nm) have all been applied to active acne
cence microscopy showed very bright emission in        in clinical trials. Ross et al. examined (62) the use
the sebaceous follicle versus normal surrounding       of the 1450-nm laser in the treatment of back acne
skin. Patients did experience significant erosions      and observed marked decreases in the number of
and hyperpigmentation. The authors noted that          inflammatory lesions 12 weeks after once weekly
an optimized approach might include lower light        treatments for 1 month. However, the number of
doses, fractionated treatments, and efforts to         lesions in the treated zones was small, and the
increase the selective accumulation of ALA in the      durability of the results beyond 12 weeks was unclear.
sebaceous glands versus the epidermis. For exam-       In a later human split-face study, they found a 47%
ple, based on models and experiments, it might         reduction in acne lesions on the treated side and 18%
be best to deliver one treatment at 1–2 hours after    on the control side (1 month after the final treatment)
ALA application, taking advantage of a possible        (FIG. 6a,b) (63). A more recent full-face study showed
“micropore” effect in the sebaceous follicles.         75% reduction in acne counts 6 weeks after the final
Depilation prior to application might speed            treatment (64). A review of MIR selective dermal
transport into the follicle and decrease epidermal     heating can be found in a recent article (65). A
damage. On the other hand, mild epidermal              biopsy is presented in FIG. 4 and a representative
damage might speed epidermal turnover and at                                                            .
                                                       patient in FIG. 6. One should note that most P acnes
least provide a temporary benefit in acne because       and enlarged sebaceous glands will lie below the level
of a desquamative effect near the follicle orifice.     of maximal heating with 1450 nm (where maximum
    ALA-assisted light treatment may work in several   heating is about 300–400 microns below the sur-
ways. In addition to direct photo-killing of P acnes
                                               .       face when coupled with DCD). Also, most heating
and injury to the gland (inhibiting sebum produc-      has shown only mild damage to the gland (65)). It
tion), follicular obstruction might be altered by      follows that the 1450-nm laser might work through
changing keratinocyte shedding and hyperkeratosis      direct heating of the infundibulum. We speculate
(likely the mechanism with short application times)    that this might improve sebum outflow and “reset”
(48). Long-term acne improvement does appear to        the keratinization pattern in the follicle.
be correlated with decreased sebum production (48).       Friedman reported an 80% mean reduction in
ALA-mediated sebum inhibition appears to require       inflammatory lesions after three monthly treatments
more aggressive treatment than killing of P acnes.
                                             .         with the 1450-nm laser (66). The 19 patients were
                                                       allowed to continue whatever medications they
ICG dye and sebaceous gland damage. Two                were on prior to accession into the study. Patients
studies have reported the use of indocyanine           were not followed-up after the end of treatments.
green (ICG) dye to damage sebaceous glands (59,           Boineau et al. used the 1540-nm laser (four treat-
60). In this scenario, the ICG is applied topically.   ments at 4-week intervals) in 25 patients. Twelve
Then an 805-nm diode laser can be used in a low        weeks after the final treatment, they observed 78%
or high power mode to incorporate PDT or simple        reduction in acne lesions. Patients reported that
photothermal damage to the sebaceous gland. In         their skin was less oily (67).
one study (60), Lloyd showed preferential accu-           A radiofrequency device (Thermage, Hayward,
mulation of ICG suspension after 24-h application.     CA) has recently been reported to be effective in
Then, applying an 810-nm light at 40 J/cm2 and         the treatment of acne vulgaris (68). Twenty-two
50 milliseconds, Lloyd showed selective damage         patients were treated and most showed a good
of the sebaceous gland without significant epidermal    response (> 75% reduction in lesions in over 90%
damage. There was long-term improvement in back        of patients). However, no controls were performed.
acne (up to 10 months after the final treatment.)       Although selective fat heating has been shown
                                                       with the device, selective sebaceous gland heating
                                                       has not been demonstrated microscopically.
“Pure” photothermal tissue interactions
Manuskiatti et al. (61) reported focal damage to
the sebaceous gland after ruby laser treatment on      Practical matters
the thigh and back. They speculated that the loss
of hair might improve sebum outflow and there-          Patient selection
fore acne. Perhaps damage to the sebaceous gland
via the hair shaft was one mechanism for the           The group of patients that benefit most from light
observed decrease in sebaceous gland size.             treatment is unclear. Because drug therapy is



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FIG. 6. (a) Before and (b) after Smoothbeam (1450 nm laser). One month after fourth treatment spaced 3 weeks
apart. Fluence of 14 J/cm2.


typically effective, the role of light will almost
                                                         Expected benefits
invariably be a complementary one. That is, as a
monotherapy, with the exception of presently im-         If one critically examines the literature (and the
practical therapies (as a result of side effects (48))   present authors consider their own experiences),
with deeply penetrating red light and long appli-        the likelihood of complete acne remission with any
cations of photosensitizers or prodrugs, most light      “painless” light-based technology is small. With
treatments produce temporary benefits and in-             most light acne therapies, remission is incomplete
complete acne remission.                                 and relapses are common. The likely outcomes
   It follows that the ideal patient is one who          range from nearly imperceptible improvement to
might achieve 40–50% improvement with topical            70–80% clearing up to 3 months after treatment.
medical therapy alone. For example, if the patient       The few examples of complete and long-term
is reluctant to use oral treatment, “painless” light     remissions with light-based technologies occur in
therapy might achieve a nearly complete remission        the singular regimen where photosensitizers work
in combination with appropriate topical therapy.         in combination with deeply penetrating red light.
Another group of “light-appropriate” patients are        However, this regimen type is associated with sig-
those who prefer “active” acne treatments com-           nificant side effects, such as desquamation, hyper-
partmentalized into a clinical appointment (e.g.,        pigmentation, crusting, and pain. One might accept
the noncompliant teenager who discards his acne          these side effects if oral isotretinoin-like results can
“concerns” after one week.). In this way, patients       be achieved. An agreeable but not completely under-
feel that they are participating in therapy and may      stood feature of acne is that is disappears (4). Most
be more likely to be compliant with their home           patients will outlive their acne, so that even a tempor-
medical therapy.                                         izing measure can have a real benefit. “Buying time”




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during the severe inflammatory phase might be               Arlington, TX) enhances penetration of the ALA.
an acceptable goal in light-based acne therapy.            Wood’s light is helpful to determine how much
   Overall, those procedures that involve low-level        fluorescence is present just prior to irradiation and
photochemistry are painless and convenient in the          is predictive of the amount of photosensitizer
sense that treatment times are short, and there is         present in the skin.
no down time. The safety profile with the various              With pulsed light, pain typically is similar to
devices is overall good. With photochemical appro-         that observed without the application of ALA.
aches involving aminolevulinic acid, a possible            However, the initial response with ALA is more
(and probably under-reported) side effect is pho-          robust as far as erythema and edema. With
totoxicity from inadvertent solar exposure within          continuous light sources (with 10–15 minutes of
30 hours after the procedure. In some cases, this          pan-facial exposures), such as the BLU-U light,
exposure can result in long-term hyperpigmenta-            pain is proportional to the time of application of
tion. The cost of laser procedures varies widely, most     the aminolevulinic acid, as well as the light dose.
practitioners charging between $200 and $500 per           Patients’ discomfort can be minimized by the use
treatment depending on the type of treatment               of an air cooler.
applied.                                                      Typical adverse effects are limited to those
   Overall, because of the lack of long-term research      observed with light devices when applied for other
in light-based acne treatment, it is difficult to           indications; for example, over-treatment with pulsed
predictably assess which treatments are best for           light systems can result in blistering, dyspigmen-
which patients. Small papules and pustules seem            tation, and even scarring. The biggest concern is
to respond best to light. Comedones and cysts              inadvertent phototoxicity with ALA. Most side
respond poorly (2).                                        effects have occurred in the postoperative period.
                                                           Often the patient inadvertently exposes himself
Equipment. There are now over 20 “machines”                to a few minutes of sunlight. This can include
available or “cleared” for light-based acne therapy.       sunlight through a skylight in the house or a car
Also, most devices previously used for telangiecta-        window. The patients must be coated with opaque
sias and pigment dyschromias have recently                 sunblock (and preferably wrap a pillowcase
gained “clearance” for acne from the Food and              around the treated area as well) on the way home.
Drug Administration. Using low-level photochem-
istry requires either a continuous-output blue light
source or longer wavelength visible light source.          Conclusions
These systems typically involve pan-facial treatment
with multiple banks of lights.                             Light-based approaches are as complicated as the
   With pulsed light systems, low fluences can be           pathophysiology of acne. Despite great enthusiasm
used with or without a photosensitizer. With low-          for new technology, one should remember that
fluence approaches such as low-fluence PDL, IPL,             many of the light-based results are temporary and
or KTP the light doses are only mildly uncomfortable       incomplete. As a home light therapy system, some
or even painless. Treatment is carried out pulse           of the red and blue light sources (Derma-Lux and
by pulse until the area is completely covered.             Happy light, cost about $200–500) might prove
This will typically require anywhere from 5 to             practical for teenagers and others who are willing
15 minutes per treatment.                                  to spend about 15 minutes a day. However, low-
   Using higher fluences with visible light tech-           powered visible light sources alone can probably
nologies (without photosensitizers), the doses are         only achieve mild acne improvement; on the other
in the typical range used for facial rejuvenation. Pain    hand, the patient might be able to use the light in
will be proportional to fluence and the relative toler-     combination with a topical medicine such as
ance of the patient. In these cases, treatment times       benzoyl peroxide and negate the need for an oral
are roughly the same as their low-fluence coun-             antibiotic. Many practical challenges remain in
terparts. Using a photochemical approach with a            the widespread implementation of laser and light
photosensitizer or prodrug such as ALA, there are          therapies in acne (69).
various schemes. In the most common approach,                 What approaches are most likely to yield long-
the practitioner applies a solution of ALA approxi-        term success in light-based acne therapy? We
mately 1–3 hours prior to irradiation. During this time,   know that sebum output returns to normal after
the patient is required to stay away from any natural                         .
                                                           isotretinoin and P acnes returns. However, after
light. Either an acetone scrub and/or some type            isotretinoin the infrainfundibulum keratinization
of microdermabrasion device (i.e., Vibraderm,              process is still normalized, pointing to this as a


264
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possibly more important feature in any long-term                         narrow-band, blue light source: an open study and in vitro
acne solution. On the other hand, as Plewig and                          investigation. J Dermatol Sci 2002: 30: 129–135.
                                                                   18.   Meffert H, Gaunitz K, Gutewort T, Amlong UJ. [Therapy of
Kligman point out, sebum “fuels” the acne fire, and                       acne with visible light. Decreased irradiation time by using
successful long-term light-based strategies have                         a blue-light high-energy lamp]. Dermatologische Monatss-
included damage to the gland. Acne does not occur                        chrift 1990: 176: 597–603.
when sebum output is low (but does not always                      19.   Papageorgiou P, Katsambas A, Chu A. Phototherapy with
occur when it is high!) We may see in the near                           blue (415 nm) and red (660 nm) light in the treatment of
                                                                         acne vulgaris. Br J Dermatol 2000: 142: 973–978.
future more sebu-selective light sources and other                 20.   Taub AF. Photodynamic therapy in dermatology: history
improved ways to achieve selective accumulation                          and horizons. J Drugs Dermatol: JDD 2004: 3: S8–S25.
of PS in the gland. For now, though, keep your                     21.   Elman M, Lebzelter J. Light therapy in the treatment of
prescription pad handy – pharmaceuticals have a                          acne vulgaris. Dermatologic Surg 2004: 30: 139–146.
100-year head start, and light-based therapy has a                 22.   Hirsch RJ, Shalita AR. Lasers, light, and acne. Cutis 2003:
                                                                         71: 353–354.
little catching up to do before being accepted as                  23.   Johansen Y, Wideroe HC, Krane J, Johnsson A. Proton
mainstream therapy.                                                      magic angle spinning NMR reveals new features in
                                                                         photodynamically treated bacteria. Zeitschrift fur Naturfor-
                                                                         schung Section C Biosciences 2003: 58: 401–407.
                                                                   24.   Collins S, Ahmadi S, Murphy GM. 005 Topical photo-
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