Optimizing Non-Antibiotic Treatments for Patients with Acne

24 Pages·2016·1.07 MB·English

by  Theresa N. Canavan

DermatolTher(Heidelb)(2016)6:555–578
DOI10.1007/s13555-016-0138-1
REVIEW
Optimizing Non-Antibiotic Treatments for Patients
with Acne: A Review
. .
Theresa N.Canavan EdwardChen Boni E.Elewski
Received:July7,2016/Publishedonline:August19,2016
(cid:2)TheAuthor(s)2016.ThisarticleispublishedwithopenaccessatSpringerlink.com
ABSTRACT maintenance therapy. While antibiotics have a
roleinacnetreatment,theyshouldnotbeused
Acne is a very common non-infectious skin as monotherapy, and lengthy courses of
condition that is frequently treated in antibiotic use are discouraged.
dermatological practices. Because acne is often
chronic and may persist for years, safe and
effective long-term maintenance therapy is Keywords: Azelaic acid; Acne; Antibiotics;
often required. Given the increasing frequency Isotretinoin; Light therapy; Retinoids;
ofantibiotic-resistantbacteriaandthegravityof Spironolactone; Subantimicrobial
the consequences of this trend, it behooves
dermatologists to maximize use of INTRODUCTION
non-antimicrobial therapy when treating acne.
In this review of the literature we present data Antibiotic overuse and the development of
regarding the efficacy and appropriate use of antibiotic-resistant bacteria, coupled with a
non-antimicrobial treatments for acne. A dearth of new antimicrobial agents, have
variety of topical and oral treatment options resulted in a serious domestic and global
exist that can be used in a step-wise manner threat [1]. The scale and magnitude of this
according to the patients’ severity and threat is severe. A recent statement issued from
therapeutic response. Non-antimicrobial the Centers for Disease Control reported that
treatments can be highly efficacious at roughly 23,000 deaths occur annually in the
controlling acne, especially when used as USA alone as a direct result of
antibiotic-resistant bacteria [1]. The trend of
Enhancedcontent Toviewenhancedcontentforthis increasingly antibiotic-resistant bacteria is
articlegotohttp://www.medengine.com/Redeem/
5CE4F06041B4C7A5. ongoing; even last-resort antibiotics, such as
colistin, which are used to treat
T.N.Canavan(cid:2)E.Chen(cid:2)B.E.Elewski(&)
multidrug-resistant infections, are becoming
DepartmentofDermatology,UniversityofAlabama
atBirmingham,Birmingham,USA ineffective. For example, E. coli harboring the
e-mail:[email protected]
556 DermatolTher(Heidelb)(2016)6:555–578
MCR-1 plasmid, which confers resistance to hidradenitis (PAPASH syndrome); synovitis,
colistin, has recently been discovered for the acne, pustulosis palmoplantaris, hyperostosis,
first time in a human in the USA [2]. osteitis (SAPHO syndrome).
Dermatologists are in a unique position to Acne can be successfully treated using a
respond to the rising threat of multipronged approach by targeting its
antibiotic-resistant bacteria: dermatologists underlying key mechanisms. Although acne is
make up just 1% of all physicians but are not caused by an overabundance of P. acnes,
responsible for 4.9% of antibiotic prescriptions antibiotics have long played a central role in
[3]. Dermatologists primarily prescribe acne therapy and have often been used as
antibiotics for the treatment of acne, and this monotherapy. Systemic antibiotics used for
prescribing practice may have contributed to acne treatment include tetracyclines
the rise of antibiotic resistance. Responsible (tetracycline, doxycycline and minocycline),
antibiotic stewardship is increasingly macrolides (erythromycin and less often
becoming recognized as an important clindamycin) and occasionally sulfonamides
principle to incorporate into dermatology (trimethoprim–sulfamethoxazole). The
practices. therapeutic effect of systemic antibiotics is
Acne is one of the most common skin thought to be due primarily to their
disorders treated by dermatologists, affecting anti-inflammatory properties, and this is
between 40–50 million Americans [4]. While especially true for the tetracyclines. Topical
acne is highly prevalent in youth with around antibiotics include clindamycin and
85%ofteenagersaffectedatsomepointintime, erythromycin.
itsoccurrenceisnotuncommoninadults[5,6]. Antibiotic overuse in the treatment of acne
The pathogenesis of acne is a multifactorial has led to changing resistance patterns in P.
processthatinvolvesthepilosebaceousunitand acnes. While only 20% of P. acnes showed
results in a combination of non-inflammatory antibiotic resistance in 1978, roughly 2/3 are
(open and closed comedones) and resistant today [7–9]. Both systemic and topical
inflammatory (papules, pustules, nodules, and antibiotics are capable of changing the
cysts) lesions. Several distinct processes antibiotic-resistance patterns in bacteria.
contribute to the development of acne, Topical erythromycin has been shown to
including the colonization of the skin with produce overgrowth of antibiotic resistance
Propionibacterium acnes, heightened levels of bacteria both locally and at distant sites
inflammation, increased sebum production [10, 11]. Similar resistance trends are also
and abnormal keratinization. Inflammation is likely to result from topical clindamycin
especially important in the disease process, and monotherapy.
several syndromes that are characterized by Collateral damage to normal skin flora also
profound systemic inflammation and occurs as a result of antibiotic use. The normal
concurrent severe acne have been described: skin biome serves as an innate defense, and
pyogenic arthritis, pyoderma gangrenosum, changes in the skin biome brought on by
acne (PAPA syndrome); pyoderma antibiotics can increase the risk of
gangrenosum, acne, suppurative hidradenitis colonization by pathologic organisms [12]. For
(PASH syndrome); pyogenic arthritis, example, long courses of tetracycline induce
pyoderma gangrenosum, acne, suppurative gram-negative bacterial overgrowth in the
DermatolTher(Heidelb)(2016)6:555–578 557
nares, and this isassociated with gram-negative reportofeitherthechangeintotallesioncount
folliculitis [13, 14]. Antibiotics used in the (TLC) for topical and oral treatments or the
treatment of acne are also associated with the change in inflammatory lesion count (ILC) for
overgrowth of Streptococcus pyogenes and studies evaluating physical treatment
Staphylococcus aureus in the oral pharynx, and modalities. Only studies that provided the
these changes may be linked to clinical number of patients in each treatment group
pharyngitis [15–17]. Furthermore, increased were included in our final review. Studies
rates of antibiotic-resistant bacteria examining investigational treatments or
colonization is seen in family members of therapies not currently available in the USA
acne patients who are treated with antibiotics were excluded. Similarly, studies that solely
[18]. examined antimicrobial dosing of antibiotics
Giventheriskassociatedwithantibioticuse, or studies that did not meet the above criteria
careful consideration must be given to the use were excluded from this review. This article is
of this class of medications when treating acne. basedonpreviouslyconductedstudiesanddoes
In this systematic review of the literature we not involve any new studies of human or
present the efficacy data from randomized animal subjects performed by any of the
clinical trials investigating non-antimicrobial authors.
treatments for acne, highlighting the
appropriate use of these treatments as Data Extraction
alternatives to long courses of systemic
antibiotics. Datacollectionincludedthenumberofpatients
per treatment group, details of treatment
METHODS regimens, severity and location of acne,
change in TLC or ILC following treatment,
Search Strategies and tolerability of treatment.
A comprehensive search of the RESULTS
English-language literature was performed on
PubMed using the following search terms: A total of 192 studies were found, of which 57
‘‘acne,’’ ‘‘treatment’’ and ‘‘randomized’’ as well met the inclusion and exclusion criteria. Study
as ‘‘photodynamic therapy,’’ ‘‘blue light’’ and size ranged from 10 to 3010 patients, and
‘‘zinc’’ or ‘‘peel’’. Bibliographies of select treatment duration ranged from 6weeks to
publications were reviewed for eligible studies. 6months. When applicable, efficacy results
from trials examining matching treatment
Data Sources regiments were reviewed together using a
weighted average. The majority of acne
We included randomized clinical studies treatment studies included either patients with
published before April 2016 that evaluated mild to moderate acne or those with moderate
presently available first- and second-line to severe acne. Mild to moderate acne is
topical, oral and physical treatment modalities characterized by a predominance of open and
for acne. Inclusion criteria required a numeric closed comedones, some papules and pustules,
558 DermatolTher(Heidelb)(2016)6:555–578
and few to no cysts or nodules. Patients with synthesized or described, only three are
predominantly inflammatory lesions, several approved for acne treatment in the USA:
nodules or cystic lesions or patients who have tretinoin, adapalene and tazarotene. The first
scarring acne are considered to have moderate retinoid to become available was a highly
or severe acne. The results below are grouped concentrated tretinoin solution whose use was
either based on the trend of acne severity limited by excessive skin irritation. With the
included in the associated studies or based on development of new vehicles, such as creams
select adjuvant treatment modalities such as and gels, the tolerability of tretinoin improved.
hormonal or physical treatment therapies. In an effort to further reduce
treatment-associated skin irritation, tretinoin
Mild to Moderate Acne Treatment can now also be delivered as a large polymer
gel or cream or as a microsphere gel.Adapalene
First-line treatment options for mild to and tazarotene are third-generation retinoids,
moderate acne include a variety of topical and each has distinct properties. Adapalene,
monotherapies and combination products: which is available as a gel, lotion, cream or
retinoids, benzoyl peroxide (BPO), pledgets, has the unique property of being
clindamycin, clindamycin combined with BPO stable in the presence of light and BPO.
and adapalene combined with BPO (Table1). Tazarotene, which is available as a cream,
Because clindamycin monotherapy is foam or gel, is also approved for treating
discouraged, its efficacy will be reviewed here psoriasis.
primarily because it is used in combination We reviewed efficacy data for the three
treatment regimens or combination products. retinoids currently used in the USA, and all
Alternative topical treatments include salicylic were effective at decreasing the TLC when used
acid, azelaic acid and dapsone. Low-dose as monotherapy (Fig.1) [22–37]. Webster et al.
isotretinoin and oral zinc represent alternative reported a 71% TLC reduction with tretinoin
systemic treatment options. 0.1%cream,whichwasthehighestaverageTLC
Studies examining first-line treatment reduction reported for all of the retinoids [36].
options for mild to moderate acne reported a TLC reductions were similar among tretinoin
range of efficacies, as measured by TLC 0.05% gel, tretinoin 0.025% gel and cream,
reductions, with the most impressive tretinoin0.01%gel,tazarotene1%foam,cream
outcomes often seen in combination therapies and gel, tazarotene 0.05% gel as well as
treatment arms (Fig.1) [19]. Clindamycin 1% adapalene 0.03% gel and adapalene 0.1%
plus BPO 3% gel was the most efficacious lotion and gel. Lower TLC reductions were
combination treatment (68.9% decrease in seen with tretinoin 0.04% microsphere gel and
TLC at 12weeks) [20, 21]. Similarly, adapalene adapalene 0.1% cream. Efficacies varied with
0.1%andBPO2.5%combinationgelwashighly thevehicle:adapalene0.1%lotionand0.1%gel
efficacious (65.4% TLC reduction at 12weeks) were similarly efficacious (53.7% and 53.6%
[22]. TLC reduction, respectively), and both were
Topical retinoids are a mainstay of acne more efficacious than adapalene 0.1% cream
treatment and have been in use since they (32.9% decrease in TLC). Similarly, tretinoin
were first approved by the FDA in 1971. 0.025% gel was more efficacious than 0.025%
Although thousands of retinoids have been cream (54.7% and 52.5% TLC reduction).
DermatolTher(Heidelb)(2016)6:555–578 559
Table1 Mechanism of action of topical products for the treatment of acne vulgaris
Dosageform/strength Primarymechanismofaction Comedonal Inflammatory
Monotherapy
Adapalene Cream,gelorlotion:0.1% Anti-inflammatory,keratolytic X X
Gel:0.3%
Tazarotene Creamorgel:0.05%,0.1% Anti-inflammatory,keratolytic X X
Foam:0.1%
Tretinoin Cream:0.02%,0.025%,0.0375%,0.05%, Anti-inflammatory,keratolytic X X
0.075%,0.1%
Gel:0.01%,0.025%,0.04%,0.05%,0.1%
Microspheregel:0.04%,0.08%,0.1%
Benzoylperoxide Gel,cream,lotion,padsorwash:2.5–10% Antimicrobial X X
Azelaicacid Cream:20% Antimicrobial,anti-inflammatory, X X
keratolytic
Foamorgel:15%
Primarymechanismofaction Comedonal Inflammatory
Combinationtreatment
Clindamycin/benzoylperoxide Antimicrobial X X
Clindamycin/tretinoin Antimicrobial,anti-inflammatory,keratolytic X X
Clindamycin/adapalene Antimicrobial,anti-inflammatory,keratolytic X X
Clindamycin/salicylicacid Antimicrobial,anti-inflammatory,desquamation X X
Dapsone/adapalene Antimicrobial,anti-inflammatory,keratolytic X X
Dapsone/benzoylperoxide Antimicrobial,anti-inflammatory X X
Erythromycin/zincacetate Antimicrobial X
Erythromycin/benzoylperoxide Antimicrobial X X
Erythromycin/tretinoin Antimicrobial,anti-inflammatory,keratolytic X X
Adapalene/benzoylperoxide Antimicrobial,anti-inflammatory,keratolytic X X
Zincpyrrolidone/seaweed-derivedoligosaccharide Antimicrobial,anti-inflammatory X X
Topical retinoids were overall well tolerated reductions (61.8% vs. 50.3% for 3% gel and
with the most commonly reported adverse 2.5%gel,respectively)[21,22,29].BPOwasalso
reactions being local skin irritation, erythema well tolerated with common side effects
and dryness. Retinoids will be discussed further including erythema and skin irritation.
in the ‘‘Discussion.’’ Although topical clindamycin is not
BPO is an antimicrobial topical medication recommended as monotherapy because of the
thatisacommoncomponentofacnetreatment risk of antibiotic resistance, its efficacy as a
regimens. There is no known bacterial singleagenthasbeenevaluatedinclinicaltrials
resistance to BPO, and it is available over the [20, 21, 30, 38–40]. Both clindamycin 1%
counter as a cream, lotion, gel or wash at nanoemulsion gel and conventional
concentrations ranging from 2.5% to 10%. clindamycin gel were highly efficacious at
When evaluated as monotherapy, BPO was decreasing TLC (69.3% vs. 51.9%,
moderately efficacious in decreasing acne respectively), while clindamycin lotion only
lesions [21, 22, 29]. Higher concentrations of produced a modest improvement (28.6%)
BPO were noted to result in larger TLC [39–41]. Clindamycin’s efficacy was enhanced
560 DermatolTher(Heidelb)(2016)6:555–578
Benzoyl
Clindamycin Peroxide Re(cid:2)noids
0.0
-10.0
-20.0
nt
u
Co -30.0
n
o -32.9
si -35.5
e -40.0
L
e -41.1
n
c -44.0 -44.0
Total A -50.0 -53.7-46.7 -50.3 -54.7-52.5 -53.7-53.6 -52.0
%) in -60.0 -60.4 -61.8 -58.1 -56.8-56.1
nge ( -70.0 -68.9-65.1 -65.4
a -71.0
h
C
-80.0
-90.0
-100.0
Fig.1 Comparison of efficacy of first-line mild to mod- adapalene 0.1%?BPO 2.5% combo gel: Gollnick et al.
erate acne treatments in reducing total acne lesion count. [22]; adapalene 0.3% gel: Thiboutot et al. [23], Pariser
BPO benzoyl peroxide. Clindamycin 1%?BPO 3% gel: et al. [24], Tanghetti et al. [25], Tirado-Sa´nchez and
Schaller et al. [20], Eichenfield et al. [21]; clindamycin Ponce-Olivera [33]; adapalene 0.1% lotion: Eichenfield
1%?BPO5%gelBID:Langneretal.[30],Jacksonetal. et al. [28]; adapalene 0.1% gel: Gollnick et al. [22],
[38]; clindamycin 1%?tretinoin 0.025% lotion: Jackson Thiboutot et al. [23], Pariser et al. [24], Babaeinejad and
et al. [38], NilFroushzadeh et al. [39]; clindamycin Fouladi [29], Langner et al. [30], Tirado-Sa´nchez and
1%?BPO 5% gel: Langner et al. [30]; clindamycin 1% Ponce-Olivera [33], Cunliffe et al. [35]; adapalene 0.1%
lotion?adapalene0.1%gel:Wolfetal.[40].BPO3%gel: cream: Shalita et al. [26], Lucky et al. [34]; tazarotene 1%
Eichenfield etal.[28];BPO 2.5%gel: Gollnicketal. [22], cream: Tanghetti et al. [25], Shalita et al. [26]; tazarotene
Babaeinejad and Fouladi [29]. Tretinoin 0.1% cream: 1%foam:Feldmanetal.[27];tazarotene0.1%gel:Shalita
Webster et al. [36]; tretinoin 0.025% gel: Cunliffe et al. etal.[37];tazarotene0.05%gel:Shalitaetal.[37].Asterisk
[35],Webster[36];tretinoin0.025%cream:Webster[36]; Treatment length varied from 12weeks to 16weeks.
tretinoin0.1%gel:Websteretal.[36];tretinoin0.05%gel: Double dagger symbol Treatment length varied from 8 to
Webster et al. [31], Tirado-Sa´nchez and Ponce-Olivera 12weeks. Dagger symbol Treatment length varied from
[33]; tretinoin 0.04% microsphere gel: Berger et al. [32]; 12weeks to 90days
DermatolTher(Heidelb)(2016)6:555–578 561
with the addition of salicylic acid: clindamycin 24) [46]. This dosing regimen, however, is
1% combined with 2% salicylic acid lotion uncommonly used because of the prescribing
resulted in a TLC reduction of 77.9% [39]. restrictions that have resulted from the
Topical clindamycin was very well tolerated, iPLEDGE system.
with side effects including mild burning, Oralzincsulfatehasalsobeenevaluatedasa
stinging and scaling. second-line systemic treatment option for mild
Azelaic acid is a non-antibiotic topical acne to moderate acne; 220mg of zinc sulfate dosed
treatmentthatisavailableasa20%creamanda three times daily produced a moderate TLC
15% gel or foam, and it is often used as an reduction (45.5% at 12weeks) [47]. This
adjuvant acne treatment. Azelaic acid has treatment, however, was very poorly tolerated
comedolytic, antimicrobial and with 40% of subjects reporting nausea or
anti-inflammatory properties. Twice daily vomiting.
application of azelaic acid 20% cream was
found to be moderately effective at treating Moderate to Severe Acne Treatment
mildtomoderateacnewitha53.9%decreasein
TLCreportedat12weeks[20].Azelaicacid15% Historically, long courses of antibiotics have
and 20% formulations will be discussed further been used as first-line therapy for patients with
in the ‘‘Discussion.’’ moderate to severe acne. Given the trend of
Second-line therapies showed modest to increasing antibiotic resistance, antibiotic
moderate improvement in TLC, with treatment as monotherapy is discouraged. In
combination treatments resulting in the lieu of long courses of antibiotics, other
highest efficacies. Dapsone 5% gel alone first-line treatment options for moderate to
resulted in a modest TLC reduction (39.0% at severe acne include oral isotretinoin or a
week 12), and this was enhanced with the subantimicrobial oral antibiotic combined
addition of adapalene 0.1% gel (51.0% at week with the topical therapies used for mild to
12) [42, 43]. Topical dapsone was very well moderate acne.
tolerated with common side effects including Isotretinoindosedat0.5–1.0mg/kgdailywas
mild pruritus and burning at the application more efficacious than doxycycline 200mg plus
site, especially whencombined with adapalene. adapalene 0.1%/benzoyl peroxide 2.5% gel at
Erythromycin 4% with zinc acetate 1.2% has reducing TLC (92.9% vs. 78.2%) [48]. Low-dose
beenreportedtoproducemoderatedecreasesin isotretinoin(20mgdaily)combinedwitha20%
TLC (64.5% in 12weeks) [44]. A salicylic acid peel applied every 2weeks was
seaweed-derived oligosaccharide complexed to more efficacious than low-dose isotretinoin
0.1% zinc pyrrolidone cream was also alone (92.5% vs. 73.4% TLC reduction at week
moderately effective (61.2% decrease in TLC in 16) [49].
8weeks) [45]. The tolerability of isotretinoin will be
Low-dose isotretinoin has been evaluated as discussed further in the ‘‘Discussion.’’ Briefly,
a second-line systemic treatment for mild to isotretinoin dosed at 1mg/kg has been
moderate acne. Isotretinoin used at low and generally well tolerated, with patients
intermittentdosing(0.5mg/kgdailyfor1outof commonly reporting xerosis, cheilitis,
every 4weeks for 24weeks) was shown to be myalgias and gastrointestinal upset. Laboratory
highlyefficacious(80.5%TLCreductionatweek abnormalities such as hypertriglyceridemia are
562 DermatolTher(Heidelb)(2016)6:555–578
also common. The most serious risk associated 20lg ethinyl estradiol/3mg drospirenone was
with isotretinoin pertains to its teratogenic moderately effective in decreasing facial and
effects. truncal TLC (46.3% and 57.3%, respectively)
Subantimicrobial doxycycline has been [55, 56]. COCs were well tolerated, with low
evaluated in the treatment of moderate to incidence of adverse events. Reported side
severe acne; 20mg of doxycycline twice daily effects include metrorrhagia, vomiting and
was more efficacious than either 40mg allergic reaction.
modified release or 100mg doxycycline once Spironolactone, which is an aldosterone
daily (52.3%, 41.7% and 35.9% TLC reduction, receptor antagonist approved for the treatment
respectively) [50, 51]. The subantimicrobial of hypertension, is known to have potent
properties of doxycycline 40mg antiandrogen properties and is used in clinical
modified-release capsules were demonstrated practice off label for adult female acne.
in a recent pharmacokinetics study: subjects Although well-designed randomized controlled
treated with doxycycline 40mg failed to trials are lacking, expert opinion supports the
achieve a mean steady-state doxycycline use of this overall well-tolerated and safe
plasma concentration that surpassed the treatment in select women [19]. Possible side
antimicrobial threshold, while those treated effects include breast tenderness, irregular
with doxycycline 50mg daily had steady-state menses and gastrointestinal upset. Because of
plasma concentrations that exceeded this the risk of developing gynecomastia, men are
threshold [52]. Low-dose antibiotics will be excluded from using this off-label treatment.
discussed further in the Discussion
section. Doxycycline was well tolerated with a Physical Therapies
minority of patients reporting headache and
nausea. Whilenotcurrentlyconsideredfirst-linetherapy
for acne, physical therapies can be useful in
Hormonal Therapies selectpatientswithmoderatetosevereacnewho
have primarily inflammatory acne lesions.
Unique therapeutic options are available when Physical therapies for the treatment of acne
treatingwomenwithacne.Hormonaltherapies, include phototherapy, photodynamic therapy
such as combined oral contraceptive pills (PDT) and chemical peels. Photo therapy
(COCs) as well as spironolactone, are known involves exposing affected skin to a specific
to improve female acne even in the absence of light source such as long pulsed dye laser
concurrent hirsutism. Four COCs have been (LPDL), intense pulsed laser (IPL) or various
approved by the FDA for acne treatment, while wavelengths of light. Often, a photosensitizer,
spironolactone is used off label for this purpose such as aminolevulinic acid (ALA) or
in women. methyl-ALA (MAL), is applied to the skin and
COCs have been evaluated for efficacy in left on the skin for a certain time prior to
treating women with persistent acne and have treatment with light. The combination of a
been found to have mild to moderate efficacy; photosensitizer with light therapy is called PDT.
20lg ethinyl estradiol/100lg levonorgestrel Although there was significant inter-study
resulted in a mild decrease in TLC (31.1%) heterogeneity with respect to acne severity,
aftertreatmentforsixcyclesof28days[53,54]; number and frequency of treatments, PDT
DermatolTher(Heidelb)(2016)6:555–578 563
occlusion time, and study design, efficacy Treatment of acne with chemical peels
trends can be appreciated when comparing the involves application of a keratolytic agent
various treatment modalities. Treatment with such as salicylic acid or glycolic acid to
IPL, which uses wavelengths of 400–1200nm, promote desquamation. Glycolic acid and
was found to have some of the most impressive amino fruit acid peels used at increasing
ILC reductions for treating mild to severe acne concentration applied over 24weeks at 2-week
(up to 90% decrease), and this efficacy may be intervals were moderately effective in
increased when treatment is combined with a decreasing non-inflammatory TLC (62.7% and
suction device to flatten the skin during 62.4%, respectively, at 6months) [86].
treatment (up to 90% decrease) [57–65]. IPL Lipohydroxy acid and salicylic acid peels
efficacy did not appear to be significantly applied over 12weeks at 2-week intervals were
enhanced when combined with PDT also moderately effective in decreasing
[62, 64–68]. IPL’s efficacy may be due in part non-inflammatory TLC (55.6% and 48.5%,
to its longer wavelengths, which have the respectively, at 98days) [87].
ability to produce selective photothermolysis
of sebaceous glands; sebum has an absorption DISCUSSION
peak at 1210nm [69]. LPDL, which uses a
wavelength of 595nm, was more effective at Acne is a chronic, multifactorial skin disease
decreasing ILC in patients with mild to severe thatisverycommonandcanleadtodisfiguring
acne when combined withPDT (67% vs. 100%) scars. Because the pilosebaceous unit is the
[70, 71]. Treatment with red (620–660nm) and primary structure involved, acne most
blue (400–500nm) light are both moderately frequently occurs in areas of high
effectiveatdecreasingILC(upto66%andupto pilosebaceous unit density such as the face,
77%, respectively), and these efficacies can be neck, chest and back [88].
enhanced when combined with PDT Acne pathogenesis is complex, and our
[58, 64, 67, 72–82]. Red light PDT appears to understanding of this disease process
be more effective when the photosensitizer is continues to evolve. Comedogenesis is
incubated under occlusion compared to no thought to be triggered by a combination of
occlusion (59.4% and 31.7% ILC reduction, abnormal desquamation of lipid-laden
respectively) [80]. Blue-red (400–500 plus keratinocytes within the sebaceous follicle plus
620–660nm) light therapy may be superior to sebaceous gland hyperactivity. Androgens,
either blue or red light alone, with ILC which control sebum production, are known
reductions of up to 90% reported [58, 83–85]. to contribute to the disease process. Increased
Side effects related to light therapy limit its production and cohesion of the corneocytes
use. The incidence of adverse events, such as narrow the pilosebaceous opening to the skin
pain and burning, is relatively high in patients and result in a bottleneck phenomenon,
using PDT. Patients have also reported thereby producing a microcomedone. As the
significant cutaneous erythema lasting for comedone develops and expands, there can be
several days post treatment. Postinflammatory disruption of the follicular epithelium with
pigmentation alteration can also be associated extrusion of sebum and corneocytes into the
with PDT treatment. interstitium, thereby leading to an
564 DermatolTher(Heidelb)(2016)6:555–578
inflammatory response. P. acnes, which is a A variety of topical retinoids are available in
ubiquitous commensal gram-positive rod, is differing strengths and vehicles: tretinoin
found in higher concentrations on 0.025–0.1% as a cream, gel or microsphere;
acne-affected skin. P. acnes is also known to adapalene 0.1–0.3% cream or 0.1% lotion;
stimulate an inflammatory response and tazarotene 0.05–0.1% cream, gel or foam. As
facilitate comedone rupture. While P. acnes is each of these products targets different
involvedinthediseaseprocess,itsdensityisnot combinations of retinoic acid receptors in the
correlated with acne severity and acne may skin, there are slight differences in terms of
occur even without its presence. For example, efficacy and tolerability between these
microcomedonesareknowntoforminchildren medications (Fig.1). Several head-to-head
with early acne prior to P. acnes colonization studies have been conducted evaluating the
[89]. Furthermore, eradicating P. acnes may efficacy of topical retinoids; however because
improve acne but will not produce a ‘‘cure’’ of differentconcentrationsandvehicleswereused
the disease [90]. it is difficult to make meaningful comparisons
A plethora of non-antibiotic topical and between these medications [23, 24, 31, 91, 92].
systemic acne treatment options are available A range of efficacies have been reported for
and include topical retinoids, BPO, topical retinoids with the majority of studies
combination products, azelaic acid, reporting a TLC reduction of between 40–60%
isotretinoin, subantimicrobial dosed (Fig.1) [23, 24, 26–28, 31, 92]. As expected,
antibiotics, hormonal therapies and physical increasing strength was on average correlated
modalities.Thesetreatmentoptionscanbeused with increased efficacy for each of the three
inastep-wisemannerdependingonthedisease retinoids.Thevehiclewasalsofoundtoplayan
severity, patient characteristics and patient’s importantroleindeterminingefficacy;withfew
therapeutic response. exceptions, gels conferred a larger TLC
In the mild to moderate acne group, reduction when compared to creams. Two
combination topical treatment is often notable exceptions to this trend were tretinoin
effective for both induction and maintenance 0.05% gel, which was found to be less
therapy. A variety of different monotherapy or efficacious than tretinoin 0.025% cream, and
combinationtreatmentoptionsexistthattarget tretinoin0.04%microspheregel,whichwasless
distinct key aspects of the acne disease process. effective than tretinoin 0.025% cream. Because
Topical retinoids, which are vitamin A these comparisons are not from head-to-head
derivatives, are one of the mainstays of acne studies, the results must be interpreted with
treatment. This class of medication targets the caution. More head-to-head studies are needed
initial step of comedogenesis by normalizing to further define the individual efficacies of
follicularkeratinization,therebypreventingthe each of the topical retinoids in relation to each
development of new comedones and hastening other.
the resolution of existing lesions. Topical Topical retinoid use is limited by skin
retinoids also have anti-inflammatory irritation, erythema and peeling, all of which
properties and are not antimicrobial. can be mitigated with the use of a less potent
Monotherapy with a topical retinoid is an retinoid for initial therapy and by starting
excellent choice for patients with treatment with alternate evening use.
predominantly comedonal acne [19]. Tolerability can also be enhanced by using