Advances in Cosmetic Surgery 6 (2023) 151–165

ADVANCES IN COSMETIC SURGERY

Acne Treatment Strategies 2023

Jordan Borash, MDa, Emmy Graber, MD, MBAa,b,*
a
Dermatology Institute of Boston, 185 Dartmouth Street, Suite 404, Boston, MA 02116, USA; bNortheastern University, Boston, MA 02116,
USA

KEYWORDS
 Acne treatments  Topical  Systemic  Antibiotics  Hormonal  Procedural  Lasers

KEY POINTS
 More than 90% of adolescents develop acne, often leading to a substantial mental and psychological burden [1]. Although
acne has the potential to resolve with treatment, some can produce permanent scarring [2].
 Treatments consist of topical medications, oral medications, and procedural therapies. Though, mild acne is commonly
treated with topical therapies, moderate-to-severe acne may require systemic agents often in combination with topical
therapies [3].
 Standard topical treatments include both prescription and over-the-counter options. Available in distinctive strengths and
formulations, topical retinoids are the foundation of topical prescription treatments. In addition, topical clindamycin,
dapsone, and clascoterone are other anti-acne agents and require prescriptions in the United States. Benzoyl peroxide,
azelaic acid, and salicylic acid are topical anti-acne products readily accessible both over the counter and by prescription.
 Oral medications consist of antibiotics, isotretinoin, and hormonal treatments in post-menarchal females. Antibiotic
resistance should be considered when prescribing antibiotics. Isotretinoin, although greatly effective, is a known
teratogen and has a side effect profile that is often concerning to patients and is burdensome to prescribe given the
regulatory constraints (ie, iPledge). Patient compliance to isotretinoin proper use guidelines should be considered before
prescribing isotretinoin. Hormonal treatments such as oral contraception pills and spironolactone may be helpful for some
women with acne.
 Many lasers have been available for potentially treating acne, but past studies are of low quality with little conclusive
evidence that they are effective. However, newer, more successful devices are recently available and show promise.

Acne treatment strategies 2023 a greater likelihood of acne scarring if treatment

Nature of acne: is delayed [5].
 Acne is an exceedingly common disorder of the pilo-
sebaceous glands, with more than 90% of adoles-
cents developing acne [1]. TREATMENTS
 The pathophysiology of acne involves abnormal The mainstay of treatments includes topical, oral, and
follicular keratinization, sebum production, inflam- procedural therapies. As shown in clinical studies,
mation, and Cutibacterium acnes activity [4]. both oral and topical treatments may take weeks to
 Acne has the possibility of resolving with treat- months for results to be evident [6]. Although mild
ment; however, even with treatment, acne can acne is commonly treated with topical therapies,
result in permanent scarring [2]. Though, there is moderate-to-severe acne may require systemic agents

*Corresponding author. Dermatology Institute of Boston, 185 Dartmouth Street, Suite 404, Boston, MA 02116. E-mail
address: [email protected]

https://doi.org/10.1016/j.yacs.2023.01.004 www.advancesincosmeticsurgery.com
2542-4327/23/ © 2023 Elsevier Inc. All rights reserved. 151
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 152 Borash & Graber

often in combination with topical therapies [3]. Oral

TABLE 1
treatment options include oral antibiotics and isotreti-
Pregnancy-Safe Acne Treatments
noin. For females, oral spironolactone or oral contra-
(ie, Pregnancy Category B)
ceptive pills (OCPs) may also be considered. These
hormonal treatments that may be used in females Frequency
must be reserved for those who are post-menarchal [7]. Drug and Dose Formulation
Each patient’s treatment regimen should be individ- Topicals
ualized. Treatment strategies depend on severity of dis-
Clindamycin 1% once or Gel, lotion, or
ease, distribution of acne (ie, facial or truncal), twice daily solution
morphology of acne lesions, prior acne therapy used,
Azelaic acid 10%, 15%, or Cream (20%),
patient gender, patient compliance, age, cost factors, pa-
20% once or gel (15%), or
tient preferences, and psychological burden of suffering
twice daily suspension (10%)
from acne. Realistic expectations should be discussed
and understood by each patient when selecting a treat- Systemic
ment strategy. Azithromycin 500 mg Tablet
Pregnant patients with acne have limitations to treat- 3 times/wk
ment as they should not be treated with isotretinoin, Or 500 mg for 3
spironolactone, tetracyclines, OCPs, topical retinoids, consecutive
days every 10 d
topical clascoterone, or topical dapsone (Table 1).
Although there are many treatment options avail- Data from Eichenfield DZ, Sprague J, Eichenfield LF. Management of
able, suggested guidelines may assist in formulating Acne Vulgaris: A Review. JAMA. 2021;326(20):2055-2067. https://doi.
treatment plans (Box 1, Table 2). org/10.1001/jama.2021.17633.

TOPICALS and Drug Administration (FDA) pregnancy category

 Numerous over-the-counter (OTC) and prescription C and tazarotene is category X [11].
topicals are readily available to treat acne.  Tretinoin, manufactured in various strengths and for-
 Topical retinoids are a cornerstone of acne treatment as mulations, is often prescribed due to its easy accessi-
they have proven efficacy for treating both non- bility. Three newer formulations are available which
inflammatory (ie, comedonal) and inflammatory each employ a different inactive delivery system: (1)
lesions (Fig. 1). They function through retinoic acid a microsphere delayed delivery technology, (2)
receptors (RARs) and retinoid X receptors (RXRs). incorporation with a polyolprepolymer (PP-2), or
Retinoids have several mechanisms of action and (3) using a polymeric emulsion technology. These
are both comedolytic and anti-inflammatory. Their newer formulations decrease the likelihood of con-
comedolytic action stems from decreased keratino- tact irritation while still permitting a greater concen-
cyte accumulation and cohesion in the piloseba- tration of medication [12]. In addition to irritation,
ceous unit [4,8]. In addition, retinoids may tretinoins may cause photosensitivity and patients
improve inflammatory lesions by blocking inflam- are advised to be vigilant with sunscreen. In general,
matory mediators via inhibition of toll-like receptor tretinoins are photolabile; hence patients are encour-
2 [9,10]. Some studies have shown that topical reti- aged to apply it in the evenings [13]. Benzoyl
noids may even improve scars via their ability to in- peroxide (BP) characteristically oxidizes and inacti-
crease procollagen formation and by amplifying the vates tretinoin except for in a novel formulation
formation of types I and III collagen [9]. Generally, where BP and tretinoin are encapsulated in their
retinoids can affect gene expression involved in cell own microspheres (TwyneoÒ) [14].
proliferation, differentiation, melanogenesis, and  Retinols, readily available OTC retinoids, have been
inflammation [4]. To lessen contact irritation found to have superior penetration compared with
frequently caused by retinoids, patients are advised tretinoins. However, topical tretinoin is typically
to apply a pea-sized amount to the face initially a 20 times more potent than retinols [15]. The OTC
few nights a week and increase to nightly as tolerated. 0.025% topical retinol has less irritation potential
Patients should be counseled that it may take eight to than 0.025% tretinoin, yet they both cause similar
12 weeks to see results. Retinoids should not be used cellular and molecular changes. Even with these
in pregnancy as tretinoin and adapalene are US Food findings, using 0.025% retinol is not practical, as

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 Acne Treatment Strategies 2023 153

BOX 1
Cleansing Guidelines
 Patients should be advised to cleanse the skin twice daily with a gentle cleanser and then apply topical acne treatments
to dry skin.
 Certain patients may be advised to use a cleanser with an active anti-acne agent such as benzoyl peroxide (BP) or
salicylic acid (SA).
 Given the propensity for BP and SA to irritate the skin, those with dry or sensitive skin should be counseled to use a
Syndet cleanser that will not disrupt the skin’s normal pH [4].
 Cleansers containing BP or SA are convenient topical treatment modalities for hard-to-reach areas of the body

most OTC retinols only have a strength of 0.04% to the United States. It is also manufactured in a com-
0.07% [16]. bination topical therapy with BP.
 Adapalene is largely considered to be the more well-  Tazarotene is generally believed to be the most effica-
tolerated prescription retinoid. It may be used cious of the topical retinoids. Although tazarotene is
concomitantly with BP and is also photostable. In both photostable in UV light and stable with
a meta-analysis, adapalene 0.1% gel resulted in concomitant BP use, it is not recommended in preg-
more rapid efficacy and increased tolerability than nancy, as it is FDA category X [11,18]. In one double-
tretinoin 0.025% gel [17]. Adapalene is available blind, randomized parallel-group trial, tazarotene
in different strengths and as a gel, lotion, and cream. 0.1% gel was compared with tretinoin 0.025% gel
Although 0.1% adapalene gel is available over the and to adapalene 0.1% gel. When comparing tazar-
counter, stronger strengths require a prescription in otene 0.1% gel and tretinoin 0.025% gel, daily

TABLE 2
American Academy of Dermatology Guideline
AAD Guidelines Recommend Oral Antibiotics as First-Line Treatment in Moderate and Severe Acne

Mild Acne Moderate Acne Severe Acne

First-line Benzoyl peroxide (BP) or Topical combination therapy Oral antibiotic 1 topical
treatment topical retinoid BP 1 antibiotic or retinoid 1 BP combination therapy*
Or or retinoid 1 BP 1 antibiotic BP 1 antibiotic
Topical combination therapy -or- Or Retinoid 1 BP
BP 1 antibiotic or retinoid 1 BP Oral antibiotic 1 topical -or-
or retinoid 1 BP 1 antibiotic retinoid 1 BP Retinoid 1 BP 1 antibiotic
-or- -or-
Oral antibiotic 1 topical Oral isotretinoin
retinoid 1 BP 1 topical
antibiotic
Alternative Add topical retinoid or BP Consider alternate Consider change in oral antibiotic
treatment (if not on already) combination therapy -or-
-or- -or- Add combined oral contraceptive
Consider alternate retinoid Consider change in oral antibiotic or oral spironolactone (females)
-or- -or- -or-
Consider topical dapsone Add combined oral contraceptive Consider oral isotretinoin
or oral spironolactone (females)
-or-
Consider oral isotretinoin

Adapted from Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris [published correction appears in
J Am Acad Dermatol. 2020 Jun;82(6):1576]. J Am Acad Dermatol. 2016;74(5):945-73.e33. https://doi.org/10.1016/j.jaad.2015.12.037; with
permission.

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 154 Borash & Graber

FIG 1 Retinoids.

tazarotene was found to be more efficacious than lesions as strengths of 5% and 10%. In addition,
daily tretinoin for decreasing papules and open the 2.5% strength was associated with less frequent
comedones. Both topicals were equally efficacious side effects than the 10% strength but equivalent
in treating closed comedones. When tazarotene to the 5% strength [25]. Side effects include dryness,
was compared with adapalene, tazarotene was irritation (dose dependent), and rarely allergic con-
applied half as frequently as adapalene but still tact dermatitis. Patients should also be aware that
showed a similar efficacy in treating acne. The trial there is potential for BP to bleach clothing, bedding,
also found that the tolerability of tazarotene gel is and rarely hair [26].
clinically similar to that of tretinoin 0.025% gel  Clindamycin, a frequently used topical antibiotic for
and adapalene 0.1% gel [19]. A newer formulation acne treatment, is available as swabs, gel, lotion,
of tazarotene 0.045% lotion has been manufactured foam and solution. Bacterial resistance habitually
in a unique formulation (polymeric emulsion tech- occurs when using clindamycin as a monotherapy.
nology), which allows for less irritation and possibly A cross-sectional study of acne patients over a 6-
greater penetration [20,21]. (Table 3). month period conducted in Jordan concluded that
 BP is a ubiquitous bactericidal, anti-inflammatory, 59% of C acnes isolates were resistant to clindamy-
comedolytic ingredient available OTC or in prescrip- cin [27,28]. Not only is resistance less probable if
tion strengths, existing in creams, lotions, gels, clindamycin is being used in combination with
washes, and pledgets. Leave-on products are ex- BP therapy, but the bactericidal effect of the anti-
pected to be more efficacious in killing C acnes biotic may also be heightened [6]. There are several
than washes, but studies are limited. One 5-week combination prescription topical products available
open-label single-center study consisting of 20 pa- that contain both clindamycin and BP (Table 4). A
tients with C acnes on their backs (>10,000 colonies 10-week, multicenter, double-blind trial with 480
per cm2) compared the efficacy of 5.3% BP emol- patients with moderate-to-severe acne, compared
lient foam against an 8% BP wash. Subjects were the efficacy of a topical gel formulation of 5% BP
treated once daily. At 2 weeks, the C acnes count in plus 1% clindamycin, 5% BP alone, 1% clindamy-
the patients using the 5.3% emollient foam had a cin alone, and vehicle gel. The patients were ran-
2.1 log reduction, whereas the patients using the domized and received twice daily treatments. The
8% wash did not have a reduction in C acnes. [22] study concluded that patients using combination
BP is regularly used in combination therapy, as C therapy compared with those using any of the 3 in-
acnes has shown no resistance to it, and it decreases dividual components had a significantly greater
resistance to oral and topical antibiotics [23,24]. decrease in the number of total and inflammatory
Three double-blind studies with 153 subjects found lesions [29].
that BP in a strength of 2.5% was equally efficacious  Dapsone, a more recently approved topical antibiotic
in decreasing the number of acne inflammatory for acne treatment, has both anti-inflammatory and

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 Acne Treatment Strategies 2023 155

TABLE 3
Retinoids
Approved for
Topical Retinoid Brand Name Photo-Stable? Stable with BP? Truncal Acne?
Tretinoin 0.01% gel Retin-AÒ No No No
Tretinoin 0.025% cream Retin-AÒ No No No
Tretinoin 0.025% gel Retin-AÒ No No No
Tretinoin 0.0375% cream Tretin-XÒ* No No No
Tretinoin 0.04% gel Retin-A MicroÒ YES YES No
Tretinoin 0.05% cream Retin-AÒ No No No
TM
Tretinoin 0.05% gel Atralin YES YES No
(micronized
Tretinoin 0.05% lotion AltrenoÒ YES YES No
(micronized)
Tretinoin 0.05% solution Retin-AÒ No No No
Tretinoin 0.06% gel Retin-A MicroÒ YES YES No
Tretinoin 0.075% cream Tretin-XÒ* No No No
Tretinoin 0.08% gel Retin-A MicroÒ YES YES No
Tretinoin 0.1% cream Retin-AÒ No No No
Tretinoin 0.1% gel Retin-A MicroÒ YES YES No
Adapalene 0.1% cream DifferinÒ YES YES No
Adapalene 0.1% gel DifferinÒ YES YES No
Adapalene 0.1% solution DifferinÒ YES YES No
Adapalene 0.1% lotion DifferinÒ YES YES No
Adapalene 0.3% gel DifferinÒ YES YES No
Tazarotene 0.045% lotion ArazloÒ YES YES No
Tazarotene cream 0.1% TazoracÒ YES YES No
Tazarotene 0.1% gel TazoracÒ YES YES No
Tazarotene foam 0.1% FabiorÒ YES YES No
Trifarotene cream 0.005% AkliefÒ Unknown Unknown YES

* Discontinued in the United States

Data from Baldwin H, Webster G, Stein Gold L, Callender V, Cook-Bolden FE, Guenin E. 50 Years of Topical Retinoids for Acne: Evolution of
Treatment. Am J Clin Dermatol. 2021;22(3):315-327. https://doi.org/10.1007/s40257-021-00594-8.

antibacterial qualities [30]. It may be prescribed in patients. Although the exact mechanism of action
strengths of 5% (applied twice daily) and 7.5% is unknown, it is believed to inhibit androgen re-
(applied once daily). Unlike oral dapsone, topical ceptors and thus decrease sebum production [32].
dapsone may be used in patients with G6PD defi- This is significant as clascoterone would be the
ciency [31]. Typically, topical dapsone is well toler- only topical acne medication to act on the seba-
ated but should not be used in tandem with BP or ceous gland, thus inhibiting a key step in acne path-
the skin may turn an orange color [14]. ogenesis. Clascoterone is available in a 1% cream
 Clascoterone is a novel FDA-approved topical cream and though no studies currently exist investigating
to treat acne vulgaris in both male and female clascoterone use with other topical agents, in our

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 156 Borash & Graber

 Salicylic acid is a readily available, lipid-soluble

TABLE 4
ingredient found in leave-on topical preparations
Combination Clindamycin/Benzoyl Peroxide
and washes OTC with comedolytic and keratolytic
Products
properties. It causes exfoliation of the stratum cor-
Strength Brand Name Formulation neum and can therefore cause a local, mild irritation
1.2% clindamycin -2.5% AcanyaÒ Gel [39,40]. Because of its irritation potential, caution
BP should be taken when using salicylic acid along
1% clindamycin-5% BP BenzaClinÒ Gel
with other anti-acne agents that have the potential
to also cause irritation.
1.2% clindamycin-5% BP DuacÒ Gel
1.2% clindamycin-3.75% OnextonÒ Gel
BP Systemic Therapies
Oral antibiotics are often used for moderate-to-severe
Data from Crm, S. (2017). t ACNE ROSACEA. The APRN’s Complete
acne, often in combination with topicals. Significant
Guide to Prescribing Drug Therapy 2018, 3.
improvement from oral antibiotics is seen weeks to
month after initiation [6]. Despite the long onset of ac-
experience it is often used as part of an anti-acne tion, several consensus groups have recommended
regimen along with other topical and/or oral med- limiting use to the shortest duration possible, preferably
ications. Clinical trials have shown a reduction of 3 to 4 months to minimize antibiotic resistance [41,42].
total acne lesion count and total inflammatory Regardless of the recommended guidelines, a retrospec-
lesion count using 1% clascoterone cream. A ran- tive study from 2004 to 2013 found that the mean dura-
domized double-blind study, consisting of 77 tion for oral antibiotic use when prescribed by a
men with facial acne, compared clascoterone 1%, dermatologist was 192 days [6]. Extended treatment
to both tretinoin and placebo. It found that treat- courses, bacteriostatic properties, and widespread use
ment with 1% clascoterone resulted in a 50% have led to increased antibiotic resistance from C acnes
improvement of total lesion count at a median of (with the exception of sarecycline) [43,44]. Resistance
43.5 days compared with a median of 57 days should be suspected in patients unresponsive to oral an-
and 58 days for that of tretinoin and placebo, tibiotics after 6 weeks of treatment. C acnes resistance
respectively. In terms of inflammatory lesion count, rates may also vary by country (Table 5) [27]. To
a 50% improvement was found with 1% clascoter- decrease the likelihood of resistance, prescribers are
one at a median of 36.5 days compared with a me- encouraged to restrict long-term use of oral antibiotics,
dian of 44 days and 58 days for tretinoin and limit antibiotic monotherapy, and combine usage with
placebo, respectively [33]. It is generally well toler- BP or a topical retinoid [45]. By avoiding antibiotic
ated, yet rarely, it may cause local irritation. One monotherapy, the duration of antibiotic use may be
practical consideration for topical clascoterone is shortened and results may be maintained even after an-
its short shelf life as once a tube has been opened, tibiotics are discontinued [42].
it will only maintain its efficacy for 30 days and The tetracyclines class of antibiotics, tetracycline,
therefore the patient needs to acquire a new tube doxycycline, minocycline, and sarecycline are both anti-
each month. inflammatory and antimicrobial in activity. When
 Azelaic acid, both comedolytic and antimicrobial, is treating acne with an antibiotic, most dermatologists
available OTC in a 10% strength, or by prescription will prescribe from the tetracycline class as this class
in a 20% cream, 15% gel or 15% foam [34]. has the most evidence for use in acne. All of the tetra-
Although, only azelaic acid 20% is FDA approved cyclines are effective but have varying side effects and
to treat acne [18]. In vitro data have found that cuta- pharmacokinetics [42] (Table 6). Tetracycline, doxycy-
neous penetration and permeation is greater with cline, and minocycline are broad-spectrum antibi-
azelaic acid 15% gel than 20% cream [35]. In addi- otics, meaning that they have antimicrobial activity
tion to its comedolytic and antimicrobial effect, it against both gram-positive and gram-negative bacte-
also decreases post-inflammatory hyperpigmenta- ria. Contrarily, sarecycline is a narrow-spectrum anti-
tion [36]. In general, azelaic acid is well tolerated, biotic with targeted activity against C acnes.
but can cause transient irritation such as stinging Sarecycline is also the only member of the tetracycline
and burning [37]. It is also one of the few acne med- class with low potential for developing C acnes resis-
ications safe to use while pregnant [38]. tance. None of the tetracyclines may be used in

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 Acne Treatment Strategies 2023 157

TABLE 5
Resistance in Cutibacterium acnes
Percentage of Cutibacterium acnes
Study Country Isolates Resistant to Doxycycline
Dreno B, et al. European Journal of Dermatology. United States 57
2014 May 1;24(3):330–4
Alkhawaja E, et al. Antibiotic resistant Cutibacterium Jordan 37
acnes among patients in Jordan: a cross-sectional
study. BMC dermatology. 2020 Dec;20(1):1–9
Sheffer-Levi S, et al. Antibiotic Susceptibility of Israel 19.4
Cutibacterium acnes strains Isolated from Israeli
Acne Patients. Acta Dermato-venerologica. 2020
Oct 20;100(17):adv00295

Data from Refs [27,45]; and Sheffer-Levi S, et al. Antibiotic Suscetibility of Cutibacterium acnes Strains Isolated from Israeli Acne Patients. Acta
Dermato-venerologica. 2020 Oct 20;100(17):adv00295.

pregnancy as they can cross the placenta and also may and gastrointestinal (GI) symptoms (including
not be taken while nursing as they are excreted in nausea, diarrhea and heartburn) [46]. To decrease
breast milk. In general, tetracyclines should not be the chance of GI adverse effects, patients are advised
used in children as they can cause harmful effects to to take doxycycline with food and water, and to
teeth and bone development. Pseudotumor cerebri avoid lying down at least 1 hour after taking [42].
is also a rare but serious side effect of potentially all  Minocycline is approved to treat acne in patients
of the tetracyclines [42]. 12 years and older [42]. It is very lipophilic, and
 Doxycycline, a derivative of tetracycline, is one of the can therefore penetrate the pilosebaceous unit bet-
most commonly prescribed oral antibiotics for acne ter than other tetracyclines, although this has never
as it is efficacious and has an overall favorable clinically manifested as superior efficacy compared
safety profile [46]. In addition, doxycycline may with other antibiotics. Because of its lipophilicity, it
also decrease free fatty acid levels thereby mini- can also penetrate the blood–brain barrier, leading
mizing the food source of C acnes. Typically dosed to vestibular adverse events [46]. Weight-based
at antimicrobial levels (50 to 100 mg twice daily), dosing may be used to decrease the risk of vestib-
resistance is common [47]. A study in the United ular side effects. Compared with other tetracyclines,
States found that more than 50% of C acnes strains minocycline has a greater adverse event profile.
isolated from acne patients are resistant to doxycy- Other rare but serious side effects include skin hy-
cline [42]. The more common side effects of doxy- perpigmentation, drug-induced lupus, and a serum
cycline include photosensitivity (dose dependent) sickness reaction [42].

TABLE 6
Comparing Tetracyclines
Can Be Taken Vestibular Spectrum of
With Food Lipophilic Photosensitivity GI Upset Adverse Events Activity
Tetracycline No 1 11 11 0a Broad
Doxycycline Yes 11 111 111 0a Broad
Minocycline Yes 111 11 11 11 Broad
Sarecycline Yes 11 0a 1 0a Narrow

Abbreviation: GI, gastrointestinal.

a
Occurs in less than 1% of patients.
From Graber, E. Treating acne with the tetracycline class of antibiotics: A review. Dermatological Reviews. 2021 Feb 11;2 (6): 321-330 https://
doi.org/10.1002/der2.49; with permission.

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 158 Borash & Graber

 Sarecycline, a novel third-generation tetracycline, is effects consist of mucocutaneous and ophthalmic

FDA approved to treat acne vulgaris in patients adverse effects, including xerosis, chapped lips,
9 years of age and older [42]. Unlike other tetracy- photosensitivity, dermatitis, mucosal dryness, and
clines, which are broad spectrum, sarecycline is a dry/irritated eyes [53]. Patients may use lip balm, pe-
narrow-spectrum antibiotic meaning that it targets troleum, and sunscreen to combat common muco-
just C acnes rather than both gram-positive and cutaneous side effects. While on isotretinoin,
gram-negative bacteria like the broad-spectrum anti- patients should be advised to avoid: waxing for hair
biotics. Therefore, sarecycline has less probability of removal, dermabrasion, and/or non-fractionated
inducing bacterial resistance compared with other ablative lasers [54].
antibiotics [48]. Its unique structure allows direct  Approximately 50% of patients may experience my-
contact with mRNA, resulting in a greater bacterio- algias while on isotretinoin [53]. If severe, creatine
static effect. Weight-based dosing from 60 mg-150 phosphokinase levels should be evaluated for poten-
mg daily, it may be taken with or without food tial, but exceedingly rare rhabdomyolysis [53,55].
[42]. As sarecycline has decreased activity against Hyperostotic changes may also develop from isotret-
gram-negative organisms that reside in the gut, it inoin, especially in patients taking higher doses and
may be less likely to cause adverse GI side effects for longer courses. Patients who have been on iso-
than other tetracyclines [48]. Compared with doxycy- tretinoin for longer periods may consider undergo-
cline and minocycline, sarecycline has very low rates ing densitometry scans. Premature epiphysial
of photosensitivity and vestibular side effects [42]. closure may be associated with higher doses and a
 Tetracycline is a broad-spectrum antibiotic, seldomly greater course duration [53]. Uncommonly, a pa-
prescribed to treat acne as it is rarely manufactured tient may experience paronychia, pyogenic granu-
today. It is contraindicated in patients less than lomas, temporary diffuse alopecia, and nail
9 years old [42]. The use of tetracycline is also brittleness [51].
complicated by the fact that it has to be taken on  Headaches may also ensue [50]. Pseudotumor cere-
an empty stomach. bri may rarely transpire, but is more likely if the pa-
 Trimethoprim-sulfamethoxazole is a bactericidal anti- tient is concomitantly taking tetracyclines [56]. If a
biotic used off-label to treat severe acne not respond- patient presents with pseudotumor cerebri symp-
ing to other treatments. It is not frequently used as toms, prompt ophthalmologic evaluation for papil-
although rare, it can cause Stevens–Johnson syn- ledema is necessary.
drome and toxic epidermal necrolysis [49].  Acute hepatitis has been associated with isotretinoin
 Macrolides are not habitually used as an acne treat- use but there is not a causal relationship, and there
ment due to resistance; a cross-sectional study found are few reported cases of pancreatitis as well [53].
that 73% of C acnes isolates were resistant to erythro-  Previously, it was believed that a likely association
mycin [27]. However, unlike the tetracyclines, mac- existed between isotretinoin and either flared or
rolides are safe to use in pregnancy. new onset inflammatory bowel disease [18].
 Cephalexin, a first-generation anti-inflammatory Conversely, a meta-analysis concluded that there is
cephalosporin, is rarely used to treat acne.as there not an increased risk for inflammatory bowel dis-
is very little evidence to support its use in acne [18]. ease, including both ulcerative colitis and Crohn’s
Isotretinoin is an oral retinoid, most often used as disease, with isotretinoin use [57]. However, patients
monotherapy. It may be used in extensive, severe, with personal or family history of inflammatory
nodular acne or in cases where the acne is less severe bowel disease should be advised of the potential,
but is spanning a broad surface area. Clinically, it is although unlikely, association and must be carefully
also used in patients with treatment-resistant acne monitored while on isotretinoin therapy.
and/or acne that results in scars or impacts psychologi-  In the past, it has been thought that there are associ-
cal well-being [50]. It is the only acne therapy that affects ations between isotretinoin and depression and/or
all four factors of acne pathogenesis [51]. Remission suicide. Yet, there is a high incidence of depression
lasts for months to years in the majority of patients and suicide in acne patients in general. A cross-
who have completed a full isotretinoin course [50]. sectional survey done with New Zealand secondary
 Isotretinoin almost always has some side effects, school students with acne found 24% had depres-
which are usually dose dependent and resolve after sive symptoms, 34% had suicidal thoughts and
discontinuation [52,53]. If needed, the dose may 13% had attempted suicide. Another study found
be adjusted accordingly. The most common side that 42.4% of patients with severe acne were severely

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 Acne Treatment Strategies 2023 159

depressed, whereas 14.5% of patients with moderate treated with isotretinoin. At the 3-year follow up
acne and 2.5% of patients with mild acne were 65.4% had some acne recurrence, whereas 22.9%
severely depressed [58]. A meta-analysis and system- needed another course of isotretinoin [60].
atic review have determined that there is not enough Numerous studies show that multiple isotretinoin
evidence to show a causal relationship between iso- courses are necessary for 16% to 23% of patients
tretinoin and depression [59]. Nevertheless, patients who experience acne relapse after completing an iso-
taking isotretinoin should be screened and moni- tretinoin course [63]. The factors increasing proba-
tored for symptoms of depression and mood bility for needing multiple courses include male
changes. gender, patients who are a younger age when initi-
 Isotretinoin is exceptionally teratogenic and affects ating isotretinoin, truncal involvement, sinus tracts,
organogenesis. The risk of pregnancy should be macrocomedones, androgen excess and not reaching
emphasized to women of childbearing age. Owing cumulative dose goals [60]. In our clinical opinion,
to the teratogenic properties, the United States has patients should wait at least 2 to 3 months before
the strictest pregnancy prevention monitoring pro- beginning another isotretinoin course.
gram, iPledge, in which patients capable of preg-  Lab monitoring: In healthy patients, alanine amino-
nancy are required to be on two different effective transferase and triglycerides should be checked
forms of birth control, take monthly pregnancy tests within a month before isotretinoin initiation and
and have monthly appointments with the prescrib- should be checked again at peak dose [64]. Elevated
ing provider [53]. However, even with this program, liver enzymes may occur in 15% to 20% of patients
pregnancy numbers while on isotretinoin have not and elevated serum triglycerides may occur in 25%
decreased since the inception of iPledge in 2006 [18]. to 44% of patients while on isotretinoin. However,
 Isotretinoin is typically dosed in the range of 0.5 to elevations are rarely high enough to warrant inter-
1 mg/kg/d and should be taken with fatty foods for vention. In a cohort study, consisting of 1863 pa-
better absorption. The daily dose may vary based tients on isotretinoin, grade 3 or greater liver and
on acne severity, side effects, lab results, and compli- triglyceride function testing abnormalities were
ance. Patients with severe acne may have increased found in less than 0.5% and 1% of patients screened,
acne flares when initiating isotretinoin and should respectively [65]. In patients with elevated triglycer-
start with a lower dose, sometimes needing doses ides, levels typically normalize within 1 month of
as low as 0.1 mg/kg/d to prevent flares. Their treat- isotretinoin discontinuation. Liver enzyme levels
ment regimens might also include a short-term usually return to baseline within a few weeks, even
course of oral steroids. Low-dose regimens have if continuing isotretinoin. Alcohol may also lead to
also been efficacious but pose a greater risk of relapse an increased triglyceride and liver enzyme level.
in severe acne. A standard isotretinoin course is Alcohol is not contraindicated with isotretinoin
around 6 months but the treatment length may but patients should be advised to avoid excessive
vary based on dosing, side effects, and results [18]. drinking especially before checking serum triglycer-
A cumulative dose of 120 to 150 mg/kg of isotreti- ides as recent alcohol use will temporarily elevate
noin is the goal for a course of therapy [50]. serum triglycerides [53].
Achieving the cumulative dose target ensures the
greatest likelihood of long-term remission from Hormonal Therapies
acne [60]. There are also some smaller studies that  Spironolactone, an androgen receptor blocker, is an
suggest that patients should be free of new acne le- off-label hormonal acne treatment commonly pre-
sions for one to 2 months before cessation of therapy scribed to post-menarchal females. It lessens sebum
[61]. Although, a prospective observational study production in the skin by competing with dihydro-
with 116 subjects at 1 year follow-up concluded testosterone (DHT) and testosterone for the
that patients who achieved a cumulative dose of  androgen receptors. In addition, spironolactone
220 mg/kg had a significantly lower relapse rate also inhibits testosterone conversion to DHT. It
than patients who had a cumulative dose of less also reduces type 2 17B-hydroxysteroid dehydroge-
than 220 mg/kg. The relapse rate in the group with nase, inhibiting androgen synthesis [66]. It is dosed
a higher cumulative dose was 26.9% compared in a wide range of 25 mg daily to 100 mg twice daily
with a relapse rate of 47.4% in the lower cumulative to treat acne. A retrospective case series with 395 pa-
dose group [62]. Another study consisting of a data- tients receiving a median dose of 100 mg spirono-
base analysis, included 179 subjects who had been lactone daily found that spironolactone is both

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 160 Borash & Graber

safe and effective in treating acne. 91.4% of patients approved OCPs to treat moderate acne are drospire-
had some improvement in acne with spironolac- none/ethinyl estradiol/levomefolate, norethindrone
tone treatment. 66.1% of patients had at least acetate/ethinyl estradiol, norgestimate/ethinyl estra-
90% improvement. 85.1% of patients had either diol, and drospirenone/ethinyl estradiol [71]. As
at least a 90% improvement or an improvement drospirenone is both antimineralcorticoid and anti-
greater than 50%. The median response times androgenic, it reduces the probability of estrogen-
were 3 months for initial response and 5 months related weight gain and bloating [72]. In addition,
for the maximum response. 10.4% of patients had drospirenone has potassium-sparing characteristics,
adverse effects. The most common side effects similar to about 25 mg of spironolactone; thus it
were fatigue, dizziness, and menstrual irregularities may be appropriate to monitor for hyperkalemia
[67]. As spironolactone is estrogenic, there has been in certain patient subsets [73] (Box 2). The data on
concern that it may increase the risk of breast can- the effects of OCPs and the risks of cervical cancer
cer. A retrospective analysis was done using the Hu- and breast cancer are varied. Patients taking OCPs
mana Insurance database examining breast cancer for more than 5 years who have consistent human
recurrence rates in patients taking spironolactone. papillomavirus infections may have an increased
Recurrence ensued in 16.5% of patients who were risk of cervical carcinoma in situ and invasive cervi-
taking spironolactone compared with recurrence cal carcinoma [73].
in 12.8% of patients who were not taking spirono-  Glucocorticoids are clinically administered for severe
lactone. After the data was adjusted based on pro- acne for limited time periods. As they are anti-
pensity matching, cox regression analysis found inflammatory, they are sometimes used at the begin-
no association between breast cancer recurrence ning of isotretinoin therapy to decrease a potential
and spironolactone use [68]. There is a black box severe acne purge with isotretinoin initiation [18].
warning that spironolactone may increase the risk Prolonged use can lead to steroid acne [74]. Low-
of some benign endocrine tumors. Studies per- dose glucocorticoids may also be prescribed to
formed in rats given 10 to 500 times the human patients with excessive androgens due to congenital
dose of spironolactone for 2 years found an adrenal hyperplasia [75].
increased risk of tumors. However, no analogous Procedural Interventions: Acne surgery, intralesional
studies have been done in humans and there is no corticosteroid injections, chemical peels, and laser
association with breast cancer development [66]. treatments are often considered in combination
Very rarely, patients may experience hyperkalemia. with other treatment methods.
Potassium levels should be monitored in those
with a greater risk for hyperkalemia. A retrospective
data analysis was recently done comparing women Acne Surgery
 In the past, mechanical extraction of acne lesions
taking spironolactone age 18 to 45 years with those
was commonly used in comedones and superficial
taking spironolactone age 46 to 65 years Women in
pustules, however, now with more comedolytic
the older age group had a significantly higher inci-
agents readily available, extraction is reserved for pa-
dence of hyperkalemia, 16.7%, compared with the
tients with treatment-resistant comedoes [71]. Ex-
women in the younger age group, less than 1%
tractions may be performed with either one of the
[69]. This analysis reinforces that potassium levels
following or a combination of: an 18G needle, a
only need to be monitored in patients taking spiro-
comedone extractor or an 11-blade [76].
nolactone over age 45 or who have other risk factors
for hyperkalemia. Common side effects consist of
menstrual irregularities (typically avoided if treat- Intralesional Glucocorticoids
ment is combined with OCP), breast tenderness,  Intralesional glucocorticoid injections may help
headaches, fatigue, and diuresis. It is contraindi- decrease nodular acne lesions. The recommendation
cated in pregnancy as the male fetus may become is 0.05 to 0.25 mL per lesion of a triamcinolone ac-
feminized if exposed in utero [70]. etate suspension (2.5 to 10 mg/mL). Although this is
 Combination oral contraceptives (estrogen 1 progestin) not a suitable long-term treatment strategy, intrale-
are efficacious in treating acne due to the net antian- sional glucocorticoids can be helpful for reducing
drogenic effect. OCPs decrease gonadal androgen or even eliminating single large nodules in a matter
production, decrease free testosterone levels and of days. Common risk factors include hypopigmen-
inhibit androgen receptors [18]. The four FDA- tation and atrophy [71].

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 Acne Treatment Strategies 2023 161

BOX 2
Some of the Contraindications to OCPS

According to World Health Organization, OCPS are not recommended for use in:
 Pregnancy
 Patients older than 35 years of age who smoke tobacco
 Hypertensive patients
 Diabetics with end-organ damage
 Patients who have had diabetes for at least 20 years
 Patients with a history of or current deep vein thrombosis/pulmonary embolism
 Patients with an increased risk of cardiovascular disease
 Patients with migraine with aura (or without aura if older than 35 years)
 Patients with breast cancer, liver disease, or liver tumor

Lasers/phototherapy  Gold microparticles and 1064-nm laser have been

Many lasers have been considered for potentially treat- used to treat acne via selective photothermolysis. In
ing acne, but the studies are of low quality and few this procedure, gold microparticles are exogenously
have conclusive evidence that they improve acne. applied to the skin and pushed into the piloseba-
However, newer, more effective devices are now ceous unit via a vibratory massage method. As gold
available and some are in the pipeline. preferentially absorbs laser light at 1064 nm, the laser
 A 650-ms 1064-nm laser has been FDA cleared to absorbs the light and converts it to heat. The heat
treat mild to moderate inflammatory acne by diffuses and causes damage to the sebocytes [80].
damaging the sebaceous gland via bulk heating of  A photopneumatic broad-spectrum light device is
the dermis. In addition, it also reduces blood supply FDA cleared for the treatment of mild-to-moderate
to the pilosebaceous unit. Patients undergoing this acne. The device first applies a negative pressure suc-
treatment do not need an anesthetic and should tion action on the skin and then immediately de-
plan on 3 to 6 treatments spaced 1 to 2 weeks apart. livers a light source ranging from approximately
Transient erythema may be present for minutes. In 500 nm to 1200 nm. In one clinical trial, patients
one double-blind randomized control study, using received four treatments spaced 2 weeks apart and
this laser, the treatment group showed a decrease saw modest improvement. The most common side
in 42% of inflammatory lesions compared with effects included erythema and purpura [81].
26% in the sham treatment group [77].  Lasers and isotretinoin. It was previously thought that
 A novel 1726-nm laser has FDA clearance in the a patient should wait 6 to 12 months upon
United States to treat mild, moderate, and severe completing an isotretinoin course before undergo-
acne. Furthermore, it has Health Canada clearance ing any laser treatments. A systematic review that
for treating both acne and acne scars. At the included more than 1400 procedures completed
1726 nm wavelength, sebum is preferentially tar- while taking isotretinoin found that there is insuffi-
geted and there is a 2 to 1 advantage of sebum to wa- cient evidence to support delaying laser treatments
ter [78]. In the clinical trial to achieve FDA clearance, and superficial chemical peels. Nonetheless, derm-
104 subjects were enrolled with various Fitzpatrick abrasion and fully ablative lasers are still not recom-
skin types and acne severity scores. Three full-face mended while taking systemic isotretinoin [54].
treatments (excluding the nose) were administered  Pulsed-dye laser (PDL) treatments may also be
to each patient, spaced 1 month apart. Approxi- helpful for treating acne, as well as acne post-
mately 80% of subjects at the 3-month post final inflammatory erythema [82]. Pulsed-dye laser treat-
treatment follow-up visit attained a 50% or greater ments in combination with low-dose isotretinoin
reduction in inflammatory acne lesions (Fig. 2). potentially may be more efficacious in treating
Downtime was minimal as only transient post- acne compared with high-dose isotretinoin as
inflammatory erythema and edema occurred but monotherapy. A prospective randomized compara-
subsided quickly, usually within minutes [79]. tive study, consisting of 46 subjects, compared

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 162 Borash & Graber

FIG 2 Photographs courtesy of Cutera. Baseline IGA 5 4 and 3 months after final treatment IGA 5 2.

high-dose isotretinoin as monotherapy verse low- requirements, pregnancy numbers while on isotreti-
dose isotretinoin in conjunction with PDL laser noin therapy have not lessened. Perhaps, in the
treatments. The study found that the combination future a newer, more effective regulatory method
of low-dose isotretinoin therapy with PDL will be developed.
treatments had statistically significantly greater im-  Although new lasers are on the horizon, more
provements in acne at both 3-month and 6-month studies with larger sample sizes and longer follow-
follow-up appointments compared with high-dose up times are needed to determine efficacy.
isotretinoin therapy as a monotherapy [83].

CLINICS CARE POINTS

SUMMARY
 Although there are abundant treatment options for
acne, it is crucial to develop a personalized acne
treatment strategy for each patient.  Antibiotics:
 As most treatment options require months to see re-  Limit oral use to 3 to 4 months.
sults, when initiating a new regimen, a 3- to 4-  Use antibiotics concomitantly with benzoyl
month follow-up visit should be considered. peroxide to prevent resistance [42].
 Topical, systemic and procedural therapies have all  As sarecycline is narrow spectrum, there is less
been efficacious in treating acne. resistance [43].
 Mile acne is frequently treated with topical therapies,  Retinoids:
whereas moderate-to-severe acne is usually treated  Trifarotene is the first US Food and Drug
with either a systemic medication or a combination Administration-approved topical therapy to treat
of systemic and topical medications. both facial and truncal acne [84].
 Oral treatment options consist of oral antibiotics  Isotretinoin:
and isotretinoin. For post-menarchal females, oral  In general, take isotretinoin with fatty foods;
spironolactone or OCPs may also be utilized. except for in one formulation (isotretinoin with li-
 Isotretinoin, still remaining controversial to many, dose), which can be taken on an empty stomach.
has proven to be a successful treatment with long  A low dose of isotretinoin taken concomitantly
remission periods. Even with the strict iPledge with a short course of low-dose steroids may be

Giovana Balbino Ernesto - [email protected] - IP: 45.171.172.139

 Acne Treatment Strategies 2023 163

[12] Quigley JW, Bucks DA. Reduced skin irritation with

necessary for patients with very severe inflam-
tretinoin containing polyolprepolymer-2, a new topical
matory acne [18].
tretinoin delivery system: a summary of preclinical and clin-
 Spironolactone: ical investigations. J Am Acad Dermatol 1998;38(4):S5–10.
 Spironolactone is effective in treating adult [13] Rosso JD, Harper J, Pillai R, et al. Tretinoin photostabil-
women with late-onset or teenage persistent ity: comparison of micronized tretinoin gel 0.05% and
acne, especially if the acne is concentrated around tretinoin gel 0.025% following exposure to fluorescent
the lower chin, jawline, and cheeks [5]. and solar light. J Clin Aesthet Dermatol 2013;6(2):25–8.
 Do not prescribe spironolactone to pregnant pa- [14] Dubina MI, Fleischer AB Jr. Interaction of topical sulface-
tients or to men [18]. tamide and topical dapsone with benzoyl peroxide. Arch
 Vitamins B2, B6, and B12 may trigger acne [5]. Dermatol 2009;145(9):1027–9.
[15] Duell EA, Kang S, Voorhees JJ. Unoccluded retinol pene-
trates human skin in vivo more effectively than unoc-
cluded retinyl palmitate or retinoic acid. J Invest
DISCLOSURES Dermatol 1997;109(3):301–5.
[16] Kang S, Leyden JJ, Lowe NJ, et al. Tazarotene cream for
E. Graber serves as a consultant/advisor for Digital Di-
the treatment of facial photodamage: a multicenter,
agnostics, Almirall, Cutera, Hovione, Keratin Biosci- investigator-masked, randomized, vehicle-controlled,
ences, La Roche Posay, Lipidor AB, Ortho parallel comparison of 0.01%, 0.025%, 0.05%, and
Dermatologics, Sebacia, SolGel, Verrica, and WebMD. 0.1% tazarotene creams with 0.05% tretinoin emollient
She serves a research investigator for Hovione, Ortho cream applied once daily for 24 weeks. Arch Dermatol
Dermatologics and Sebacia. She serves as a speaker for 2001;137(12):1597–604.
Almirall. She serves as a shareholder for Digital Diag- [17] Cunliffe WJ, Poncet M, Loesche C, et al. A comparison of
nostics and Cutera. She receives royalties from Wolters the efficacy and tolerability of adapalene 0.1% gel versus
Kluwer Health. J. Borash has no disclosures. tretinoin 0.025% gel in patients with acne vulgaris: a
meta-analysis of five randomized trials. Br J Dermatol
1998;139(Suppl 52):48–56.
[18] Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of
REFERENCES care for the management of acne vulgaris. J Am Acad
[1] Gan SD, Graber EM. Papular scars: an addition to the Dermatol 2016;74(5):945–73.e33 [published correction
acne scar classification scheme. J Clin Aesthet Dermatol appears in J Am Acad Dermatol 2020;82(6):1576].
2015;8(1):19–20. [19] Kakita L. Tazarotene versus tretinoin or adapalene in the
[2] Gollnick HP, Finlay AY, Shear N. Global Alliance to treatment of acne vulgaris. J Am Acad Dermatol 2000;
Improve Outcomes in Acne. Can we define acne as a 43(2 Pt 3):S51–4.
chronic disease? If so, how and when? Am J Clin Derma- [20] Kircik LH, Gold LS, Beer K, et al. Once-Daily Polymeric Ta-
tol 2008;9(5):279–84. zarotene 0.045% Lotion for Moderate-to-Severe Acne:
[3] Fox L, Csongradi C, Aucamp M, et al. Treatment Modal- Pooled Phase 3 Analysis by Sex. J Drugs Dermatol 2020;
ities for Acne. Molecules 2016;21(8):1063. 19(8):777–83.
[4] Decker A, Graber EM. Over-the-counter Acne Treatments: [21] Baldwin H, Webster G, Stein Gold L, et al. 50 Years of
A Review. J Clin Aesthet Dermatol 2012;5(5):32–40. Topical Retinoids for Acne: Evolution of Treatment. Am
[5] Layton AM. Top Ten List of Clinical Pearls in the Treatment J Clin Dermatol 2021;22(3):315–27.
of Acne Vulgaris. Dermatol Clin 2016;34(2):147–57. [22] Leyden JJ. Efficacy of benzoyl peroxide (5.3%) emollient
[6] Eichenfield DZ, Sprague J, Eichenfield LF. Management of foam and benzoyl peroxide (8%) wash in reducing Pro-
Acne Vulgaris: A Review. JAMA 2021;326(20):2055–67. pionibacterium acnes on the back. J Drugs Dermatol
[7] Dréno B. Treatment of adult female acne: a new chal- 2010;9(6):622–5.
lenge. J Eur Acad Dermatol Venereol 2015;29(Suppl 5): [23] Tanghetti EA, Popp KF. A current review of topical ben-
14–9. zoyl peroxide: new perspectives on formulation and uti-
[8] Schmidt N, Gans EH. Tretinoin: A Review of Its Anti- lization. Dermatol Clin 2009;27(1):17–24.
inflammatory Properties in the Treatment of Acne. [24] Leyden JJ, Mitchell W, Baldwin EK. Antibiotic-resistant
J Clin Aesthet Dermatol 2011;4(11):22–9. Propionibacterium acnes suppressed by a benzoyl
[9] Kang S. The mechanism of action of topical retinoids. peroxide cleanser 6%. Cutis 2008;82(6):417–21.
Cutis 2005;75(2 Suppl):10–3. [25] Mills OH Jr, Kligman AM, Pochi P, et al. Comparing
[10] Miller LS. Toll-like receptors in skin. Adv Dermatol 2008; 2.5%, 5%, and 10% benzoyl peroxide on inflammatory
24:71–87. acne vulgaris. Int J Dermatol 1986;25(10):664–7.
[11] Motamedi M, Chehade A, Sanghera R, et al. A Clinician’s [26] Worret WI, Fluhr JW. Acne therapy with topical benzoyl
Guide to Topical Retinoids. J Cutan Med Surg 2022; peroxide, antibiotics and azelaic acid. JDDG J der Deut-
26(1):71–8. schen Dermatol Gesellschaft 2006;4(4):293–300.

Giovana Balbino Ernesto - [email protected] - IP: 45.171.172.139

 164 Borash & Graber

[27] Alkhawaja E, Hammadi S, Abdelmalek M, et al. Antibiotic [46] Del Rosso JQ. Oral Doxycycline in the Management of
resistant Cutibacterium acnes among acne patients in Jordan: Acne Vulgaris: Current Perspectives on Clinical Use and
a cross sectional study. BMC Dermatol 2020;20(1):17. Recent Findings with a New Double-scored Small Tablet
[28] S. Crm, ACNE ROSACEA. t. The APRN’s Complete Guide Formulation. J Clin Aesthet Dermatol 2015;8(5):19–26.
to Prescribing, Drug Ther 3 (2017) (2018) 5–8. [47] Skidmore R, Kovach R, Walker C, et al. Effects of
[29] Leyden JJ, Berger RS, Dunlap FE, et al. Comparison of the subantimicrobial-dose doxycycline in the treatment of
efficacy and safety of a combination topical gel formula- moderate acne. Arch Dermatol 2003;139(4):459–64.
tion of benzoyl peroxide and clindamycin with benzoyl [48] Zhanel G, Critchley I, Lin LY, et al. Microbiological Pro-
peroxide, clindamycin and vehicle gel in the treatments file of Sarecycline, a Novel Targeted Spectrum Tetracy-
of acne vulgaris. Am J Clin Dermatol 2001;2(1):33–9. cline for the Treatment of Acne Vulgaris. Antimicrob
[30] Ghaoui N, Hanna E, Abbas O, et al. Update on the use of Agents Chemother 2018;63(1):e01297-18.
dapsone in dermatology. Int J Dermatol 2020;59(7): [49] Baldwin H. Oral Antibiotic Treatment Options for Acne
787–95. Vulgaris. J Clin Aesthet Dermatol 2020;13(9):26–32.
[31] Webster GF. Is topical dapsone safe in glucose-6- [50] Leyden JJ. The role of isotretinoin in the treatment of
phosphate dehydrogenase-deficient and sulfonamide- acne: personal observations. J Am Acad Dermatol 1998;
allergic patients? J Drugs Dermatol 2010;9(5):532–6. 39(2 Pt 3):S45–9.
[32] Hebert A, Thiboutot D, Stein Gold L, et al. Efficacy and [51] Ward A, Brogden RN, Heel RC, et al. Isotretinoin. A re-
Safety of Topical Clascoterone Cream, 1%, for Treatment view of its pharmacological properties and therapeutic
in Patients With Facial Acne: Two Phase 3 Randomized efficacy in acne and other skin disorders. Drugs 1984;
Clinical Trials. JAMA Dermatol 2020;156(6):621–30. 28(1):6–37.
[33] Sanchez C, Keri J. Androgen Receptor Inhibitors in the [52] Vallerand IA, Lewinson RT, Farris MS, et al. Efficacy and
Treatment of Acne Vulgaris: Efficacy and Safety Profiles adverse events of oral isotretinoin for acne: a systematic
of Clascoterone 1% Cream. Clin Cosmet Investig Derma- review. Br J Dermatol 2018;178(1):76–85.
tol 2022;15:1357–66. [53] Brelsford M, Beute TC. Preventing and managing the side
[34] Gollnick H, Schramm M. Topical therapy in acne. J Eur effects of isotretinoin. Semin Cutan Med Surg 2008;
Acad Dermatol Venereol 1998;11(Suppl 1):S8–29. 27(3):197–206.
[35] Del Rosso JQ. Azelaic Acid Topical Formulations: Differ- [54] Spring LK, Krakowski AC, Alam M, et al. Isotretinoin and
entiation of 15% Gel and 15% Foam. J Clin Aesthet Der- Timing of Procedural Interventions: A Systematic Review
matol 2017;10(3):37–40. With Consensus Recommendations. JAMA Dermatol
[36] Callender VD, St Surin-Lord S, Davis EC, et al. Postinflam- 2017;153(8):802–9.
matory hyperpigmentation: etiologic and therapeutic [55] Marson JW, Baldwin HE. Elevated creatine kinase levels,
considerations. Am J Clin Dermatol 2011;12(2):87–99. exercise, and isotretinoin for acne. JAAD Case Rep 2022;
[37] Gupta AK, Gover MD. Azelaic acid (15% gel) in the treat- 21:133–5, Published 2022 Jan 22.
ment of acne rosacea. Int J Dermatol 2007;46(5):533–8. [56] Lee AG. Pseudotumor cerebri after treatment with tetra-
[38] Bayerl C. Acne therapy in pregnancy. Der Hautarzt; Zeits- cycline and isotretinoin for acne. Cutis 1995;55(3):
chrift fur Dermatologie, Venerologie, und verwandte Ge- 165–8.
biete 2013;64(4):269–73. [57] Etminan M, Bird ST, Delaney JA, et al. Isotretinoin and
[39] Arif T. Salicylic acid as a peeling agent: a comprehensive risk for inflammatory bowel disease: a nested case-
review. Clin Cosmet Investig Dermatol 2015;8:455–61. control study and meta-analysis of published and un-
[40] Zander E, Weisman S. Treatment of acne vulgaris with published data. JAMA Dermatol 2013;149(2):216–20.
salicylic acid pads. Clin Ther 1992;14(2):247–53. [58] Sood S, Jafferany M, Vinaya Kumar S. Depression, psy-
[41] Nast A, Dréno B, Bettoli V, et al. European evidence- chiatric comorbidities, and psychosocial implications
based (S3) guidelines for the treatment of acne. J Eur associated with acne vulgaris. J Cosmet Dermatol 2020;
Acad Dermatol Venereol 2012;26(Suppl 1):1–29. 19(12):3177–82.
[42] Graber E. Treating acne with the tetracycline class of an- [59] Huang YC, Cheng YC. Isotretinoin treatment for acne
tibiotics: A review. Dermatological Reviews 2021;2(6): and risk of depression: A systematic review and meta-
321–30. analysis [published correction appears in J Am Acad Der-
[43] George S, Muhaj FF, Nguyen CD, et al. Part I Antimicro- matol. 2017 Nov 14. J Am Acad Dermatol 2017;76(6):
bial resistance: Bacterial pathogens of dermatologic sig- 1068–76, e9.
nificance and implications of rising resistance. J Am [60] Leyden JJ, Del Rosso JQ, Baum EW. The use of isotreti-
Acad Dermatol 2022;86(6):1189–204. noin in the treatment of acne vulgaris: clinical consider-
[44] Swallow MA, Fan R, Cohen J, et al. Antibiotic Resistance ations and future directions. J Clin Aesthet Dermatol
Risk with Oral Tetracycline Treatment of Acne Vulgaris. 2014;7(2 Suppl):S3–21.
Antibiotics 2022;11(8):1032. [61] Tran PT, Berman HS, Leavitt E, et al. Analysis of factors
[45] Dreno B, Thiboutot D, Gollnick H, et al. Antibiotic stew- associated with relapse in patients on their second course
ardship in dermatology: limiting antibiotic use in acne. of isotretinoin for acne vulgaris. J Am Acad Dermatol
Eur J Dermatol 2014;24(3):330–4. 2021;84(3):856–9.

Giovana Balbino Ernesto - [email protected] - IP: 45.171.172.139

 Acne Treatment Strategies 2023 165

[62] Blasiak RC, Stamey CR, Burkhart CN, et al. High-dose [73] Mazori DR. The ABCs of COCs: a guide for dermatology
isotretinoin treatment and the rate of retrial, relapse, residents on combined oral contraceptives. Cutis 2019;
and adverse effects in patients with acne vulgaris. JAMA 104(1):E10–4.
Dermatol 2013;149(12):1392–8. [74] Oray M, Abu Samra K, Ebrahimiadib N, et al. Long-term
[63] Del Rosso JQ. Face to face with oral isotretinoin: a closer side effects of glucocorticoids. Expert Opin Drug Saf
look at the spectrum of therapeutic outcomes and why 2016;15(4):457–65.
some patients need repeated courses. J Clin Aesthet Der- [75] Bachelot A, Chakthoura Z, Rouxel A, et al. Classical
matol 2012;5(11):17–24. forms of congenital adrenal hyperplasia due to 21-hy-
[64] Xia E, Han J, Faletsky A, et al. Isotretinoin Laboratory droxylase deficiency in adults. Horm Res 2008;69(4):
Monitoring in Acne Treatment: A Delphi Consensus 203–11.
Study. JAMA Dermatol 2022;158(8):942–8.
[76] E. Graber, Acne surgery. Krakowski, Andrew C. Proce-
[65] Barbieri JS, Shin DB, Wang S, et al. The clinical utility of
dural Pediatric Dermatology, Lippincott Williams & Wil-
laboratory monitoring during isotretinoin therapy for
kins, Philadelphia, PA, 2020.
acne and changes to monitoring practices over time.
J Am Acad Dermatol 2020;82(1):72–9. [77] Kesty K, Goldberg DJ. 650 usec 1064nm Nd:YAG laser
[66] Graber EM. K1larity for Spironolactone: At Last. JAMA treatment of acne: A double-blind randomized control
Dermatol 2015;151(9):926–7. study. J Cosmet Dermatol 2020;19(9):2295–300.
[67] Roberts EE, Nowsheen S, Davis MDP, et al. Treatment of [78] Sakamoto FH, Doukas AG, Farinelli WA, et al. Selective
acne with spironolactone: a retrospective review of 395 photothermolysis to target sebaceous glands: theoretical
adult patients at Mayo Clinic, 2007-2017. J Eur Acad estimation of parameters and preliminary results using a
Dermatol Venereol 2020;34(9):2106–10. free electron laser. Lasers Surg Med 2012;44(2):175–83.
[68] Wei C, Bovonratwet P, Gu A, et al. Spironolactone use [79] Data on file. FDA clearance study. Cutera Inc.
does not increase the risk of female breast cancer recur- [80] Paithankar D, Hwang BH, Munavalli G, et al. Ultrasonic
rence: A retrospective analysis. J Am Acad Dermatol delivery of silica-gold nanoshells for photothermolysis of
2020;83(4):1021–7. sebaceous glands in humans: Nanotechnology from the
[69] Thiede RM, Rastogi S, Nardone B, et al. Hyperkalemia in bench to clinic. J Contra Release 2015;206:30–6.
women with acne exposed to oral spironolactone: A
[81] Wanitphakdeedecha R, Tanzi EL, Alster TS. Photopneu-
retrospective study from the RADAR (Research on
matic therapy for the treatment of acne. J Drugs Derma-
Adverse Drug Events and Reports) program. Int J
tol 2009;8(3):239–41.
Womens Dermatol 2019;5(3):155–7.
[70] George R, Clarke S, Thiboutot D. Hormonal therapy for [82] Bae-Harboe YS, Graber EM. Easy as PIE (Postinflamma-
acne. Semin Cutan Med Surg 2008;27(3):188–96. tory Erythema). J Clin Aesthet Dermatol 2013;6(9):46–7.
[71] Mohsin N, Hernandez LE, Martin MR, et al. Acne treat- [83] Ibrahim SM, Farag A, Hegazy R, et al. Combined Low-
ment review and future perspectives [published online Dose Isotretinoin and Pulsed Dye Laser Versus
ahead of print, 2022 Jul 16]. Dermatol Ther 2022; standard-Dose Isotretinoin in the Treatment of Inflam-
e15719. https://doi.org/10.1111/dth.15719. matory Acne. Lasers Surg Med 2021;53(5):603–9.
[72] Rapkin AJ, Winer SA. Drospirenone: a novel progestin. [84] Trifarotene (Aklief)-A New Topical Retinoid for Acne.
Expert Opin Pharmacother 2007;8(7):989–99. JAMA 2020;323(13):1310–1.

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