Diagnosis and Treatment of Acne
`
`STEPHEN TITUS, MD, and JOSHUA HODGE, MD, Fort Belvoir Community Hospital Family Medicine Residency,
`Fort Belvoir, Virginia
`
`Acne is a chronic inflammatory skin disease that is the most common skin disorder in the United States. Therapy
`targets the four factors responsible for lesion formation: increased sebum production, hyperkeratinization, coloni-
`zation by Propionibacterium acnes, and the resultant inflammatory reaction. Treatment goals indude scar preven-
`tion, reduction of psychological morbidity, and resolution of lesions. Grading ache based on lesion type and severity
`can help guide treatment. Topical retinoids are effective in treating
`inflammatory and noninflammatory lesions by preventing comedo-
`nes, reducing existing comedones, and targeting inflammation. Ben-
`zoyl peroxide is an over-the-counter bactericidal agent that does not
`lead to bacterial resistance. Topical and oral antibiotics are effective
`as monotherapy, but are more effective when combined with topi-
`cal retinoids. The addition of benzoyl peroxide to antibiotic therapy
`reduces the risk of bacterial resistance. Oral isotretinoin is approved
`for the treatment of severe recalcitrant ache and can be safely admin-
`istered using the iPLEDGE program. After treatment goals are
`reached, maintenance therapy should be initiated. There is insuf-.
`ficient evidence to recommend the use of laser and light therapies.
`Referral to a dermatologist should be considered if treatment goals
`are not met. (Am Fam Physician. 2012;86(8):734-740. Copyright ©
`2012 American Academy of Family Physicians.)
`
`> m
`
`Acne is the most common skin disor- Evaluation
`¯ Patient information:
`A handout on acnetreat-
`/__~der in the United States, affecting Acne is diagnosed by the identification of
`ments, written by the
`lesions. The spectrum of acne lesions ranges
`~"’~ 40 to 50 million persons of all ages
`authors of this article, is
`from noninflammatory open or closed
`available athttp://www...A. JL.and races.1 Potential outcomes
`aafp.orglafp12012110151
`include physical scars, persistent hyperpig-
`comedones (blackheads and whiteheads;
`p734-sl .html. Access to
`mentation, and psychological sequelae.
`Figure 1) to inflammatory lesions, which may
`the handout is free and
`be papules, pustules, or nodules (Figures 2
`unrestricted. Let us know
`through 4). Lesions are most likely to occur
`what you think about AFP
`putting handouts online
`on the face, neck, chest, and back, where
`only; e-mail the editors at
`there is a higher concentration of sebaceous
`afpcomment@aafp.org,
`glands. Other conditions can mimic acne,
`and even include the term acne in their
`nomenclature, but they lack the presence of
`comedones. Table 1 outlines the differential
`diagnosis for acne.* Grading acne based on
`the type oflesions and their severity can help
`in deciding which therapies are warranted
`(Figure 5); however, there is no consensus on
`the best grading system?
`
`Pathogenesis
`Ache is a chronic inflammatory disease
`involving the pilosebaceous unit. It is typi-
`fled by the eruption of a comedo within the
`follicle, which is preceded by a microcom-
`edo.1 Four main factors lead to the forma-
`tion of acne lesions: (1) increased sebum
`production by sebaceous glands, in which
`androgens have an important role; (2)
`hyperkeratinization of the follicle, leading to
`a microcomedo that eventually enlarges into
`a comedo; (3) colonization of the follicle by
`the anaerobe Propionibacterium acnes; and
`(4) an inflammatory reaction.2 The inflam- Treatment
`matory events may begin before hyperkera-
`TOPICAL THERAPIES: PRESCRIPTION
`tinization of the follicle? Current therapies Topical retinoids are versatile agents in the
`target these four factors for acute control of
`treatment of acne (Table 2).6,7 They pre-
`flare-ups and long-term maintenance,
`vent the formation and reduce the number
`
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`

`Figure 3. Moderate inflammatory acne lesions with com-
`edones, several papules and pustules, and few nodules.
`
`Figure 1. Noninflammatory acne lesions consisting of
`open andclosed comedones.
`
`..~
`~ ~’~ ’l !.
`
`Figure 4. Severe inflammatory acne lesions with comedo-
`Figure 2. Mild inflammatory acne lesions with comedones nes, several papules and pustules, multiple nodules, and
`and few papules and pustules, scarring.
`
`of comedones, making them useful against
`noninflammatory lesions. Topical retinoids
`
`also possess anti-inflammatory proper-
`
`ties, making them somewhat useful in the
`treatment of inflammatory lesions.6 Topical
`
`retinoids are indicated as monotherapy for
`noninflammatory acne and as combination
`therapy with antibiotics to treat inflamma-
`
`tory acne. Additionally, they are useful for
`
`Table 1. Differential Diagnosis of Acne
`
`Diagnosis
`
`Distinguishing features
`
`Bacterial Abrupt eruption; spreads with scratching or shaving;
`folliculitis variable distribution
`Drug-induced
`Use of androgens, adrenocorticotropic hormone,
`bromides, corticosteroids, oral contraceptives,
`acne
`iodides, isoniazid, lithium, phenytoin (Dilantin)
`
`maintenance after treatment goals have been
`
`reached and systemic drugs are discontin-
`ued.2 Overall, adapalene (Differin) is the
`
`Hidradenitis
`suppurativa
`
`Miliaria
`
`Double comedo; starts as a painful boil; sinus tracts
`
`"Heat rash" in response to exertion or heat exposure;
`nonfollicular papules, pustules, and vesicles
`
`best tolerated topical retinoid. Limited evi-
`
`dence suggests that tazarotene (Tazorac) is
`more effective than adapalene and tretinoin
`
`(Retin-A). There is no evidence that any for-
`mulation is superior to another.6
`
`Topical antibiotics are used predomi-
`nantly for the treatment of mild to moderate
`inflammatory or mixed acne. Clindamy-
`
`Papules and pustules confined to the chin and nasolabial
`Perioral
`dermatitis folds; clear zone around the vermilion border
`Affects curly-haired persons who regularly shave
`Pseudofolliculitis
`closely
`barbae
`Rosacea Erythema and telangiectasias; no comedones
`
`Seborrheic
`dermatitis
`
`Greasy scales and yellow-red coalescing macules or
`papules
`
`cin and erythromycin are the most stud-
`
`Information from reference4.
`
`ied (Table 3).2,5,7 They are sometimes used
`
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`

`Management of Acne
`
`Determine lesion type and severity
`
`Comedones
`
`I. Mild inflammatory
`papules and pustules
`
`I. Moderate inflammatory papules
`and pustules _+ few nodules
`
`Severe inflammatory papules
`and pustules _+ multiple nodules
`
`Topical retinoid
`
`Effective?
`
`No
`
`Topical retinoid plus
`benzoyl peroxide
`
`~,
`
`~,
`
`~
`Nodules Papules and pustules
`
`~
`Nodules
`
`Papules and pustules
`
`Effective? --
`~
`~
`~Yes/ ~ No
`Topical retinoid plus
`Topical retinoid plus benzoyl
`Oral isotretinoin
`|Yes
`Maintenance therapy:
`benzoyl peroxide
`peroxide plus topical antibiotic
`topical retinoid
`plus oral antibiotic
`~
`Maintenance therapy:
`topical retinoid
`
`~
`Effective?
`
`Maintenance therapy: topical
`retinoid plus benzoyl peroxide
`
`or
`
`~No
`
`Topical retinoid plus benzoyl
`lYes
`Topical retinoid plus Maintenance therapy: peroxide plus topical antibiotic
`benzoyl peroxide
`topical retinoid
`plus oral antibiotic
`
`Figure 5. Severity-based approach to treating acne.
`
`Maintenance therapy: topical
`retinoid plus benzoyl peroxide
`
`as monotherapy, but are more effective in combina-
`tion with topical retinoids.5 Because of the possibil-
`ity that topical antibiotics may induce resistance, it is
`recommended that benzoyl peroxide be added to these
`regimens.2
`Table 4 summarizes the additional topical therapies
`
`that are available.5,s 11Azelaic acid should be considered
`for use in pregnant women. The cream formulation
`(Azelex) is approved by the U.S Food and Drug Admin-
`istration (FDA) for the treatment of acne vulgaris, but
`the gel (Finacea) has significantly better bioavailability,s
`It has mixed antimicrobial and anticomedonal effects,
`
`Table 2. Selected Topical Retinoids for the Treatment of Acne Vulgaris
`
`Agent
`
`FDA pregnancy
`category
`
`Adverse effects
`
`Available formulations
`
`Estimated cost generic
`(brand)*
`
`Adapalene
`(Differin)
`
`C
`
`Local erythema, peeling,
`dryness, pruritus, stinging
`
`Tazarotene
`(Tazorac)
`
`Tretinoin
`(Retin-A)
`
`X
`
`C
`
`Local erythema, peeling,
`dryness, pruritus, stinging
`
`Local erythema, peeling,
`dryness, pruritus, stinging
`
`Cream, lotion (0.1%)
`
`$125 ($363)
`
`Gel (0.1%, 0.3%)
`
`Adapalene/benzoyl peroxide
`(Epiduo) gel (0.1%/2.5%)
`
`NA ($269)
`
`Cream, gel (0.05%, 0.1%)
`
`NA ($240)
`
`Cream (0.025%, 0.05%, 0.1%)
`
`$27 ($130)
`
`Gel (0.01%, 0.025%, 0.05%)
`
`$24 ($19 to $105)
`
`Microsphere gel (0.04%, 0.1%)
`
`NA ($170)
`
`FDA = U.S. Food and Drug Administration," NA = not a vailable.
`
`*--Estimated retail price of one month’s treatment based on information obtained at http://wwwlowestmed.com (accessed September 18, 2012).
`
`Information from references 6 and Z
`
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`Table 3. Selected Topical Antibiotics for the Treatment of Acne Vulgaris
`
`Adverse effects
`
`Available formulations
`
`Estimated cost generic (brand)*
`
`Foam, gel, lotion, solution
`(1.0%)
`Clindamycin/benzoyl peroxide
`(Benzaclin) gel (1%/5%,
`1.2%/2.5%)
`Clindamycin/tretinoin gel
`(Veltin, Ziana; 1.2%/0.025%)
`Gel, solution, ointment (2%)
`Erythromycin/benzoyl peroxide
`(Benzamycin) gel (3%/5%)
`
`$12 to $96, depending on
`formulation ($46 to $213)
`$107 ($210)
`
`NA ($180 Veltin, $250 Ziana)
`
`$25 (NA)
`$62 ($313)
`
`Agent
`
`FDA pregnancy
`category
`
`Clindamycin
`
`B
`
`Local erythema, peeling,
`dryness, pruritus,
`burning, oiliness
`
`Erythromycin
`
`B
`
`Local erythema, peeling,
`dryness, pruritus,
`burning, oiliness
`
`NOTE: Topical antibiotics are more effective when combined with a topical retinoid.
`
`FDA = U.S. Food and Drug Administration," NA = not a vailable.
`
`*--Estimated retail price of one month’s treatment based on information obtained at http://wwwlowestmed.com (accessed September 18, 2012).
`
`Information from references 2, 5, and Z
`
`topical formulation causes hemolytic anemia or severe
`skin reactions?
`
`and may be effective for the treatment of mild to moder-
`ate inflammatory or mixed acne.5
`Dapsone is the first agent in a new class of topical
`acne medications to achieve FDA approval in the past
`10 years.9 Although it is an antibiotic, it likely improves Benzoyl peroxide is an over-the-counter bactericidal
`acne by inhibiting inflammation. In studies, dapsone
`agent that comes in a wide array of concentrations and
`formulations. No particular form has been proven bet-
`was minimally more effective than placebo in reduc-
`ing inflammatory and noninflammatory lesions, but it
`ter than another.5 Benzoyl peroxide is unique as an anti-
`has never been compared with other topical agents)° microbial because it is not known to increase bacterial
`Unlike oral dapsone, there is no evidence that the
`resistance.H It ismost effective forthetreatment of mild
`
`TOPICAl. THERAPIES: OVER THE COUNTER
`
`Table 4. Selected Nonantibiotic Topical Therapies for the Treatment of Acne Vulgaris
`
`Agent
`
`FDA pregnancy
`category
`
`Azelaic acid
`
`B
`
`Adverse effects
`
`Available formulations
`
`Estimated cost generic
`(brand)*
`
`Hypopigmentation,
`burning, stinging,
`tingling, pruritus
`
`Cream (Azelex, 20%; approved for ache NA ($210)
`vulgaris)
`Gel (Finacea, 15%; approved for rosacea)
`
`Benzoyl
`peroxide
`
`Dapsone
`
`C
`
`C
`
`Salicylic acid
`
`C
`
`Dry skin, local
`erythema
`
`Bar, cream, gel, lotion, pad, wash
`(2.5% to 10%)
`
`Local oiliness, peeling,
`dryness, erythema
`
`Gel (Aczone, 5%)
`
`Dryness, mild skin
`irritation
`
`Cream, dressing, foam, gel, liquid, lotion,
`ointment, pad, paste, shampoo, soap,
`solution, stick (0.5% to 3%)
`
`$5 over the counter
`$8 to $36 prescription
`(NA)
`
`NA ($193)
`
`$5 over the counter
`
`FDA = U.S. Food and Drug Administration," NA = not a vailable.
`
`*--Estimated retail price of one month’s treatment based on information obtained at http://www Iowestmed.com and http://www, drugstore, com
`(accessed September 18, 2012).
`
`Information from references 5, and 8 through 11.
`
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`Table 5. Selected Oral Antibiotics for the Treatment of Acne Vulgaris
`
`FDA pregnancy
`category
`
`Adverse effects
`
`Dosage
`
`Agent
`
`Doxycycline
`
`Erythromycin
`
`Minocycline
`(Minocin)
`
`Tetracycline
`
`Trimethoprim/
`sulfamethoxazole
`(Bactrim, Septra)
`
`D
`
`B
`
`D
`
`C
`
`C
`
`Estimated cost
`generic (brand)*
`
`$15 ($71 to $363)
`
`Photosensitivity, pseudotumor cerebri,
`50 to 100 mg once or
`esophageal irritation twice per day
`
`Gastrointestinal upset
`
`Vestibular dysfunction, photophobia,
`hepatotoxicity, lupus-like reaction,
`pseudotumor cerebri
`
`250 to 500 mg two to
`four times per day
`
`$73 to $340 (NA)
`
`50 to 100 mg once or
`twice per day
`
`$21 to $59 ($173 to
`$675)
`
`Gastrointestinal upset, photosensitivity,
`pseudotumor cerebri
`
`250 to 500 mg once
`or twice per day
`
`$8 (NA)
`
`Allergic reactions
`
`160/800 mg twice
`per day
`
`$33
`($194)
`
`FDA = U.S. Food and Drug Administration," NA = not a vailable.
`
`*--Estimated retail price of one month’s treatment based on information obtained at http://wwwlowestmed.com (accessed September 18, 2012).
`
`Information from references 2, 5, 10, and 12.
`
`to moderate mixed acne when used in combination with
`topical retinoids.2 Benzoyl peroxide may also be added
`to regimens that include topical and oral antibiotics to
`decrease the risk of bacterial resistance.2
`Salicylic acid is present in a variety of over-the-counter
`cleansing products. These products have anticomedonal
`properties and are less potent than topical retinoids, but
`there have been only limited high-quality studies exam-
`ining their effectiveness.5
`
`ORAL THERAPIES
`
`retinoids for maintenance therapy.2 Topical retinoids are
`sufficient to prevent relapses in most patients with acne
`vulgaris, especially if the disease was originally classified
`as mild or moderate. If the patient’s acne was initially
`classified as severe inflammatory, benzoyl peroxide with
`or without an antibiotic can be added for maintenance
`therapy.2
`Oral isotretinoin is FDA-approved for the treatment
`of severe recalcitrant acne. Evidence suggests that it is
`also useful for less severe acne that is treatment resis-
`tant.5 The usual dosage for severe treatment-resistant
`acne is 0.5 to 1.0 mg per kg per day for about 20 weeks,
`Oral antibiotics are effective for the treatment ofmoder-
`or a cumulative dose of 120 mg per kg)3 Initial flare-
`ate to severe acne5 (Table 52’5’1°’12). The best-studied anti-
`ups can be minimized with a beginning daily dosage of
`biotics include tetracycline and erythromycin. Based on
`expert consensus on relative effectiveness, the American
`0.5 mg or less per kg.5 Total cumulative doses of less
`than 120 mg increase relapse rates, and doses of more
`Academy of Dermatology recommends using doxycycline
`than 150 mg increase the incidence of adverse effects
`and minocycline (Minocin) rather than tetracycline.5
`Trimethoprim/sulfamethoxazole (Bactrim, Septra)and without producing greater benefits.~3 Approximately
`trimethoprim alone may be used if tetracycline or eryth-
`40 percent of patients achieve long-term remission with a
`romycin cannot be tolerated. Because of the potential for
`120-mg cumulative dose, 40 percent require retreatment
`bacterial resistance with topical therapy or oral antibiotics, and 20 percent
`with the use of an
`require retreatment with isotretinoin)<~5 Patients with
`oral antibiotic, it moderate acne may respond to lower dosages (0.3 mg
`is recommended
`per kg per day) and experience fewer adverse effects)6
`that benzoyl per-
`Physicians, distributors, pharmacies, andpatientsmust
`oxide be added to
`register in the iPLEDGE program (http://www.ipledge
`anyregimen of oral
`program.com) before using isotretinoin. This program
`antibiotics.2 Tetracycline is preferred over erythromycin was established to prevent pregnancy in patients taking
`because of the higher rates of resistance associated with
`the medication. Isotretinoin is a potent teratogen and
`erythromycin.5
`is associated with abnormalities of the face, eyes, ears,
`After individual treatment goals have been met, oral
`skull, central nervous system, cardiovascular system,
`antibiotics can be discontinued and replaced with topical
`thymus, and parathyroid glands. Negative pregnancy
`
`Topical dapsone is the first
`drug in a newclass of acne
`therapy to receive approval
`in the past 10 years,
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`

`Clinical recommendation
`
`Evidence
`rating
`
`References
`
`Topical retinoids are effective in the treatment
`of noninflammatory and inflammatory acne.
`Oral antibiotics are effective for the treatment
`of moderate to severe acne.
`Benzoyl peroxide should be used in
`conjunction with topical and oral antibiotics
`to reduce the risk of bacterial resistance,
`After treatment goals are reached, oral
`antibiotics should be replaced with topical
`retinoids for maintenance therapy.
`Topical antibiotics are more effective when
`used in conjunction with topical retinoids.
`
`A
`
`A
`
`C
`
`C
`
`A
`
`Combined oral contraceptives can be used to A
`treat inflammatory and noninflammatory
`acne.
`
`2, 5, 6
`
`2, 5
`
`2
`
`2
`
`2, 5
`
`19
`
`A = consistent, good-quality patient-oriented evidence," B = inconsistent or limited-
`quality patient-oriented evidence," C = consensus, disease-oriented evidence, usual
`practice, expert opinion, or case series. For information about the SORT evidence
`rating system, go to http.’//wwwaafp.org/afpsort.xml,
`
`Acne
`
`systematic review found insufficient evi-
`
`dence to recommend the use of spironolac-
`tone for the treatment of acne.2° Common
`adverse effects include menstrual irregu-
`larities and breast tenderness. It is a potas-
`
`sium-sparing diuretic and may cause severe
`
`hyperkalemia. Additionally, it is a potential
`
`teratogen.21
`
`LASER AND LIGHT THERAPIES
`
`Light and laser therapies can be used for the
`treatment of acne. Examples include visible
`
`light, pulsed-dye laser, and photodynamic
`therapies. There is insufficient evidence to
`recommend the routine use of these therapies
`for the treatment of acne.2 Studies of these
`products typically lack controls, have small
`sample sizes, are short term, and do not com-
`pare these therapies with validated pharma-
`
`tests are mandated before starting therapy, then monthly
`before receiving a prescription refill, immediately after
`taking the last dose, and one month after taking the
`
`cologic treatments. There are no established guidelines
`on the optimal dosing, device, timing, and frequency to
`beused.22
`
`last dose. The use of isotretinoin has been suggested to
`worsen depression and increase the risk of suicide, but OTHER THERAPIES
`no causal relationship has been established.5 Required
`Table 6 summarizes other therapies that are used in the
`
`laboratory monitoring during therapy includes a com-
`
`plete blood count, fasting lipid panel, and measure-
`ment of liver transaminase levels. Common
`
`treatment ofacne, with varyinglevels of evidence to sup-
`port their use.5’2326
`
`adverse effects include headaches, dry skin
`
`and mucous membranes, and gastrointesti-
`nal upset)7
`
`Several estrogen-containing oral contra-
`ceptives are FDA-approved for the treatment
`
`of acne)7 These agents generally are consid-
`
`ered second-line therapies, but they may be
`considered first-line treatments in women
`with adult-onset acne or perimenstrual flare-
`
`ups)s A 2009 Cochrane review found that
`
`these agents are effective in reducing inflam-
`
`matory and noninflammatory lesions.19
`However, there is insufficient evidence to
`recommend one agent over another, includ-
`
`ing those that are FDA approved versus those
`that are not. There is also no evidence to sup-
`
`port their use over other studied therapies.5
`Spironolactone (Aldactone) is an andre-
`
`gen receptor antagonist with unclear effec-
`
`tiveness in the treatment ofacne. It is usually
`
`reserved as a second- or third-line agent, or
`as an alternative to isotretinoin for women
`who cannot use this medication. A 2009
`
`Table 6. Miscellaneous Therapies for the Treatment
`of Acne
`
`Therapy
`
`Evidence
`
`Acupuncture
`
`Avoidance of chocolate
`or sugar consumption
`
`Biofeedback
`
`Chemical peel (glycolic/
`salicylic acid)
`
`Ah-shi acupuncture is no better than general
`acupuncture treatment
`
`No evidence of effectiveness
`
`May enhance response to medical treatment
`for acne
`
`No studies of effectiveness
`
`Comedo removal
`
`May help with treatment-resistant comedones
`and provide short-term reductions in the
`number of noninflammatory lesions
`May improve individual large cystic lesions
`Intralesional steroids
`No evidence of effectiveness
`Microdermabrasion
`Effective for total lesion reduction of papules,
`Tea tree (Melaleuca
`alternifolia) oil pustules, and comedones in mild to
`moderate acne
`
`Information from references 5. and 23 through 26.
`
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`
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`

`Acne
`
`Reassessment and Referral
`
`Treatment goals in patients with acne include the preven-
`tion of scars, the reduction of psychological morbidity,
`and the resolution of noninflammatory and inflamma-
`
`tory lesions. Therapy should be continued for a mini-
`
`mum of eight weeks before a treatment response can be
`accurately assessed. Referral to a dermatologist should
`
`be considered when treatment goals are not met or when
`
`there is significant scarring.27
`
`Data Sources: We performed electronic searches of PubMed, the
`Cochrane database, Essential Evidence Plus, and the National Guideline
`Clearinghouse using the MESH terms acne, vulgaris, treatment, treat,
`and therapy. Search date: March 2011.
`
`The opinions and assertions contained herein are the private views of the
`authors and are not to be construed as official, or as reflecting the views
`of the U.S. Army Medical Corps or the U.S. Army at large,
`
`Figures 1 through 4 provided by Melissa Scorza, MD.
`
`The Authors
`
`STEPHEN TITUS, MD, is a faculty member at the National Capital Consor-
`tium Fort Belvoir (Va.) Community Hospital Family Medicine Residency,
`and an assistant professor of family medicine at the Uniformed Services
`University of the Health Sciences, Bethesda, Md.
`
`JOSHUA HODGE, MD, is the associate program director of the National
`Capital Consortium Fort Belvoir Community Hospital Family Medicine
`Residency, and an assistant professor of family medicine at the Uniformed
`Services University of the Health Sciences.
`
`Address correspondence to Stephen Titus, MD, Fort Belvoir Com-
`munity Hospital, 9501 Farrell Rd., Fort Belvoir, VA 22060 (e-mail:
`stephen.j.titus2@us.army.mil). Reprints are not available from the
`authors.
`
`Author disclosure: No relevant financial affiliations to disclose,
`
`REFERENCES
`
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`740 American Family Physician
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`www.aafp.org/afp
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`Volume 86, Number 8 * October 15, 2012
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`7 of 7
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