FROM THE ACADEMY
`
`This report reflects the best available data at the time the report was prepared, but caution should be exercised
`in interpreting the data;
`the results of
`future studies may require alteration of
`the conclusions or
`recommendations set forth in this report.
`
`Guidelines of care for acne vulgaris management
`
`Work Group: John S. Strauss, MD, Chair,a Daniel P. Krowchuk, MD,b James J. Leyden, MD,c
`Anne W. Lucky, MD,d Alan R. Shalita, MD,e Elaine C. Siegfried, MD,f Diane M. Thiboutot, MD,g
`Abby S. Van Voorhees, MD,c Karl A. Beutner, MD, PhD,h Carol K. Sieck, RN, MSN,i
`and Reva Bhushan, PhDi
`Iowa City, Iowa; Winston-Salem, North Carolina; Philadelphia, Pennsylvania; Cincinnati,
`Ohio; Brooklyn, New York; St Louis, Missouri; Hershey, Pennsylvania;
`Palo Alto, California; and Schaumburg, Illinois
`
`Disclaimer: Adherence to these guidelines will not ensure successful treatment in every situation.
`Furthermore, these guidelines should not be deemed inclusive of all proper methods of care or exclusive of
`other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding
`the propriety of any specific therapy must be made by the physician and the patient in light of all the
`circumstances presented by the individual patient.
`
`From the Department of Dermatology, Roy J. and Lucille A.
`Carver College of Medicine, University of Iowa, Iowa Citya; the
`Departments of Pediatrics and Dermatology, Wake Forest
`University School of Medicine, Brenner Children’s Hospital,
`Winston-Salemb; the Department of Dermatology, University
`of Pennsylvania Hospital, Philadelphiac; the Division of Pediatric
`Dermatology, Cincinnati Children’s Hospital Medical Center
`and University of Cincinnati School of Medicine, Cincinnatid;
`the Department of Dermatology, State University of New York
`Downstate Medical Center, Brooklyne;
`the Department of
`Dermatology, St Louis University School of Medicine, St Louisf;
`the Department
`of Dermatology,
`Pennsylvania
`State
`University College of Medicine, Milton S. Hershey Medical
`Center, Hersheyg; Anacor Pharmaceuticals, Inc, Palo Altoh; and
`the American Academy of Dermatology, Schaumburg.i
`Clinical Guidelines Task Force: Karl A. Beutner, MD, PhD, Chair,
`Mark A. Bechtel, MD, Michael E. Bigby, MD, Craig A. Elmets, MD,
`Steven R. Feldman, MD, PhD, Joel M. Gelfand, MD, Brad P. Glick,
`DO, MPH, Cindy F. Hoffman, DO, Judy Y. Hu, MD, Jacqueline M.
`Junkins-Hopkins, MD, Jeannine L. Koay, MD, Gary D. Monheit,
`MD, Abrar A. Qureshi, MD, MPH, Ben M. Treen, MD, Carol K.
`Sieck, RN, MSN.
`Funding sources: None.
`Disclosure: Dr Strauss was a consultant and investigator for Roche
`Laboratories receiving honoraria and grants, and a consultant
`for Medicis receiving honoraria. Dr Krowchuk has no relevant
`conflicts of interest to disclose. Dr Leyden was a consultant for
`Stiefel and SkinMedica, receiving honoraria; served on the
`Advisory Board and was a consultant for Galderma and Obaj,
`receiving honoraria; was on the Advisory Board and was a
`consultant and investigator for Connetics, Collagenex, Allergan,
`and Medicis, receiving honoraria. Dr Lucky was an investigator
`for Connetics, Dow, Galderma, Healthpoint, Johnson & Johnson,
`QLT, and Stiefel, receiving grants and an investigator and
`consultant for Berlex receiving grants and honoraria. Dr Shalita
`was a consultant,
`investigator, stockholder, and speaker for
`Allergan, receiving grants and honoraria; a consultant for
`
`Bradley/Doak receiving honoraria; served on the Advisory Board
`and was a consultant for Collagenex, receiving honoraria; was
`a consultant and investigator for Connetics receiving grants and
`honoraria; an Advisory Board member, consultant, investigator,
`and speaker for Galderma receiving grants and honoraria;
`a consultant, speaker, and stockholder for Medicis receiving
`honoraria; an Advisory Board member for Ranbaxy receiving
`honoraria; and a consultant, investigator, and speaker for Stiefel,
`receiving grants and honoraria. Dr Siegfried was an investigator
`for Atrix receiving salary. Dr Thiboutot served on the Advisory
`Board and was an investigator and speaker for Allergan and
`Galderma, receiving honoraria; was on the Advisory Board and
`was a consultant and investigator for Collagenex receiving
`honoraria; was on the Advisory Board and was an investigator
`for Connetics, Dermik, and QLT, receiving honoraria; and was
`a consultant, investigator, and speaker for Intendis, receiving
`honoraria. Dr Van Voorhees served on the Advisory Board and
`was an investigator and speaker for Amgen, receiving grants
`and honoraria; was an investigator for Astellas, Bristol Myers
`Squibb, and GlaxoSmithKline, receiving grants; was an Advisory
`Board Member and investigator for Genentech and Warner
`Chilcott, receiving grants and honoraria; was on the Advi-
`sory Board for Centocor receiving honoraria; was a speaker
`for Connetics receiving honoraria; and was a stockholder
`of Merck, owning stock and stock options. Dr Beutner was an
`employee of Anacor receiving salary and stock options and
`a stockholder of Dow Pharmaceutical Sciences receiving stock.
`Ms Sieck and Dr Bhushan have no relevant conflicts of interest
`to disclose.
`Reprints not available from the authors; available for download
`on the American Academy of Dermatology Web site:
`www.aad.org.
`Published online February 6, 2007.
`J Am Acad Dermatol 2007;56:651-63.
`0190-9622/$32.00
`ª 2007 by the American Academy of Dermatology, Inc.
`doi:10.1016/j.jaad.2006.08.048
`
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`
`INTRODUCTION/METHODOLOGY
`A work group of recognized experts was convened
`to determine the audience for the guidelines, define
`the scope of the guidelines, and identify nine clinical
`questions to structure the primary issues in diagnosis
`and management. Work group members were asked
`to complete a disclosure of commercial support, and
`this information will be in the acne technical report
`available on www.aad.org.
`An evidence-based model was used and some
`evidence was obtained by a vendor using a search of
`MEDLINE and EMBASE databases spanning the years
`1970 through 2006. Only English-language publica-
`tions were reviewed.
`The available evidence was evaluated using a
`unified system called the Strength of Recommenda-
`tion Taxonomy (SORT) developed by editors of
`the US family medicine and primary care journals
`(ie, American Family Physician, Family Medicine,
`Journal of Family Practice, and BMJ-USA). This
`strategy was supported by a decision of the Clinical
`Guidelines Task Force in 2005 with some minor
`modifications for a consistent approach to rating
`the strength of the evidence of scientific studies.1
`Evidence was graded using a three-point scale based
`on the quality of methodology as follows:
`
`d I. Good quality patient-oriented evidence.
`d II. Limited quality patient-oriented evidence.
`d III. Other evidence including consensus guide-
`lines, extrapolations from bench research, opin-
`ion, or case studies.
`
`Clinical recommendations were developed on
`the best available evidence tabled in the guidelines
`and explained further in the technical report. These
`are ranked as follows:
`
`A. Recommendation based on consistent and good-
`quality patient-oriented evidence.
`B. Recommendation based on inconsistent or lim-
`ited quality patient-oriented evidence.
`C. Recommendation based on consensus, opinion,
`or case studies.
`
`These guidelines have been developed in accor-
`dance with the American Academy of Dermatology/
`American Academy of Dermatology Association
`‘‘Administrative Regulations
`for Evidence-Based
`Clinical Practice Guidelines,’’ which include the op-
`portunity for review and comment by the entire AAD
`membership and final review and approval by the
`AAD Board of Directors.
`
`including
`the consequences of disease,
`but not
`the scarring, post-inflammatory erythema, or post-
`inflammatory hyperpigmentation. The topic of light
`and laser therapy will be the subject of another
`guideline.
`
`Definitions
`Acne vulgaris is a chronic inflammatory dermato-
`sis which is notable for open and/or closed comedo-
`nes (blackheads and whiteheads) and inflammatory
`lesions including papules, pustules, or nodules.
`
`Issues
`The task force identified the following clinical
`issues relevant to the management of acne: grading
`and classification;
`the role of microbiologic and
`endocrine testing; and the efficacy and safety of
`various treatments, such as topical agents, systemic
`antibacterial agents, hormonal agents, isotretinoin,
`miscellaneous therapies, complementary/alternative
`therapies, and dietary restriction.
`
`I. SYSTEMS FOR THE GRADING AND
`CLASSIFICATION OF ACNE
`Table I shows the recommendations for a grading
`and classification system.
`
`Recommendation
`d Clinicians may find it helpful to use a consistent
`classification/grading scale (encompassing the
`numbers and types of acne lesions as well as
`disease severity) to facilitate therapeutic decisions
`and assess response to treatment.
`
`DISCUSSION
`The rating of disease severity is useful for the
`initial evaluation and management of acne, to aid
`in the selection of appropriate therapeutic agents,
`and to evaluate response to treatment.2,3
`Several systems for grading acne exist; most
`employ lesion counting combined with some type
`of global assessment of severity (eg, mild, moderate,
`severe) that represents a synthesis of the number,
`size, and extent of lesions. However, there is no con-
`sensus on a single or best grading or classification
`system.2-15
`
`II. MICROBIOLOGIC AND
`ENDOCRINOLOGIC TESTING
`Microbiologic testing
`Table II shows the recommendations for micro-
`biologic testing.
`
`Scope
`These guidelines address the management of
`adolescent and adult patients presenting with acne
`
`Recommendations
`d Routine microbiologic testing is unnecessary in the
`evaluation and management of patients with acne.
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`
`Strauss et al 653
`
`Table I. Recommendations for a grading
`and classification system
`
`Table III. Recommedations for endocrinologic
`testing
`
`Strength of
`recommendation
`
`Level of
`evidence
`
`References
`
`Recommendation
`
`Strength of
`recommendation
`
`Level of
`evidence References
`
`B
`
`II
`
`2-5, 7, 11
`
`Endocrinologic testing
`
`A
`
`I
`
`20, 22
`
`Recommendation
`
`Grading/
`classification
`system
`
`Table II. Recommendations for microbiologic
`testing
`
`Recommendation
`
`Strength of
`recommendation
`
`Level of
`evidence References
`
`Microbiologic testing
`
`B
`
`II
`
`16-19
`
`d Those who exhibit acne-like lesions suggestive of
`gram-negative folliculitis may benefit from micro-
`biologic testing.
`
`DISCUSSION
`The prevalent bacterium implicated in the clinical
`course of acne is Propionibacterium acnes (P acnes),
`a gram-positive anaerobe that normally inhabits the
`skin and is implicated in the inflammatory phase of
`acne.
`Gram-negative folliculitis is typically character-
`ized by pustules and/or nodules most commonly
`located in the perioral and nasal areas. Gram-nega-
`tive folliculitis is caused by a variety of bacteria and
`is unresponsive to conventional antibiotic therapy
`for acne. Bacterial cultures, including antibacterial
`sensitivities, are usually of value in establishing the
`diagnosis and in determining therapy.16-19
`
`Endocrinologic testing
`Table III shows the recommendations for endo-
`crinologic testing.
`
`Recommendation
`d Routine endocrinologic evaluation (eg, for andro-
`gen excess) is not indicated for the majority of
`patients with acne. Laboratory evaluation is indi-
`cated for patients who have acne and additional
`signs of androgen excess. In young children this
`may be manifested by body odor, axillary or pubic
`hair, and clitoromegaly. Adult women with symp-
`toms of hyperandrogenism may present with re-
`calcitrant or late-onset acne, infrequent menses,
`hirsutism, male or female pattern alopecia, infer-
`tility, acanthosis nigricans, and truncal obesity.
`
`DISCUSSION
`Although androgens play an important role in
`the pathogenesis of acne, most patients have normal
`
`Table IV. Recommendations for topical therapy
`
`Recommendation
`
`Retinoids
`Benzoyl peroxide
`Antibiotics
`Other agents
`
`Strength of
`recommendation
`
`Level of
`evidence
`
`A
`A
`A
`A
`
`I
`I
`I
`I
`
`References
`
`25, 28, 38, 41
`42, 48, 50, 51
`52-58, 62, 65
`70, 72, 73, 75, 79
`
`hormone levels. Presently, there is little evidence
`from peer-reviewed literature indicating that routine
`endocrinologic testing has clinical value in the eval-
`uation of patients with acne. Patients whose history
`or physical examination suggests hyperandrogenism
`may, however, benefit from such testing. In prepu-
`bertal children, the signs include acne, early-onset
`body odor, axillary or pubic hair, accelerated growth,
`advanced bone age, and genital maturation. After
`puberty, common virilizing signs and symptoms are
`infrequent menses, hirsutism, male or female pattern
`alopecia, infertility, polycystic ovaries, clitoromeg-
`aly, acanthosis nigricans, and truncal obesity.20-24 In
`prepubertal children, a hand film for bone age is a
`practical screen prior to specific hormonal testing.
`Increased awareness of clinical signs of androgen
`excess will help identify those patients who may
`benefit from further evaluation and treatment by an
`endocrinologist or gynecologic endocrinologist. It
`is the opinion of the experts that the following
`laboratory tests may be helpful: free testosterone,
`dehydroepiandrosterone sulfate,
`leutinizing hor-
`mone, and follicule-stimulating hormone.
`
`III. TOPICAL THERAPY
`Recommendations for topical therapy are shown
`in Table IV.
`
`Recommendations
`d Topical
`therapy is a standard of care in acne
`treatment.
`d Topical retinoids are important in acne treatment.
`d Benzoyl peroxide and combinations with eryth-
`romycin or
`clindamycin are effective acne
`treatments.
`d Topical antibiotics (eg, erythromycin and clinda-
`mycin) are effective acne treatments. However,
`the use of these agents alone can be associated
`with the development of bacterial resistance.
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`d Salicylic acid is moderately effective in the treat-
`ment of acne.
`d Azelaic acid has been shown to be effective in
`clinical trials, but its clinical use, compared to other
`agents, has limited efficacy according to experts.
`d Data from peer-reviewed literature regarding the
`efficacy of sulfur, resorcinol, sodium sulfaceta-
`mide, aluminum chloride, and zinc are limited.
`d Employing multiple topical agents that affect dif-
`ferent aspects of acne pathogenesis can be useful.
`However, it is the opinion of the work group that
`such agents not be applied simultaneously unless
`they are known to be compatible.
`
`DISCUSSION
`Topical retinoids
`The effectiveness of topical retinoids in the treat-
`ment of acne is well documented.25-41 These agents
`act to reduce obstruction within the follicle and
`therefore are useful
`in the management of both
`comedonal and inflammatory acne. There is no
`consensus about the relative efficacy of currently
`available topical
`retinoids (tretinoin, adapalene,
`tazarotene, and isotretinoin). The concentration
`and/or vehicle of any particular retinoid may impact
`tolerability.33,35 Topical isotretinoin is not currently
`available in the United States.
`
`Benzoyl peroxide
`Benzoyl peroxide is a bactericidal agent that has
`proven effective in the treatment of acne. It is avail-
`able in a variety of concentrations and vehicles; how-
`ever, there is insufficient evidence to evaluate and
`compare the efficacy of these different formulations.
`It has the ability to prevent or eliminate the develop-
`ment of P acnes resistance.42-51 Because of concerns
`of resistance, it is often used in the management of
`patients treated with oral or topical antibiotics.
`
`Topical antibiotics
`The value of topical antibiotics in the treatment of
`acne has been investigated in many clinical trials.
`Both erythromycin52-58 and clindamycin59-66 have
`been demonstrated to be effective and are well
`tolerated. Decreased sensitivity of P acnes to these
`antibiotics can limit the use of either drug as a single
`therapeutic agent.58,61
`
`Combinations: Retinoids, benzoyl peroxide,
`and topical antibiotics
`A combination of topical retinoids and topical
`erythromycin or clindamycin is more effective than
`either agent used alone.67-71 Combining erythromy-
`cin or clindamycin with benzoyl peroxide eliminates
`
`or reduces bacterial resistance and enhances effi-
`cacy. The combinations are more effective than
`either of the individual components alone.72-75
`
`Salicylic acid
`Salicylic acid has been used for many years for the
`treatment of acne, although few well-designed trials
`of its safety and efficacy exist. Its comedolytic prop-
`erties are considered less potent than topical reti-
`noids. It often is used when patients cannot tolerate
`a topical retinoid because of skin irritation.76
`
`Other topical agents
`Azelaic acid has been reported to possess come-
`dolytic and antibacterial properties. Data from clin-
`ical trials indicate that it is effective.77-79 Although
`sulfur and resorcinol have been used for many years
`in the treatment of acne, evidence from peer-
`reviewed literature supporting their efficacy is lack-
`ing.80 Aluminum chloride possesses antibacterial
`activity and, therefore, has been investigated in the
`treatment acne. Of two studies in the peer-reviewed
`literature, one found benefit81 and one did not.82
`Topical zinc alone is ineffective.83-85 There is some
`evidence to suggest efficacy for sodium sulfaceta-
`mide.86-88
`
`IV. SYSTEMIC ANTIBIOTICS
`The recommendations of systemic antibiotics are
`shown in Table V.
`
`Recommendations
`d Systemic antibiotics are a standard of care in the
`management of moderate and severe acne and
`treatment-resistant forms of inflammatory acne.
`d Doxycycline and minocycline are more effective
`than tetracycline, and there is evidence that min-
`ocycline is superior to doxycycline in reducing
`P acnes.
`d Although erythromycin is effective, use should be
`limited to those who cannot use the tetracyclines
`(ie, pregnant women or children under 8 years of
`age because of the potential for damage to the
`skeleton or teeth). The development of bacterial
`resistance is also common during erythromycin
`therapy.
`d Trimethoprim-sulfamethoxazole and trimethoprim
`alone are also effective in instances where other
`antibiotics cannot be used.
`d Bacterial resistance to antibiotics is an increasing
`problem.
`d The incidence of significant adverse effects with
`antibiotic use is low. However, adverse effect
`profiles may be helpful for each systemic antibi-
`otic used in the treatment of acne.
`
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`J AM ACAD DERMATOL
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`
`Table V. Recommendations for systemic
`antibiotics
`
`Strauss et al 655
`
`Table VI. Recommendations for hormonal agents
`
`Recommendation
`
`Tetracyclines
`Macrolides
`
`Trimethoprim-
`sulfamethoxazole
`
`Strength of
`recommendation
`
`Level of
`evidence
`
`A
`A
`
`A
`
`I
`I
`
`I
`
`References
`
`90, 91, 95, 121
`102, 108, 111,
`115
`117
`
`Recommendation
`
`Contraceptive
`agents
`Spironolactone
`Antiandrogens
`Oral
`corticosteroids
`
`Strength of
`recommendation
`
`Level of
`evidence
`
`A
`
`B
`B
`B
`
`I
`
`II
`II
`II
`
`References
`
`122-125
`
`132
`134, 135
`137
`
`DISCUSSION
`Antibiotics have been widely used for many years
`in the management of acne. There is evidence to
`support the use of tetracycline, doxycycline, mino-
`cycline, erythromycin, trimethoprim-sulfamethoxa-
`zole, trimethoprim, and azithromycin.89-120 Studies
`do not exist for the use of ampicillin, amoxicillin, or
`cephalexin. However, any antibiotic which can re-
`duce the P acnes population in vivo and interfere
`with the organism’s ability to generate inflammatory
`agents should be effective. It is the opinion of the
`expert panel that while published data are conflict-
`ing, minocycline and doxycycline are more effective
`than tetracycline.101,105
`A major problem affecting antibiotic therapy of
`acne has been bacterial resistance, which has been
`increasing.18,121 For this reason, it is the opinion of
`the work group that patients with less severe
`forms of acne should not be treated with oral
`antibiotics, and where possible the duration of
`such therapy should be limited. Resistance has
`been seen with all antibiotics, but is most common
`with erythromycin.
`The use of oral antibiotics for the treatment of
`acne may be associated with adverse effects. Vaginal
`candidiasis may complicate the use of all oral
`antibiotics.102,103,107,108 Doxycycline can be associ-
`ated with photosensitivity. Minocycline has been
`associated with pigment deposition in the skin,
`mucous membranes and teeth particularly among
`patients receiving long-term therapy and/or higher
`doses of the medication. Pigmentation occurs most
`often in acne scars, anterior shins, and mucous
`membranes. Autoimmune hepatitis, a systemic lupus
`erythematosus-like syndrome, and serum sickness-
`like reactions occur rarely with minocycline.102,107
`
`V. HORMONAL AGENTS
`Hormonal agent recommendations are shown in
`Table VI.
`
`d Oral antiandrogens, such as spironolactone and
`cyproterone acetate, can be useful in the treat-
`ment of acne. While flutamide can be effective,
`hepatic toxicity limits its use. There is no evidence
`to support the use of finasteride.
`d There are limited data to support the effectiveness
`of oral corticosteroids in the treatment of acne.
`There is a consensus of expert opinion that oral
`corticosteroid therapy is of temporary benefit in
`patients who have severe inflammatory acne.
`d In patients who have well-documented adrenal
`hyperandrogenism, low-dose oral corticosteroids
`may be useful in treatment of acne.
`
`DISCUSSION
`Oral contraceptives
`There are clinical trials of estrogen-containing con-
`traceptive agents for the treatment of acne.122-125
`Those currently approved by the US Food and Drug
`Administration (FDA) for the management of acne
`contain norgestimate with ethinyl estradiol (Ortho
`Tri-cyclen; Ortho-MacNeil Pharmaceutical,
`Inc,
`Raritan, NJ) and norethindrone acetate with ethinyl
`estradiol (Estrostep; Warner Chilcott, Rockaway,
`NJ).122-128 There is good evidence and consensus
`opinion that other estrogen-containing oral contra-
`ceptives are also equally effective.129,130 The effect
`on acne of other estrogen-containing contraceptives
`(eg, transdermal patches, vaginal rings) has not been
`studied.
`
`Spironolactone
`Spironolactone is an anti-androgen that exerts its
`effects by blocking androgen receptors at higher
`doses.131 Dosages of 50 mg to 200 mg have been
`shown to be effective in acne. Spironolactone may
`cause hyperkalemia, particularly when higher doses
`are prescribed or when there is cardiac or renal
`compromise.
`It occasionally causes menstrual
`irregularity.132,133
`
`Recommendations
`d Estrogen-containing oral contraceptives can be
`useful in the treatment of acne in some women.
`
`Cyproterone acetate
`Cyproterone combined with ethinyl estradiol (in
`the form of an oral contraceptive) has been found to
`
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`
`Table VII. Isotretinoin recommendations
`
`Recommendation
`
`Strength of
`recommendation
`
`Level of
`evidence
`
`References
`
`Isotretinoin
`
`A
`
`I
`
`141, 148, 150-153,
`155, 159, 161
`
`be effective in the treatment of acne in females.134-136
`Higher doses have been found to be more effective
`than lower doses. Cyproterone/estrogen-containing
`oral contraceptives are not approved for use in the
`United States.
`
`Flutamide
`Flutamide, a non-steroidal antiandrogen approved
`for the management of prostatic hypertrophy or
`cancer and hirsutism, has had some success in the
`management of acne, but its use is limited because of
`the potential of hepatic failure.
`
`Other antiandrogens
`Finasteride and other compounds with possible
`antiandrogenic effects (eg, cimetidine and ketocon-
`azole) have not been reported to be effective in acne.
`
`Oral corticosteroids
`Oral corticosteroids may have two modes of
`activity in the treatment of acne. One study demon-
`strated that low dose corticosteroids suppress adre-
`nal activity in patients who have proven adrenal
`hyperactivity.137 Expert opinion is that short-courses
`of higher dose oral corticosteroids may be beneficial
`in patients with highly inflammatory disease.
`
`VI. ISOTRETINOIN
`Isotretinoin recommendations are shown in
`Table VII.
`
`Recommendations
`d Oral isotretinoin is approved for the treatment of
`severe recalcitrant nodular acne.
`d It is the unanimous opinion of the acne work-
`group that oral isotretinoin is also useful for the
`management of lesser degrees of acne that are
`treatment-resistant or for the management of acne
`that is producing either physical or psychological
`scarring.
`d Oral isotretinoin is a potent teratogen. Because of
`its teratogenicity and the potential for many other
`adverse effects, this drug should be prescribed
`only by those physicians knowledgeable in its
`appropriate administration and monitoring.
`d Female patients of child-bearing potential must
`only be treated with oral isotretinoin if they are
`
`participating in the approved pregnancy preven-
`tion and management program (iPLEDGE; see
`below).
`ideation,
`d Mood disorders, depression, suicidal
`and suicides have been reported in patients tak-
`ing this drug. However, a causal relationship has
`not been established.
`
`DISCUSSION
`Indications
`The approved indication for the use of oral
`isotretinoin has remained severe nodular treatment-
`resistant acne since the drug was introduced more
`than 20 years ago. However, it is the opinion of the
`expert work group that this drug is also indicated for
`all cases of acne that are either treatment-resistant
`or producing physical or psychological scarring.
`
`Dosage
`The approved dosage is 0.5 to 2.0 mg/kg/day. The
`drug is usually given over a 20-week course.138-158
`Drug absorption is greater when the drug is taken
`with food. The acne expert work group feels strongly
`that initial flaring can be minimized with a beginning
`dose of 0.5 mg/kg/day or less. Alternatively, lower
`doses can be used for longer time periods, with a total
`cumulative dose of 120 to 150 mg/kg.138 In patients
`who have severely inflamed acne, even greater initial
`reduction of dose may be required. In the most
`severe cases of acne, consideration of pre-treatment
`with oral corticosteroids may also be appropriate.
`
`Adverse effects
`Isotretinoin, a vitamin A derivative, interacts with
`many of the biologic systems of the body, and
`consequently has a significant pattern of adverse
`effects. The pattern is similar to that seen in hyper-
`vitaminosis A. Side effects include those of
`the
`mucocutaneous, musculoskeletal, and ophthalmic
`systems, as well as headaches and central nervous
`system effects. Most of the adverse effects are tem-
`porary and resolve after the drug is discontin-
`ued.139,141,143-145,149,152-158
`While hyperostosis, premature epiphyseal clo-
`sure, and bone demineralization have been observed
`with prolonged use of higher dose retinoids, in the
`usual course of acne treatment these findings have
`not been identified. Therefore it is the unanimous
`opinion of the acne work group that routine screen-
`ing for these issues is not required. Laboratory mon-
`itoring during therapy should include triglycerides,
`cholesterol,
`transaminase, and complete blood
`counts.153,155,157,159
`Changes in mood, suicidal ideation, and suicide
`have been reported sporadically in patients taking
`
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`VOLUME 56, NUMBER 4
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`Strauss et al 657
`
`Table VIII. Recommendations for miscellaneous
`therapies
`
`Table IX. Recommendations for complementary
`therapies
`
`Recommendation
`
`Intralesional steroids
`Chemical peels
`Comedo removal
`
`Strength of
`recommendation
`
`Level of
`evidence References
`
`C
`C
`C
`
`III
`III
`III
`
`168, 169
`170-172
`173
`
`Recommendation
`
`Herbal agents
`Psychological
`approaches
`Hypnosis/biofeedback
`
`Strength of
`recommendation
`
`Level of
`evidence References
`
`B
`C
`
`B
`
`II
`III
`
`II
`
`174-176
`177
`
`178
`
`isotretinoin. While these events have been seen,
`a causal relationship has not been established. None-
`theless, there are instances in which withdrawal of
`isotretinoin has resulted in improved mood and re-
`introduction of isotretinoin has resulted in the return
`of mood changes. The symptoms mentioned are
`quite common in adolescents and young adults, the
`age range of patients who are likely to receive iso-
`tretinoin. Treatment of severe acne with isotretinoin
`is often associated with mood improvement. There is
`epidemiologic evidence that the incidence of these
`events is less in isotretinoin-treated patients than in
`an age-matched general population. There is also
`evidence that the risk of depressed mood is no greater
`during isotretinoin therapy than during therapy of an
`age-matched acne group treated with conservative
`therapy. Nonetheless, patients must be made aware
`of this possibility and treating physicians should
`monitor patients for psychiatric adverse effects.159-165
`Some patients experience a relapse of acne after
`the first course of treatment with isotretinoin. The
`panel feels relapses are more common in younger
`adults or when lower doses are used.147-149,151,166,167
`
`iPLEDGE
`Because of the teratogenic effects of isotretinoin
`on the fetus, the FDA and the manufacturers have
`approved a new risk management program for
`isotretinoin.154,155 Prescribers, patients, pharmacies,
`drug wholesalers, and manufacturers in the United
`States are required to register and comply with the
`iPLEDGE program. This program requires manda-
`tory registration of all patients receiving this drug.
`Detailed information can be found on the iPLEDGE
`web site (www.ipledgeprogram.com).
`
`VII. MISCELLANEOUS THERAPY
`Recommendations for miscellaneous therapies
`are shown in Table VIII.
`
`Recommendations
`d Intralesional corticosteroid injections are effective
`in the treatment of individual acne nodules.
`d There is limited evidence regarding the benefit of
`physical modalities including glycolic acid peels
`and salicylic acid peels.
`
`Table X. Recommended dietary restrictions
`
`Recommendation
`
`Effect of diet
`
`Strength of
`recommendation
`
`Level of
`evidence
`
`B
`
`II
`
`References
`
`179, 180
`
`DISCUSSION
`Intralesional steroids
`In the opinion of experts, the effect of intralesional
`injection with corticosteroids is a well established and
`recognized treatment for large inflammatory lesions.
`It has been found that patients receiving intralesional
`steroids for the treatment of cystic acne improved.168
`Systemic absorption of steroids may occur. Adrenal
`suppression was observed in one study.169 The
`injection of intralesional steroids may be associated
`with local atrophy. Lowering the concentration
`and/or volume of steroid utilized may minimize these
`complications.
`
`Chemical peels
`Both glycolic acid-based and salicylic acid-
`based peeling preparations have been used in the
`treatment of acne. There is very little evidence from
`clinical trials published in the peer-reviewed litera-
`ture supporting the efficacy of peeling regimens.170-172
`Further research on the use of peeling in the treat-
`ment of acne needs to be conducted in order to
`establish best practices for this modality.
`
`Comedo removal
`There is limited evidence published in peer-
`reviewed medical literature that addresses the effi-
`cacy of comedo removal for the treatment of acne,
`despite its long-standing clinical use.173 It is, however,
`the opinion of the work group that comedo removal
`may be helpful in the management of comedones
`resistant to other therapies. Also, while it cannot affect
`the clinical course of the disease, it can improve the
`patient’s appearance, which may positively impact
`compliance with the treatment program.
`
`VIII. COMPLEMENTARY THERAPY
`Complementary therapy recommendations are
`shown in Table IX.
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`
`J AM ACAD DERMATOL
`APRIL 2007
`
`Recommendation
`d Herbal and alternative therapies have been used
`to treat acne. Although these products appear to
`be well tolerated, very limited data exist regarding
`the safety and efficacy of these agents.
`
`DISCUSSION
`A single clinical trial has demonstrated that topical
`tea tree oil is effective for the treatment of acne,
`although the onset of action is slower compared
`to other topical treatments.174 Other herbal agents,
`such as topical and oral ayurvedic compounds, have
`been reported to have value in the treatment of
`acne.175,176
`
`Psychological approaches/hypnosis/
`biofeedback
`The psychological effects of acne may be pro-
`found, and it is the unanimous opinion of the expert
`workgroup that effective acne treatment can improve
`the emotional outlook of patients. There is weak
`evidence of the possible benefit of biofeedback-
`assisted relaxation and cognitive imagery.177,178
`
`IX. DIETARY RESTRICTION
`Recommended dietary restrictions are shown in
`Table X.
`
`Recommendation
`d Dietary restriction (either specific foods or food
`classes) has not been demonstrated to be of benefit
`in the treatment of acne.
`
`DISCUSSION
`There are few clinical studies available in the peer-
`reviewed literature that directly evaluate the e