Acne vulgaris medical resident chief
Transcription
Acne vulgaris medical resident chief
BMJ 2013;346:f2634 doi: 10.1136/bmj.f2634 (Published 8 May 2013) Page 1 of 7 Clinical Review CLINICAL REVIEW Acne vulgaris 1 Annelise L Dawson medical resident , Robert P Dellavalle chief 234 Department of Internal Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 2Department of Dermatology, University of Colorado Denver, Aurora, Colorado, USA; 3Dermatology Service, Department of Veterans’ Affairs Medical Center, Denver, CO 80220, USA ; 4Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA 1 Acne vulgaris is a common inflammatory skin condition. Although often perceived as a self limited disease of adolescence, its prevalence remains high into adulthood. Nearly 90% of teenagers have acne, and half of them continue to experience symptoms as adults.1-3 By age 40 years, 1% of men and 5% of women still have lesions.4 Recent analyses show an increasing prevalence of acne in children, perhaps because of pubertal onset.5 Given that acne may persist for decades and require long term therapy, there has been a recent effort to reclassify acne as a chronic disease.2 6 Acne has clear detrimental psychosocial effects and may lead to permanent scarring.7 It is therefore not surprising that patients are motivated to seek medical care. In the United Kingdom, acne accounts for more than 3.5 million annual visits to general practitioners,3 8 who must therefore be equipped to treat acne. Several prominent groups—including the Global Alliance to Improve Outcomes in Acne, the European Dermatology Forum, and the American Academy of Dermatology—have published comprehensive treatment recommendations detailing comparable therapeutic strategies.9-11 Here we provide a streamlined outline of treatment intended for the non-specialist. What are the clinical characteristics of acne? A spectrum of lesions may be present, including non-inflammatory open and closed comedones (blackheads and whiteheads, respectively) and inflammatory papules, pustules, nodules, and cysts. Lesions may be present on the face, neck, chest, or back—areas with the greatest density of pilosebaceous units.12 Comedone formation is intrinsic to the diagnosis of acne vulgaris—when not clinically apparent, consider alternative diagnoses. Diseases that mimic acne include rosacea, folliculitis, angiofibromas, perioral dermatitis, and keratosis pilaris.5 13 14 The patient’s age may also help to distinguish these disorders from acne. Keratosis pilaris and perioral dermatitis, for example, tend to present in childhood, whereas rosacea tends to affect older adults. In cases of diagnostic uncertainty, referral to specialist care is warranted. Several groups have proposed standardized measures for classifying acne, although none has been universally accepted.10 13 15 Classification is important because it helps to inform treatment strategies.3 11 Acne is categorized broadly into mild, moderate, and severe forms. Mild acne is typically limited to the face and is characterized by the presence of non-inflammatory closed and open comedones with few inflammatory lesions. Moderate acne is characterized by an increased number of inflammatory papules and pustules on the face and often mild truncal disease. Finally, acne is considered to be severe when nodules and cysts are present. In these cases, facial lesions are often accompanied by widespread truncal disease. What causes acne? Acne is an inflammatory disease of the pilosebaceous duct that results from four primary pathophysiologic processes: • Abnormal keratinocyte proliferation and desquamation that leads to ductal obstruction • Androgen driven increase in sebum production • Proliferation of Propionibacterium acnes • Inflammation.2 9 13 16 17 Increased androgen production causes abnormal epithelial desquamation and follicular obstruction, which lead to the primary precursor lesion in acne—the microcomedone. Microcomedones are pathological structures not visible to the naked eye that evolve into visible lesions.18 An increase in circulating androgens also promotes sebum production, causing these obstructed follicles to fill with lipid rich material and form visible open and closed comedones.12 19 Sebum serves as a substrate for bacterial growth, leading to proliferation of P acnes. Finally, P acnes releases chemical mediators that promote inflammation, which is propagated by traumatic rupture of comedones into the surrounding dermis.2 17 This inflammation manifests through the development of inflammatory papules, pustules, nodules, and cysts. Correspondence to: R P Dellavalle, Dermatology Service, Department of Veteran Affairs Medical Center, Denver, CO, USA [email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe BMJ 2013;346:f2634 doi: 10.1136/bmj.f2634 (Published 8 May 2013) Page 2 of 7 CLINICAL REVIEW Summary points Do not underestimate the impact of acne on patient quality of life and mental health Topical retinoids are now a mainstay of treatment Avoid prolonged antibiotic courses and antibiotic monotherapy because of the risk of bacterial resistance For women with refractory acne or lesions confined to the lower half of the face, consider the addition of combined oral contraceptives Oral isotretinoin is the most effective treatment for severe acne Assess treatment adherence, which may be limited by irritation or regimen complexity Sources and selection criteria We performed a Medline database search using the term “acne” together with “antibiotic resistance”, “antibiotics”, “azelaic acid”, “benzoyl peroxide”, “classification”, “depression”, “diet”, “epidemiology”, “isotretinoin”, “oral contraceptives”, “pathogenesis”, “retinoids”, “scarring”, “smoking”, “treatment”, “treatment guidelines”, and “vulgaris.” We also searched the Cochrane Database of Systematic Reviews using the term “acne”. The successful management of acne requires an understanding of these four facets of the pathophysiology of acne. Clinicians should select mechanistically driven treatment regimens that target each patient’s predominant lesion types. Can acne be prevented? Myths about the causes of acne abound. The central discoloration in blackheads is not dirt, but oxidized melanin.20 A comprehensive systematic review found little evidence for an association between acne and poor facial hygiene and provided minimal support for frequent face washing.21 Aggressive cleansing may cause irritation, thereby exacerbating active lesions or limiting the patient’s tolerance of therapy.21 22 Basic care with twice daily washing and use of a moisturizer that does not contribute to comedone formation (noncomedogenic) is an accepted standard.9 Although misconceptions about dietary triggers have been largely dispelled, recent reports—including a systematic review of dietary influences on acne and a randomized investigator masked controlled trial of glycemic load and acne severity—suggest that acne is associated with high dairy diets and those with a high glycemic load.23-27 Finally, a cross sectional analysis found a significant dose dependent association between smoking and acne severity.20 28 How is acne treated? Careful assessment of the morphology and severity of acne is an important first step in management, because lesion morphology largely dictates the optimal treatment approach. Treatment should be designed to target precursor lesions (microcomedones) and active inflammatory lesions. Milder cases are best managed with topical regimens, whereas systemic drugs are indicated in more severe cases. The box summarises the mechanisms of action of the most commonly used agents. The table⇓ provides a treatment framework based on disease severity. Topical agents Retinoids Retinoids are vitamin A derivatives that normalize keratinocyte desquamation and adhesion, leading to comedolysis and preventing formation of new microcomedones. Some retinoids also display anti-inflammatory properties.11 15 29-32 Perhaps the most notable recent development in the treatment of acne is the increased use of topical retinoids.29 Many randomized trials show the efficacy of these drugs relative to vehicle, and they For personal use only: See rights and reprints http://www.bmj.com/permissions are recommended for all cases of acne, except when oral retinoids are used.9 11 Studies show improvements within weeks, with maximal benefit after three to four months.13 15 18 Mild non-inflammatory comedonal acne may be treated with retinoid monotherapy. When inflammatory lesions are present, retinoids should be combined with antimicrobial therapy or benzoyl peroxide.9 16 Because retinoids prevent the development of microcomedones, they can also be used for maintenance therapy.9 Several topical retinoid products exist, including tretinoin, isotretinoin (not available in the United States), adapalene, and tazarotene (not licensed for treatment of acne in the United Kingdom).18 These products are available in cream, gel, liquid, and microsphere formulations, each at multiple concentrations. Formulations vary by country.9 18 Use of retinoids is limited by transient skin irritation, which may be prevented by selecting lower concentration or cream based formulations.18 29 31 A meta-analysis of five randomized controlled trials suggests that adapalene is the best tolerated retinoid, whereas several moderately sized randomized studies found tazarotene to be most efficacious at the expense of irritation.13 18 29 31-38 In addition, anecdotal evidence suggests that some patients experience an initial “flare” in acne lesions, which subsides with continued use.2 18 31 Lastly, pregnant and breastfeeding women should avoid topical retinoids.18 Women of child bearing age should be counselled about the need for contraception.17 Topical antibiotics The primary topical antibiotics used for acne are clindamycin and erythromycin.30 These agents have bacteriostatic and anti-inflammatory properties.11 30 32 Topical antibiotics are used for mild to moderate acne when inflammatory lesions are present.16 Antibiotic resistance is a growing concern and has prompted efforts to limit the duration of antibiotic courses and to emphasize combined regimens.2 Patterns of P acnes resistance correspond to trends in antibiotic use.2 39 Treatment outcomes worsen when resistance is present—systematic reviews show decreasing antibiotic efficacy over time, particularly for erythromycin and clindamycin.2 32 40 41 P acnes resistance is not the only concern—Staphylococcus and Streptococcus resistance may also develop.39 42 In practice, this means avoiding antibiotic monotherapy and maintenance therapy.19 20 Instead, topical antibiotics should always be used with retinoids, and possibly benzoyl peroxide. Several double blind randomized controlled trials have found that the addition of retinoid or benzoyl peroxide therapy to topical antibiotics improves treatment outcomes.9 10 17 39 43 44 Retinoids do not decrease resistance but Subscribe: http://www.bmj.com/subscribe BMJ 2013;346:f2634 doi: 10.1136/bmj.f2634 (Published 8 May 2013) Page 3 of 7 CLINICAL REVIEW Effects of the different agents used to treat acne Topical retinoids: Comedolytic and sometimes anti-inflammatory Antibiotics: Antimicrobial and anti-inflammatory Benzoyl peroxide: Antimicrobial plus weakly anti-inflammatory and comedolytic Hormonal agents: Sebosuppressive Oral retinoids: Comedolytic, sebosuppressive, antimicrobial, and anti-inflammatory promote antibiotic efficacy by improving penetration and providing synergistic comedolytic and anti-inflammatory effects.18 45 Benzoyl peroxide has bactericidal properties, thereby minimizing bacterial resistance.39 45 Topical antibiotic courses should be limited to 12 weeks’ duration when possible.9 16 46 Finally, combined topical and oral antibiotics should be avoided.15 47 Administration, although it has been approved in many European countries, so receives greater emphasis in the European literature.10 55 A small double blind randomized trial demonstrated efficacy of azelaic acid relative to placebo.56 Studies comparing azelaic acid with other topical agents are limited. Azelaic acid is well tolerated but poses a risk of hypopigmentation in darker skinned patients.17 Benzoyl peroxide Salicylic acid Benzoyl peroxide is a non-antibiotic antimicrobial agent that has bactericidal effects by generating reactive oxygen species within the follicle.15 32 48 49 It also has weak comedolytic and anti-inflammatory properties.32 Owing to its bactericidal properties, benzoyl peroxide produces rapid improvement in inflammatory lesions and prevents the development of antibiotic resistance.15 32 39 45 48-52 Although data on the comparative efficacy and tolerability of benzoyl peroxide and topical retinoid monotherapy are conflicting, most guidelines recommend a mechanistically driven approach, with the addition of benzoyl peroxide mainly when inflammatory lesions are present.9 10 17 Some studies, including a small double blind randomized trial, show that inflammatory lesions improve more rapidly with benzoyl peroxide than with topical retinoids.53 Benzoyl peroxide is available in numerous formulations, in concentrations ranging from 2.5% to 10%,29 none of which show clear superiority in systematic reviews, although irritation increased with higher concentrations.27 32 48 52 Irritation typically resolves with continued use. In addition, patients should be warned that benzoyl peroxide may bleach clothing, bedding, and hair.13 32 Finally, because all retinoids except adapalene are unstable with benzoyl peroxide, these agents should be applied separately.18 31 32 Combination products The benefits of combined regimens include complementary mechanisms of action, reduced risk of antibiotic resistance, and improved treatment outcomes.2 9 10 13 15 17 18 30 47 48 An increasing number of antibiotic-retinoid and antibiotic-benzoyl peroxide combinations are now available. Retinoid-benzoyl peroxide combinations are limited by retinoid instability in the presence of benzoyl peroxide. The biggest drawback to combined products is cost. Individual generic components are typically less expensive and can be applied simultaneously with equivalent effects.32 46 Nevertheless, a small investigator blinded randomized controlled trial found that combined products improve patient adherence by simplifying daily regimens.54 For many clinicians and patients, this improved ease of application and corresponding increase in adherence justifies the cost of combined therapies. Other topical treatments Azelaic acid Azelaic acid is an alternative to retinoids that has comedolytic, antimicrobial, and anti-inflammatory properties.9 13 17 This agent has not been approved for acne by the US Food and Drug For personal use only: See rights and reprints http://www.bmj.com/permissions Salicylic acid is an over-the-counter agent with desquamating and comedolytic properties that is less potent than retinoids.48 Few studies of salicylic acid exist, although available studies show that it is less effective but better tolerated than other agents.17 29 48 Salicylic acid may be used when patients cannot tolerate standard agents. Systemic agents Systemic agents should be considered for patients with moderate to severe acne. These therapies are useful in patients with truncal disease in whom application of topical agents would be difficult. Hormonal therapies Hormonal therapies are a useful adjunct to treatment in women with moderate to severe acne, especially those who desire oral contraception or in whom traditional therapy has failed.27 Anecdotal evidence suggests that women with lesions confined to the lower face and jaw are most likely to benefit.15 57 Hormonal agents are available in two primary forms: combined oral contraceptives, which suppress ovarian androgen production, and androgen receptor blockers, such as cyproterone acetate, spironolactone, and flutamide. In the UK, a combined oral contraceptive containing cyproterone acetate and ethinylestradiol is licensed for the treatment of acne.13 57 58 These agents decrease androgen mediated effects on the sebaceous follicle.57 Although hyperandrogenic states such as polycystic ovarian syndrome are associated with acne, most women with acne have normal androgen levels but still benefit from antiandrogen therapy.57 Full benefit is seen after three to six months of treatment.15 A recent Cochrane review confirmed the efficacy of combined oral contraceptives in treating inflammatory and non-inflammatory acne but found few differences in efficacy between the different types, including cyproterone acetate, which is often recommended.59 60 It is therefore not clear whether formulations containing cyproterone acetate should be favored, especially because this agent may increase the risk of venous thromboembolism.27 57 59 Progesterin only contraceptives may worsen acne.9 Oral antibiotics Systemic antibiotics are indicated for moderate to severe inflammatory acne.9 Like topical antibiotics, oral antibiotics have antimicrobial and anti-inflammatory effects.13 39 50 Doxycycline, minocycline, lymecycline, tetracycline, and Subscribe: http://www.bmj.com/subscribe BMJ 2013;346:f2634 doi: 10.1136/bmj.f2634 (Published 8 May 2013) Page 4 of 7 CLINICAL REVIEW A patient’s story I first developed acne in high school. My family encouraged me to wash my face often with several over-the-counter products, which mostly exacerbated my symptoms. I was so embarrassed about my skin that I started to avoid spending time with friends. When my mother noticed this change, she agreed to take me to a dermatologist, who suggested topical antibiotics and benzoyl peroxide. These treatments caused substantial irritation, so I stopped using them promptly. I was sure that my acne was incurable, so I learned to live with it. When I reached adulthood, I began taking oral contraceptive pills, not knowing that they could affect the acne. Within a month of starting treatment, my acne improved dramatically. After six months, my lesions had nearly disappeared. I was thrilled to be disease free for the first time in nearly a decade but felt sad that this therapy had not been offered to me years earlier. I suspect this would have substantially improved my teenage confidence and self esteem. erythromycin are most commonly used. Few comparative studies exist, although a systematic review of systemic therapy with tetracyclines found no antibiotic to be more effective than another.17 41 46 Although minocycline was previously favored by clinicians, a recent Cochrane review found no clear evidence of superiority.61 62 Given the lack of comparative data, antibiotic selection may be driven by side effect profiles and patterns of P acnes resistance. Tetracyclines must be avoided in pregnant women and children given the associated risk of tooth discoloration. Women of childbearing age should be advised to use contraception when taking these agents. Doxycyline causes photosensitivity. In rare cases minocycline leads to skin hyperpigmentation and drug induced systemic lupus erythematosus. Limecycline has gained popularity in Europe but is not available in the US.63 Increasing P acnes resistance has decreased reliance on erythromycin and tetracycline.11 42 49 50 As with topical antibiotics, oral antibiotics should be combined with other agents to minimize the development of bacterial resistance and improve treatment efficacy. Always use oral antibiotics in conjunction with a topical retinoid or benzoyl peroxide16 50—several small to moderate sized randomized controlled trials have shown that this increases efficacy.64-66 Assess treatment response at six to eight weeks, at which point a decision to continue or change antibiotics may be made.50 When possible, limit antibiotic courses to 12 weeks’ duration.2 16 46 Isotretinoin Isotretinoin is remarkably efficacious in the treatment of severe acne, as well as treatment resistant moderate disease, and is now the first line treatment in such cases.10 13 Isotretinoin is thought to target all four components involved in the development of acne by normalizing follicular desquamation, decreasing sebum secretion, inhibiting the growth of P acnes, and exerting anti-inflammatory effects.13 31 49 Given these broad effects and the potential for adjunctive therapy to compound adverse effects, isotretinoin is prescribed as monotherapy. Patients typically complete a 16-24 week course of isotretinoin, taking 0.5-1 mg per kg per day to target a cumulative dose of 120-150 mg per kg.11 16 49 The dose is slowly increased as tolerated. Effects are not usually seen for the first one or two months.67 Meta-analyses show that at least half of patients are permanently cured after a single course, and only 20% of patients require repeat treatment.15 17 31 49 68 69 Relapse is most common in younger patients, in women with hormonally driven acne, and when goal cumulative dosing is not achieved.31 57 70 71 Use of oral isotretinoin is tightly regulated because of its well known teratogenic effects and is available through specialist care only in many countries.42 Female patients must demonstrate a negative pregnancy test and use contraception.49 Although charged with having detrimental psychological effects, there is no clear evidence that isotretinoin leads to depression or suicidality.72-74 Other adverse reactions include chapped skin, dry eyes, epistaxis, myalgias, and alterations in serum lipid and For personal use only: See rights and reprints http://www.bmj.com/permissions transaminase concentrations, most of which resolve after treatment is stopped.11 13 31 49 What are the consequences of acne? Although many people dismiss acne vulgaris as an inconsequential disease of adolescence, it has clear long lasting psychosocial and physical effects. Many studies have shown an association between acne and depression and anxiety, independent of disease severity.7 75 Psychological effects improve with treatment.76 Furthermore, acne may cause permanent scarring that is difficult to correct. Finally, because of its frequency and chronicity, the economic burden of acne is substantial, with associated expenditure in the US alone exceeding $2.5bn (£1.64bn; €1.93bn) annually.20 To reduce these effects, patients with acne should receive early, aggressive, mechanistically driven therapy. Contributors: Both authors had full access to the content of this review and are guarantors. ALD searched the literature, compiled the references, and drafted the manuscript. RPD critically revised the manuscript for intellectual content. Competing interests: We have read and understood the BMJ Group policy on declaration of interests and declare the following interests: None. Provenance and peer review: Commissioned; externally peer reviewed. Patient consent obtained. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Yentzer BA, Hick J, Reese EL, Uhas A, Feldman SR, Balkrishnan R. Acne vulgaris in the United States: a descriptive epidemiology. Cutis 2010;86:94-9. Thiboutot D, Gollnick H, Bettoli V, Dreno B, Kang S, Leyden JJ, et al. New insights into the management of acne: an update from the global alliance to improve outcomes in acne group. J Am Acad Dermatol 2009;60(5 suppl):S1-50. Purdy S, de Berker D. Acne. BMJ 2006;333:949-53. Goulden V, Stables GI, Cunliffe WJ. Prevalence of facial acne in adults. J Am Acad Dermatol 1999;41:577-80. Friedlander SF, Baldwin HE, Mancini AJ, Yan AC, Eichenfield LF. The acne continuum: an age-based approach to therapy. Semin Cutan Med Surg 2011;30(3 suppl):S6-11. Gollnick HP, Finlay AY, Shear N. Can we define acne as a chronic disease? If so, how and when? Am J Clin Dermatol 2008;9:279-84. Barnes LE, Levender MM, Fleischer AB Jr, Feldman SR. Quality of life measures for acne patients. Dermatol Clin 2012;30:293-300, ix. Newton JN. How cost-effective is oral isotretinoin? Dermatology 1997;195(suppl 1):10-4; discussion 38-40. Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol 2003;49(1 suppl):S1-37. Nast A, Dreno B, Bettoli V, Degitz K, Erdmann R, Finlay AY, et al. European evidence-based (S3) guidelines for the treatment of acne. J Eur Acad Dermatol Venereol 2012;26(suppl 1):1-29. Strauss JS, Krowchuk DP, Leyden JJ, Lucky AW, Shalita AR, Siegfried EC, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol 2007;56:651-63. Brown SK, Shalita AR. Acne vulgaris. Lancet 1998;351:1871-6. Haider A, Shaw JC. Treatment of acne vulgaris. JAMA 2004;292:726-35. Archer CB, Cohen SN, Baron SE. Guidance on the diagnosis and clinical management of acne. Clin Exp Dermatol 2012;37(suppl 1):1-6. James WD. Clinical practice. Acne. N Engl J Med 2005;352:1463-72. Abad-Casintahan F, Chow SK, Goh CL, Kubba R, Miyachi Y, Noppakun N, et al. Toward evidence-based practice in acne: consensus of an Asian Working Group. J Dermatol 2011;38:1041-8. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet 2012;379:361-72. Thielitz A, Gollnick H. Topical retinoids in acne vulgaris: update on efficacy and safety. Am J Clin Dermatol 2008;9:369-81. Chen W, Thiboutot D, Zouboulis CC. Cutaneous androgen metabolism: basic research and clinical perspectives. J Invest Dermatol 2002;119:992-1007. Knutsen-Larson S, Dawson AL, Dunnick CA, Dellavalle RP. Acne vulgaris: pathogenesis, treatment, and needs assessment. Dermatol Clin 2012;30:99-106, viii-ix. Subscribe: http://www.bmj.com/subscribe BMJ 2013;346:f2634 doi: 10.1136/bmj.f2634 (Published 8 May 2013) Page 5 of 7 CLINICAL REVIEW Areas for future research Large randomized controlled trials on the treatment of acne are needed Comparative effectiveness research should be prioritized, as cited by the Institute of Medicine77 Study of the cutaneous microbiome, including disease associations with Propionibacterium acnes strains, may improve our understanding of the pathogenesis of acne and open up new therapeutic approaches78 Additional educational resources Resources for healthcare professionals American Academy of Dermatology: Strauss JS, Krowchuk DP, Leyden JJ, Lucky AW, Shalita AR, Siegfried EC, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol 2007;56:651-63 European Dermatology Forum: Nast A, Dreno B, Bettoli V, Degitz K, Erdmann R, Finlay AY, et al. European evidence-based (S3) guidelines for the treatment of acne. J Eur Acad Dermatol Venereol 2012;26(suppl 1):1-29 Global Alliance to Improve Oucomes in Acne: Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol 2003;49(1 suppl):S1-37 National Institute of Health and Care Excellence (www.cks.nhs.uk/acne_vulgaris)—Clinical knowledge summary on acne vulgaris Resources for patients American Academy of Dermatology (www.aad.org/skin-conditions/dermatology-a-to-z/acne)—Basic patient information regarding acne treatment with particular emphasis on adult acne British Association of Dermatologists (www.bad.org.uk/site/793/default.aspx)—General overview of acne treatment National Institute of Health and Care Excellence (www.cks.nhs.uk/acne_vulgaris)—Clinical knowledge summary on acne vulgaris UpToDate Patient Information (www.uptodate.com/contents/acne-beyond-the-basics)—Patient oriented guide to the pathophysiology and treatment of acne 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 Magin P, Pond D, Smith W, Watson A. A systematic review of the evidence for “myths and misconceptions” in acne management: diet, face-washing and sunlight. Fam Pract 2005;22:62-70. Goodman G. Cleansing and moisturizing in acne patients. Am J Clin Dermatol 2009;10(suppl 1):1-6. Smith RN, Mann NJ, Braue A, Makelainen H, Varigos GA. The effect of a high-protein, low glycemic-load diet versus a conventional, high glycemic-load diet on biochemical parameters associated with acne vulgaris: a randomized, investigator-masked, controlled trial. J Am Acad Dermatol 2007;57:247-56. Spencer EH, Ferdowsian HR, Barnard ND. Diet and acne: a review of the evidence. Int J Dermatol 2009;48:339-47. Bowe WP, Joshi SS, Shalita AR. Diet and acne. J Am Acad Dermatol 2010;63:124-41. Ingram JR, Grindlay DJ, Williams HC. Management of acne vulgaris: an evidence-based update. Clin Exp Dermatol 2010;35:351-4. Smith EV, Grindlay DJ, Williams HC. What’s new in acne? An analysis of systematic reviews published in 2009-2010. Clin Exp Dermatol 2011;36:119-22; quiz 23. Schafer T, Nienhaus A, Vieluf D, Berger J, Ring J. Epidemiology of acne in the general population: the risk of smoking. Br J Dermatol 2001;145:100-4. Ramanathan S, Hebert AA. Management of acne vulgaris. J Pediatr Health Care 2011;25:332-7. Tan HH. Topical antibacterial treatments for acne vulgaris : comparative review and guide to selection. Am J Clin Dermatol 2004;5:79-84. Chivot M. Retinoid therapy for acne. A comparative review. Am J Clin Dermatol 2005;6:13-9. Gamble R, Dunn J, Dawson A, Petersen B, McLaughlin L, Small A, et al. Topical antimicrobial treatment of acne vulgaris: an evidence-based review. Am J Clin Dermatol 2012;13:141-52. Cunliffe WJ, Poncet M, Loesche C, Verschoore M. A comparison of the efficacy and tolerability of adapalene 0.1% gel versus 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. Cunliffe WJ, Danby FW, Dunlap F, Gold MH, Gratton D, Greenspan A. Randomised, controlled trial of the efficacy and safety of adapalene gel 0.1% and tretinoin cream 0.05% in patients with acne vulgaris. Eur J Dermatol 2002;12:350-4. Galvin SA, Gilbert R, Baker M, Guibal F, Tuley MR. Comparative tolerance of adapalene 0.1% gel and six different tretinoin formulations. Br J Dermatol 1998;139(suppl 52):34-40. Leyden JJ, Tanghetti EA, Miller B, Ung M, Berson D, Lee J. Once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.1% microsponge gel for the treatment of facial acne vulgaris: a double-blind randomized trial. Cutis 2002;69(2 suppl):12-9. Webster GF, Guenther L, Poulin YP, Solomon BA, Loven K, Lee J. A multicenter, double-blind, randomized comparison study of the efficacy and tolerability of once-daily tazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acne vulgaris. Cutis 2002;69(2 suppl):4-11. Tanghetti E, Dhawan S, Green L, Del Rosso J, Draelos Z, Leyden J, et al. Randomized comparison of the safety and efficacy of tazarotene 0.1% cream and adapalene 0.3% gel in the treatment of patients with at least moderate facial acne vulgaris. J Drugs Dermatol 2010;9:549-58. Leyden JJ, Del Rosso JQ, Webster GF. Clinical considerations in the treatment of acne vulgaris and other inflammatory skin disorders: a status report. Dermatol Clin 2009;27:1-15. Simonart T, Dramaix M. Treatment of acne with topical antibiotics: lessons from clinical studies. Br J Dermatol 2005;153:395-403. Simonart T, Dramaix M, De Maertelaer V. Efficacy of tetracyclines in the treatment of acne vulgaris: a review. Br J Dermatol 2008;158:208-16. Harper JC. An update on the pathogenesis and management of acne vulgaris. J Am Acad Dermatol 2004;51(1 suppl):S36-8. Lookingbill DP, Chalker DK, Lindholm JS, Katz HI, Kempers SE, Huerter CJ, et al. Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with For personal use only: See rights and reprints http://www.bmj.com/permissions 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 clindamycin gel, benzoyl peroxide gel and vehicle gel: combined results of two double-blind investigations. J Am Acad Dermatol 1997;37:590-5. Leyden JJ, Krochmal L, Yaroshinsky A. Two randomized, double-blind, controlled trials of 2219 subjects to compare the combination clindamycin/tretinoin hydrogel with each agent alone and vehicle for the treatment of acne vulgaris. J Am Acad Dermatol 2006;54:73-81. Elston DM. Topical antibiotics in dermatology: emerging patterns of resistance. Dermatol Clin 2009;27:25-31. Ozolins M, Eady EA, Avery AJ, Cunliffe WJ, Po AL, O’Neill C, et al. Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: randomised controlled trial. Lancet 2004;364:2188-95. Simpson RC, Grindlay DJ, Williams HC. What’s new in acne? An analysis of systematic reviews and clinically significant trials published in 2010-11. Clin Exp Dermatol 2011;36:840-3; quiz 43-4. Bowe WP, Shalita AR. Effective over-the-counter acne treatments. Semin Cutan Med Surg 2008;27:170-6. Newman MD, Bowe WP, Heughebaert C, Shalita AR. Therapeutic considerations for severe nodular acne. Am J Clin Dermatol 2011;12:7-14. Del Rosso JQ, Kim G. Optimizing use of oral antibiotics in acne vulgaris. Dermatol Clin 2009;27:33-42. Cunliffe WJ, Holland KT, Bojar R, Levy SF. A randomized, double-blind comparison of a clindamycin phosphate/benzoyl peroxide gel formulation and a matching clindamycin gel with respect to microbiologic activity and clinical efficacy in the topical treatment of acne vulgaris. Clin Thera 2002;24:1117-33. Fakhouri T, Yentzer BA, Feldman SR. Advancement in benzoyl peroxide-based acne treatment: methods to increase both efficacy and tolerability. J Drugs in Dermatol 2009;8:657-61. Hughes BR, Norris JF, Cunliffe WJ. A double-blind evaluation of topical isotretinoin 0.05%, benzoyl peroxide gel 5% and placebo in patients with acne. Clin Exp Dermatol 1992;17:165-8. Yentzer BA, Ade RA, Fountain JM, Clark AR, Taylor SL, Fleischer AB Jr, et al. Simplifying regimens promotes greater adherence and outcomes with topical acne medications: a randomized controlled trial. Cutis 2010;86:103-8. Thiboutot D. Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris. J Drugs Dermatol 2008;7:13-6. Iraji F, Sadeghinia A, Shahmoradi Z, Siadat AH, Jooya A. Efficacy of topical azelaic acid gel in the treatment of mild-moderate acne vulgaris. Indian J Dermatol Venereol Leprol 2007;73:94-6. George R, Clarke S, Thiboutot D. Hormonal therapy for acne. Semin Cutan Med Surg 2008;27:188-96. Van Vloten WA, Sigurdsson V. Selecting an oral contraceptive agent for the treatment of acne in women. Am J Clin Dermatol 2004;5:435-41. 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Cite this as: BMJ 2013;346:f2634 © BMJ Publishing Group Ltd 2013 Subscribe: http://www.bmj.com/subscribe BMJ 2013;346:f2634 doi: 10.1136/bmj.f2634 (Published 8 May 2013) Page 7 of 7 CLINICAL REVIEW Table Table 1| General treatment algorithm according to acne severity Topical retinoid Benzoyl peroxide Topical antibiotic Oral antibiotic Hormonal agent* Maintenance Recommended treatment Possible treatment No No Possible treatment No No Mild Recommended treatment Possible treatment No No No Alternative treatment No Mild-moderate Recommended treatment Possible treatment Recommended treatment No No Alternative treatment No Moderate Recommended treatment Recommended treatment Possible treatment Alternative treatment Monotherapy† Moderate-severe Recommended treatment Recommended treatment No Recommended Possible treatment treatment Alternative treatment Monotherapy† No No No No Monotherapy† Severity Severe Recommended treatment‡ No No Azelaic acid Oral retinoid† *Female patients only. †Oral retinoids are prescribed as monotherapy. ‡Select oral or topical antibiotic only. 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