Professional Documents
Culture Documents
Page 1 of 7
Clinical Review
CLINICAL REVIEW
Acne vulgaris
1
234
Department of Internal Medicine, Brigham and Womens 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
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 groupsincluding
the Global Alliance to Improve Outcomes in Acne, the European
Dermatology Forum, and the American Academy of
Dermatologyhave published comprehensive treatment
recommendations detailing comparable therapeutic strategies.9-11
Here we provide a streamlined outline of treatment intended for
the non-specialist.
Correspondence to: R P Dellavalle, Dermatology Service, Department of Veteran Affairs Medical Center, Denver, CO, USA
robert.dellavalle@ucdenver.edu
For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
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
Topical agents
Retinoids
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
Page 3 of 7
CLINICAL REVIEW
Benzoyl peroxide
Salicylic acid
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.
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
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
Page 4 of 7
CLINICAL REVIEW
A patients 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.
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.
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
Page 5 of 7
CLINICAL REVIEW
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. Whats 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
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, ONeill 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. Whats 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.
Arowojolu AO, Gallo MF, Lopez LM, Grimes DA, Garner SE. Combined oral contraceptive
pills for treatment of acne. Cochrane Database System Rev 2007;1:CD004425.
Arowojolu AO, Gallo MF, Lopez LM, Grimes DA. Combined oral contraceptive pills for
treatment of acne. Cochrane Database System Rev 2012;7:CD004425.
Garner SE, Eady EA, Popescu C, Newton J, Li WA. Minocycline for acne vulgaris: efficacy
and safety. Cochrane Database System Rev 2003;1:CD002086.
Garner SE, Eady A, Bennett C, Newton JN, Thomas K, Popescu CM. Minocycline for
acne vulgaris: efficacy and safety. Cochrane Database System Rev 2012;8:CD002086.
Bossuyt L, Bosschaert J, Richert B, Cromphaut P, Mitchell T, Al Abadie M, et al.
Lymecycline in the treatment of acne: an efficacious, safe and cost-effective alternative
to minocycline. Eur J Dermatol 2003;13:130-5.
Thiboutot DM, Shalita AR, Yamauchi PS, Dawson C, Arsonnaud S, Kang S. Combination
therapy with adapalene gel 0.1% and doxycycline for severe acne vulgaris: a multicenter,
investigator-blind, randomized, controlled study. Skinmed 2005;4:138-46.
Subscribe: http://www.bmj.com/subscribe
Page 6 of 7
CLINICAL REVIEW
65
66
67
68
69
70
71
72
Gold LS, Cruz A, Eichenfield L, Tan J, Jorizzo J, Kerrouche N, et al. Effective and safe
combination therapy for severe acne vulgaris: a randomized, vehicle-controlled,
double-blind study of adapalene 0.1%-benzoyl peroxide 2.5% fixed-dose combination gel
with doxycycline hyclate 100 mg. Cutis 2010;85:94-104.
Cunliffe WJ, Meynadier J, Alirezai M, George SA, Coutts I, Roseeuw DI, et al. Is combined
oral and topical therapy better than oral therapy alone in patients with moderate to
moderately severe acne vulgaris? A comparison of the efficacy and safety of lymecycline
plus adapalene gel 0.1%, versus lymecycline plus gel vehicle. J Am Acad Dermatol
2003;49(3 suppl):S218-26.
DiGiovanna JJ. Systemic retinoid therapy. Dermatol Clin 2001;19:161-7.
White GM. Acne therapy. Adv Dermatol 1999;14:29-58; discussion 59.
Wessels F, Anderson AN, Kropman K. The cost-effectiveness of isotretinoin in the
treatment of acne. Part 1. A meta-analysis of effectiveness literature. South Afr Med J
1999;89(7 Pt 2):780-4.
White GM, Chen W, Yao J, Wolde-Tsadik G. Recurrence rates after the first course of
isotretinoin. Arch Dermatol 1998;134:376-8.
Stainforth JM, Layton AM, Taylor JP, Cunliffe WJ. Isotretinoin for the treatment of acne
vulgaris: which factors may predict the need for more than one course? Br J Dermatol
1993;129:297-301.
Goldsmith LA, Bolognia JL, Callen JP, Chen SC, Feldman SR, Lim HW, et al. American
Academy of Dermatology Consensus Conference on the safe and optimal use of
isotretinoin: summary and recommendations. J Am Acad Dermatol 2004;50:900-6.
73
74
75
76
77
78
Jacobs DG, Deutsch NL, Brewer M. Suicide, depression, and isotretinoin: is there a causal
link? J Am Acad Dermatol 2001;45:S168-75.
Marqueling AL, Zane LT. Depression and suicidal behavior in acne patients treated with
isotretinoin: a systematic review. Semin Cutan Med Surg 2007;26:210-20.
Dunn LK, ONeill JL, Feldman SR. Acne in adolescents: quality of life, self-esteem, mood,
and psychological disorders. Dermatol Online J 2011;17:1.
Hahm BJ, Min SU, Yoon MY, Shin YW, Kim JS, Jung JY, et al. Changes of psychiatric
parameters and their relationships by oral isotretinoin in acne patients. J Dermatol
2009;36:255-61.
Committee on Comparative Effectiveness Research Prioritization, Institute of Medicine.
Initial national priorities for comparative effectiveness research. National Academies
Press, 2009. www.nap.edu/catalog.php?record_id=12648.
Fitz-Gibbon S, Tomida S, Chiu BH, Nguyen L, Du C, Liu M, et al. Propionibacterium acnes
strain populations in the human skin microbiome associated with acne. J Invest Dermatol
2013; published online 21 Jan.
Subscribe: http://www.bmj.com/subscribe
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
Alternative
treatment
Monotherapy
No
No
No
No
Monotherapy
Severity
Severe
Recommended treatment
No
No
Azelaic acid
Oral retinoid
Subscribe: http://www.bmj.com/subscribe