referat besar (8)

8/20/2019 Referat Besar (8)

http://slidepdf.com/reader/full/referat-besar-8 1/7

Acne vulgaris

Annelise L Dawson medical resident 1, Robert P Dellavalle chief

2 3 4

1Department 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

Acne vulgaris is a common inflammatory skin condition.Although often perceived as a self limited disease of

adolescence, its prevalence remains high into adulthood. Nearly90% of teenagers have acne, and half of them continue toexperience symptoms as adults.1-3 By age 40 years, 1% of men

and 5% of women still have lesions.4 Recent analyses show anincreasing 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 psychosocialeffects and may lead to permanent scarring.7 It is therefore not

surprising that patients are motivated to seek medical care. Inthe United Kingdom, acne accounts for more than 3.5 millionannual visits to general practitioners,3 8 who must therefore be

equipped to treat acne. Several prominent groups—includingthe Global Alliance to Improve Outcomesin Acne, the EuropeanDermatology Forum, and the American Academy of

Dermatology—have published comprehensive treatmentrecommendations 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 andwhiteheads, 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 pilosebaceousunits.12 Comedone formation is intrinsic to the diagnosis of acnevulgaris—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 tospecialist care is warranted.

Several groups have proposed standardized measures forclassifying acne, although none has been universally

accepted.10 13 15 Classification is important because it helps toinform treatment strategies.3 11 Acne is categorized broadly intomild, 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 fewinflammatory lesions. Moderate acne is characterized by an

increased number of inflammatory papules and pustules on theface and often mild truncal disease. Finally, acne is consideredto be severe when nodules and cysts are present. In these cases,

facial lesions are often accompanied by widespread truncaldisease.

What causes acne?

Acne is an inflammatory disease of the pilosebaceous duct thatresults 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 epithelialdesquamation and follicular obstruction, which lead to theprimary precursor lesion in acne—the microcomedone.Microcomedones are pathological structures not visible to the

naked eye that evolve into visible lesions.18 An increase incirculating androgens also promotes sebum production, causingthese obstructed follicles to fill with lipid rich material and form

visible open and closed comedones.12 19 Sebum serves as asubstrate 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 inflammationmanifests 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, [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) of 7

Clinical Review

CLINICAL REVIEW

http://www.bmj.com/permissions

http://www.bmj.com/subscribe





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”, “benzoylperoxide”, “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 theterm “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 thattarget 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 foran 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 moisturizerthat does not contribute to comedone formation

(noncomedogenic) is an accepted standard.9 Althoughmisconceptions about dietary triggers have been largelydispelled, recent reports—including a systematic review of

dietary influences on acne and a randomized investigator maskedcontrolled trial of glycemic load and acne severity—suggestthat acne is associated with high dairy diets and those with a

high glycemic load.23-27 Finally, a cross sectional analysis founda significant dose dependent association between smoking andacne severity.20 28

How is acne treated?

Careful assessment of the morphology and severity of acne is

an important first step in management, because lesionmorphology largely dictates the optimal treatment approach.Treatment should be designed to target precursor lesions

(microcomedones) and active inflammatory lesions. Mildercases are best managed with topical regimens, whereas systemicdrugs 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 diseaseseverity.

Topical agents

Retinoids

Retinoids are vitamin A derivatives that normalize keratinocyte

desquamation and adhesion, leading to comedolysis andpreventing formation of new microcomedones. Some retinoidsalso display anti-inflammatory properties.11 15 29-32 Perhaps the

most notable recent development in the treatment of acne is theincreased use of topical retinoids.29 Many randomized trialsshow the efficacy of these drugs relative to vehicle, and they

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 Mildnon-inflammatory comedonal acne may be treated with retinoid

monotherapy. When inflammatory lesions are present, retinoidsshould be combined with antimicrobial therapy or benzoylperoxide.9 16 Because retinoids prevent the development of

microcomedones, they can also be used for maintenancetherapy.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 UnitedKingdom).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 selectinglower concentration or cream based formulations.18 29 31 A

meta-analysis of five randomized controlled trials suggests thatadapalene is the best tolerated retinoid, whereas severalmoderately 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 aninitial “flare” in acne lesions, which subsides with continued

use.2 18 31 Lastly, pregnant and breastfeeding women shouldavoid topical retinoids.18 Women of child bearing age shouldbe counselled about the need for contraception.17

Topical antibiotics

The primary topical antibiotics used for acne are clindamycinand erythromycin.30 These agents have bacteriostatic andanti-inflammatory properties.11 30 32 Topical antibiotics are usedfor mild to moderate acne when inflammatory lesions are

present.16

Antibiotic resistance is a growing concern and has promptedefforts to limit the duration of antibiotic courses and toemphasize combined regimens.2 Patterns of P acnes resistance

correspond to trends in antibiotic use.2 39 Treatment outcomesworsen when resistance is present—systematic reviews showdecreasing antibiotic efficacy over time, particularly for

erythromycin and clindamycin.2 32 40 41 P acnes resistance is notthe only concern—Staphylococcus and Streptococcus resistance

may also develop.

39 42

In practice, this means avoiding antibioticmonotherapy and maintenance therapy.19 20 Instead, topicalantibiotics should always be used with retinoids, and possibly

benzoyl peroxide. Several double blind randomized controlledtrials have found that the addition of retinoid or benzoyl peroxidetherapy to topical antibiotics improves treatment

outcomes.9 10 17 39 43 44 Retinoids do not decrease resistance but



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 andproviding synergistic comedolytic and anti-inflammatoryeffects.18 45 Benzoyl peroxide has bactericidal properties, thereby

minimizing bacterial resistance.39 45 Topical antibiotic coursesshould be limited to 12 weeks’ duration when possible.9 16 46

Finally, combined topical and oral antibiotics should be

avoided.15 47

Benzoyl peroxide

Benzoyl peroxide is a non-antibiotic antimicrobial agent thathas bactericidal effects by generating reactive oxygen specieswithin the follicle.15 32 48 49 It also has weak comedolytic and

anti-inflammatory properties.32 Owing to its bactericidalproperties, benzoyl peroxide produces rapid improvement ininflammatory lesions and prevents the development of antibiotic

resistance.15 32 39 45 48-52 Although data on the comparative efficacyand tolerability of benzoyl peroxide and topical retinoidmonotherapy are conflicting, most guidelines recommend a

mechanistically driven approach, with the addition of benzoylperoxide 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 withbenzoyl peroxide than with topical retinoids.53

Benzoyl peroxide is available in numerous formulations, inconcentrations ranging from 2.5% to 10%,29 none of which show

clear superiority in systematic reviews, although irritationincreased with higher concentrations.27 32 48 52 Irritation typicallyresolves 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 areunstable with benzoyl peroxide, these agents should be applied

separately.18 31 32

Combination products

The benefits of combined regimens include complementarymechanisms of action, reduced risk of antibiotic resistance, and

improved treatment outcomes.2 9 10 13 15 17 18 30 47 48 An increasingnumber of antibiotic-retinoid and antibiotic-benzoyl peroxidecombinations are now available. Retinoid-benzoyl peroxidecombinations are limited by retinoid instability in the presence

of benzoyl peroxide.

The biggest drawback to combined products is cost. Individualgeneric components are typically less expensive and can beapplied simultaneously with equivalent effects.32 46 Nevertheless,

a small investigator blinded randomized controlled trial foundthat combined products improve patient adherence bysimplifying daily regimens.54 For many clinicians and patients,

this improved ease of application and corresponding increasein 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 agenthas not been approved for acne by the US Food and Drug

Administration, although it has beenapprovedin manyEuropeancountries, so receives greater emphasis in the Europeanliterature.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 arelimited. Azelaic acid is well tolerated but poses a risk of

hypopigmentation in darker skinned patients.17

Salicylic acid

Salicylic acid is an over-the-counter agent with desquamatingand 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 otheragents.17 29 48 Salicylic acid may be used when patients cannottolerate standard agents.

Systemic agents

Systemic agents should be considered for patients with moderate

to severe acne. These therapies are usefulin patientswith truncaldisease in whom application of topical agents would be difficult.

Hormonal therapies

Hormonal therapies are a useful adjunct to treatment in womenwith 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 confinedto the lower face and jaw are most likely to benefit.15 57

Hormonal agents are available in two primary forms: combinedoral contraceptives, which suppress ovarian androgenproduction, and androgen receptor blockers, such as cyproterone

acetate, spironolactone, and flutamide. In the UK, a combinedoral contraceptive containing cyproterone acetate andethinylestradiol is licensed for the treatment of acne.13 57 58 These

agents decrease androgen mediated effects on the sebaceousfollicle.57 Although hyperandrogenic states such as polycystic

ovarian syndrome are associated with acne, most women withacne have normal androgen levels but still benefit fromantiandrogen therapy.57 Full benefit is seen after three to sixmonths of treatment.15

A recent Cochrane review confirmed the efficacy of combinedoral contraceptives in treating inflammatory andnon-inflammatory acne but found few differences in efficacy

betweenthe different types, including cyproterone acetate, whichis often recommended.59 60 It is therefore not clear whetherformulations containing cyproterone acetate should be favored,

especially because this agent may increase the risk of venousthromboembolism.27 57 59 Progesterin only contraceptives mayworsen acne.9

Oral antibiotics

Systemic antibiotics are indicated for moderate to severeinflammatory acne.9 Like topical antibiotics, oral antibiotics

have antimicrobial and anti-inflammatory effects.13 39 50

Doxycycline, minocycline, lymecycline, tetracycline, and



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 mostlyexacerbated my symptoms. I was so embarrassed about my skin that I started to avoid spending time with friends. When my mother noticedthis change, she agreed to take me to a dermatologist, who suggested topical antibiotics and benzoyl peroxide. These treatments causedsubstantial 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 startingtreatment, my acne improved dramatically. After six months, my lesions had nearly disappeared. I was thrilled to be disease free for the firsttime in nearlya decadebut felt sad that this therapy had notbeenoffered to meyears earlier.I suspect this would have substantially improvedmy teenage confidence and self esteem.

erythromycin are most commonly used. Few comparative studies

exist, although a systematic review of systemic therapy withtetracyclines found no antibiotic to be more effective thananother.17 41 46 Although minocycline was previously favored by

clinicians, a recent Cochrane review found no clear evidenceof superiority.61 62 Given the lack of comparative data, antibioticselection may be driven by side effect profiles and patterns of

P acnes resistance. Tetracyclines must be avoided in pregnantwomen and children given the associated risk of tooth

discoloration. Women of childbearing age should be advised touse contraception when taking these agents. Doxycyline causesphotosensitivity. In rare cases minocycline leads to skinhyperpigmentation and drug induced systemic lupus

erythematosus. Limecycline has gained popularity in Europebut is not available in the US.63 Increasing P acnes resistancehas decreased reliance on erythromycin and tetracycline.11 42 49 50

As with topical antibiotics, oral antibiotics should be combinedwith other agents to minimize the development of bacterialresistance and improve treatment efficacy. Always use oral

antibiotics in conjunction with a topical retinoid or benzoylperoxide16 50—several small to moderate sized randomizedcontrolled trials have shown that this increases efficacy.64-66

Assess treatment response at six to eight weeks, at which pointa 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 nowthe 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 sebumsecretion, inhibiting the growth of P acnes, and exerting

anti-inflammatory effects.13 31 49 Given these broad effects andthe 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 astolerated. Effects are not usually seen for the first one or two

months.67 Meta-analyses show that at least half of patients arepermanently 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 drivenacne, and when goal cumulative dosing is not achieved.31 57 70 71

Use of oral isotretinoin is tightly regulated because of its wellknown teratogenic effects and is available through specialist

care only in many countries.

42

Female patients must demonstratea negative pregnancy test and use contraception.49 Althoughcharged with having detrimental psychological effects, there is

no clear evidence that isotretinoin leads to depression orsuicidality.72-74 Other adverse reactions include chapped skin,dry eyes, epistaxis, myalgias, and alterations in serum lipid and

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 aninconsequential disease of adolescence, it has clear long lasting

psychosocial and physical effects. Many studies have shown anassociation between acne and depression and anxiety,

independent of disease severity.

7 75

Psychological effectsimprove with treatment.76 Furthermore, acne may causepermanent scarring that is difficult to correct. Finally, becauseof its frequency and chronicity, the economic burden of acne is

substantial, with associated expenditure in the US aloneexceeding $2.5bn (£1.64bn; €1.93bn) annually.20 To reducethese 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 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.

2 Thiboutot D, Gollnick H, Bettoli V, Dreno B, Kang S, Leyden JJ, et al. New insights into

themanagementof acne:an updatefromtheglobal allianceto improve outcomesin acne

group. J Am Acad Dermatol 2009;60(5 suppl):S1-50.

3 Purdy S, de Berker D. Acne. BMJ 2006;333:949-53.

4 Goulden V, Stables GI, Cunliffe WJ. Prevalence of facial acne in adults. J Am Acad

Dermatol 1999;41:577-80.

5 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.

6 Gollnick HP, Finlay AY, Shear N. Can we define acne as a chronic disease? If so, how

and when? Am J Clin Dermatol 2008;9:279-84.7 BarnesLE, LevenderMM, FleischerAB Jr,FeldmanSR. Qualityof life measuresfor acne

patients. Dermatol Clin 2012;30:293-300, ix.

8 NewtonJN. Howcost-effectiveis oral isotretinoin? Dermatology 1997;195(suppl 1):10-4;

discussion 38-40.

9 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.

10 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.

11 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.

12 Brown SK, Shalita AR. Acne vulgaris. Lancet 1998;351:1871-6.

13 Haider A, Shaw JC. Treatment of acne vulgaris. JAMA 2004;292:726-35.

14 Archer CB, Cohen SN, Baron SE. Guidance on the diagnosis and clinical management

of acne. Clin Exp Dermatol 2012;37(suppl 1):1-6.

15 James WD. Clinical practice. Acne. N Engl J Med 2005;352:1463-72.

16 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.

17 Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet 2012;379:361-72.

18 Thielitz A, Gollnick H. Topical retinoids in acne vulgaris: update on efficacy and safety.

Am J Clin Dermatol 2008;9:369-81.

19 Chen W, Thiboutot D, Zouboulis CC. Cutaneous androgen metabolism: basic research

and clinical perspectives. J Invest Dermatol 2002;119:992-1007.

20 Knutsen-Larson S, Dawson AL, Dunnick CA, DellavalleRP. Acnevulgaris: pathogenesis,

treatment, and needs assessment. Dermatol Clin 2012;30:99-106, viii-ix.



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 Medicine 77

Study of thecutaneousmicrobiome, including diseaseassociations with Propionibacterium acnes strains,may improveour 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 ofcare 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 ofacne: 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 acnetreatment 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 pathophysiologyand treatment of acne

21 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.

22 Goodman G. Cleansing and moisturizing in acne patients. Am J Clin Dermatol

2009;10(suppl 1):1-6.

23 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

parametersassociated withacne vulgaris: a randomized,investigator-masked, controlled

trial. J Am Acad Dermatol 2007;57:247-56.

24 Spencer EH, Ferdowsian HR, Barnard ND. Diet and acne: a review of the evidence. Int J Dermatol 2009;48:339-47.

25 Bowe WP, Joshi SS, Shalita AR. Diet and acne. J Am Acad Dermatol 2010;63:124-41.

26 Ingram JR, Grindlay DJ, Williams HC. Management of acne vulgaris: an evidence-based

update. Clin Exp Dermatol 2010;35:351-4.

27 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.

28 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.

29 Ramanathan S, Hebert AA. Management of acne vulgaris. J Pediatr Health Care

2011;25:332-7.

30 TanHH.Topical antibacterial treatments foracnevulgaris: comparativereview andguide

to selection. Am J Clin Dermatol 2004;5:79-84.

31 Chivot M. Retinoid therapy for acne. A comparative review. Am J Clin Dermatol

2005;6:13-9.

32 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.

33 Cunliffe WJ, Poncet M, Loesche C, Verschoore M. A comparison of the efficacy and

tolerabilityof adapalene 0.1%gel versus tretinoin0.025% gelin patientswith acnevulgaris:

a meta-analysis of five randomized trials. Br J Dermatol 1998;139(suppl 52):48-56.

34 Cunliffe WJ, Danby FW, Dunlap F, Gold MH, Gratton D, Greenspan A. Randomised,

controlled trial ofthe efficacy andsafetyof adapalenegel0.1%and tretinoincream 0.05%

in patients with acne vulgaris. Eur J Dermatol 2002;12:350-4.

35 Galvin SA, Gilbert R, Baker M, Guibal F, Tuley MR. Comparative tolerance of adapalene

0.1%gel andsix differenttretinoinformulations. BrJ Dermatol 1998;139(suppl 52):34-40.

36 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.

37 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.

38 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.

39 Leyden JJ, Del Rosso JQ, Webster GF. Clinical considerations in the treatment of acne

vulgarisand other inflammatoryskin disorders: a status report. Dermatol Clin 2009;27:1-15.

40 Simonart T, Dramaix M. Treatment of acne with topical antibiotics: lessons from clinicalstudies. Br J Dermatol 2005;153:395-403.

41 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.

42 HarperJC.An updateon thepathogenesisand management ofacnevulgaris. J AmAcad

Dermatol 2004;51(1 suppl):S36-8.

43 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

clindamycin gel,benzoyl peroxidegel andvehiclegel: combinedresults of twodouble-blind

investigations. J Am Acad Dermatol 1997;37:590-5.

44 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.

45 Elston DM. Topical antibiotics in dermatology: emerging patterns of resistance. Dermatol

Clin 2009;27:25-31.

46 Ozolins M, Eady EA, Avery AJ, Cunliffe WJ, Po AL, O’Neill C, et al. Comparison of five

antimicrobial regimens for treatmentof mildto moderateinflammatory facial acnevulgarisin the community: randomised controlled trial. Lancet 2004;364:2188-95.

47 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.

48 Bowe WP, Shalita AR. Effective over-the-counter acne treatments. Semin Cutan Med

Surg 2008;27:170-6.

49 Newman MD, Bowe WP, Heughebaert C, Shalita AR. Therapeutic considerations for

severe nodular acne. Am J Clin Dermatol 2011;12:7-14.

50 Del Rosso JQ, Kim G. Optimizing use of oral antibiotics in acne vulgaris. Dermatol Clin

2009;27:33-42.

51 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.

52 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.

53 Hughes BR,Norris JF, CunliffeWJ. A double-blind evaluationof topical isotretinoin 0.05%,

benzoyl peroxide gel 5% and placebo in patients with acne. Clin Exp Dermatol

1992;17:165-8.

54 Yentzer BA,Ade RA,Fountain JM,ClarkAR,TaylorSL, FleischerAB Jr,et al.Simplifying

regimens promotes greater adherence and outcomes with topical acne medications: a

randomized controlled trial. Cutis 2010;86:103-8.

55 ThiboutotD. Versatility ofazelaic acid 15%gelin treatmentof inflammatoryacnevulgaris.

J Drugs Dermatol 2008;7:13-6.

56 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.

57 George R, Clarke S, Thiboutot D. Hormonal therapy for acne. Semin Cutan Med Surg

2008;27:188-96.

58 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.

59 ArowojoluAO,GalloMF, LopezLM, GrimesDA, GarnerSE.Combinedoralcontraceptive

pills for treatment of acne. Cochrane Database System Rev 2007;1:CD004425.

60 Arowojolu AO, Gallo MF, Lopez LM, Grimes DA. Combined oral contraceptive pills for

treatment of acne. Cochrane Database System Rev 2012;7:CD004425.

61 GarnerSE,Eady EA,PopescuC, NewtonJ, LiWA. Minocyclinefor acne vulgaris:efficacy

and safety. Cochrane Database System Rev 2003;1:CD002086.

62 Garner SE, Eady A, Bennett C, Newton JN, Thomas K, Popescu CM. Minocycline foracne vulgaris: efficacy and safety. Cochrane Database System Rev 2012;8:CD002086.

63 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.

64 ThiboutotDM, ShalitaAR, Yamauchi PS,Dawson C,ArsonnaudS, 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.



CLINICAL REVIEW

http://www.cks.nhs.uk/acne_vulgaris

http://www.aad.org/skin-conditions/dermatology-a-to-z/acne

http://www.bad.org.uk/site/793/default.aspx


http://www.uptodate.com/contents/acne-beyond-the-basics





http://www.uptodate.com/contents/acne-beyond-the-basics


http://www.bad.org.uk/site/793/default.aspx

http://www.aad.org/skin-conditions/dermatology-a-to-z/acne




65 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-blindstudy of adapalene0.1%-benzoyl peroxide 2.5%fixed-dose combinationgel

with doxycycline hyclate 100 mg. Cutis 2010;85:94-104.

66 CunliffeWJ, MeynadierJ, Alirezai M,George SA,CouttsI, 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):S218-26.67 DiGiovanna JJ. Systemic retinoid therapy. Dermatol Clin 2001;19:161-7.

68 White GM. Acne therapy. Adv Dermatol 1999;14:29-58; discussion 59.

69 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.

70 White GM, Chen W, Yao J, Wolde-Tsadik G. Recurrence rates after the first course of

isotretinoin. Arch Dermatol 1998;134:376-8.

71 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.

72 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 Jacobs DG,Deutsch NL,BrewerM. Suicide,depression, and isotretinoin: istherea causal

link? J Am Acad Dermatol 2001;45:S168-75.

74 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.

75 Dunn LK,O’Neill JL,FeldmanSR. Acnein adolescents: quality oflife,self-esteem,mood,

and psychological disorders. Dermatol Online J 2011;17:1.

76 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;36:255-61.77 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.

78 Fitz-GibbonS, TomidaS, Chiu BH,NguyenL, DuC, LiuM, etal. Propionibacteriumacnes

strain populations in the human skin microbiome associated with acne. J Invest Dermatol

2013; published online 21 Jan.

Cite this as: BMJ 2013;346:f2634

© BMJ Publishi ng Group Ltd 2013



CLINICAL REVIEW

http://www.nap.edu/catalog.php?record_id=12648





http://www.nap.edu/catalog.php?record_id=12648



Table

Table 1| General treatment algorithm according to acne severity

Oral retinoid†Azelaic acid

Hormonal agent*Oral antibioticTopical

antibioticBenzoyl peroxideTopical retinoidSeverity

NoNoPossible treatmentNoNoPossible treatmentRecommended

treatment

Maintenance

NoAlternative

treatment

NoNoNoPossible treatmentRecommended

treatment

Mild

NoAlternative

treatment

NoNoRecommended

treatment

Possible treatmentRecommended

treatment

Mild-moderate

Monotherapy†Alternative

treatment

Possible treatmentRecommended treatment‡Recommended

treatment

Recommended

treatment

Moderate

Monotherapy†Alternative

treatment

Possible treatmentRecommended

treatment

NoRecommended

treatment

Recommended

treatment

Moderate-severe

Monotherapy†NoNoNoNoNoNoSevere

*Female patients only.

†Oral retinoids are prescribed as monotherapy.

‡Select oral or topical antibiotic only.



CLINICAL REVIEW





referat besar (8)

Documents