MANAGEMENT OF ACNE

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TABLE OF CONTENTS

No. TITLE Page

Statement of Intent iii
Levels of Evidence and Grades of Recommendation iv
Guidelines Development and Objectives v
Guidelines Development Group ix
Review Committee x
External Reviewers xi
Algorithm on Management of Acne xiii

1. INTRODUCTION 1

2. EPIDEMIOLOGICAL CHARACTERISTICS 2

3. PATHOPHYSIOLOGY 3

4. RISK AND AGGRAVATING FACTORS 6

5. ROLE OF DIET AND SUPPLEMENTS 7

6. PATTERN OF ANTIBIOTIC RESISTANCE 10

7. PRINCIPLES OF MANAGEMENT 11
7.1 Grading Acne Severity 11
7.2 Treatment 13
7.2.1 Induction Therapy 13
a. Topical Treatment 13
b. Systemic Treatment 24
7.2.2 Maintenance Therapy 35
7.2.3 Intralesional Corticosteroid Injection 37
7.2.4 Physical Therapy 38
7.2.5 Complementary and Alternative Medicines (CAMs) 45

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8. QUALITY OF LIFE (QoL) 48

9. REFERRAL 50

10. IMPLEMENTING THE GUIDELINES 52

REFERENCES 53

Appendix 1 Search Terms 66

Appendix 2 Clinical Questions 67

Appendix 3 Food List According to Glycaemic Index (GI) Classification 69

Appendix 4 Clinical Characteristics of Acne Patients in Studies on Antibiotic

Resistance & Resistance Rates of Systemic Antibiotics Used 71

Appendix 5 Suggested Medication Dosages and Side Effects 74

List of Abbreviations 81

Acknowledgements 82

Disclosure Statement 82

Sources of Funding 82

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STATEMENT OF INTENT
These clinical practice guidelines (CPG) are meant to be guides for clinical practice, based
on the best available evidence at the time of development. Adherence to these guidelines
may not necessarily guarantee the best outcome in every case. Every healthcare provider
is responsible for the management of his/her unique patient based on the clinical picture
presented by the patient and the management options available locally.

These guidelines are issued in 2012 and will be reviewed in 2015 or sooner if new
evidence becomes available.

CPG Secretariat
Health Technology Assessment Section
Medical Development Division
Ministry of Health Malaysia
4th Floor, Block E1, Parcel E
62590 Putrajaya

Electronic version available on the following website:

http://www.moh.gov.my
http://www.acadmed.org.my

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LEVELS OF EVIDENCE
Level Study design

I Evidence from at least one properly randomised controlled trial

Evidence obtained from well-designed controlled trials without

II -1
randomisation

Evidence obtained from well-designed cohort or case-control analytic

II-2
studies, preferably from more than one centre or group

Evidence from multiple time series with or without intervention.

Dramatic results in uncontrolled experiments (such as the results of
II-3
the introduction of penicillin treatment in the 1940s) could also be
regarded as this type of evidence

Opinions of respected authorities based on clinical experience;

III
descriptive studies and case reports; or reports of expert committees
SOURCE: US / CANADIAN PREVENTIVE SERVICES TASK FORCE

GRADES OF RECOMMENDATION

At least one meta analysis, systematic review, or RCT, or

A evidence rated as good and directly applicable to the target
population

Evidence from well conducted clinical trials, directly applicable

to the target population, and demonstrating overall consistency
B
of results; or evidence extrapolated from meta analysis,
systematic review, or RCT

Evidence from expert committee reports, or opinions and /

C or clinical experiences of respected authorities; indicates
absence of directly applicable clinical studies of good quality
SOURCE: MODIFIED FROM THE SCOTTISH INTERCOLLEGIATE GUIDELINES NETWORK (SIGN)

Note: The grades of recommendation relate to the strength of the evidence

on which the recommendation is based. It does not reflect the clinical
importance of the recommendation.

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GUIDELINES DEVELOPMENT AND OBJECTIVES

GUIDELINES DEVELOPMENT

The development group (DG) for this Clinical Practice Guidelines (CPG) comprised
of members from the Ministry of Health (MOH) and Ministry of Higher Education.
This consists of dermatologists, family medicine specialists, a public health
physician, a pharmacist, a dietitian and a psychologist. There was active
involvement of a multidisciplinary review committee (RC) during the process of
developing these guidelines.

Literature search was carried out using the following electronic databases:
Guidelines International Network (G-I-N); Pubmed; Cochrane Database of Systemic
Reviews (CDSR) and Journal full text via OVID search engine; International Health
Technology Assessment websites (refer to Appendix 1 for Search Terms). In
addition, the reference lists of all retrieved literature and guidelines were searched
to identify relevant studies. Experts in the field were also contacted to identify
further studies. Literature search was officially conducted between 8 July 2009
and 31 December 2010. It was repeated for all clinical questions at the end of
the CPG development process allowing any relevant papers published until 31
July 2011 to be considered. Future CPG updates will consider evidence published
after this cut-off date. The details of the search strategy can be obtained upon
request from CPG Secretariat.

Reference was also made from other guidelines on acne such as American
Academy of Dermatology (2007) – Guidelines of care for acne vulgaris
management. These CPGs were evaluated using the Appraisal of Guidelines for
Research and Evaluation (AGREE) prior to use.

A total of 27 clinical questions were developed under three main sections.

Members of the DG were assigned with individual questions within these
sections (refer to Appendix 2 for Clinical Questions). The DG members
met for a total of 24 times throughout the development of these guidelines.
All the literature retrieved were appraised by at least two DG members,
presented in evidence tables and further discussed during DG meetings.
All statements and recommendations were formulated and agreed
by both the DG and RC. In areas where the evidence was insufficient,
recommendations were made based on consensus agreement of the DG and RC.
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These guidelines are largely based on the findings of systematic reviews, meta-
analyses and clinical trials, taking into consideration the local practices.

The literature used in these guidelines were graded using the US/Canadian
Preventive Services Task Force Level of Evidence (2001), while the grading of
recommendation was modified from grades of recommendation of the Scottish
Intercollegiate Guidelines Network (SIGN).

Upon completion, the draft of this guidelines was sent to external reviewers
for review. The draft was also posted on the MOH Malaysia official website for
feedback from any interested parties. The draft was finally presented to the
Technical Advisory Committee for CPG, and the HTA and CPG Council MOH
Malaysia for review and approval.

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OBJECTIVES
The aim of these guidelines is to assist clinicians and other healthcare providers
in making evidence-based decisions about the appropriate management and
treatment of acne i.e. to address:-
i. risk and aggravating factors
ii. pathophysiology
iii. clinical diagnostic criteria and severity grading
iv. psychosocial impact and quality of life
v. appropriate treatment
vi. indications for referral to dermatologists/plastic surgeons

CLINICAL QUESTIONS
Refer to Appendix 2

TARGET POPULATION
a. Inclusion criteria
Adolescents and adults presenting with acne ranging from mild, moderate to
severe

b. Exclusion criteria
Patients with the following conditions:
•฀ Acne฀variants฀for฀example฀acne฀conglobata,฀acne฀fulminans,฀acne฀cosmetic,฀
drug-induced acne and chloracne
•฀ Acne฀scar
•฀ Post฀inlammatory฀hyperpigmentation
•฀ Rosacea
•฀ Folliculitis

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TARGET GROUP/USER
These guidelines are applicable to any healthcare providers such as:-
i. Medical Officers
ii. General Practitioners (GPs)
iii. Family Medicine Specialists
iv. Specialists from other disciplines
v. Pharmacists
vi. Dietitians
vii. Nutritionists
viii. Paramedics
ix. Dermatologists
x. Policy makers

HEALTHCARE SETTINGS
Outpatient, inpatient and community settings

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GUIDELINES DEVELOPMENT GROUP

Chairperson

Datin Dr. Asmah Johar

Head of Department & Senior Consultant Dermatologist
Hospital Kuala Lumpur

Members (alphabetical order)

Dr. Chang Choong Chor Dr. Ng Ting Guan
Consultant Dermatologist Consultant Dermatologist
Hospital Kuala Lumpur Hospital Kuala Lumpur
Assoc. Prof. Dr. Leelavathi Muthupalaniappen Dr. Noor Zalmy Azizan
Lecturer & Consultant Family Medicine Specialist Consultant Dermatologist
Pusat Perubatan Universiti Kebangsaan Hospital Kuala Lumpur
Malaysia
Dr. Lee Yin Yin Dr. Norraliza Md. Zain
Senior Lecturer, Dermatologist & Family Medicine Specialist
Consultant Physician Klinik Kesihatan Kuala Selangor
Pusat Perubatan Universiti Malaya
Ms Lui Wei Qi Dr. Siti Irma Fadhilah Ismail
Pharmacist Clinical Psychologist
Hospital Kuala Lumpur Faculty of Medicine & Health Science
Universiti Putra Malaysia
Ms Mariammah Krishnasamy Dr. Zahara Abdul Manaf
Scientific Officer Lecturer & Dietitian
Medical Device Control Division Faculty of Health Sciences
Ministry of Health Universiti Kebangsaan Malaysia
Dr. Mohd. Aminuddin Mohd. Yusof
Public Health Physician
Health Technology Assessment Section
Ministry of Health

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REVIEW COMMITTEE
The draft of these guidelines were reviewed by a panel of independent expert
referees, from both public and private sectors, who mainly looked at the
comprehensiveness and accuracy in interpretating the evidence which support
the recommendations in these guidelines.

Chairperson

Datuk Dr. Roshidah Baba

Head of Department & Senior Consultant Dermatologist
Hospital Melaka

Members (alphabetical order)

Dr. Choon Siew Eng Datin Dr. Rugayah Bakri
Head of Department & Senior Deputy Director
Consultant Dermatologist Health Technology Assessment Section
Hospital Sultanah Aminah Ministry of Health Malaysia
Dr. Mardziah Alias Puan Sri Datuk Dr. Suraiya H. Hussein
Consultant Pediatrician & Consultant Dermatologist
Paediatric Dermatologist Sunmed Specialist Centre
Damansara Specialist Hospital Kuala Lumpur
Kuala Lumpur
Dr. Mohd. Noh Idris Dr. Suraya Yusoff
Consultant Dermatologist Head of Department &
Klinik Pakar Kulit Mohd. Noh Senior Consultant Psychiatrist
Kuala Lumpur Hospital Sultan Ismail
Dr. Pubalan Muniandy Dr. Ting Hoon Chin
Head of Department & Consultant Dermatologist
Senior Consultant Dermatologist Ting Skin Specialist Clinic
Hospital Umum Sarawak Kuala Lumpur
Dr. Rohna Ridzwan
Head of Department &
Senior Consultant Dermatologist
Hospital Selayang

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EXTERNAL REVIEWERS (alphabetical order)

The following external reviewers provided feedback on the draft:

Dr Barakatun Nisak Mohd Yusof

Senior Lecturer & Dietitian
Faculty of Medicine and Health Sciences
Universiti Putra Malaysia, Serdang

Dr. Diane Thiboutot

Professor & Vice Chair for Research
Department of Dermatology &
Director of Clinical and Translational Sciences Research Education
Pennsylvania State University College of Medicine, Hershey
United States of America

Ms. Fudziah Dato Ariffin

Head of Department & Pharmacist
Department of Pharmacy
Hospital Kuala Lumpur

Dr. Jerry K.L. Tan

Adjunct Professor, Department of Medicine
Schulich School of Medicine and Dentistry
University of Western Ontario
London, Ontario, Canada

Dr. Koh Chuan Keng

Consultant Dermatologist
Koh Skin Specialist Clinic
Petaling Jaya

Dr. Mastura Ismail

Family Medicine Specialist
Klinik Kesihatan Seremban 2

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Prof. Dr. Nopadon Noppakun

Division of Dermatology, Department of Medicine
Faculty of Medicine
Chulalongkorn University
Bangkok, Thailand

Dr. Steven K.W. Chow

Senior Consultant Dermatologist
Pantai Hospital
Kuala Lumpur

Dr. Suganthi Thevarajah

Senior Consultant Dermatologist
Hospital Kuala Lumpur

Prof. Dr. Taufiq Teng Cheong Lieng

Head of Department & Consultant Primary Care Physician
International Medical University
Seremban

Dr. Zubaidah Jamil Osman

Lecturer & Clinical Psychologist
Faculty of Medicine and Health Science
Universiti Putra Malaysia
Serdang

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DIAGNOSIS & SEVERITY ASSESSMENT OF ACNE
(BASED ON CASS)*

MILD MODERATE SEVERE

Predominantly comedones Predominantly papules/pustules Predominantly comedones Predominantly papules/pustules Nodules and cysts

FIRST LINE Topical benzoyl peroxide OR Topical retinoid** OR

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Combination of 2 topical agents Topical agent(s) + Oral antibiotic

TREATMENT Topical azelaic acid OR Topical salicylic acid

Combination of 2 topical agents +

Combination of
Oral antibiotic
2 topical agents
SECOND LINE Combination of Topical agent(s) + OR
OR
TREATMENT 2 topical agents Oral antibiotic Hormonal therapy
First line topical agent +
(females only) ± topical agent
topical antibiotic

MANAGEMENT OF ACNE
THIRD LINE Refer dermatologist for physical therapy Refer dermatologist for oral isotretinoin ± Physical therapy
TREATMENT

Maintenance therapy with topical retinoid or topical benzoyl peroxide

* Severity assessment is based on CASS (mild 1 - 2, moderate 3, severe 4 - 5). Quality of life should be taken into consideration. ** Topical retinoids are to be avoided in pregnancy.
†If there is no improvement in 3 months, consider the next line of treatment. ‡Oral antibiotic is recommended to be used for 4 - 6 months.
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1. INTRODUCTION
Acne is a common problem among adolescents and young adults. There are
different beliefs as to what causes acne especially in a multiracial country with
different cultural practices. As acne is a medical disease, medical treatment by
healthcare providers is required. If left untreated, acne may have a profound
psychological and emotional impact.

Embarrassment and complications may or may not be an important factor as

every individual perceives acne differently at various stages of life. The medical
attention provided is very much dependent upon the individual’s initiative to seek
treatment.

Acne presents with different spectrums of disease severity and there are
numerous treatment options currently available. All these factors along with
variable exposure to dermatology in medical schools result in a wide variation in
prescribing patterns. Hence, there is a necessity to assess acne and its treatment
options in a more objective manner.

The aim of these Clinical Practice Guidelines (CPG) is to provide an evidence-

based guidance for primary care physicians and other healthcare providers to
identify the appropriate management of acne.

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2. EPIDEMIOLOGICAL CHARACTERISTICS
There is a wide variation in the prevalence of acne among various countries.
However, these population based studies were done among different age groups.
The prevalence was 17.3 % among children of 6 - 11 years old in Taiwan,1, level III
9.8% among children (6 - 12.5 years old) and adolescent (12.5 - 21 years old) in
Hong Kong2, level III and 67.5% among adolescent (13 - 18 years old) in two small
district secondary schools in Malaysia.3, level III A recent study in China showed a
prevalence of 10.5% among children (10 - 14 years old), 38% among adolescent
(15 - 19 years old), 36% in young adults (20 - 24 years old) and 31% in those
above 25 years old in China.4, level III The peak age for acne was between 12.5 to 18
years and this represented 85% of the total number of students with acne.2, level III
While another study showed almost similar result with a peak age between 15 to
24 years (81.3% of total study population).4, level III There was a high prevalence of
82.1% among children of 10 - 12 years old in Portugal.5, level III In a study among
adults (>25 years old) in United Kingdom, the prevalence was 54% in women
and 40% in men.6, level III

The earliest appearance of comedones is by age of 7 years1, level III and

papulopustules by 10 - 11 years.7, level III Although there is no gender difference in
the prevalence of acne, 2 - 5, level III; 8, level III it tends to be more severe in males.5, level III There
is also no difference in acne severity among age and ethnic groups.8, level III The
most commonly affected site of acne is the face followed by the trunk.5, level III; 9 - 10, level III

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3. PATHOPHYSIOLOGY
The pathogenesis of acne is multifactorial. Acne vulgaris can be divided into non-
inflammatory (open and closed comedones) and inflammatory (papules, pustules
and nodules) lesions. The most important factors involved are:
a. Increased sebum production
b. Propionibacterium acnes proliferation
c. Altered follicular keratinisation
d. Inflammation

a. Increased Sebum Production

i. Androgen Mediated Sebum Production

Sebum production is increased,11 - 12, level III either by overstimulation
of the gland by high levels androgens or by hypersensitivity of
normal levels androgens.12, level III Androgens, such as testosterone,
dehydroepiandrosterone sulfate (DHEAS) and dihydrotestosterone
(DHT), are known to regulate genes responsible for sebaceous
gland growth and sebum production.13, level III There is a possibility of
increased androgen production within the pilosebaceous follicle.
The pilosebaceous unit possesses the steroid metabolising enzymes
that convert DHEAS to testosterone and DHT.14, level III Testosterone is
also converted to the more potent androgen i.e. DHT by the enzyme
5α-reductase.12, level III; 14 - 15, level III It is not known whether androgens act
alone or in combination with growth factors, such as fibroblast growth
factor, epidermal growth factor or insulin like growth factor.14, level III

ii. Peroxisome Proliferator-Activated Receptors (PPARs)

Sebaceous lipids are at least partly regulated by PPARs and sterol
response element binding proteins. PPARs act in concert with retinoid
X receptors to regulate epidermal growth and differentiation, and lipid
metabolism.13, level III; 15. level III Lipid production is increased in sebocytes
treated with agonists of the PPARs, which are the transcription factors
involved in regulating lipogenic genes.12, level III; 16, level II-2

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b. Propionibacterium (P) acnes Proliferation

Propionibacterium acnes is the main organism and a normal anaerobic
resident of pilosebaceous unit that colonises acne prone areas of the
skin (in sebaceous hair follicle).11, level III The proliferation of these bacteria
is responsible for the initiation of inflammation. P. acnes releases many
enzymes such as proteinases, lipases and hyaluronidases which break down
sebum to free fatty acids and peptides. It also releases chemotactic factors
which are integral to the inflammatory cascade. These factors contribute
to the inflammatory nature of acne by inducing monocytes to secrete
proinflammatory cytokines such as TNF-α, interleukin (IL)-1β and IL-8.17, level III
The inflammatory response to the bacterium and these metabolic by
products leads to the formation of papules, pustules, and nodules.18, level III

P. acnes also stimulates the host’s innate immune response by activating

Toll-Like Receptors. This in turn leads to the activation of nuclear factor
(NF-kB) which promotes expression of genes responsible for the production
of chemokines, cytokines and adhesion molecules. P. acnes also activates
Toll-Like Receptor-2, resulting in increased levels of IL-8, IL-12, tumour
necrosis factor-α and IL-1β.11, level III; 17, level III

c. Altered Follicular Keratinisation

In patients with acne, the rate of keratinocyte desquamation at the follicular
infundibulum is altered. The keratinocytes accumulate and become
interwoven with monofilaments and lipid droplets. This accumulation
of cells and sebum results in the formation of microcomedones, the
microscopic precursor to all acne lesions.19, level III There is also the presence
of 5α-reductase activity in the infrainfundibular segments of sebaceous
follicles which increases androgen production and subsequent follicular
hyperkeratosis.12, level III

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d. Inflammation
Cellular products from P. acnes stimulate the recruitment of CD4
lymphocytes and subsequently neutrophils. These inflammatory cells
penetrate the follicular wall, causing disruption of the follicular barrier.
This leads to the release of lipids, shed keratinocytes and P. acnes into the
surrounding dermis, inciting further recruitment of inflammatory cytokines
and neuropeptides including substance P.19, level III

Linoleic acid has also been found to regulate IL-8 secretion and reduce
the inflammatory reaction.20, level III Hence, deficiency of linoleic acid may
increase hyperkeratinisation of the epidermis.14, level III

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4. RISK AND AGGRAVATING FACTORS

a. Risk Factors
The role of genetic factors influencing acne has been established. However
the exact mode of inheritance is yet to be determined. Obesity is closely
related to hyperandrogenism and hence those with high BMI may be prone
to develop acne. But there are very few good studies to demonstrate this
fact. The following risk factors have been identified for the development of
acne:-

i. A significant positive family history of acne has been demonstrated

especially when acne is found in:
•฀ twins฀(p<0.0001)21, level III
•฀ mother฀(OR=2.8,฀95%฀CI฀1.8฀-฀4.5)22, level III
•฀ irst฀ degree฀ relative฀ [(OR=4.0,฀ 95%฀ CI฀ 3.4-4.7)฀ 23, level II-2
and
(OR=3.9,฀95%฀CI฀2.7฀-฀5.5)24, level II-2]
•฀ multiple฀family฀members฀(p<0.0005)22, level III

ii. A significant association between obesity and acne in children

(p<0.001)25, level III

There is no retrievable evidence regarding gender as a risk factor for acne.

b. Aggravating Factors
A number of factors have been postulated to aggravate acne. However, the
evidence is limited. The following factors have been shown to aggravate
acne:-

i.฀ Smoking฀[(OR฀for฀male฀smokers=2.3,฀95%฀CI฀1.4฀-฀3.8)26, level III and (OR

for฀active฀smokers=2.0,฀95%฀CI฀1.4฀-฀2.9)27, level III]
•฀ ฀฀฀A฀dose฀dependent฀relationship฀has฀also฀been฀shown฀(p=0.001).
27, level III
However, another study does not support this finding.28, level III
ii. Stress฀[(r=0.23,฀p=0.029)29, level II-2 and฀(r=0.61,฀p<0.01)30, level II-2]
iii. Facial therapy or salon facial massage.31, level III
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5. ROLE OF DIET AND SUPPLEMENTS

a. Diet
The following are the dietary factors that may exacerbate acne:

i. Glycaemic Load Diet

Low glycaemic load diet significantly reduces total acne lesion count
(-23.5 ± 3.9) compared to high glycaemic load diet (-12.0 ± 3.5)
in individuals aged 15 - 25 years (p=0.03).32, level I In a local study
conducted in individuals aged 18 - 30 years, the risk of acne increased
significantly with the increment of dietary glycaemic load at the 50th
and 75th percentiles (p<0.01).33, level II-2

The glycaemic load (GL) concept describes the quality (the glycaemic index
[GI]฀of฀the฀food)฀and฀quantity฀(the฀amount)฀of฀carbohydrate฀in฀a฀meal฀or฀diet.฀
The GL of a typical serving of food is the product of the amount of available
carbohydrate in that serving and the GI of the food.34 Dietary GL is the sum of
the GLs for all foods consumed in the diet.

The dietary GL can be reduced either by choosing a carbohydrate food from a

low GI variety, reducing the amount of carbohydrate intake or both.

The GI is a numerical system used to classify carbohydrate food based on the

impact they produce on the postprandial blood glucose level. The higher the GI
value of the food, the greater the blood glucose response.35 In general, most
refined carbohydrate devoid of fibre is high in GI while intact carbohydrate
(whole grains products), legumes, milk (and milk products), fruits and
vegetables are low GI foods.

Calculation of GL
GL฀=฀∑ (GI for food item x its carbohydrate content in g/100)

Refer to Appendix 3 for a food list according to GI classification.

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ii. Milk and Milk Products

There is a weak association between all types of milk with worsening of
acne฀among฀adolescent฀girls฀(9฀-฀15฀years฀old);฀whole฀milk฀(OR=1.19,฀
95%฀CI฀1.06฀to฀1.32),฀low฀fat฀milk฀(OR=1.17,฀95%฀CI฀1.04฀to฀1.31)฀
and฀skimmed฀milk฀(OR=1.19,฀95%฀CI฀1.08฀to1.31).36, level lll However,
there is only a weak association between skimmed milk consumption
and฀acne฀among฀boys฀(OR=1.19,฀95%฀CI฀1.01฀to฀1.40).37, level III

A local study showed that the risk of acne increased by:-

•฀ four-fold฀ when฀ milk฀ intake฀ frequency฀ increased฀ from฀ less฀ than฀
once฀a฀week฀to฀daily฀consumption฀(OR=4.0,฀95%฀CI฀1.4฀to฀11.4)฀฀
•฀ seven-fold฀when฀ice฀cream฀intake฀frequency฀is฀between฀less฀than฀
once a week to daily consumption compared to no consumption
(OR=7.0,฀95%฀CI฀2.4฀to฀19.7)฀
No significant differences were found in frequencies of other milk
products (yogurt and cheese) consumption between acne patients and
controls (p>0.05).33, level II-2

iii. Sugar, Fibre and Fat

There is no acne occurrence among two non-western communities
(Kavitan in Papua New Guinea and Ache in Paraguay) who consume
non-western diet consisting of high fibre and low fat content with
negligible added sugars.38, level III

iv. Chocolate, Oily Foods and Nuts

There is no good evidence for oily foods in the pathogenesis of acne.
In a local study, no significant differences were found in the frequency
of chocolate and nuts intake between acne patients and controls
(p>0.05).33, level II-2

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RECOMMENDATION
•฀ A฀low฀glycaemic฀load฀diet฀and฀high฀ibre฀diet฀should฀be฀encouraged฀for฀
acne patients. (Grade B)

b. Dietary Supplements
There is no conclusive statement on the effectiveness of zinc supplement in
acne.39, level lll In addition, there is no retrievable evidence on the efficacy of vitamin
A, vitamin C, vitamin E and omega-3 fatty acids in the management of acne.

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6. PATTERN OF ANTIBIOTIC RESISTANCE

Antibiotic therapy has been the mainstay in the treatment of acne for many years.
However prolonged usage may lead to antibiotic resistance resulting in treatment
failure.

There was one systematic review (SR) and eight primary papers retrieved on the
pattern of antibiotic resistance in acne treatment. The resistance pattern differs
with different antibiotics (Appendix 4).40-48, level III Resistance rates to erythromycin
was the highest in majority of the studies. This was followed by clindamycin
(Table 1).

Table 1: Resistance Rate of Different Antibiotics in Acne Treatment

Antibiotics Resistance Rate
Erythromycin 4.0 - 92.0%
Clindamycin 4.0 - 95.0%
Tetracycline 0 - 29.9%
Minocycline 0 - 0.6%
Doxycycline 0 - 9.5%
Co-trimoxazole 0 - 21.7%

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7. PRINCIPLES OF MANAGEMENT
The aims of acne management are:-
•฀ to฀induce฀clearance฀of฀lesions฀
•฀ to฀maintain฀remission฀and฀prevent฀relapse฀
•฀ to฀prevent฀physical฀and฀psychological฀complications

Management of acne is based on acne severity and the predominant lesions

(refer to Section 7.1 on Grading Acne Severity). Modalities of treatment consist
of pharmacological and non-pharmacological measures. This is summarised in
the algorithm on Management of Acne (page xiii).

7.1 Grading Acne Severity

Grading of acne severity can be done by using grading scale, lesion counting and
photographic methods. Leeds technique grading scale is accurate, reproducible,
rapid and suitable to be used in the clinic.49, level III Counting technique is more
suitable for clinical trials.49, level III; 50, level I

Photographs may be obtained to establish accurate and achievable records of

subjects. However small, non inflammed lesions can be difficult to detect.51, level II-1

Various techniques have been used for grading of acne severity (Table 2).
Table 2: Comparison among Acne Severity Grading Techniques
Type of Inter-rater Intra-rater
Grading Technique Reproducibility
Assessment Reliability Reliability
Grading scale and
Leed’s Technique49, level III Yes Yes Yes
lesion counting

Investigator Global Grading scale and

Yes Yes Not available
Assessment50, level I lesion counting
Grading scale
Cook Acne Severity
and photographic Yes Yes Not available
Grading scales51, level II-1
method
Comprehensive Acne Grading scale and
Yes Yes Yes
Severity Scale52, level III counting lesion

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 MANAGEMENT OF ACNE

A new grading system named Comprehensive Acne Severity Scale – CASS

(modiication฀of฀an฀Investigator฀Global฀Assessment฀[IGA]฀of฀Acne฀Severity)฀is฀a฀
validated tool which significantly correlates with the Leeds technique for face
(r=0.82),฀ chest฀ (r=0.85)฀ and฀ back฀ (r=0.87).฀ It฀ is฀ simpler฀ to฀ use฀ in฀ clinical฀
practice.52, level III Refer to Table 3 for grading using CASS.

Table 3: Comprehensive Acne Severity Scale (CASS)

GRADE* DESCRIPTION
No lesions to barely noticeable ones. Very few
Clear 0
scattered comedones and papules.
Hardly visible from 2.5 metre away. A few scattered
Almost clear 1
comedones, few small papules and very few pustules.
Easily recognisable; less than half of the affected area
Mild 2
is involved. Many comedones, papules and pustules.
More than half of the affected area is involved.
Moderate 3
Numerous comedones, papules and pustules.
Entire area is involved. Covered with comedones,
Severe 4
numerous pustules and papules, a few nodules and cyst.
Highly inflammatory acne covering the affected area,
Very severe 5
with nodules and cyst present.
*These guidelines recommend using the CASS for grading of acne severity in clinical
practice.

Inspection is done at a distance of 2.5 meters away for acne on face, chest and back.

Chest area defined as:

•฀ Anterior฀torso฀superiorly฀deined฀by฀suprasternal฀notch฀extending฀laterally฀to฀
shoulders and inferiorly by a horizontal line defined by the xiphoid process.

Back area defined as:

•฀ (Is฀dermacated฀by฀the)฀superior฀aspects฀of฀the฀shoulders฀extending฀to฀the฀
neck and inferiorly by the costal margins.

RECOMMENDATION
•฀ Comprehensive Acne Severity Scale (CASS) may be used for grading of
acne severity in clinical practice. (Grade C)

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 MANAGEMENT OF ACNE

7.2 Treatment

Acne treatment can be pharmacological and non-pharmacological. As acne is

a chronic disease, pharmacological treatment can be divided into two phases:-
•฀ Induction฀therapy
•฀ Maintenance฀therapy
Non-pharmacological treatment includes physical therapy such as laser,
phototherapy, chemical peels and comedone extraction. However, these are not
the mainstay of acne treatment.

7.2.1 Induction Therapy

This phase of treatment aims to induce acne remission which can be achieved
using topical or systemic agents.

a. Topical Treatment

Topical therapy is the mainstay of treatment for mild acne. It is also useful for
moderate acne where comedones are predominant. It plays an important role in
induction of remission and maintenance phases of the treatment.

There are a variety of preparations available. The commonly used agents are
topical benzoyl peroxide (BPO), retinoids and antibiotics. Newer agents available
are fixed combination preparations of these agents.

i. Topical Benzoyl Peroxide (BPO)

BPO is an organic peroxide agent which functions as an effective

bactericidal, keratolytic, and anti-inflammatory agent. The use of this
agent has not been associated with the development of bacterial
resistance 53, level III

Topical BPO is effective in reducing both inflammatory and non-

inflammatory lesions.54 - 55, level I The lesion reduction rates achieved with
8 to 12 weeks of therapy are between 42% and 58% for inflammatory
lesions (p<0.05) and between 30% and 58% for non-inflammatory
lesions (p<0.05).54, level I; 56 - 55, level I

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 MANAGEMENT OF ACNE

Topical BPO of various concentrations (2.5%, 5% and 10%) and in

various vehicles (alcohol, water, acetone, gel or lotion) are equally
effective.57, level I BPO 2.5% and 5% gel are equally effective in reducing
inflammatory lesions at 2, 4, 6 and 8 weeks.58, level II-1

The adverse effects of topical BPO such as erythema, dryness, peeling,

stinging/burning and itching are usually mild and transient. However,
frequency of the adverse effects is higher for BPO 10% compared to
BPO 2.5% and 5%.58, level II-1

ii. Topical Retinoids

Topical retinoids are synthetic derivatives of vitamin A (retinol). They

bind to retinoic acid receptors and have anti-comedogenic, comedolytic
and anti-inflammatory properties. They are effective in the treatment
of mild to moderate acne vulgaris for both inflammatory and non-
inflammatory lesions.

•฀฀Topical฀Tretinoin

Topical tretinoin/retinoic acid was the first topical retinoid used in

the treatment of acne.

The lesion reduction rates achieved with 8 to 12 weeks of

topical tretinoin therapy are between 42% and 72% (p<0.05) for
inflammatory lesions and between 33% and 70% (p<0.05) for
non-inflammatory lesions.59 - 60, level I

Topical tretinoin is available in various concentrations (0.025%,

0.05% and 0.1%) and formulations. However, evidence that higher
concentrations confer better efficacy is controversial.57, level I; 61, level I

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 MANAGEMENT OF ACNE

Topical tretinoin is as effective as topical adapalene, BPO and

azelaic acid in reducing both inflammatory and non-inflammatory
lesions.57, level I; 62 - 60, level I; 63, level I However, compared to adapalene gel
0.1%, tretinoin gel 0.025% was shown to be less well tolerated
in a meta-analysis of five randomised controlled trials (RCTs) with
p<0.001. It was associated with significantly higher occurrence of
burning and erythema.60, level I

The adverse effects of topical tretinoin such as erythema, dryness,

peeling, stinging/burning and itching are usually mild and transient.
Incidence of moderate to severe local adverse effects of tretinoin
0.025% gel in a meta-analysis of five RCTs ranged from 6.5% to
38%.60, level I Tretinoin 0.1% cream is poorly tolerated57, level I while
tretinoin microsphere gel (both 0.04% and 0.1%) preparations are
well-tolerated.61, level I

•฀ Topical฀Adapalene

Topical adapalene is a naphtoic acid derivative which is a receptor

selective retinoid analogue.

The lesion reduction rates achieved with 3 to 12 weeks of topical

adapalene therapy are between 47% and 75% for inflammatory
lesions (p<0.05), and between 50% and 74% for non-inflammatory
lesions (p<0.05).54, level I; 62 - 60, level I; 64 - 66, level I

Topical adapalene demonstrates dose-dependent effect, where

0.3% gel is superior to 0.1% in reduction of inflammatory lesions
(62.5% vs 57.8% at week 12; p=0.015).64, level I

Topical adapalene is as effective as topical tretinoin, isotretinoin and

tazarotene in reducing both inflammatory and non-inflammatory
lesions. 60, level I; 63, level I; 65 - 69, level I

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 MANAGEMENT OF ACNE

Topical adapalene is also as effective as topical BPO in treating

inflammatory and non-inflammatory acne lesions. However, BPO
4% gel has an earlier onset of action compared to topical adapalene
0.1% gel.54, level I

The adverse effects of topical adapalene are erythema, dryness,

peeling, stinging/burning and itching. Most adverse effects are
mild. Topical adapalene is better tolerated compared with topical
tretinoin,60, level I topical isotretinoin,65, level I and topical tazarotene.67
- 68, level I
In a recent RCT, adapalene microsphere formulation was
better tolerated than conventional gel formulation with significantly
less incidence of erythema and dryness (p<0.01).70, level I

•฀ Topical฀Isotretinoin

Topical isotretinoin (13 cis-retinoic acid) is a non receptor-selective

synthetic retinoid. It is available as 0.05% cream or gel and 0.1%
cream.

The lesion reduction rates achieved with 12 weeks of topical

isotretinoin therapy are between 57% and 77% for inflammatory
lesions, and between 68% and 78% for non-inflammatory
lesions.65, level I; 71, level I Topical isotretinoin 0.05% and 0.1% are
equally effective.57, level I

Topical isotretinoin is as effective as topical retinoic acid and topical

adapalene in treating both non-inflammatory and inflammatory
acne lesions.65, level I However when compared to topical BPO, it
is equally effective for non-inflammatory acne lesions but less
effective for inflammatory lesions (p<0.01).72, level I

Adverse effects of topical isotretinoin are generally mild such as

erythema, scaling, burning and pruritus. The incidence of adverse
effects is similar to topical BPO and retinoic acid but significantly
higher than topical adapalene (p<0.05).65, level I; 71 - 72, level I

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 MANAGEMENT OF ACNE

• Topical Tazarotene

Topical tazarotene is a receptor selective retinoid. It is available

as gel or cream in concentration of 0.05% or 0.1%. There is no
retrievable evidence to show superiority in terms of efficacy in
these two concentrations and preparations.

The lesion reduction rates achieved with 4 to 12 weeks of topical

tazarotene therapy are between 37% and 70% for inflammatory
lesions (p<0.05), and between 37% and 75% for non-inflammatory
lesions (p<0.05).73- 76, level I

Topical tazarotene is as effective as topical adapalene and tretinoin

in reducing inflammatory and non-inflammatory lesions.67, level I; 73, level I
However, a recent RCT showed that tazarotene 0.1% cream is
more effective than adapalene 0.3% gel in reducing total lesion
counts and decreasing post-inflammatory hyperpigmentation,
while having comparable tolerability.77, level I

Adverse effects of topical tazarotene are generally mild, consisting

of erythema, dryness, peeling, burning and pruritus. There is no
significant difference in incidence of adverse effects between
tazarotene 0.1% cream and adapalene 0.1% cream.75, level I

iii. Topical Antibiotics

Topical antibiotics are useful in the treatment of mild to moderate

inflammatory acne. Topical clindamycin and erythromycin are the
most widely prescribed antibiotics as these are effective and relatively
well tolerated. The use of topical antibiotics as monotherapy should
be avoided to prevent bacterial resistance.78, level III The anti-bacterial
properties of these antibiotics are found to inhibit the colonisation of
pilosebaceous glands by Propionibacterium acnes and have limited
anti-comedogenic effect.79, level I

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 MANAGEMENT OF ACNE

•฀ Topical฀Clindamycin

Topical clindamycin is effective in reducing both inflammatory

and non-inflammatory lesions. A Health Technology Assessment
(HTA) of eight clinical trials showed that clindamycin was superior
to placebo.57, level I Rizer RL et al. reported that topical clindamycin
effectively reduced inflammatory lesions by 54.9% (p=0.015)
and non-inflammatory lesions by 26.4% (p=0.043) at week 12 of
treatment.79, 2001, level I

In the same HTA mentioned above, five clinical trials showed that
topical clindamycin was as effective as topical erythromycin.57, level I

Various combination (fixed and non-fixed) preparations of

clindamycin with either BPO, tretinoin or adapalene show superiority
over clindamycin alone (p<0.05).57, level I; 80. level I; 81, level II-1

Comparison of daily versus twice daily application of topical

clindamycin does not show any significant differences in the
reduction of both inflammatory (p=0.810) and non-inflammatory
lesions (p=0.184).79, level I

The efficacy of topical clindamycin is similar whether the vehicle

used is a gel, lotion or solution.57, level I

The adverse effects of clindamycin such as erythema, peeling,

dryness, scaling, stinging, burning and itching are mild and
transient. 57, level I; 79 - 81, level II-1; 82, level I; 83, level II-1

•฀ Topical฀Erythromycin

Topical erythromycin is effective in reducing both inflammatory and

non-inflammatory lesions.57, level I; 84 - 85, level II-3; 86, level I; 87, level II-1; 88 - 89, level I

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 MANAGEMENT OF ACNE

Significant lesion reduction rates achieved with 6 to 12 weeks of

therapy are between 42% and 74% for inflammatory lesions and
between 25% and 74% for non-inflammatory lesions.57, level I; 84 - 85,
level II-3; 86, level I; 87, level II-1; 88 - 89, level I

Topical retinoic acid 0.05% and BPO 10% are superior to topical
erythromycin in reducing non-inflammatory lesions but not in
inflammatory lesions.84, level II-3

Addition of zinc in topical erythromycin (topical zineryt) is more

efficacious compared to erythromycin alone in reducing papules
and pustules (p<0.001).86, level I

Adverse effects of topical erythromycin such as dry skin, itching,

burning, erythema, scaling and dermatitis are localised, mild and
transient.85, level II-3; 86, level I; 87, level II-1; 88; level I

iv. Topical Azelaic Acid (AA)

AA is a naturally occurring dicarboxylic acid which has comedolytic,

antimicrobial and anti-inflammatory properties.

Topical AA causes reduction in total lesion count by 60.6% and Acne

Severity Index by 65.2% in six weeks.90, level I A systematic review
(SR) and two trials showed that it was effective in reducing both
inflammatory and non-inflammatory lesions.57, level I; 90 - 91, level I

Topical AA is as effective as topical BPO and adapalene in reducing

both inflammatory and non-inflammatory acne lesions.91, level I

Topical AA reduces sebum production by an average of 13.9% on the

forehead and 14.2% on the cheek. Its therapeutic activity, however,
does not depend on its capacity in sebum reduction.91, level I

Adverse effects of topical AA are generally mild and transient, with an

overall incidence of approximately 3%. These include pruritus, burning,
stinging and tingling.90, level I

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 MANAGEMENT OF ACNE

v. Topical Salicylic Acid (SA)

SA is a keratolytic agent which has been shown to be effective for

mild to moderate acne. It has both comedolytic and antimicrobial
properties.92, level I

Topical salicylic acid effectively reduces both inflammatory and non-

inflammatory acne, with reduction rates of 44% and 19% respectively
at week 12 (p<0.001).92, level I

Salicylic acid of 1.5% and 2% concentrations are effective compared

to placebo.57, level I

Adverse effects of salicylic acid such as pruritus, burning, tingling,

desquamation and erythema are mild and transient.57, level I;.92, level I

vi. Topical Sulfur and Its Combination

Sulfur has long been used in the treatment of acne. It has anti-
inflammatory and mild keratolytic properties. There is no sufficient
evidence to support the use of sulfur alone.57, level I However, the
combination of sulfur with other agents is effective in treating mild to
moderate acne.93, level II-3

Combination therapy of 5% sulfur and 10% sulfacetamide is effective

in reducing 78% of total lesions and 82.9% of inflammatory lesions in
women with mild to moderate acne at week 12 (p<0.001).93, level II-3

Combinations of sulfur (2% to 6%) in calamine lotion have long been

used in the treatment of facial and truncal acne.94, level III However, there
is no retrievable clinical study demonstrating its efficacy.

Adverse effects include transient mild dryness and pruritus.93, level II-3

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 MANAGEMENT OF ACNE

vii. Topical Dapsone

Topical dapsone is assumed to have similar mechanisms of action on

acne as oral dapsone. It has antimicrobial (bacteriostatic) and anti-
inflammatory properties.

Topical dapsone is effective in the treatment of mild to moderate acne,

reducing both inflammatory and non-inflammatory lesions. Significant
reduction rates achieved with 12 weeks of therapy are between 30%
and 49% for inflammatory lesions (p<0.001), and between 5% and
32% for non-inflammatory lesions (p<0.001). Its onset of action on
inflammatory lesions occurs as early as four weeks.95-96, level I; 97, level
II-3
Sustained effectiveness was demonstrated in a 12-month study
showing lesion reduction of 58% for inflammatory lesions (p<0.001)
and 19.5% for non-inflammatory lesions (p=0.002).97, level II-3 However,
there is no head-to-head study comparing the efficacy of topical
dapsone with other topical agents.

Topical dapsone is well tolerated for up to 12 months. Adverse

effects, reported in 14 - 38% of patients, are mostly mild or moderate.
Common effects include dryness, rash, sunburn, burning sensation,
erythema and pruritus.95, level I; 97, level II-3 Topical dapsone is safe for use
in Glucose-6-phosphate dehydrogenase (G6PD) deficient patients with
acne for up to 12 weeks, with no significant increase in the incidence
of hemolysis.95, level I; 98, level I No studies have been done in pregnancy and
children aged less than 12 years.99, level III

viii. Topical Fixed Combination

Fixed combination therapies are new anti-acne treatment. Combination

preparations with topical benzoyl peroxide, retinoids or antibiotics are
more effective than either agent used alone.100

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•฀ Topical Clindamycin/BPO (CBP)

CBP is effective in reducing both inflammatory and non-inflammatory

lesions when compared to vehicle (p<0.05), clindamycin (p<0.05)
and BPO (p<0.05) alone.101, level I; 102, level I; 103, level I

The lesion reduction rates achieved at week 2 to 12 weeks of

CBP therapy are between 30% and 60% for inflammatory lesions
(p<0.05) and between 10% and 43% for non-inflammatory lesions
(p<0.05).101, level I; 102, level I; 103, level I

There is no statistically significant difference between the local

irritant effects of combination preparation compared to either agent
on its own. However, treatment with either CBP or BPO resulted in
higher frequency of peeling than clindamycin alone.103, level I

The preparations currently available are clindamycin 1% in

combination with 2.5% BPO or 5% BPO.

•฀ Topical฀Adapalene/BPO฀(ABP)฀

ABP is effective in reducing inflammatory and non-inflammatory

lesions when compared to vehicle (p<0.05), adapalene (p<0.05)
and BPO (p<0.05) alone.104 - 105, level I

Success rates (clear to almost clear) at week 12 are 27.5% to 38%

with ABP compared to adapalene 15.5% to 22% and BPO 15.4%
to 27% (p< 0.05).104 - 105, level I

Adverse effects are mild to moderate in severity without any

residual effects.

The preparation currently available is adapalene 0.1% in

combination with 2.5% BPO.

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 MANAGEMENT OF ACNE

•฀ Topical฀Erythromycin/BPO฀(EBP)

EBP is effective in reducing both inflammatory and non-inflammatory

lesions. However, this effect was slower in the latter.57, level I

Reduction rates achieved at week 4 and week 10 are between 50%

and 75% for inflammatory lesions (p<0.05) while at week 8 and
week 10, they are between 50% and 53% for non-inflammatory
lesions (p< 0.05).106, level I

Adverse effects such as scaling and skin tightness had been

reported.57, level I

•฀ Topical฀Clindamycin/Tretinoin฀

Topical clindamycin (1%)/tretinoin (0.025%) in hydrogel demonstrates

superior efficacy to clindamycin, tretinoin and vehicle alone (p<0.05).
The reduction rates at week 12 are 53.4% for inflammatory lesions
and 45.2% for non-inflammatory lesions. Adverse effects are minor
and well tolerated.107, level I

Practical tips on topical agents

•฀ Apply฀a฀thin฀layer฀to฀the฀entire฀susceptible฀areas
•฀ Topical฀retinoids฀are฀to฀be฀avoided฀during฀pregnancy.
•฀ Topical฀azelaic฀acid฀may฀be฀useful฀in฀acne฀patients฀with฀hyperpigmentation
•฀ Topical฀ antibiotics฀ should฀ not฀ be฀ used฀ as฀ monotherapy฀ to฀ minimise฀
antibiotic resistance

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RECOMMENDATION
• Topical benzoyl peroxide, topical retinoid, topical antibiotics, topical
azelaic acid or topical salicylic acid are indicated for mild to moderate
acne. (Grade A)

•฀ Topical฀sulfur฀combinations฀can฀be฀used฀in฀for฀mild฀to฀moderate฀acne.
(Grade C)

•฀ Benzoyl฀peroxide฀should฀be฀initiated฀at฀a฀concentration฀of฀2.5%฀or฀5%.฀
(Grade A)

•฀ Topical฀ ixed฀ combination฀ such฀ as฀ clindamycin฀ and฀ benzoyl฀ peroxide฀

or adapalene and benzoyl peroxide can be used as an option for the
treatment of mild to moderate acne. (Grade A)

b. Systemic Treatment

i. Oral Antibiotics

Oral antibiotics have been widely used for moderate to severe

acne vulgaris. The anti-Propionibacterium acnes properties found
in antibiotics are able to inhibit the colonisation of pilosebaceous
glands by the bacteria and prevent further inflammation. Tetracycline
antibiotics have also been shown to exert direct anti-inflammatory
effect by inhibiting chemotaxis and matrix metalloproteinases.
However, prolonged use of oral antibiotics may be associated with
bacterial resistance.

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 MANAGEMENT OF ACNE

•฀ Oral Tetracycline

Tetracycline has been widely used in the management of moderate

to severe acne. It has antimicrobial and direct anti-inflammatory
properties. However, its use is contraindicated in children aged less
than eight, pregnancy and lactation. Absorption of tetracycline from
the gastrointestinal tract is impaired by food, milk, dairy products,
iron salts and antacids. Hence it should be taken one hour before or
two hours after meals with a full glass of water, in upright position.
A SR of 18 trials showed that oral tetracycline in doses ranging
from 250 to 500 mg twice daily for 8 to 24 weeks was effective
for both inflammatory and non-inflammatory lesions in mild to
moderate acne. Lesions reduction rates were between 19% and
84% for inflammatory lesions and between 25% and 63% for non-
inflammatory lesions.108, level I

There is lack of retrievable evidences to show any difference in

efficacy among different dosages of oral tetracycline. However,
there is no statistical difference between the available tetracyclines
preparations in terms of the efficacy in reducing inflammatory
(p=0.898) and non-inflammatory lesions (p=0.429).108, level I

Majority of the adverse events are mild and transient. Common

adverse effects are nausea, vomiting, diarrhoea, cramping,
erythema, abdominal pain, esophagitis, oral candidiasis and vaginal
candidiasis.57, level I; 109, level II-1; 110, level II-3

•฀ Oral฀Doxycycline

Doxycycline is a tetracycline derivative. In contrast to tetracycline,

the absorption of doxycycline is less affected by food. It is
contraindicated in children aged less than eight, pregnancy and
lactation.

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 MANAGEMENT OF ACNE

Oral doxycycline 50 to 100 mg daily is effective in reducing both

inflammatory and non-inflammatory lesions. The lesion reduction
rates achieved with three months treatment of oral doxycycline
were between 14% and 50% for non-inflammatory lesions
(p<0.05), and between 30% and 75% for inflammatory lesions
(p<0.05).57, level I; 111, level I; 112, level II-1; 113, level II-2; 114, level I

A sub-antimicrobial dosage of oral doxycycline 20 mg BD for

six months was found to exert a 50% reduction in inflammatory
lesions (p<0.04) and 54% reduction in non-inflammatory lesions
(p<0.01).115, level I

Common adverse effects are mainly gastrointestinal such as

diarrhoea, nausea, vomiting, dyspepsia and abdominal pain. Less
common adverse effects are headache, photosensitivity, photo-
onycholysis and rash.57, level I; 111, level I; 112, level II-1; 113, level II-2; 114 - 115, level I

•฀ Oral฀Erythromycin

Erythromycin is a macrolide antibiotic. It exerts direct anti-

inflammatory activities by reducing neutrophil chemotatic factors
and reactive oxygen species.

Oral erythromycin is effective in reducing both inflammatory and

non-inflammatory lesions. In a study by Greenwood R et al., oral
erythromycin 250 mg twice daily for four months showed 21 -
45% improvement in Leed’s acne severity grading in patients with
moderate to severe acne (p<0.05). Facial acne responded better
than truncal acne, giving an acne severity reduction of 66.5% and
51.5% respectively (p<0.05).116, level II-1

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 MANAGEMENT OF ACNE

In similar study, doubling the dose of erythromycin from 500 mg daily

to 1 g daily significantly increased the response from 47% to 79%
after six months (p<0.001). The relapse rate (defined as a return of
the acne to >50% of original severity) with erythromycin 1g daily
was lower compared to 500 mg daily i.e. 35% vs 72%.116, level II-1

Treatment with erythromycin-base 333 mg three times a day

for four weeks followed by 333 mg once daily for eight weeks
produced lesion reduction rates of 67% for inflammatory and 22%
for non-inflammatory lesions.117, level I

A SR of three clinical trials comparing the use of oral erythromycin

and oral tetracycline showed that both were equally effective.57, level I

Common adverse effects of erythromycin are mainly gastrointestinal

such as nausea and diarrhoea. Other adverse effects such as
headache, dizziness and rashes are mild and transient.116, level II-1;
117, level I; 118, level II-1
Doubling the dose of erythromycin from 500 mg
daily to 1g daily does not cause an increase in the incidence of
adverse effects.57, level I; 116, level II-1

•฀ Oral฀Minocycline

Minocycline is a tetracycline antibiotic that has been used in the

treatment of moderate to severe acne vulgaris. It is contraindicated
in children aged less than eight, pregnancy and lactation. Compared
to the first-generation tetracyclines, it only needs to be taken once
or twice a day and can be taken with food. However, it is more
expensive.119, level I

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 MANAGEMENT OF ACNE

A Cochrane SR of 27 RCTs found that the RCTs were generally

small and of poor quality. The efficacy of minocycline relative to
other acne therapies could not be reliably determined due to the
poor methodological quality of the trials and inconsistent outcome
measures. In the same SR, there was no evidence to support
the benefits of minocycline in acne which is resistant to other
therapies.119, level I

Minocycline was shown to have comparable efficacy with

tetracycline, doxycycline and lymecycline.109, level II-1; 114, level I; 120 - 121, level I

Dose regimes of minocycline used in the above studies were 50 mg

to 100 mg once to twice daily. However, there are no studies which
compare different dose regimes of the medication.119, level I

There is concern about its safety. Overall, 11% of patients

experienced adverse reactions that are attributed to the
therapy. Of these, 2.9% were severe enough to warrant
in therapy withdrawal. These include moniliasis, abnormal
pigmentation, vertigo, urticaria, renal failure and fixed drug
eruption. 57, level I; 109, level II-1; 114, level I; 119-120, level I There is evidence
to suggest that the risk of minocycline-induced pigmentation
increases with cumulative dose especially above 100 g.119, level I

•฀ Oral฀Azithromycin฀

Azithromycin is a macrolide antibiotic. It has a long half-life of 68

hours and therefore can be given three times a week.

Pulse treatment of oral azithromycin at a dose of 500 mg three

times a week is effective in reducing both inflammatory and non-
inflammatory lesions in patients with moderate to severe
acne. 112, level I; 113, level II-1; 122, level I; 123, level II-3

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 MANAGEMENT OF ACNE

The lesion reduction rates achieved with three months treatment

of oral azithromycin are 50% for non-inflammatory lesions
(p<0.05) and 70% for inflammatory lesions (p<0.05).112, level I
Overall improvement of more than 80% is seen in 52% to 53% of
patients.112, level I; 113, level II-1; 123, level II-3

Common adverse effects include gastrointestinal intolerances such

as diarrhoea, minor gastric discomfort and nausea. Majority of the
adverse effects are mild and transient.112, level I; 113, level II-1; 122, level I; 123, level II-3

•฀ Oral฀Co-trimoxazole฀and฀Trimethoprim฀Alone

Co-trimoxazole is a combination of trimethoprim and sulfamethoxazole.

It should be avoided in patients with hypersensitivity to sulfonamides.
Trimethoprim has also been used alone.

In a RCT, oral co-trimoxazole one tablet daily (trimethoprim 80 mg

and sulfamethoxazole 400 mg) for three months was found to
reduce acne severity in 81% patients and was comparable to
oxytetracycline 250 mg daily (p>0.01). A further reassessment
after a month of treatment cessation found no significant difference
in the rate of relapse (p>0.1).124, level I

Trimethoprim 100 mg three times a day achieved lesion reduction

rates of 60% for inflammatory lesions (p<0.01) and 18% for
macules (p<0.01) at eight weeks. These findings are comparable
to oxytetracycline given 250 mg three times a day.125, level I

Adverse effects are mainly flatulence, abdominal pain, dizziness,

headache, macular erythema and desquamation.57,level I; 125,level I Erythema
multiforme, Stevens-Johnson syndrome and toxic epidermal
necrolysis are uncommon but potentially serious adverse effects.

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Practical tips on oral antibiotics

• Oral tetracycline, doxycycline, minocycline or co-trimoxazole are

contraindicated in pregnancy.

•฀ Sulfonamide฀ antibiotics฀ have฀ been฀ reported฀ to฀ cause฀ severe฀ adverse฀

drug reactions such as Stevens-Johnson syndrome and toxic epidermal
necrolysis.

•฀ Oral฀antibiotics฀should฀not฀be฀prescribed฀continuously฀for฀more฀than฀six฀
months.

RECOMMENDATION
•฀฀ Oral฀tetracycline,฀oral฀doxycycline,฀oral฀erythromycin฀or฀oral฀minocycline may
be used as treatment for moderate to severe acne. (Grade A)

ii. Oral Hormonal Therapy

Hormonal therapy is an alternative treatment for managing acne in

women. This option may be particularly valuable for those requiring
contraception or with signs of hyperandrogenism.

•฀ Combined฀Oral฀Contraceptive฀(COC)฀

COCs are thought to reduce acne by several mechanisms. COCs

decrease free testosterone levels, increase sex hormone-binding
globulin and prevent conversion of free testosterone to DHT.

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COCs containing different progestins and oestrogen dosages are

prescribed for acne. In a Cochrane SR, five RCTs showed that
COCs significantly reduced inflammatory and non-inflammatory
facial lesions counts, severity grades and self-assessed acne when
compared to placebo.126, level I

Comparison on the effectiveness of different COCs was less clear.

COCs that contained chlormadinone acetate (CMA) or cyproterone
acetate (CPA) improved acne better than those with levonorgesterol
and desogestrel, although this apparent advantage was based
on limited data or conflicting results. Studies comparing COC
containing levonorgestrel and desogestrel also showed conflicting
results.126, level I

Adverse events include nausea, vomiting, breast tenderness,

headaches, menstrual disturbances and venous thrombosis.126, level I

•฀ Spironolactone

Spironolactone is an anti-androgen and aldosterone antagonist. It

competes with DHT for androgen receptors in the skin.

Spironolactone is not effective for acne although there is some

evidence on its effectiveness in the treatment of hirsutism.57, level I;
127, level I

•฀ Other฀Anti-Androgens

Flutamide, a potent non-steroidal anti-androgen, is usually

prescribed for prostatic cancer and also effective for women with
idiopathic hirsutism and polycystic ovarian syndrome. Low dose
flutamide (250mg/day) and CPA were effective in reducing acne
scores from baseline (p<0.01).128, level I However, flutamide should
be used with caution as it can potentially cause liver failure.

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Finasteride, a specific inhibitor of 5-α reductase, has been shown

to be less effective for the treatment of acne in hyperandrogenic
women when compared to flutemide and cyproterone acetate
(p<0.05).128, level I

Cimetidine, a H2 receptor antagonist drug used mainly for inhibition

of gastric acid secretion, is also noted to have anti-androgenic
property but there is no evidence to show that it improves acne.57, level I

RECOMMENDATION
•฀฀ Combined oral contraceptives may be used in the treatment of acne in
females patients with moderate acne, particularly in those who require
concomitant contraception and/or those with hyperandrogenism. (Grade A)

iii. Oral Isotretinoin

Oral isotretinoin (13-cis-retinoic acid) is a retinoid compound commonly

used for the treatment of nodulocystic and severe acne. It targets all
pathophysiologic factors in acne. It decreases the size and secretion of
sebaceous glands, normalises follicular keratinisation, indirectly inhibits
P. acnes growth in hair follicle and exerts an anti-inflammatory action.

Isotretinoin is teratogenic. Strict contraceptive practice is required for female

patients and isotretinoin should only be prescribed by dermatologists.

Oral isotretinoin is effective in the treatment of nodulocystic acne

as evident by a placebo-controlled clinical trial showing reduction
in nodules and cysts by 17% after one month (p<0.001) and 32%
after two months (p<0.008). The average maximum dose received
was 1.2 mg/kg/day (range of 0.5 to 3.2). The mean time for complete
clearance with one course of therapy was six months. Those who
cleared completely were in remission for 38 months in average.129, level I
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Various doses of oral isotretinoin have been used. A study comparing

0.1, 0.5 and 1 mg/kg/day doses in the treatment of nodulocystic acne
showed significant clinical response to treatment with all three doses
(p<0.01) without significant difference between doses. However,
relapse rates were higher in the lower dose groups (0.1 and 0.5 mg/
kg/day). With a dose of 0.5 mg/kg/day, 20% needed to be re-treated
while those on 0.1 mg/kg/day, 42% needed to be re-treated during the
three month post-therapy follow up.130 - 131, level I A cumulative dosage of
120 mg/kg is associated with a lower relapse rate.78, level III

Low-dose oral isotretinoin has been used to treat mild to moderate

acne unresponsive to conventional therapy. However, there was
marked heterogeneity in the dosing regimens making it difficult to
compare between them:-

• A dose of 0.5 mg/kg/day for one week each month over a period
of six months significantly reduced both total acne grades and
inflamed lesion count with 88% resolution (p<0.0001). Twelve
months after completing treatment, 61% of those who responded
remained significantly improved (p<0.0001).132, level II-3

• A dose of 0.5 - 0.75 mg/kg/day for one week each month

over a period of six months resulted in 82.9% complete and
11.6% partial healing. This study however did not monitor for
relapses.133, level II-3

• A dose of 20 mg/day for six months showed complete or almost

complete remission in 94.8% of patients aged 12 - 20 years old
and 92.6% aged 21 - 35 years old. Failures of treatment were
5.2% and 7.4% respectively. Within the four-year follow up period,
relapses occurred in 3.9% aged 12 - 20 years old and 5.9% aged
21 - 35 years old.134, level II-3

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• A RCT studied intermittent and conventional dosing of isotretinoin

where฀ 66฀ patients฀ were฀ randomised฀ to฀ three฀ groups฀ [Group฀ 1฀
(0.5 mg/kg for first 10 days of the month for six months), Group
2 (0.5 mg/kg every day for one month, then first 10 days for five
months) and Group 3 (0.5 mg/kg per day everyday for six months)].
No statistically significant differences were obtained among the
treatment protocols in patients with moderate acne. However, there
was a significant difference in severe acne between Groups 1 and
3 at the end of follow up period (p=0.013). The frequency and
severity of isotretionin-related side effects were found to be lower
in Groups 1 and 2 compared with Group 3.135, level I

• A RCT compared the effectiveness of isotretinoin in conventional

dose (0.5 - 0.7 mg/kg daily), low-dose (0.25 - 0.4 mg/kg daily) and
intermittent dose (0.5 - 0.7 mg/kg daily for 1 week out of every 4
weeks) in moderate acne. The conventional and low-dose regimens
were superior to the intermittent dose regimens in the improvement
of Global Acne Grading System (GAGS) scores with p<0.001 and p
=0.044฀ respectively.฀ There฀ was฀ no฀ signiicant฀ difference฀ between฀
conventional and low dose regimens. One year after the end of
treatment, the relapse rates were 13% in the conventional group, 18%
in the low dose group and 56% in the intermittent group.136, level I

Side effects are dose-dependent, mostly limited to the skin and

mucous membrane, and well tolerated and reversible. Common
side effects include cheilitis, dermatitis, conjunctivitis, xerosis and
dryness of the nasal mucosa with nosebleeds. Other rare side
effects are arthralgia, decreased appetite and fatigue. Laboratory
abnormalities are limited to elevations of serum aspartate, alanine
transaminases and hypertriglycerides which all return to normal
after discontinuation of therapy.129 - 131, level I There is no consensus
yet on depression and suicide from the use of oral isotretinoin.
However, caution is advised in patients with history of depression
and mood swings.78, level III

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RECOMMENDATION
•฀ Oral฀ isotretinoin฀ can฀ be฀ used฀ for฀ nodulocystic฀ or฀ severe฀ acne. (Grade A)
•฀ Oral฀isotretinoin฀may฀also฀be฀used฀for฀moderate฀acne฀as฀third฀line฀therapy.฀
(Grade B)

7.2.2 Maintenance Therapy

Recurrence of acne lesions after successful treatment is common. Hence,

maintenance therapy is an important modality as part of a comprehensive
management of acne. The mainstay of maintenance treatment is topical therapy.

i. Topical Adapalene

Following an induction therapy (BPO 2.5% and adapalene gel 0.1%)

for eight weeks, maintenance therapy for 12 weeks with adapalene gel
0.1% daily or alternate day led to a further reduction of microcomedones
count in mild to moderate acne compared to vehicle.137, level I

In another study on moderate to moderately severe acne, after 12

weeks of maintenance therapy with adapalene gel 0.1% once daily,
there were further reduction in total (p=0.049) and non-inflammatory
(p<0.001) lesions compared to vehicle.138, level I

Zhang et al. reported a reduction in total, inflammatory and non-

inflammatory lesions after 12 weeks of maintenance therapy in
moderate to moderately severe acne with adapalene gel 0.1%
monotherapy as compared to control group.139, level I

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ii. Topical Tazarotene

Leyden et al. compared three maintenance regimens in patients with

moderately severe to severe acne. Tazarotene 0.1% gel plus placebo,
vehicle plus oral minocycline and tazarotene gel plus oral minocycline
were associated with sustained improvement in both non-inflammatory
and inflammatory lesions during the 12-week maintenance phase.
However, there was no statistically significant difference between the
maintenance regimens.140, level I

iii. Topical Azelaic Acid (AA)

Maintenance therapy with topical 20% AA monotherapy showed

improvement after three months in both inflammatory and non-
inflammatory lesion counts in severe acne.141, level I

iv. Topical Adapelene-Benzoyl Peroxide

A fixed combination gel of adapelene 0.1% and BPO 2.5% (adapelene-

BPO) is an effective maintenance therapy agent. It prevents relapse and
continues to reduce disease symptoms during six month maintenance
therapy in severe acne.142, level I

There is no retrievable evidence on the use of topical antibiotics as

maintenance therapy.

However, the Global Alliance recommends BPO or BPO-antibiotic

combination with topical retinoid, such as adapalene gel 0.1% and
tazarotene, as effective maintenance therapy.13, level III

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RECOMMENDATION
•฀ Maintenance฀ treatment฀ of฀ acne฀ should฀ be฀ commenced฀ after฀ an฀ initial฀
successful induction therapy to sustain remission. (Grade A)
•฀ Topical฀ retinoid฀ monotherapy฀ should฀ be฀ considered฀ for฀ maintenance฀
therapy in patients with acne. (Grade A)
•฀ Combination฀therapy฀of฀adapalene-benzyl฀peroxide฀gel฀may฀be฀considered฀
for maintenance therapy in severe acne. (Grade A)

7.2.3 Intralesional Corticosteroid Injection

Intralesional corticosteroid injection is indicated for the treatment of acne

nodules and cysts.143, level III It is a simple and useful technique in rapidly reducing
inflammation and resolving lesions in order to minimise scarring.143 - 144, level III

Corticosteroids should be injected at the lowest effective dose, which can be

determined by individual doctor’s experience with the types of lesions and the
patient’s response. Intralesional triamcinolone acetonide 2.5 to 5 mg/ml is
commonly used.143, level III

There is evidence of systemic absorption following intralesional corticosteroid

injection. Adrenal suppression occurs in doses of more than 15 mg per session.
Suppression persists for 2 to 3 days with 20 - 35 mg and at least 5 days with 50
mg dose.145, level II-3

Local adverse effects include skin atrophy, pigmentary changes, telangiectasias,

haematoma and infection.143 - 144, level III

A combination of intralesional triamcinolone 2.5 mg/ml and lincomycin

hydrochloride 75 mg/ml was shown to be superior over intralesional triamcinolone
alone in the treatment of nodulocystic lesions of acne.146, level II-3

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Intralesional corticosteroid injection should be used with caution due to

potential local and systemic adverse effects.

RECOMMENDATION
•฀฀ Intralesional฀ corticosteroid฀ injection฀ may฀ be฀ used฀ in฀ the฀ treatment฀ of
selected acne cases (acne nodules/cysts) but cannot replace conventional
treatment. (Grade C)

7.2.4 Physical Therapy

Physical therapy can be used as an adjunct or alternative treatment in acne.

However, it is not widely available and can only be provided by trained personnel.

i. Comedone Extraction

Physical removal such as comedone extraction by a variety of techniques

can provide immediate clinical improvement and patient satisfaction.
However, published article describing the use of comedone extraction
is sparse.147, level III Comedone extraction using Shamberg or Saalfeld
comedone extractor is effective in superficial acne but not in cystic
acne.148, level III

In a study by Kaya TI et al. using cautery and standard dissecting

forceps for closed macrocomedones >3 mm in diameter, all patients
tolerated the procedure and judged the cosmetic results as very
good.149, level III

The disadvantages of comedone extraction include incomplete

extraction, tissue damage and recurrence.

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ii. Chemical Peels

Chemical peels are used as adjuvants in the treatment of facial acne.

Various chemical preparations are used for epidermal exfoliation.
Commonly used peeling agents include glycolic acid and salicylic acid.

•฀ Glycolic฀Acid฀฀

Glycolic acid, an α-hydroxy acid, is a hydrophilic compound

often used in chemical peels due to its desquamating properties.
Desquamation reduces corneocyte cohesion and keratinocyte
plugging. This enables the extrusion of contents which prevent
comedone formation.

Both 70% glycolic acid and Jessner’s solution twice a week on mild
to moderate acne for six weeks were effective in the treatment
of facial acne. Improvement was noted after three treatment
sessions. However, there were no significant differences
between the two solutions. Both solutions resulted in erythema
which resolved within four days. Jessner’s solution caused more
significant exfoliation compared to glycolic acid (p< 0.01).150, level I
In another study, Atzori et al. reported that 70% glycolic acid
peel improved comedones more rapidly than papulo-pustules
and nodulo-cystic lesions.151, level III

In moderate to moderately severe acne, glycolic acid peel (35%

or 50%) for four sessions at 3-weekly intervals together with pre-
and post-treatment use of 15% glycolic acid at home peel resulted
in significant resolution of comedones, papules and pustules.

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 MANAGEMENT OF ACNE

Physician’s assessment at week 11 showed a 50% improvement in

about one third of patients with comedones or papules and one fifth
in those with pustules.152, level II-3 Grover et al. reported that glycolic
acid (10 to 30%) at fortnightly interval significantly reduced the
number of comedones and papulo-pustules in patients with mild to
moderate acne.153, level III

The most common side effect is erythema. Other reported side

effects include post- inflammatory hyperpigmentation, local herpes
simplex infection and mild skin irritation.151, level III; 152, level II-3

•฀ Salicylic฀Acid฀(SA)

SA, a lipophilic β-hydroxy acid, reduces corneocyte cohesion and

acts well on sebaceous areas of the face. It has excellent keratolytic
effect and is useful against comedones. It is also effective against
inflammatory lesions.

In mild to moderately severe acne, both 30% salicylic acid and

30% glycolic acid were noted to be effective after two treatments
(p<0.05). At two months post-treatment, salicylic acid was able
to sustain its effectiveness (p<0.01). However some patients
were also on topical retinoid, oral antibiotics and other topical acne
therapy at enrollment which could have confounded the results.154, level I

Lee HS et al. reported that 30% salicylic acid at 2-weekly intervals

for five sessions were effective in both non-inflammatory and
inflammatory acne lesions. The mean acne grading reduction by
Leed’s grading system from baseline to week 12 was 1.29 with a
range of 1.67 to 0.38 (p<0.01).155, level II-1

Adverse events include peeling, redness and scaling which are

highest in first two sessions.154, level I; 155, level II-1

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RECOMMENDATION
•฀฀ Chemical฀peel฀with฀glycolic฀acid฀or฀salicylic฀acid฀may฀be฀used฀as฀adjuvant฀
treatment for acne. (Grade B)

iii. Phototherapy and Photodynamic Therapy

Phototherapy and photodynamic therapy are alternative therapeutic

options for patients who either fail or unable to tolerate other standard
acne therapies. These are specialised procedures and should be carried
out by dermatologists. The development of light-based therapies was
based on the observation that sunlight exposure may improve acne.

The proposed mechanisms of action are photothermal heating

of sebaceous glands and photochemical inactivation of P. acnes.
Porphyrins which may be produced by P. acnes can absorb light at a
peak of 415 nm to form singlet oxygen radicals that kill the bacteria.

•฀ Phototherapy฀

These include pulsed dye laser, potassium titanyl phosphate

laser, infrared diode laser, intense pulse light and broad spectrum
continuous wave visible light sources such as blue and blue-red
light. Many studies have been published with varying qualities and
results.

o Pulsed Dye Laser (PDL)

A SR of two RCTs evaluated the efficacy of PDL vs placebo

and untreated control on facial acne with ambiguous results.

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 MANAGEMENT OF ACNE

Seaton ED et al. reported 49% improvement in PDL on

inflammatory acne lesions vs 10% improvement in the placebo
at 12 weeks after one treatment (p=0.007). However, Orringer
JS et al. found no significant differences in inflammatory or
non-inflammatory lesions in a split-face study comparing one
or two PDL treatments vs no treatment.156, level I

Adverse effects following PDL treatment are minimal which

include pain, erythema, purpura and post-inflammatory
hyperpigmentation.156, level I

o Potassium Titanyl Phosphate (KTP) Laser

Improvement in total acne lesion scores by 35% at one week

(p<0.01) and 21% at four week (p=0.09) after KTP laser
treatment was observed compared to no improvement with
placebo.156, level I

o Infrared Diode Laser

A SR of four RCTs evaluated the efficacy of infrared lasers

at 1320 nm or 1450 nm vs control (untreated or cryogen).
Treatment with 1320 nm laser showed 27% reduction
of open comedones vs 12% deterioration in the untreated
control at one week post-treatment. The 1450 nm laser
showed improvement up to six months after four treatments
on the upper back (mean reduction 98%) vs cryogen alone
(mean reduction 6%) in the same period.156, level I

Another study involving 26 patients with inflammatory facial

acne using 1450 nm diode laser (four treatments) at three to
four weeks interval reported reduction of mean acne lesions
by 29% (p<0.01) and 40% (p<0.03) after four weeks and six
months respectively.157, level II-3

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Noborio R et al. reported reduction in mean acne grading

from 3.9 to 1.4 in inflammatory acne using 1450 nm
diode laser within 5 to 10 sessions at 2 - 4 week intervals
(p<0.01).158, level II-3

o Intense Pulse Light (IPL)

A SR showed that IPL by itself was not beneficial. The

efficacy of IPL was evaluated in one RCT and two clinical
trials, involving a total of 59 patients. The trials evaluated the
efficacy of IPL vs IPL assisted PDT in two and three treatment
sessions with topical 5-aminolaevulinic acid (ALA) and in
four treatment sessions with topical methyl aminolaevulinate
(MAL).156, level I IPL-assisted PDT with topical ALA or topical was
more effective than placebo in inflammatory acne (reduction
of 87.7% vs 66.8%; p<0.05) after 12 weeks. In a split-face
trial, there was no statistical difference between treatment
with BPO as monotherapy and BPO with IPL treatment. Side
effect of IPL was mild with minimal erythema for a few hours
after treatment.159, level I

o Visible Light Sources

There were two SR comprising eight RCTs for this comparison.

The devices studied were 532 nm pulsed laser (green light),
585 nm pulsed laser (yellow light), 405 - 420 nm (blue light),
635 - 670 nm (red light) and 415 nm with 600 nm laser
(blue-red light). Below were the results:-156, level I; 159, level I

– Blue and blue-red light treatment showed significant

moderate to large improvement when compared
to controls. Blue-red light was significantly more
effective than blue light alone in the short term, but
by 12 weeks there was no difference between the two
treatments.

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– Red light treatment showed significant improvement

but the study was not blinded.

– Green light had either no difference or a small to

moderate improvement.

– Yellow light showed either no difference or a moderate

improvement.

In a local study on mild to moderately severe acne receiving

blue light twice a week for 10 sessions, reduction of
comedones (50.2 %), papules (73.1%) and pustules (61.5%)
was observed at five weeks. Inflammatory lesions responded
better than comedones.160, level III

Side-effects included moderate pain during the procedure,

itch, erythema and swelling which resolved within hours.
Few patients had postinflammatory hyperpigmentation which
resolved within three months.156, level I; 159, level I

•฀฀ Photodynamic฀Therapy฀(PDT)฀฀

PDT uses light-activated cream (photosensitiser) which is absorbed

into the pilosebaceous unit to amplify the response to light therapy.
Commonly used photosensitisers include ALA and MAL. Porphyrin
photoexcitation occurs optimally within the Soret band (360 – 405
nm) with four smaller peaks between 500 nm and 635 nm.

A SR involving five RCTs, 12 clinical studies and two case reports

showed that topical ALA or MAL at 2 - 4 week intervals for a total of
two to four treatments produced greatest clinical effect. In all Fitzpatrick
skin types, papulopustular acne responded better compared to non-
inflammatory acne. However, patients with darker skin types had a
higher risk of post- inflammatory hyperpigmentation.161, level I
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In another SR by Hamilton FL et al., the following findings were

noted:159, level I
o PDT was superior to light therapy or placebo. However, the
number of participants in each trial was small.
o No significant differences between red light with MAL or ALA
were observed. More pronounced adverse effects (such as
stinging, burning, erythema and oedema) were seen with ALA
than with MAL except for pain scores.
o Comparison with three different light sources (600 - 850 nm
IPL, 580 - 980 nm IPL and bipolar radiofrequency, and blue
light) showed the best improvement in lesion count occurred
with blue light but was not statistically significant.

Side effects of PDT include varying degree of erythema, oedema,

blistering, acute acneiform eruptions and post inflammatory
hyperpigmentation. These side effects are often severe enough for
patient to discontinue treatment.159, level I

RECOMMENDATION
•฀ Phototherapy฀and฀photodynamic฀therapy฀may฀be฀used฀as฀an฀alternative฀
therapeutic options for patients who fail or unable to tolerate other
standard acne therapies. (Grade B)

7.2.5 Complementary and Alternative Medicines (CAMs)

CAMs are commonly used to treat acne vulgaris. However, there is insufficient
evidence on these therapies.

A SR listed a broad range of CAMs available for the management of acne.

However, the primary papers in this review were generally of poor methodology
with no strong evidence to show the efficacy of these therapies.162, level I

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Five percent topical tea tree oil gel had been shown to be an effective treatment
option for mild to moderate acne vulgaris in one RCT. Compared to the placebo,
there was a greater reduction in mean total lesion count by 43.6% versus 12.0%
after six weeks of treatment (p<0.001). Adverse effects of this treatment included
pruritus, burning and scaling.163, level I

Ayurverdic formulations have also been used for the management of acne vulgaris
with different efficacy. ‘Sunder Vati’ shows significant clinical improvement in
the severity of both inflammatory and non inflammatory acne. However, the
exact mechanism of action remains unknown.164, level I In addition, there were
methodological flaws in this study in terms of randomisation.

There is insufficient evidence to recommend any specific CAMs for the

treatment of acne.

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8. QUALITY OF LIFE (QoL)

QoL refers to the patient’s ability to enjoy a normal life. Acne vulgaris affects
patients’ perceptions of themselves which may limit goals, standards, and
expectations in everyday activities.

A review on medication adherence among acne patients found that in general,

patients with better QoL impact were more adherent to treatment. Study results
among acne patients in community-based dermatologists found a similar pattern,
where adherence was significantly positively correlated with QoL impact.

Patients with better QoL are more adherent to treatment.165, level III A local study in
Sarawak showed a positive correlation between QoL and adherence to treatment
(r=0.24,฀p=0.003).166, level III Another local study looking at acne prevalence among
secondary school children in Muar, Johor, found considerable impact on QoL
among study subjects.3, level III

QoL is important as it may affect treatment adherence and subsequent

treatment outcomes.

a.฀Impairment฀of฀QoL฀

In a study conducted among university students in Hong Kong, the majority of acne
sufferers (81.8%, 95% CI 78.1 to 85.6) indicated that their QoL was impaired
by acne in terms of psychological and social consequences, and subjective
assessment of acne severity.167, level III

Negative effects of acne on patient’s QoL were found in their symptoms and
feelings, daily activities, leisure, work and study, personal relationships and
treatment. In addition, when compared to a non-acne group, acne patients had
significantly higher scores on psychological issues such as obsession (p=0.01),
sensitivity (p=0.001), depression (p=0.001), anxiety (p=0.01), paranoid ideation
(p=0.02), and psychoticism (p=0.001).168, level III

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The QoL of acne patients with psychological distress significantly affects activities
of daily living (p=0.033), social activities (p=0.016), performance at work or at
school (p=0.003), feelings (p=0.0002), and overall mental health (p=0.0001).169,
level III

In a local study in Sarawak, more than two-thirds (66.5%) of acne patients from
government clinics reported QoL impairment, with symptoms and feelings as the
main domain affected.170, level III

In patients with mild to moderate acne, treatment improved QoL in domains of

symptoms (p<0.01), emotions (p<0.01) and function (p<0.01), in addition to
improvement in acne severity.171, level III

b.฀฀Predictive฀Factors฀of฀QoL฀

Identified factors predicting QoL impairment are:

i. Severity of acne
Studies found significant correlation between severity of acne and QoL
impairment.167 - 168, level III; 170 - 171, level III

ii. Gender
Three studies identified that females in all categories of acne severity
had significantly higher QoL impairment compared to males.167, level III;
171 - 172, level III
This is contrary to the findings of a study by Abdel-Hafez et
al. where males were more affected.168, level III

iii. Duration of acne

Significant positive correlation was found between the duration of acne
and impairment of QoL.168, level III; 172, level III

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iv. Age
Older patients have worse acne related QoL.171 - 172, level III

Various tools were used for QoL assessment in the above studies, out
of which only three measured acne-specific QoL namely Skindex, Cardiff
Acne Disability Index (CADI) and Acne Quality of Life (Acne-QoL). However,
none of these tools have been validated locally.

RECOMMENDATION
•฀฀ Quality of life assessment may be considered in the management of
patients with acne. (Grade C)

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9. REFERRAL

The urgency for referral is dependent upon various factors. It should follow
accepted guidelines based on acuteness of severity and psychological impact.
The urgency for referral is divided into the following categories:
Urgent : Within 24 hours
Seen Early : Within one to four weeks
Non-urgent : Based on available appointment date

a. Urgent referral (to a psychiatrist)

Major depression or any suicidal behaviour

b.฀฀฀Seen฀Early

i. Severe acne or nodulocystic acne that may need isotretinoin173 - 178, level III
ii. Severe social or psychological problems including a morbid
f e a r o f def o rm ity (dysmorp hop hob ia) 1 7 3 , l e v e l I I I ; 1 7 6 , l e v e l I I I a nd
depression 174, level III; 175, level III

c. Non-urgent

i. For diagnosis
•฀ Suspected฀rosacea176, level III
•฀ Suspected฀drug-induced฀acne176, level III
•฀ Acne฀beginning฀or฀persisting฀outside฀the฀normal฀age฀range฀for฀the฀
condition or late onset acne176, level III
•฀ Suspected฀occupational฀causes176, level III
•฀ Suspected฀ underlying฀ endocrinological฀ cause฀ (such฀ as฀ Polycystic฀
Ovarian Syndrome) requiring further assessment173 - 174, level III; 177, level III

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•฀ Rare฀variants฀of฀acne฀such฀as฀acne฀excoriae,฀chloracne฀and฀acne฀
fulminans177, level III
•฀ Suspected฀Demodex฀folliculitis177, level III
•฀ Pityrosporum฀folliculitis177, level III
•฀ Gram฀negative฀folliculitis

ii. Specialist services

•฀ Resistance฀or฀intolerance฀to฀current฀treatment174, level III
•฀ Moderate฀or฀severe฀acne174, level III; 176, level III
•฀ Possible฀scarring฀or฀failure฀to฀achieve฀adequate฀response174, level III
•฀ Failed฀oral฀antibiotic฀therapy177, level III; 179, level III
•฀ Pregnancy฀with฀moderate฀and฀severe฀acne177, level III
•฀ Acne฀ requiring฀ surgery฀ (such฀ as฀ incision฀ and฀ drainage฀ of฀
cysts)178, level III
•฀ For฀specialised฀physical฀treatment

If patient exhibits suicidal behaviour, an urgent referral to psychiatry is warranted.

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10. IMPLEMENTING THE GUIDELINES

To assist healthcare providers on appropriate management for acne, it is

important to develop valid guidelines by a sound methodology and to ensure the
implementation of evidence-based recommendations.

a. Facilitating and Limiting Factors

The facilitating factors in implementing these CPG are:-

i. Wide dissemination of these CPG to healthcare providers (hard copy & soft copy)
ii. Annual dermatology update course for primary care doctors

The limiting factors in the implementation are:-

i. Cost and availability of treatment
ii. Variation in treatment practice and preferences

b.฀฀Potential฀Resource฀Implications

In implementing recommendations in these CPG, the possible resource implications are:-

i. Expensive topical medications in the primary care setting
ii. Insufficient financial and human resource in conducting training

To enhance the utilisation of these CPG on Management of Acne, the following

clinical audit indicators for quality management are proposed:-
Number of acne patients treated with
Percentage of acne
antibiotic as monotherapy for 12 weeks
patients treated with
= x 100%
topical antibiotic
as monotherapy Total number of acne patients receiving
treatment in the same period

Number of acne patients referred to

Percentage of acne dermatologist/ plastic surgeon/psychiatrist
patients referred = x 100%
to specialist
Total number of acne patients receiving
treatment in the same period

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137. Thielitz A, Sidou F, Gollnick H. Control of microcomedone formation throughout a maintenance treatment
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138. Alirezai M, George SA, Coutts I, et al. Daily treatment with adapalene gel 0.1% maintains initial
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139. Zhang JZ, Li LF, Tu YT, et al. A successful maintenance approach in inflammatory acne with adapalene gel
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140. Leyden J, Thiboutot DM, Shalita AR, et al. Comparison of tazarotene and minocycline maintenance
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141. Gollnick HP, Graupe K, Zaumseil RP. Comparison of combined azelaic acid cream plus oral minocycline
with oral isotretinoin in severe acne. Eur J Dermatol. 2001 Nov-Dec;11(6):538-44.

142. Poulin Y, Sanchez NP, Bucko A, et al. A 6-month maintenance therapy with adapalene-benzoyl peroxide
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145. Potter RA. Intralesional triamcinolone and adrenal suppression in acne vulgaris. J Invest Dermatol. 1971
Dec;57(6):364-70.

146. Mahajan BB, Garg G. Therapeutic efficacy of intralesional triamcinolone acetonide versus intralesional
triamcinolone acetonide plus lincomycin in the treatment of nodulocystic acne. Indian J Dermatol
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147. Gollnick H, Cunliffe W, Berson D, et al. Management of acne: a report from a Global Alliance to Improve
Outcomes in Acne. J Am Acad Dermatol. 2003 Jul;49(1 Suppl):S1-37.

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JAMA. 1964 Sep;28 (189):1000-2.

149. Kaya TI, Tursen U, Kokturk A et al. An effective extraction technique for the treatment of closed
macrocomedones. Dermatol Surg. 2003 Jul;29(7):741-4.

150. Kim SW, Moon SE, Kim JA et al. Glycolic acid versus Jessner’s solution: which is better for facial acne
patients? A randomized prospective clinical trial of split-face model therapy. Dermatol Surg. 1999
Apr;25(4):270-3.

151. Atzori L, Brundu MA, Orru A et al. Glycolic acid peeling in the treatment of acne. J Eur Acad Dermatol
Venereol. 1999 Mar;12(2):119-22.

152. Wang CM, Huang CL, Hu CT et al. Effect of glycolic acid on the treatment of acne in Asian skin. Dermatol
Surg. 1997 Jan;23(1):23-9.

153. Grover C, Reddu BS. The therapeutic value of glycolic acid peels in dermatology. Indian J Dermatol
Venereol Leprol. 2003 Mar-Apr;69(2):148-50.

154. Kessler E, Flanagan K, Chia C et al. Comparison of alpha- and beta-hydroxy acid chemical peels in the
treatment of mild to moderately severe facial acne vulgaris. Dermatol Surg. 2008 Jan;34(1):45-50.

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155. Lee HS, Kim IH. Salicylic acid peels for the treatment of acne vulgaris in Asian patients. Dermatol Surg.
2003 Dec;29(12 ):1196-9.

156. Haedersdal M, Togsverd-Bo K, Wulf HC. Evidence-based review of lasers, light sources and photodynamic
therapy in the treatment of acne vulgaris. J Eur Acad Dermatol Venereol. 2008 Mar;22(3):267-78.

157. Yeung CK, Shek SY, Yu CS et al. Treatment of inflammatory facial acne with 1,450-nm diode laser
in type IV to V Asian skin using an optimal combination of laser parameters. Dermatol Surg. 2009
Apr;35(4):593-600.

158. Noborio R, Nishida E, Morita A. Clinical effect of low-energy double-pass 1450 nm laser treatment for
acne in Asians. Photodermatol Photoimmunol Photomed. 2009 Feb;25(1):3-7.

159. Hamilton FL, Car J, Lyons C et al. Laser and other light therapies for the treatment of acne vulgaris:
systematic review. Br J Dermatol. 2009 Jun;160(6):1273-85.

160. Penny PL Lim, CC Chang, A Johar et al., editor. Acne Phototherapy with high a intensity, blue light
source. 31st Annual Congress of Dermatology and Annual General Meeting; 19th to 22nd August 2006;
Penang.

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2009 Jun;160(6):1140-8.

162. Magin PJ, Adams J, Pond CD, et al. Topical and oral CAM in acne: a review of the empirical evidence and
a consideration of its context. Complement Ther Med. 2006 Mar;14(1):62-76.

163. Enshaieh S, Jooya A, Siadat AH, et al. The efficacy of 5% topical tea tree oil gel in mild to moderate acne
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2007 Jan-Feb;73(1):22-5.

164. Paranjpe P, Kulkarni PH. Comparative efficacy of four Ayurvedic formulations in the treatment of acne
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15;49(3):127-32.

165. Lott R, Taylor SL, O’Neill JL, et al. Medication adherence among acne patients: a review. J Cosmet
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to topical acne treatment. J Cutan Med Surg. 2009 Jul-Aug;13(4):204-8.

167. Law MPM, Chuh AAT, Lee A, et al. Acne prevalence and beyond: acne disability and its predictive
factors฀among฀Chinese฀late฀adolescents฀in฀Hong฀Kong.[Erratum฀appears฀in฀Clin฀Exp฀Dermatol.฀2010฀
Apr;35(3):339]. Clin Exp Dermatol. 2010 Jan;35(1):16-21.

168. Abdel-Hafez K, Mahran AM, Hofny ERM, et al. The impact of acne vulgaris on the quality of life and
psychologic status in patients from upper Egypt. Int J Dermatol. 2009 Mar;48(3):280-5.

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169. Mosam A, Vawda NB, Gordhan AH, et al. Quality of life issues for South Africans with acne vulgaris. Clin
Exp Dermatol. 2005 Jan;30(1):6-9.

170. Yap BB. Acne Vulgaris: Quality of life and cost of illness in government clinics in Sarawak (thesis). Kuala
Lumpur: Universiti Kebangsaan Malaysia; 2010.

171. Jones-Caballero M, Chren MM, Soler B, et al. Quality of life in mild to moderate acne: relationship to
clinical severity and factors influencing change with treatment. J Eur Acad Dermatol Venereol. 2007
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175. The Alfred Hospital Referral & Management Guidelines. Dermatology: The Alfred; June 2006 (updated
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[cited฀2010฀20฀July฀2011]:฀Available฀from:฀http://www.medscape.org/viewprogram/2032.

178. Taylor MB. Treatment of acne vulgaris. Guidelines for primary care physicians. Postgrad Med. 1991 Jun
1991 Jun;89(8):40-2.

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Appendix 1
SEARCH TERMS
The following MeSH terms or free text terms were used either singly or in combination:

“acne฀ vulgaris”[MeSH],฀ acne,฀ “nodulocystic฀ acne”,฀ “epidemiology”[Mesh],฀

pathophysiology,฀ “risk฀ factors”[MeSH],฀ age,฀ “sex”[Mesh],฀ ฀ gender,฀ genetics”[MeSH],฀
“obesity”[MeSH],฀“body฀mass฀index”[MeSH],฀BMI,฀“hormones”[MeSH],฀“pituitary฀tumor”,฀
adrenal,฀ “ovarian฀ tumor”,฀ “polycystic฀ ovarian฀ syndrome”,฀ “smoking”[MeSH],฀ stress,฀
“cosmetics”[MeSH],฀“facial฀therapy”,฀“diet”[MeSH],฀diary,฀“milk”[MeSH],฀chocolate,฀sugar,฀
“glycemic฀index”[MeSH],฀“glycaemic฀index”,฀“glycemic฀load”,฀“glycaemic฀load”,฀“clinical฀
presentation”,฀ “diagnosis”[Mesh],฀ “physical฀ examination”[Mesh],฀ “biopsy”[Mesh],฀ “skin฀
biopsy”,฀ “histology”[Mesh],฀ “microbiology”[Mesh],฀ “microbiological฀ techniques”[Mesh],฀
“microbiologic฀ testing”,฀ “microbial฀ sensitivity฀ tests”[Mesh],฀ “laboratory฀ techniques฀
and฀ procedures”[Mesh],฀ “folliculitis”[Mesh],฀ “infective฀ folliculitis”,฀ “clinical฀ diagnosis”,฀
“clinical฀ response”,฀ “treatment฀ response”,฀ “drug฀ resistance,฀ microbial”[Mesh],฀
“antibiotic฀ resistance”,฀ “diagnostic฀ criteria”,฀ grading,฀ severity,฀ “classiication”[Mesh],฀
“global assessment”, “grading system”, “Leeds grading system”, “Leeds technique”,
“therapeutics”[Mesh],฀ treatment,฀ eficacy,฀ response,฀ “treatment฀ failure”[Mesh],฀
“administration,฀ topical”[Mesh],฀ gel,฀ cream,฀ lotion,฀ “benzoyl฀ peroxide”[MeSH],฀
“retinoids”[Mesh],฀ “tretinoin”[Mesh],฀ adapalene,฀ tazarotene,฀ “isotretinoin”[MeSH],฀
“clindamycin”[Mesh],฀ “erythromycin”[Mesh],฀ “salicylic฀ acid”[Mesh],฀ “sulfur”[Mesh],฀
“sulfacetamide”[Mesh],฀ “hydrocortisone”[Mesh],฀ azelaic฀ acid,฀ “dapsone”[Mesh],฀
“administration,฀oral”[Mesh],฀“anti-bacterial฀agents”[Mesh],฀antibiotics,฀“oral฀anitibiotics”,฀
“tetracycline”[Mesh],฀ “oxytetracycline”[Mesh],฀ “doxycycline”[Mesh],฀ “erythromycin฀
stearate”,฀ “zinc฀ acetate”[Mesh],฀ “azithromycin”[Mesh],฀ “minocycline”[Mesh],฀
“lymecycline”[Mesh],฀ “fusidic฀ acid”[Mesh],฀ diane,฀ “doxycycline”[Mesh],฀ “trimethoprim-
sulfamethoxazole฀ combination”[Mesh],฀ cotrimoxazole,฀ bactrim,฀“oxytetracycline”[Mesh],฀
“maintenance฀therapy”,฀“remission฀induction”[Mesh],฀monotherapy,฀combination,฀“drug฀
therapy,฀combination”[Mesh],฀“contraceptives,฀oral”[Mesh],฀“combined฀oral฀contraceptives”,฀
“spironolactone”[Mesh],฀ “lutamide”[Mesh],฀ “inasteride”[Mesh],฀ “cimetidine”[Mesh],฀
“oral฀isotretinoin”,฀“13-cis฀retinoic฀acid”,฀“injections,฀intralesional”[Mesh],฀corticosteroid,฀
“intralesional฀ corticosteroid”,฀ “photochemotherapy”[Mesh],฀ “photodynamic฀ therapy”,฀
“laser฀ therapy”[Mesh],฀ “chemical฀ peel”,฀ “trichloroacetic฀ acid”[Mesh],฀ “glycolic฀ acid”,฀
“alfa-hydroxyacid”,฀ “beta-hydroxyacid”,฀ “fatty฀ acids,฀ omega-3”[MeSH],฀ ibre,฀ “herbal฀
therapy”,฀ “traditional฀ therapy”,฀ “phytotherapy”[MeSH],฀ “quality฀ of฀ life”[Mesh],฀ “referral฀
and฀consultation”[Mesh],฀referral,฀“physician฀referral”

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Appendix 2
CLINICAL QUESTIONS

1. What are the epidemiological characteristics of acne?

2. What is the pathophysiology of acne?
3. What are the risk factors for acne?
4. What are the aggravating factors for acne?
5. What is the role of diet in acne?
6. What is the role of supplements in acne?
7. What is the resistance pattern to oral antibiotics?
8. How is acne severity graded?
9. Is maintenance therapy after induction of remission effective in the
treatment of acne?
10. Is combination therapy, compared to monotherapy, more effective in
maintenance phase of acne treatment?
11. Is topical benzoyl peroxide effective in the treatment of acne?
12. Is topical retinoid effective in the treatment of acne?
13. Is topical antibiotic effective in the treatment of acne?
14. Is topical salicylic acid effective in the treatment of acne?
15. Is topical sulphur effective in the treatment of acne?
16. Is topical azelaic acid effective in the treatment of acne?
17. Is fixed combination preparation compared to monotherapy more effective
in acne treatment?
18. Is oral antibiotic effective in the treatment of acne?
19. Is oral hormonal therapy effective in the treatment of acne?
20. Is oral isotretinoin effective in the treatment of acne?
21. Is intralesional corticosteroid injection effective in the treatment of acne?
22. Is photodynamic therapy or laser therapy effective in the treatment of acne?

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23. Is chemical peel effective in the treatment of acne?

24. Is comedone extraction effective in the treatment of acne?
25. Is alternative therapy or complement therapy (herbal, traditional or
complementary) effective in the treatment of acne?
26. How does acne affect the quality of life?
27. When should acne patient be referred to a dermatologist or plastic surgeon?

68
 Appendix 3
FOOD LIST ACCORDING TO GLYCAEMIC INDEX (GI) CLASSIFICATION
Classification of GL Categories of GI (based on glucose as the reference)
Low : ≤10 Low : <55
Moderate : 11 - 19 Medium : 55 - 70
High : ≥20 High : >70

Low GI Medium GI High GI

Foods/ Drinks
69

Example GI Example GI Example GI

Rice Rice, parboiled 48 Brown rice, boiled 68 White rice, boiled 73
Basmati, white, boiled 58 Glutinous rice, white 98

Bread Whole grain bread 51 Pita bread 57 Whole meal bread 74

Chapatti 52 White bread 75
Sardine sandwich 73

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Breakfast cereals Oat bran, raw 50 Instant porridge, oats 66 Cornflakes 81
Cocoa-flavoured puffed rice 77

Pasta and noodles Spaghetti, whole meal, boiled 37 Rice noodles, dried, boiled 61 Fried meehoon 99
Fried macaroni 74

Tubers Yam 51 Sweet potato, boiled 63 Potato, boiled 78

Potato, French fries 63
 Low GI Medium GI High GI
Foods/ Drinks
Example GI Example GI Example GI
Legumes Kidney beans 24
Lentils 32
Soya beans 16
Vegetables Carrots, boiled 39 Pumpkin 75
Broccoli 15
Cauliflower 15
Fruits Apple, raw 38 Pineapple, raw 59 Watermelon, raw 76
Orange, raw 43
Banana, raw 51

Dairy products and Milk, full fat 27 Ice cream 61

alternatives Milk, skim 32
70

Ice cream, low fat 50

Yogurt 36
Low-fat yogurt, fruit, sugar. 33
Soy milk 32
Snack products Chocolate 40 Popcorn 65
Soft drink/soda 59
Potato crisps 56

MANAGEMENT OF ACNE
Sugars Fructose 19 Sucrose 68 Glucose 99
Honey 61 Teh tarik 78

Source:
1. Foster-Powell K, Holt SH, Brand-Miller JC. International table of glycemic index and glycemic load values: 2002. Am J Clin Nutr. 2002 Jul;76(1):5-56
2. Nik Shanita S. Development and determination of glycaemic index and types of carbohydrate in endurance athletes’ food choices. Final Report UKM N14/2000 grant. Universiti Kebangsaan Malaysia, Kuala
Lumpur, 2006 (unpublished document)
 Appendix 4
CLINICAL CHARACTERISTICS OF ACNE PATIENTS IN STUDIES ON ANTIBIOTIC RESISTANCE
Authors / year of No. of studies / Prior antibiotic Characteristic of patients Overall resistance rate of
No. Study period
publication / country study subjects* usage (including type of severity) P. Acne

1. Cooper AJ, 1998, UK SR of 12 Primary papers published Not mentioned 3,049 respondents 20% in 1978 - 62% in 1996
and USA40, level III studies between January 1976 & (selected four key studies)
January 1997

2. Coates P et al., 2002, 4,274 patients Data collected between All received prior 2,173 males, age: 6 months to Ranges from 31.5 - 64% in 10
UK41, level III 1991 & 2000 antibiotic therapy 86 years old 2,101 females, age: years period
1 to 77 years old
71

3. Zandi S et al., 2011, 100 patients March - December 2008 Not mentioned 36 males & 64 females, Overall resistance to at least
Iran42, level III >14 years old, one antibiotic: 31%
moderate to very severe acne

4. Dumont-Wallon G et 273 patients Not mentioned Numbers 39% males & 61% females, • Erythromycin฀=฀75%
al., 2010, France43, undetermined ≥12 years old, • Tetracycline฀=฀9.5%
level III
moderate acne • Resistance to doxycycline
(no nodules, <40 comedones (in those resistance to

MANAGEMENT OF ACNE
& at least 25 papules &/or tetracycline)฀=฀100%
pustules)

5. Oprica C et al., 2004, 130 patients March 1999 - May 2000 100 patients Age: 12 - 45 years old, 39% among treated group, only
Sweden44, level III (on oral antibiotic moderate to severe inflammatory 3% in untreated group
last 2 - 6 months) acne OR=3.8฀(95%฀CI฀2.1฀to฀6.7)
 Authors / year of No. of studies / Prior antibiotic Characteristic of patients Overall resistance rate of
No. Study period
publication / country study subjects* usage (including type of severity) P. Acne

6. Bettoli V et al., 2006, 1,206 patients April 2000 - June 2004 Not mentioned Age: 12 - 42 years old (mean prevalence of resistance)
Italy45, level III • Erythromycin฀=฀49.8%฀
• Clindamycin฀=฀40.9%
• Tetracycline฀=฀1.8%฀
• Minocycline฀=฀0.6%

7. Ross JI et al., 2003, 644 patients October 1999 -February 2001 Numbers Age: ≥12 years old 50.8 - 93.6%
UK, Italy, Sweden, undetermined (lowest in Hungary & highest
Hungary, Greece, in Spain)
Spain46, level III
72

8. Kurokawa I et al., 50 patients November 1994 - August 1995 17 patients 19 males & 31 females, • 2 (4%) strains resistant to
1999, Japan47, level III Age: 11 - 34 years old erythromycin
Had acne for 1 week to 15 years • 2 (4%) strains resistant to
clindamycin
• 1 (2%) strain each to
doxycycline & tetracycline

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9. Tang JJ, 2010, 100 patients January - June 2010 Not mentioned ≥12 years old 15.1% of positive isolates
Malaysia48, level III

*All attended dermatology clinic

 RESISTANCE RATES OF SYSTEMIC ANTIBIOTICS USED
Authors /
No. Erythromycin Clindamycin Tetracycline Doxycycline Minocycline Others
year of publication / country
20.0 - 72.5% 34.2 - 35.6%
1. Cooper AJ, 1998, UK, USA40, level III <1% Trimethoprim (17.5%)
Cross-resistance Cross-resistance

2. Coates P et al., 2002, UK41, level III 57.6%** 50.0%** NA NA NA NA

• Co-trimoxazole (24.1%)
3. Zandi S et al., 2011, Iran42, level III 12.1% 10.3% 0% 0% NA
• Azithromycin (0%)

Dumont-Wallon G et al., 2010, 9.5%

4. 75.1% NA NA NA
France43, level III Cross-resistance
73

5. Oprica C et al., 2004, Sweden44, level III 19.9% 27.4% NA NA NA Co-trimoxazole ( 0% )

6. Bettoli V et al., 2006, Italy45, level III mean - 49.8% mean - 40.9% NA NA mean - 0.6% NA

Ross JI et al., 2003, UK, Italy, Sweden,

7. 47 - 92%*** 43 - 95%*** NA NA NA NA
Hungary, Greek, Spain46, level III

8. Kurokawa I et al., 1999, Japan47, level III 4.0% 4.0% 2.0% 2.0% 0% NA

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9. Tang JJ, 2010, Malaysia48, level III 7.5% 15.1% 5.7% 5.7% 0% NA

NA฀=฀Not฀available
**highest prevalence in 10 years duration
***approximate percentage from the figures in the study
 Appendix 5
SUGGESTED MEDICATION DOSAGES AND SIDE EFFECTS
Drug Recommended Dosage Common Adverse Effects Contraindications Special Precautions

Topical benzoyl peroxide Apply once to twice daily Contact dermatitis, dryness, Hypersensitivity to benzoyl Avoid contact with eyes, eyelids, lips and
skin discolouration, skin rash, peroxide mucous membranes.
peeling, transient local oedema May bleach fabrics or hair.

Topical tretinoin Apply once in the evening Initial exacerbation of symptoms, Hypersensitivity to tretinoin, Avoid concomitant use of topical
before retiring skin irritation, stinging, pregnancy, lactation, keratolytic agents.
oedema, blistering, crusting eczema, sunburn conditions Avoid exposure to sunlight or ultraviolet
of skin, erythema, scaling, (UV) light.
74

photosensitivity, temporary
Avoid contact with eyes, mouth, angles
hypo/hyperpigmentation
of nose, mucous membranes and open
wounds.
Avoid facial scrub.
Avoid use of topical preparations with high
concentration of alcohol, menthol, spices
or lime.

MANAGEMENT OF ACNE
Topical adapalene Apply once daily to affected Mild skin irritation, scaling, Hypersensitivity to adapalene Avoid contact with eyes, lips, angles of
areas after washing in the erythema, dryness, stinging, nose and mucous membranes.
evening before retiring burning, pruritus Avoid cuts, abrasions, eczematous skin or
sunburned skin.
Minimise exposure to sunlight.
 Drug Recommended Dosage Common Adverse Effects Contraindications Special Precautions

Topical tazarotene* Apply once in the evening Pruritus, burning, stinging, Hypersensitivity, pregnancy, Avoid contact with eyes, mouth and
before retiring erythema, skin peeling, irritation, lactation, eczema, sunburn mucous membranes.
rash, dryness, localised conditions Avoid exposure to sun or UV light.
oedema, desquamation, contact
Women of child bearing potential should
dermatitis, discolouration of
take birth control measures. Negative
skin, photosensitivity
pregnancy test to be obtained within 2
weeks prior to initiation and start therapy
during normal menstrual period.

Topical isotretinoin Apply once daily in the Stinging, burning, slight Pregnancy, lactation, Avoid lips, mouth, eyes, mucous
evening before retiring irritation, erythema, peeling personal or family history of membranes, angles of nose, broken,
cutaneous epithelioma eczematous and sunburned skin.
75

Avoid exposure to sunlight.

Topical clindamycin Apply twice daily Irritation, dryness, stinging, Hypersensitivity to Alcohol base solution may cause burning
erythema, contact dermatitis clindamycin or lincomycin, and irritation of the eyes especially in
ulcerative colitis, antibiotic- atopic individuals.
related colitis

Topical erythromycin Apply twice daily Dryness, erythema, burning, Hypersensitivity to Avoid contact with eyes and other mucous

MANAGEMENT OF ACNE
pruritus erythromycin membranes.

Topical salicylic acid Apply once to thrice daily Irritation, sensitivity, excessive Hypersensitivity to salicylic Avoid prolonged use in high
dryness acid concentrations and over large areas of
the body.
Avoid broken skin, mouth, eyes and
mucous membranes.
 Drug Recommended Dosage Common Adverse Effects Contraindications Special Precautions

Topical sulfur and its Apply once to twice daily. Skin irritation, dermatitis Hypersensitivity to sulfur, Avoid contact with eyes, mouth and other
combinations Initiate with once daily, then children less than 2 years old mucous membranes.
increase gradually. May stain the skin black and emit foul
smell when applied concomitantly with
mercurial compounds.

Topical azelaic acid Apply twice daily Skin irritation, mostly burning or Hypersensitivity to propylene Avoid broken skin, mouth, eyes and
itching, occasionally erythema glycol mucous membranes.
and scaling

Topical dapsone* Apply twice daily Dryness, erythema, oiliness and Hypersensitivity to dapsone, G6PD deficiency, methaemoglobinaemia,
peeling pregnancy and lactation Hemoglobin M.
76

Oral tetracycline 500 mg - 1 g daily in 2 Gastrointestinal disturbances, Hypersensitivity to Should be administered with plenty of
divided doses discolouration of teeth and tetracyclines, water, while sitting or standing, 1 hour
nails, photosensitivity, visual children ≤8 years old, before or 2 hours after meals to avoid
disturbances pregnancy, lactation oesophageal ulceration. Absorption is
impaired by food, milk, dairy products, iron
salts and antacids.

MANAGEMENT OF ACNE
Oral doxycycline 50 - 100 mg once to twice Gastrointestinal disturbances, Hypersensitivity to Should be administered with plenty of water,
daily photosensitivity, hypersensitivity, tetracyclines, while sitting or standing, 1 hour before or
permanent staining of teeth, children ≤8 years old, 2 hours after meals to avoid oesophageal
rash pregnancy, lactation ulceration.
 Drug Recommended Dosage Common Adverse Effects Contraindications Special Precautions

Oral erythromycin Erythromycin Ethyl Gastrointestinal disturbances, Hypersensitivity to Hepatic and renal impairment,
Succinate (EES): rash, urticaria, headache, erythromycin prolonged QT interval,
400 - 800 mg twice daily dizziness concomitant therapy with colchicine
Erythromycin Stearate: (toxicity) and lovastatin (rhabdomyolysis)
250 - 500 mg twice daily

Oral azithromycin 500 mg thrice weekly112, Neutropenia, hearing Hypersensitivity to Severe renal and hepatic disease,
113, 122, 123
impairment, vertigo, azithromycin or other myasthenia gravis, prolonged QT interval
gastrointestinal disturbances, macrolides, and cardiac repolarisation
abnormal liver function, rash, hepatic dysfunction,
angioedema jaundice

Oral minocycline 50 - 100 mg once to twice Gastrointestinal disturbances, Hypersensitivity to Hepatic and renal impairment,
77

daily vestibular disturbances, minocycline and other concomitant use of isotretinoin

abnormal hyperpigmentation, tetracyclines,
photosensitivity, teeth children ≤8 years old,
discolouration in children pregnancy, lactation
*Potentially serious adverse
reactions - autoimmune
hepatitis, drug-induced lupus
erythematosus

MANAGEMENT OF ACNE
Oral co-trimoxazole 1 tablet daily Gastrointestinal disturbances, Hypersensitivity to Haematological disorders, elderly,
(trimethoprim 80 mg and skin rashes, hepatitis, dizziness, sulfonamides or G6PD deficiency, folate deficiency
sulfamethoxazole 400 mg)124 headache, erythema multiforme trimethoprim,
*Uncommon but serious adverse severe renal and hepatic
reaction - Stevens-Johnson impairment,
syndrome, toxic epidermal megaloblastic anaemia
necrolysis due to folate deficiency,
pregnancy, lactation
 Drug Recommended Dosage Common Adverse Effects Contraindications Special Precautions

Oral trimethoprim 100 mg thrice daily125 Gastrointestinal disturbances, Hypersensitivity to Hepatic and renal impairment,
pruritus, rash, dizziness, trimethoprim, folate deficiency
headache, erythema multiforme megaloblastic anaemia
*Uncommon but serious adverse due to folate deficiency
reaction - Stevens-Johnson
syndrome, toxic epidermal
necrolysis

Oral isotretinoin 0.5 - 1 mg/kg/day Dryness of skin or mucosa, Hypersensitivity to History of depression or other psychiatric
exanthema, pruritus, facial isotretinoin or any of its disorders, increased intracranial pressure
erythema/dermatitis, hair components, and seizures.
thinning, photosensitivity, pregnancy due to Avoid blood donation during treatment and
78

muscle and joint pain, teratogenicity, lactation, within 1 month after treatment cessation.
headache, dyslipidaemia hypervitaminosis A,
excessively elevated blood
lipid values

Oral cyproterone acetate 1 tablet daily for 21 days, Gastrointestinal disturbances, Hypersensitivity to ethinyl Risk of venous thromboembolism,
2 mg, ethinyl estradiol followed by 7 days of tablet- headache, depression, breast estradiol and cyproterone hypertriglyceridaemia, acute or chronic
35 mcg free period tenderness, weight changes acetate or any of its disturbances of liver function

MANAGEMENT OF ACNE
excipients,
history of severe liver
impairment,
genital tract or breast
carcinoma, pregnancy
and lactation, presence of
thromboembolic events
 Drug Recommended Dosage Common Adverse Effects Contraindications Special Precautions

Oral chlormadinone 1 - 2 mg/day Gastrointestinal and menstrual Hypersensitivity to History of cardiovascular or renal
acetate* disturbances, weight changes, chlormadinone, impairment, diabetes mellitus, asthma,
fluid retention, allergic skin history of severe liver epilepsy, migraine, depression
rashes, urticaria, depression, impairment,
breast tenderness genital tract or breast
carcinoma,
arterial disease,
undiagnosed vaginal
bleeding and porphyria,
pregnancy and lactation

Oral levonorgestrel + 1 tablet daily for 21 days, Gastrointestinal and menstrual Hypersensitivity to ethinyl Past ectopic pregnancy, functional ovarian
ethinyl estradiol followed by 7 days of tablet- disturbances, headache, estradiol and levonorgestrel cysts, history of cardiovascular or renal
79

free period dizziness, breast tenderness, or any of its excipients, impairment, diabetes mellitus, depression
weight changes, fluid retention, history of severe liver
depression impairment,
genital tract or breast
carcinoma,
arterial disease,
undiagnosed vaginal

MANAGEMENT OF ACNE
bleeding and porphyria,
pregnancy and lactation,
presence of thromboembolic
events
 Drug Recommended Dosage Common Adverse Effects Contraindications Special Precautions

Oral desogestrel + 1 tablet daily for 21 days, Menstrual disturbances, breast Hypersensitivity to May increase risk of breast cancer,
ethinyl estradiol followed by 7 days of tablet tenderness, pain, nausea, ethinylestradiol and glucose intolerance and thromboembolism
free period vomiting, headache, migraine, desogestrel or any of its Familial defects of lipoprotein metabolism
depression, fluid retention, excipients,
Cardiovascular or renal impairment
weight changes suspected oestrogen
dependent neoplasms,
pregnancy and lactation,
presence of thromboembolic
events

Oral flutamide 250 mg daily128 Breast tenderness, hot flushes, Hypersensitivity to flutamide, Monitor liver function test
decreased libido, impotence, hepatic impairment,
80

diarrhoea, nausea, vomiting pregnancy and lactation

*These medications are currently not available in Malaysia

Sources:
1. MIMS Malaysia (internet communication, 28 June 2011 at http://www.mims.com/)
2. Thomson Reuters. Micromedex®1.0 (Healthcare Series). Greenwood Village Thomson Reuters; 2011

MANAGEMENT OF ACNE
3. Product Package Insert

Disclaimer:
• The outline of drug dosage and administration is intended as a general guide to therapy.
• The adverse effects listed are not exhaustive.
• Caution is advised when prescribing for patients with other medical problems or on multiple drugs.
 MANAGEMENT OF ACNE

LIST OF ABBREVIATIONS
AA Azelaic acid
ABP Adapalene/BPO
ALA 5-aminolaevulinic acid
BPO Benzoyl peroxide
CAMs Complementary and alternative medicines
CASS Comprehensive acne severity scale
CBP Clindamycin/BPO
CI Confidence interval
CMA Chlormadinone acetate
COC Combined oral contraceptive
CPA Cyproterone acetate
CPG(s) Clinical Practice Guidelines
DG Development group
DHEAS Dehydroepiandrosterone sulfate
DHT Dihydrotestosterone
EBP Erythromycin/BPO
g Gram
G6PD Glucose-6-phosphate dehydrogenase
GI Glycaemic index
GL Glycaemic load
HTA Health Technology Assessment
IPL Intense pulsed light
IL Interleukin
kg Kilogram
KTP Potassium titanyl phosphate
MAL Methyl aminolaevulinate
mg miligram
MOH Ministry of Health
OR Odds ratio
P. acnes Propionibacterium acnes
PDL Pulsed dye laser
PDT Photodynamic therapy
PPARs Peroxisome proliferator-activated receptors
QoL Quality of life
RC Review Committee
RCT(s) Randomised controlled trial(s)
SA Salicylic acid
SR Systematic review
UV Ultraviolet
vs Versus

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 MANAGEMENT OF ACNE

ACKNOWLEDGEMENT

The members of development group of these guidelines would like to express

their gratitude and appreciation to the following for their contributions:
•฀ Panel฀of฀external฀reviewers฀who฀reviewed฀the฀draft

•฀ Ms฀Sin฀Lian฀Thye฀(Nursing฀Matron)฀and฀Ms฀Loong฀Ah฀Moi฀(Nursing฀Sister)

•฀ Technical฀Advisory฀Committee฀for฀CPG฀for฀their฀valuable฀input฀and฀feedback

•฀ All฀those฀who฀have฀contributed฀directly฀or฀indirectly฀to฀the฀development฀of฀the฀
CPG

DISCLOSURE STATEMENT

The panel members of both Development Group and Review Committee had
completed disclosure forms. None held shares in pharmaceutical firms or acts
as consultants to such firms. (Details are available upon request from the CPG
Secretariat)

SOURCES OF FUNDING

The development of the CPG on Management of Acne was supported financially

in its entirety by the Ministry of Health.

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