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Guidelines of Care for Acne Vulgaris Management
Technical Report
2
Acne Vulgaris
Table of Contents
Page No.
Introduction ................................................................................................ 3
Clinical questions ....................................................................................... 3
Method of evaluation of evidence .............................................................. 4
Grading and classification systems............................................................ 7
Microbiological and endocrine testing ...................................................... 12
Topical agents.......................................................................................... 18
Systemic agents....................................................................................... 30
Hormonal agents...................................................................................... 36
Isotretinoin ............................................................................................... 42
Miscellaneous therapies .......................................................................... 49
Complementary/alternative therapies ...................................................... 53
Dietary restriction ..................................................................................... 58
Graded References.................................................................................. 60
3
Introduction
Approximately 40-50 million people in the United States have acne vulgaris. It is the
most common skin disease, especially in adolescents and young adults. Acne affects
more than 85% of teenagers. There is no mortality associated with acne disease, but
there is often significant physical and psychological morbidity such as permanent
scarring, poor self-image, depression and anxiety. The direct cost of acne is estimated to
exceed $1 billion per year, with $100 million spent on over-the-counter acne products in
the United States.
Acne is a multifactorial disease affecting the pilosebaceous follicles of the skin. Some
factors that play an important role in the pathogenesis of acne are follicular
hyperkeratinization, microbial colonization, sebum production inflammation following
chemotaxis and the release of various pro-inflammatory mediators. Appropriate
evaluation and management of acne vulgaris are important. At present there are many
topical and systemic therapeutic options available for the treatment of acne because of
the multifactorial etiology of acne vulgaris. Various therapies are discussed in the
“Guidelines of care for acne vulgaris management” (J Am Acad Dermatol. 2007
Apr;56(4):651-63).
Clinical Questions
This is a comprehensive search of the peer-reviewed biomedical literature and analysis
of the evidence regarding therapies for acne as a basis for the development of the
American Academy of Dermatology (AAD) clinical guidelines of care for the treatment of
acne.
Specific Clinical Questions addressed in the acne guidelines are the following:
I.
What systems are most commonly used for the grading and classification of adult
acne and acne vulgaris in adolescents (11 to 21 years) to adults?
II. What is the role of microbiological and endocrine testing in evaluating patients
with adult acne and acne vulgaris in adolescents to adults?
III. What is the effectiveness and what are the potential side effects of the following
topical agents in the treatment of adult acne and acne vulgaris in adolescents to
adults including:
a) retinoids and retinoid-like drugs
b) benzoyl peroxide
c) topical antibiotics
d) salicylic/azelaic acids
e) sulfur and resorcinol
f) aluminum chloride
g) zinc
h) combinations of topical agents
IV. What is the effectiveness and what are the potential side effects of the following
systemic antibacterial agents in the treatment of adult acne and acne vulgaris in
adolescents to adults including:
a) tetracyclines: doxycycline, minocycline
b) macrolides: erythromycin
4
c) clindamycin
d) trimethoprim
e) ampicillin/amoxicillin
V. What is the effectiveness and what are the potential side effects of hormonal
agents in the treatment of adult acne and acne vulgaris in adolescents to adults
including:
a) contraceptive agents, especially oral preparations
b) spironolactone
c) antiandrogens
d) oral corticosteroids
VI. What is the effectiveness and what are the potential side effects of isotretinoin in
the treatment of adult acne and acne vulgaris in adolescents to adults?
VII. What is the effectiveness and what are the potential side effects of miscellaneous
therapies in the treatment of adult acne and acne vulgaris in adolescents to
adults including:
a) chemical peels
b) comedo removal
c) intralesional steroids
VIII. What is the effectiveness and what are the potential side effects of
complementary/alternative therapies in the treatment of adult acne and acne
vulgaris in adolescents to adults including:
a) herbal agents
b) homeopathy
c) psychological approaches
d) massage therapy
e) hypnosis/biofeedback
IX. What is the effectiveness of dietary restriction in the treatment of adult acne and
acne vulgaris in adolescents to adults?
Method
Evidence evaluated for this report was obtained primarily from a search of MEDLINE
and EMBASE databases spanning the years 1966 to 2006.
The available evidence was evaluated using a unified system called the Strength of
Recommendation Taxonomy (SORT) developed by editors of the US family medicine
and primary care journals (i.e., American Family Physician, Family Medicine, Journal of
Family Practice and BMJ-USA). This strategy was supported by a decision of the Clinical
Guidelines Task Force in 2005 with some minor modifications for a consistent approach
to rating the strength of the evidence of scientific studies.1 Evidence was graded using a
three-point scale based on the quality of methodology as follows:
I
II
Good quality patient-oriented evidence
Limited quality patient-oriented evidence
5
III
Other evidence including consensus guidelines, extrapolations
from bench research, opinion or case studies
6
Clinical recommendations were developed based on evidence tabled in the guideline
and explained further in the technical report. These are ranked as follows:
A. Recommendation based on consistent and good-quality patient-oriented evidence
B. Recommendation based on inconsistent or limited quality patient-oriented evidence
C. Recommendation based on consensus, opinion or case studies
For each intervention within the Clinical Questions, an effort was made to identify and
present the best evidence regarding its use in the treatment of acne. Studies of clinical
measurements of outcome were considered for analysis whether or not the clinical
outcome was the primary outcome measured.
Disclosure of Significant Relationships with Relevant Commercial
Companies/Organizations
The Academy must ensure balance, independence, objectivity and scientific rigor in its
evidence-based guidelines of care. The Board of Directors requires that all participating
members of the guidelines of care associated work groups must comply with regulations
governing disclosure.
All participants are expected to disclose in the document “Authors’ Conflict of Interest
Disclosure Statement” any significant financial interest or other relationship with the
manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services
discussed by them. The intent of this disclosure is not to prevent anyone with a
significant financial or other relationship from participating, but rather to provide readers
of the guidelines with information on which to make their own judgments. It remains for
the reader to determine whether any work member’s interests or relationships may
influence the discussion. Following are the Work Group members that developed the
acne guidelines along with their affiliation and disclosure of potential conflict of interest:”
John Strauss, MD, Chair Acne Work Group – the Department of Dermatology, Roy J.
and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa
Dr. Strauss was a consultant and investigator for Roche Laboratories receiving
honoraria and grants, and a consultant for Medicis receiving honoraria.
Karl R. Beutner, MD, PhD, Chair Clinical Guidelines Task Force – Anacor
Pharmaceuticals, Inc., Palo Alto, California
Dr. Beutner was an employee of Anacor receiving salary and stock options and a
stockholder of Dow Pharmaceutical Sciences receiving stock.
Daniel Krowchuk, MD – the Departments of Pediatrics and Dermatology, Wake Forest
University School of Medicine, Brenner Children’s Hospital, Winston-Salem, North
Carolina
Dr. Krowchuk had no relevant conflicts of interest to disclose.
James J. Leyden, MD – the Department of Dermatology, University of Pennsylvania
Hospital, Philadelphia, Pennsylvania
Dr. Leyden was a consultant for Stiefel and SkinMedica, receiving honoraria; served on
the Advisory Board and was a consultant for Galderma and Obaj, receiving honoraria;
was on the Advisory Board and was a consultant and investigator for Connetics,
Collagenex, Allergan, and Medicis, receiving honoraria.
7
Anne W. Lucky, MD – the Division of Pediatric Dermatology, Cincinnati Children's
Hospital Medical Center and the University of Cincinnati School of Medicine, Cincinnati,
Ohio
Dr. Lucky was an investigator for Connetics, Dow, Galderma, Healthpoint, Johnson &
Johnson, QLT, and Stiefel, receiving grants, and an investigator and consultant for
Berlex receiving grants and honoraria.
Alan R. Shalita, MD – the Department of Dermatology, State University of New York
Downstate Medical Center, Brooklyn, New York
Dr. Shalita was a consultant, investigator, stockholder, and speaker for Allergan,
receiving grants and honoraria; a consultant for Bradley/Doak receiving honoraria;
served on the Advisory Board and was a consultant for Collagenex, receiving honoraria;
was a consultant and investigator for Connetics receiving grants and honoraria; an
Advisory Board member, consultant, investigator, and speaker for Galderma receiving
grants and honoraria; a consultant, speaker, and stockholder for Medicis receiving
honoraria; an Advisory Board member for Ranbaxy receiving honoraria; and a
consultant, investigator, and speaker for Stiefel, receiving grants and honoraria.
Elaine C. Siegfried, MD – the Department of Dermatology, St. Louis University School of
Medicine, St. Louis, Missouri
Dr. Siegfried was an investigator for Atrix receiving salary.
Diane M. Thiboutot, MD – the Department of Dermatology, Pennsylvania State
University College of Medicine, Milton S. Hershey Medical Center, Hershey,
Pennsylvania
Dr. Thiboutot served on the Advisory Board and was an investigator and speaker for
Allergan and Galderma, receiving honoraria; was on the Advisory Board and was a
consultant and investigator for Collagenex receiving honoraria; was on the Advisory
Board and was an investigator for Connetics, Dermik, and QLT, receiving honoraria; and
was a consultant, investigator, and speaker for Intendis, receiving honoraria.
Abby S. Van Voorhees, MD – the Department of Dermatology, University of
Pennsylvania Hospital, Philadelphia, Pennsylvania
Dr. Van Voorhees served on the Advisory Board and was an investigator and speaker
for Amgen, receiving grants and honoraria; was an investigator for Astellas, Bristol
Myers Squibb, and GlaxoSmithKline, receiving grants; was an Advisory Board member
and investigator for Genentech and Warner Chilcott, receiving grants and honoraria; was
on the Advisory Board for Centocor receiving honoraria; was a speaker for Connetics
receiving honoraria; and was a stockholder of Merck, owning stock and stock options.
Carol Sieck, RN, MSN – the American Academy of Dermatology, Schaumburg, Illinois
C. Sieck had no relevant conflicts of interest to disclose.
Reva Bhushan, PhD - the American Academy of Dermatology, Schaumburg, Illinois
Dr. Bhushan had no relevant conflicts of interest to disclose.
8
I.
Grading and classification systems of adult acne and acne vulgaris in
adolescents (11 to 21 years) to adults
Many acne grading and classification systems have been proposed but at present there
is not any one system universally accepted for assessing and grading acne severity. The
grading and classification of acne is essential for the initial evaluation as a base of
comparison during treatment and as a method to assess clinical trials. Acne severity is
generally considered the most important patient characteristic used in determining
individual treatment profiles. There are several grading/classification systems; most
include lesion counting combined with some type of global severity assessment. Global
evaluation takes into account the total impact of the disease. Grading systems are
mainly used in clinical studies for the evaluation of acne treatment. Comparing
therapeutic efficacy in different studies because of the lack of a validated classification
system becomes difficult. It is important to standardize a specific and reproducible
method to grade the severity of acne.
II
II
Level
of Evidence
Global evaluation of
lesions.
Pochi et al.,
J Am Acad Dermatol 1991;
24: 495-500.3
AAD Consensus conference
on acne classification.
Includes a total evaluation of lesions
and complications; categorizes
inflammatory lesions as mild, moderate
or severe.
The search was an expert-advised
structured literature synthesis.
The target population for the review
was all patients with acne who did not
have complicating co-morbidities such
as endocrinopathies.
Review of acne
clinical trials to
provide clinicians the
background needed
to interpret current
and future clinical
trials, and scientists a
basis for further
studies.
Lehmann et al., J Am Acad
Dermatol 2002; 47: 231-40.2
Methodological review of
literature and
recommendations.
Method of Assessment
Type of scale
Author/Date/
study design
Table 1. Acne Grading/Classification Systems
The consensus panel recommendations did not
include non-inflammatory lesions.
The clinical diagnosis of acne severity should be
based on persistent or recurrent inflammatory
nodules, papulopustular disease, ongoing scarring,
drainage from lesions or the presence of sinus
tracks and psychological factors.
A strictly quantitative definition of acne severity
cannot be established because of the variable
expression of the disease.
It is the opinion of the consensus panel that acne
grading can be accomplished by the use of a
pattern-diagnosis system, which includes a global
(total) evaluation of lesions and their complications.
Dividing acne into 4 grades of severity was overly
simplistic.
Panel recommendations:
The authors made recommendations for the
scientists for future clinical trials.
250 papers were reviewed. There were more than
25 different methods of assessment of acne
severity and 19 methods of counting lesions. There
were many different ways the outcomes were
expressed. There was no standard approach to
describing side effects, and no standard follow-up
times.
Conclusions
9
II
Level
of Evidence
The GAGS considers 6 locations on the
face and chest/upper back, with factor
for each location based on surface
area, distribution and density of
pilosebaceous units. Each of the six
locations is graded separately on a 0-4
scale. The global score is a summation
of each factor.
Global Acne Grading
System (GAGS)
Doshi et al., Int J Dermatol
1997; 36: 416-8.4
This paper proposed a new
grading system called Global
Acne Grading System
(GAGS).
Method of Assessment
Type of scale
Author/Date/
study design
Patients with numerous lesions confined to only 1
or 2 locations may end up with a lower total score
and less severe classification than observed
clinically.
Includes both inflammatory and non-inflammatory
lesions.
The authors suggest that time saved in grading can
be spent on counseling patients.
This system is accurate and reproducible. Grading
with the GAGS system takes under 1 minute in an
office setting.
Conclusions
10
II
II
Level
of Evidence
Double-blinded, placebocontrolled trial to determine a
method of grading of acne
severity.
Cook et al., Arch Dermatol
1979; 115: 571-5.7
Randomized, double-blinded,
placebo-controlled trial to
evaluate grading of acne
severity.
Allen and Smith, Arch
Dermatol 1982; 118: 23-5.5
Author/Date/
study design
Acne severity grading
scale.
Acne severity and
comedo grading scale
including lesion
counts.
Type of scale
Uses photographic reference
standards; photographs taken at each
visit become part of patient’s clinical
record.
Double-blinded, controlled clinical trial.
Ranges from 0 (no or few comedones)
to 8 (all of facial area involved with
large, prominent nodules).
Photographs of all the subjects were
also used for evaluations.
Severity scale ranges from 0 (no or few
comedones) to 8 (all of facial area
involved with large, prominent
nodules). This study used the acne
grading scale devised by Cook et al.7
Study 2. Physicians and research
technician evaluated 141 male college
students with acne at baseline and
every two weeks independently for 10
weeks. All subjects at each visit
received a severity grade, papule
count, pustule count and comedo
grade. Comedo count was also done.
Study 1. Physicians and research
technician evaluated 190 subjects male college students with acne at
baseline and every two weeks
independently for 12 weeks. All
subjects at each visit received a
severity grade, papule count, pustule
count and comedo grade. Comedo
counts were not performed in this
study.
Method of Assessment
This method includes both inflammatory and noninflammatory lesions.
The photograph creates a permanent record.
The overall severity grade based on the 0 to 8
scale with the photographic reference standards
showed to be useful, reliable and sensitive.
This study does not include the back and chest. It
uses half of the face for comedo and papule
counts; both sides of the face for pustule counts
and severity grades.
The authors concluded that acne grading scales
and papule counts are equally reproducible
methods of grading inflammatory acne. The
comedo grading scale and comedo count are
equally reproducible.
Conclusions
11
II
Level
of Evidence
The aim of the study was to
create and validate a simple
questionnaire to measure the
quality of life in children with
skin disease.
Lewis-Jones and Finlay,
Br J Dermatol 1995; 132:
942-9.11
Author/Date/
study design
Children’s
Dermatology Life
Quality Index
(CDLQI).
Type of scale
A 10-item questionnaire was used in
this study, similar to the adult DLQI
questions. The questionnaire was
designed for a child. It may sometimes
require parent’s help. Each question
was scored individually. The CDLQI
score was calculated by adding the
scores of the 10 questions. Scores
range from 0-30, 0 being the best
score.
This study was conducted on 169
children aged 3-16 years in a pediatric
dermatology clinic for 1 year.
Method of Assessment
This is a simple scoring method. This method can
be used for clinical trials and clinical practice.
CDLQI provides a new technique for comparative
purposes.
The CDLQI is based on the Dermatology Life
Quality Index (DLQI).
Conclusions
12
13
II.
The role of microbiological and endocrine testing in evaluating patients with
adult acne and acne vulgaris in adolescents to adults
The most prevalent bacterium implicated in the clinical course of acne is
Propionibacterium acnes (P. acnes), a gram-positive anaerobic bacterium that normally
inhabits the skin. Studies have found that in patients affected with acne, the population
of P. acnes is higher than in the unaffected general population. Routine microbiologic
testing is unnecessary in the evaluation and management of patients with acne. In
patients who exhibit acne-like lesions, microbiologic testing may be helpful. Gramnegative folliculitis is an uncommon complication often observed following long-term
systemic treatment of acne.
Adrenal and gonadal androgens play an integral role in the pathogenesis of acne.
Laboratory evaluation is indicated for those with acne and additional signs of androgen
excess. Most people with acne have normal levels of androgenic hormones, despite the
importance of androgens in this disorder. However, in females, acne severity and other
virilizing signs are associated with subtle differences in circulating androgens. These
include elevated free testosterone and DHEA-S, and reduced sex hormone-binding
globulin (SHBG). Presently, routine endocrinologic testing is not indicated for the
majority of patients with acne. Laboratory tests like free testosterone DHEA-S, LH and
FSH may be helpful.
II
Level
of
Evidence
Cove et al., Br J Dermatol
1980; 102: 277-80.16
2 separate studies to determine
levels of P. acnes and
Micrococcaceae.
(1) This study compared
bacterial populations on
foreheads of patients with mild
to moderate acne.
(2) This study compared
bacterial populations and acne
grade pre-treatment and posttreatment with tetracycline
250 mg twice daily for 3 months.
Author(s)/Date/
Study Design
Method of
Assessment
Degree of acne
was graded on a
simple scoring
system:
bacteria sampled
using scrub
method.
CFU (colonyforming units) were
determined by
plating out ten-fold
serial dilutions.
Colonies were
counted after 7
days or 48 hours
anaerobically for P.
acnes and
Micrococcaceae.
Study Population
Ages 18-20 years.
(1) 35 patients with
mild acne and 35
patients with
moderate acne
were compared for
level of P. acnes
and Micrococcaceae.
(2) 12 patients on
250 mg of
tetracycline twice
daily for 3 months
were compared for
bacterial
populations of P.
acnes and
Micrococcaceae.
Table 2a. Microbiological Testing
This study showed no difference in
the number of microorganisms
between mild and moderate study
groups.
There was no significant decrease in
bacterial populations after 3 months
of tetracycline.
There was not a significant decrease
in the number of P. acnes or
Micrococcaceae after the 3 months of
treatment of either bacterium.
There was a significant decrease in
the acne grade in patients after 4
weeks of therapy.
Results
There is no co-relationship
between the severity of acne
and the number of bacteria.
There is no direct relationship
between the size of the
bacterial population and the
extent of acne severity.
Greater numbers of bacteria
are not associated with
increasing severity of acne. The
effectiveness of oral
tetracycline in treating acne
cannot be explained by the
reduction in the number of
viable bacteria.
Conclusions
14
II
Level
of
Evidence
Bojar et al., Drugs 1995; 49
Suppl 2: 164-7.17
Double-blinded, randomized
clinical study to assess 1%
nadifloxacin compared to 2%
erythromycin to determine the
susceptibility of all cutaneous
microorganisms isolated before
and after treatment of patients
with mild/moderate facial acne.
Author(s)/Date/
Study Design
86 volunteers with
mild/moderate
acne:
1% nadifloxacin
(n=43);
2% erythromycin
(n=43).
Study Population
Used the scrub
technique.
Method of
Assessment
Erythromycin-resistant P. acnes and
erythromycin-resistant
Micrococcaceae were isolated from
27.9% and 97.7% erythromycintreated subjects respectively.
After 12 weeks of treatment with
nadifloxacin, no resistant bacteria
were isolated.
(MIC)
Minimum inhibitory concentration
values were determined.
The carriage of Micrococcaceae was
reduced in the nadifloxacin treated
group only.
Significant reduction in the number of
propionibacteria with both 1%
nadifloxacin and 2% erythromycin
after 12 weeks.
Results
Widespread incidence of
erythromycin-resistant
propionibacteria may limit future
usefulness of erythromycin as a
therapeutic agent.
It was demonstrated that topical
1% nadifloxacin is clinically as
effective as and
microbiologically superior to 2%
erythromycin.
Conclusions
15
II
Level
of
Evidence
Study Population
51 patients on oral
erythromycin and
53 patients on
topical clindamycin
were included in the
study; 100 control
subjects.
Author(s)/Date/
Study Design
Eady et al., Br J Dermatol
1989; 121: 51-7.18
Controlled study to determine
the incidence of erythromycinresistant propionibacteria in
various groups treated with
antibiotics for acne.
Bacterial samples
were obtained by
detergent scrub
technique.
MIC of each
antibiotic was
recorded as the
lowest
concentration
yielding no growth.
Method of
Assessment
There was an increased incidence of
erythromycin-resistant bacteria in
clindamycin patients who had used
erythromycin previously compared to
those who received no erythromycin.
42-51 bacteria were isolated from the
skin surface of both erythromycinand clindamycin-treated patients
compared to 3% of controls.
Patients responding to erythromycin
carried less erythromycin-resistant
bacteria compared to patients who
did not respond or those who had
relapsed.
Results
This study suggests that use of
oral erythromycin should be
limited to patients with no
previous exposure to the drug
and therapy should be
discontinued after 6 months to
allow any resistant bacteria to
be overgrown by sensitive
bacteria. The use of benzoyl
peroxide alone for a short
period may eradicate resistant
bacteria.
This study showed that the use
of oral erythromycin has
developed more resistant
bacteria than the use of topical
clindamycin.
Conclusions
16
II
Level
of
Evidence
Study Population
Harkaway et al., Br J Dermatol 60 subjects (30
1992; 126: 586-90.19
male, 30 female)
ages 18-30 years.
2% erythromycin
Controlled trial to examine the
development of antibiotic
(n=20)
5% benzoyl
resistance in coagulaseperoxide (n=20)
negative staphylococci during
treatment with of erythromycin,
5% benzoyl
benzoyl peroxide or combination peroxide + 3%
erythromycin (n=20)
of the two for 16 weeks.
Author(s)/Date/
Study Design
Cultures obtained
from the forehead
at 0, 4, 8, 12 and
16 weeks of
treatment.
Method of
Assessment
Treatment with benzoyl peroxide and
the combination of benzoyl peroxide
+ erythromycin resulted in significant
decrease in the number of aerobic
bacteria without any change in
resistance pattern to erythromycin or
other antibiotics.
There was also an increased
resistance to tetracycline and
clindamycin.
After 12 weeks of treatment with the
erythromycin group, the aerobic flora
dominated by S. epidermis (2/3)
which was completely erythromycinresistant.
Results
These results showed that
topical erythromycin excretes a
selective pressure.
Erythromycin-resistant strains
were suppressed the same as
sensitive strains.
The use of benzoyl peroxide
interferes with the selection or
the induction of erythromycinresistant bacteria.
Conclusions
17
I
I
Moderate to severe acne
(simple acne) (n=24);
Lawrence et al.,
Clin Endocrinol
(Oxf) 1981; 15: 8791.20
5-year longitudinal
cohort study to
determine which
factors in early
pubertal girls might
be predictive of later
severe facial acne.
Lucky et al., J
Pediatr 1997; 130:
30-9.22
Mean acne scores, level
of sex steroid hormones
and testosterone-estrogen
binding globulin (TEBG)
were compared among
the 3 groups.
Subjects were placed in 3
groups based on severity
of acne at year 5.
871 fourth and fifth grade
girls were in this study
Black (n=439)
White (n=432)
Moderate to severe acne
and with hirsutism and/or
Controlled cohort trial irregular menstrual cycles
to determine levels of (complicated acne)
SHBG, testosterone
(n=23);
and free testosterone
Unaffected women as
in women with
controls (n=15);
moderate to severe
acne and hirsutes.
No patients or controls
were receiving oral
contraceptives.
Study Population/
Intervention
Author(s)/Date/
Study Design
Level
of
Evidence
Table 2b. Endocrine testing
Severe – more than 25
lesions; given a numerical
value of 25.
Conclusion
Those who developed severe inflammatory acne
had more inflammatory and comedonal lesions
from -36 months to +36 months from menarche
compared with girls who developed mild acne.
There were more comedones at early age in girls
who later developed severe acne.
No racial differences in acne or hormonal levels
were found.
There were no differences in estradiol,
progesterone and TEBG.
The DHEAS
concentration is
higher in those girls
destined to have
severe acne.
The results suggest
that the early
development of
comedonal acne
may be the best
predictor of later
more severe
disease.
29% of women with acne had elevated
This study shows
testosterone levels and 41% had free testosterone that a deficiency in
elevated values.
SHBG and an
elevation in derived
Testosterone concentrations were higher in both
free testosterone is
acne groups compared with controls.
a frequent finding in
women with severe
There was no correlation between the
acne.
concentration of testosterone and SHBG.
Results
Facial comedonal and
nodular inflammatory lesions
were recorded in the following
Girls who developed mild acne had significantly
way:
later menarche than girls who developed severe
Mild – up to 10 lesions; given acne.
a numerical value of 5.
Girls who developed severe comedonal acne had
significantly increased DHEAS and somewhat
Moderate – 11-25 lesions;
given a numerical value of 17. increased testosterone and free testosterone.
Blood samples were obtained
at first, third and fifth years of
study.
The degree of facial acne
was classified annually as
mild, moderate or severe.
Testosterone concentration
was measured by
chromatography and RIA.
Method of Assessment
18
19
III.
Topical agents in the treatment of adult acne and acne vulgaris in
adolescents and adults
The effectiveness of topical therapy for acne is well-known. Topical retinoids are the
most effective comedolytic agents and since the microcomedo is thought to be the
precursor of all other acne lesions, they are appropriate for comedonal and inflammatory
acne. The effectiveness of topical retinoids (adapalene, tazarotene, tretinoin and
isotretinoin) is well documented. Topical retinoids such as tretinoin and adapalene
correct abnormalities in follicular keratinocytes. Topical isotretinoin is not available in the
United States. Salicylic acid and azelaic acid are weaker comedolytic agents, but may
be useful when retinoids are not tolerated. Topical antimicrobials include benzoyl
peroxide and topical antibiotics. Topical antibiotics such as clindamycin, tetracycline, and
erythromycin are bacteriostatic for P. acnes and are effective for mild to moderate
inflammatory acne. Benzoyl peroxide is bactericidal and improves both inflammatory and
non-inflammatory lesions. It is an oxidizing agent that works by introducing oxygen into
follicles, which then kills P. acnes. This is why P. acnes does not develop resistance to
benzoyl peroxide. In addition, there is increasing resistance to antibiotics by P. acnes.
Combining benzoyl peroxide with antibiotics reduces or eliminate this resistance. Sulfur,
resorcinol, aluminum chloride and sodium sulfacetamide are weaker antimicrobial
agents which can be useful in selected circumstances. Topical zinc alone is ineffective
but may enhance the activity of antimicrobial agents. Combination therapy, involving
benzoyl peroxide or retinoids and oral antibiotics, is effective treatment for acne.
I
I
Level of
Evidence
Facial inflammatory
and noninflammatory
lesions were
counted and overall
acne grade
assigned using
Cook’s et al.
method (0-8). 7
313 subjects (age range 13-30
years) with at least 12
inflammatory lesions, 12 noninflammatory lesions, and no
more than 3 facial nodulocystic
lesions.
231 patients completed the
study.
Subjects were evaluated at 0, 2,
5, 8, 10-11, and 12-14 weeks of
treatment.
Multicenter, randomized,
double-blinded, controlled
clinical trial to determine
the efficacy of 0.05%
268 subjects completed the
topical isotretinoin gel in the study.
treatment of acne
Subjects were randomized to
compared its vehicle.
receive 0.05% isotretinoin or
vehicle gel twice daily for 12-14
weeks.
Chalker et al., J Am Acad
Dermatol 1987; 17: 2514.28
Tretinoin 0.02% cream,
Tretinoin 0.05% cream,
Placebo vehicle control.
Double-blinded,
randomized clinical trial to
evaluate the effect of
topical tretinoin in patients
with of acne.
Patients were evaluated at
baseline, 2, 4, and 8 weeks of
treatment.
The effect of
treatment was
determined by
counting the
comedones,
papules, pustules
and cysts and
scoring each type of
acne lesion at
baseline and at 2, 4,
and 8 weeks.
Method of
Assessment
256 patients with acne were
randomized to receive 1 of the
following daily for 12 weeks:
Study Population/
Intervention
Christiansen et al.,
Dermatologica 1974; 148:
82-9.25
Author(s)/Date/
Study Design
Table 3a. Use of Topical Retinoids
isotretinoin treated vs. placebo
peeling:
71%
51%
erythema: 76%
62%
Mean acne severity grade was
reduced by 40% after 12 weeks
Inflammatory and non-inflammatory
lesion counts were reduced by 55%
and 46% respectively in the treated
group compared to 25% and 14%
reduction in the placebo group.
At 8 weeks, the non-inflammatory
lesion count was significantly
reduced in the isotretinoin-treated
group compared to the placebo
group.
Local adverse reactions such as
erythema and peeling were noted by
40% of placebo group, and 81% and
86% in the 0.05% and 0.02% groups
respectively.
Pustule and cyst counts were not
significantly different for all the 3
groups.
0.05% cream had a quicker onset of
action and had quantitatively greater
effect than 0.02% cream.
There was a statistically significant
reduction in comedones and papules
compared to placebo.
Results
More adverse effects
were observed in the
treated group than in
the placebo group.
0.05% isotretinoin gel
is effective in the
treatment of acne.
A very high rate of
adverse effects was
seen.
Tretinoin is very
successful in reducing
comedones and
papules.
Conclusions
20
I
I
Level of
Evidence
Study Population/
Intervention
The formulation tested ethanol
gel containing 0.025% tretinoin
gel and polyolprepolymer-2, (n71) vehicle control (n-70) and
commercially available 0.025%
tretinoin gel (n-72).
Multicenter, double-blinded,
randomized, parallel-group,
vehicle-controlled trial to
evaluate the safety and
efficacy of tretinoin with
polyolprepolymer-2
compared with
commercially available
0.025% tretinoin gel in the
treatment of acne.
Evaluations were performed at
day 0, 7, 14, 28, 56 and 84.
215 patient study; patients were
randomized to receive any one
of the treatments.
Lucky et al., J Am Acad
Dermatol 1998; 38: S1723.41
Shalita et al., Cutis 1999;
63: 349-54.38
446 subjects (14-44 years) with
mild to moderate facial acne
were randomized to receive
Multicenter, double-blinded,
tazarotene 0.1% gel, tazarotene
randomized, parallel-group,
0.05% gel, or vehicle-only
controlled trial to evaluate
placebo daily for 12 weeks.
the safety and efficacy of
Patients were evaluated at 0, 4,
tazarotene in the treatment
8, and 12 weeks of treatment.
of acne.
333 subjects completed the
study.
Author(s)/Date/
Study Design
Efficacy
assessments were
measured by lesion
counts and Physical
Global Evaluation
(PGE).
Pharmacokinetics
and safety analyses
were conducted.
Percentage of
change was
determined by
lesion count and
global evaluation
response to
treatment methods.
Method of
Assessment
Results
The gel containing polyolprepolymer2 caused significantly less peeling
and drying than the commerciallyavailable gel by day 84 of the study.
The efficacy of both treatments was
comparable and more effective than
the control vehicle.
0.1% gel tazarotene had of 68%,
0.05% gel tazarotene had 51% and
placebo had 40% reduction of noninflammatory and total lesion counts.
There was significant reduction in
non-inflammatory and total lesion
count at week 12.
Both treatments
demonstrated
comparable efficacy.
There were few
adverse events.
Both concentrations
had acceptable
tolerability.
Tazarotene 0.1% and
0.05% aqueous gels
were safe and effective
in reducing acne lesion
count.
Conclusions
21
I
I
Level of
Evidence
A multicenter, randomized,
double-blinded, placebocontrolled study to
determine the effect of a
5% benzoyl peroxide lotion
in the treatment of acne
compared to its base.
Schutte et al., Br J
Dermatol 1982; 106: 914.48
Patients were randomly
assigned to receive 0.05%
vitamin A acid cream or benzoyl
peroxide 5% gel treatments for 8
weeks.
Randomized, controlled
clinical trial to compare the
effectiveness of topical
benzoyl peroxide and
tretinoin in the treatment of
acne.
Patients were randomly
assigned 5% benzoyl peroxide
lotion or placebo/base.
65 patients ages 17-23 years
with acne.
Subjects were evaluated at
baseline and after 2, 4, and 8
weeks for the response to the
treatments.
69 patients ages 15-30 with
acne.
Study Population/
Intervention
Belknap, Cutis 1979; 23:
856-9.42
Author(s)/Date/
Study Design
Table 3b. Use of Benzoyl Peroxide
The degree of
redness and scaling
was recorded.
Facial fluorescence
by ultraviolet
photography was
done.
Patients were
evaluated by lesion
count before the
start of therapy and
after 5 days after
treatment.
Overall evaluation
of clinical response
was done for each
patient.
Patients were
evaluated by total
lesion counts.
Method of
Assessment
There was a significant reduction of
lesions seen in the treatment group
and there was significantly reduced
facial prophyrin fluorescence.
The control preparation had no effect
on the number of papules or
pustules.
Larger populations of
patients are required
in studies to prove
safety and efficacy.
The mechanism of
action of benzoyl
peroxide lotion should
be studied.
This study indicates
that 5% benzoyl
peroxide lotion does
have a rapid effect in
resolving inflamed
lesions.
This study should
have used proper
controls especially
because the trial is
comparing gel versus
cream. Each treatment
should have had its
respective vehicle as a
control.
Statistically, there was
no significant
difference between the
two drugs after 8
weeks.
Both treatment groups were effective
in reducing lesions.
There was significantly less peeling
in the benzoyl peroxide compared to
the vitamin A acid group after 4
weeks.
The benzoyl peroxide
group showed
improvement earlier
than the retinoic acid
group.
Conclusions
A significantly higher percentage of
patients in the benzoyl peroxide
group exhibited excellent overall
response compared to the retinoic
acid group.
Results
22
I
Level of
Evidence
A multicenter, randomized,
double-blinded, controlled
study to evaluate the effect
of 20% benzoyl peroxide
lotion in the treatment of
acne.
Smith et al., Cutis 1980;
25:90-2.50
Author(s)/Date/
Study Design
Patients were
evaluated for
efficacy by counting
all lesions on the
face.
Erythema and
peeling were also
assessed.
59 patients (mean age 20 years,
range 18-30) with at least 10
inflammatory lesions and 3 or
fewer nodulocystic lesions were
selected for the study.
The patients were randomized to
receive 20% benzoyl peroxide
lotion or placebo lotion base
twice daily for 12 weeks:
Subjects were evaluated at
baseline and every 2 weeks.
Placebo control lotion (n=30).
Benzoyl peroxide 20% lotion
(n=29);
Method of
Assessment
Study Population/
Intervention
Redness and peeling were observed
in both groups but more in the active
treated group.
Benzoyl peroxide treated group had
an excellent response compared to
the placebo group.
Results
Study with a larger
number of population
is required to prove
safety and efficacy.
There was some
improvement in the
placebo group also.
This study showed
that 20% benzoyl
peroxide is effective in
reducing the lesions of
acne.
Conclusions
23
I
I
Level of
Evidence
Randomized, doubleblinded, placebo-controlled
trial to evaluate the
effectiveness of topical 2%
erythromycin compared to
its vehicle in the treatment
of acne.
Jones and Crumley, Arch
Dermatol 1981; 117: 5513.53
175 subjects (ages 12 years and
over) with inflammatory acne
were randomized to receive 2%
erythromycin (n-90) solution or
placebo control (n-85) twice daily
for 12 weeks.
Patients were evaluated at
baseline and after 2, 4, 8 and 12
weeks.
348 patients (age range 13-30
years) with inflammatory acne
were randomized to receive 2%
erythromycin solution (n=178) or
placebo control (n=170) twice
daily for 8 weeks.
Bernstein and Shalita, J
Am Acad Dermatol 1980;
2: 318-21.52
Randomized, placebocontrolled trial to evaluate
the effectiveness of topical
2% erythromycin compared
to its vehicle in the
treatment of acne.
Study Population/
Intervention
Author(s)/Date/
Study Design
Table 3c. Use of Topical Antibiotics
Efficacy was
assessed by total
lesion count and
inflammatory
papulopustule
count.
Physician global
severity rating was
assessed at
baseline and after
2, 4, and 8 weeks of
treatment.
Efficacy was
assessed by total
lesion count and
papulopustule
count.
Method of
Assessment
Topical erythromycin is
effective in the
treatment of
papulopustular acne.
Conclusions
62% of subjects in the topical 2%
erythromycin group had good to
excellent response compared to 27%
in the blank vehicle.
After 12 weeks, there was a 56%
papule reduction in the treated group
compared to 33% in the blank
vehicle group.
The total count of inflammatory
pustules was significantly reduced
after therapy in the 2% erythromycin
group.
Adverse effects were
similar in both groups.
Study confirms the
effectiveness of topical
erythromycin in the
treatment of acne.
Topical 2%
erythromycin
demonstrated
significantly better
results than the blank
vehicle.
Comedones and cysts and total
Vehicle base
lesions were not significantly different preparation contained
after 8 weeks in both groups.
alcohol and
polyethylene which are
Fewer adverse effects were noted in
local irritants.
the active preparation compared to
the placebo group.
There was a significant reduction in
papulopustule count in the treatment
group compared to the placebo
group.
Results
24
I
I
I
Level of
Evidence
Study Population/
Intervention
Subjects were evaluated at
baseline and after 2, 4, 8, 10,
and 12 weeks of treatment.
Dobson and Bellknap, J
Am Acad Dermatol 1980;
3: 478-82.57
253 patients were randomized to
receive either topical 1.5%
erythromycin solution (n=127) or
placebo vehicle control (n=126)
Multicenter, double-blinded,
twice daily for 12 weeks.
controlled clinical trial to
assess the effectiveness of Patients were evaluated at
topical 1.5% erythromycin
baseline and at 2, 4, 8, 10 and
12 weeks of treatment.
solution compared to its
vehicle in the treatment of
acne.
Pochi et al., Cutis 1988;
41: 132-6.56
187 patients (range 13-48 years)
with mild to moderate acne were
randomized to receive topical
Multicenter, double-blinded,
2% erythromycin gel (n=93)
controlled clinical trial to
compared to placebo vehicle
assess the effectiveness of
control (n=94) twice daily for 8
topical 2% erythromycin gel
weeks.
compared to its vehicle in
the treatment of acne.
Patients were evaluated at
baseline, 4 and 8 weeks after
treatment.
Lesher et al., J Am Acad
Dermatol 1985; 12: 52631.55
225 subjects (range 14-30 years)
with at least 10 inflammatory
lesions, 10 non-inflammatory
lesions, and no more than 3
Multicenter, double-blinded,
nodulocystic lesions were
controlled clinical trial to
randomized to receive topical
assess the effectiveness of
2% erythromycin ointment
topical 2% erythromycin in
(n=112) or placebo vehicle
the treatment of acne.
control (n=113) twice daily for 12
weeks.
Author(s)/Date/
Study Design
Conclusions
The reduction in the number of
inflammatory lesions, papules, and
pustules was significantly greater in
the erythromycin treated group.
The global evaluation of the clinical
response correlated well with the
reduction in the lesion counts.
Global physician
evaluation was also
performed after 2,
4, 8, 10 and 12
weeks of treatment.
Side effects were generally mild and
transient, with no significant
differences noted between the
groups.
After 8 weeks, 60% of the treated
group had a good to excellent
response compared to 36% of the
vehicle group.
2% erythromycin gel proved to be
significantly more effective than the
placebo in the reduction of the
number of inflammatory and noninflammatory lesions.
Erythromycin group had 46% mean
lesion count reductions compared to
19% in the placebo group after 12
weeks of treatment.
No serious or
irreversible adverse
effects were seen.
This study
demonstrated a
statistically significant
benefit in the patients
with acne receiving
1.5% erythromycin
solution compared to
its vehicle.
A strong placebo effect
was noted.
2% erythromycin gel
was effective and well
tolerated in the
treatment of acne.
This study showed that
2% erythromycin
ointment was
significantly more
effective than its
Topical 2% erythromycin group had a
placebo control in
40% reduction in mean acne severity
decreasing
grade compared to 23% reduction for
inflammatory acne
the vehicle group.
lesions.
No significant differences were noted
between groups for side effects.
Results
Total lesion count
was used for
evaluation of the
treatment.
Adverse effects
were evaluated on
mild-to-severe
scale.
Facial lesions were
counted at each
visit and a grade
was based on
percentage of
overall
improvement.
Facial inflammatory
lesions were
counted and overall
severity grade was
assessed using
Cook’s et al. 7
grading scale for
acne severity 0-8
scale.
Method of
Assessment
25
I
I
Level of
Evidence
Leyden et al., J Am Acad
Dermatol 1987; 16: 8227.62
Multicenter, randomized
parallel-group clinical trial
to assess the effectiveness
of topical 2% erythromycin
in the treatment of acne.
Mills et al., Acta Derm
Venereol 2002; 82: 26058
5.
Randomized, singleblinded, controlled clinical
trial to assess the
effectiveness of topical
2% erythromycin gel
compared to its vehicle in
the treatment of acne and
to determine the bacterial
resistance associated with
its use.
Author(s)/Date/
Study Design
Patients were evaluated at
baseline and at 4, 8, and 12
weeks of treatment.
102 patients (14 to 34 years)
were randomized to receive
either topical 2% erythromycin
gel or 1% clindamycin phosphate
solution twice daily for 12 weeks.
To study the regression of any
bacteriologic changes at 12
weeks, the patients on active
treatment were switched over to
placebo. The patients on
placebo continued their placebo
treatments.
Global physician
evaluation was also
performed.
Acne severity was
evaluated by total
facial lesion count.
Bacteriologic
samples were also
assessed at
baseline and at 4,
12, 16 and 24
weeks of treatment.
Acne severity was
evaluated by total
lesion count and the
use of photographs.
208 patients were randomized to
receive either topical 2%
erythromycin gel or placebo
vehicle control twice daily for 12
weeks.
Patients were evaluated at
baseline and after 2, 4, 8, 10 and
12 weeks of treatment.
Method of
Assessment
Study Population/
Intervention
This suggests that
topical treatment with
erythromycin may
result in higher
carriage rates and
dissemination of
erythromycin-resistant
S. aureus from nares.
No anti-acne efficacy
was observed.
Resistance
development was
confined to the
macrolide class of
antibiotics.
Conclusions
Side effects included peeling,
erythema, burning, and itching.
Topical antibiotics
have advantages over
systemic therapy
because of direct local
There was no significant difference of
application on the
lesion count detected between the
affected areas of the
treatment groups after 8 and 12
skin and a resultant
weeks of treatment.
decrease in systemic
side effects.
At the end of 12 weeks, about 50%
of patients had a good to excellent
response.
Both medications significantly
reduced the number of papules and
open and closed comedones.
Nearly all bacteria were highly
resistant (MIC > 128ug/ml).
The prevalence of erythromycin
coagulase-negative staph on the
face was high at 87% at baseline. At
the end of 12 weeks of erythromycin,
coagulase-negative staph increased
to 98% in the erythromycin-treated
group.
Results
26
I
Level of
Evidence
Becker et al., Arch
Dermatol 1981; 117: 4825.65
Multicenter, double-blinded,
controlled clinical trial to
evaluate the effectiveness
of topical clindamycin
hydrochloride and
clindamycin phosphate
compared to placebo in the
treatment of acne.
Author(s)/Date/
Study Design
Patients were evaluated at
baseline and after 2, 4, 6, and 8
weeks of treatment.
Acne severity was
evaluated by
counting pustules,
papules, and
nodules over the
entire face.
413 patients (14-29 years) with
acne were randomized to
receive either 1% clindamycin
phosphate solution (n=123), 1%
clindamycin hydrochloride
solution (n=120) or placebo
vehicle control (n=112) twice
daily for 8 weeks.
Mean change in
lesion count in each
group was reported.
Method of
Assessment
Study Population/
Intervention
Side effects included peeling,
erythema, burning, and itching.
86% of patients in the clindamycin
hydrochloride group, 77% of the
clindamycin phosphate group, and
56% of the placebo group reported
improvement.
Results
Both clindamycin
phosphate and
clindamycin
hydrochloride
treatment had
significant reduction in
lesion count when
compared to baseline
and placebo group.
Conclusions
27
I
I
Level of
Evidence
Randomized, doubleblinded, placebo-controlled
clinical trial to determine if
topical erythromycin and
benzoyl peroxide were
effective in the treatment of
acne. This study also
compared the combination
to its vehicle base.
Chalker et al., J Am Acad
Dermatol 1983; 9: 933-6.72
Multicenter, randomized,
single-blinded, controlled
clinical trial to compare the
efficacy and safety of 1%
clindamycin/0.025%
tretinoin gel formulation
(CTG) to 1% clindamycin
lotion (CLN) for the
treatment of acne.
209 patients (aged 14-26 years)
were randomized to receive
either CTG once (n=104) or CLN
(n=105) twice daily for 12 weeks.
Zouboulis et al., Br J
Dermatol 2000; 143: 498505.70
Method of
Assessment
All patients were evaluated at
baseline and every 2 weeks for
10 weeks.
3% erythromycin/5% benzoyl
peroxide gel (n=44);
5% benzoyl peroxide gel (n=44);
3% erythromycin gel (n=45);
placebo gel base, vehicle control
(n=44).
165 subjects (age 15-30 years)
with grade 3 acne on the Cook et
al. scale7 were randomized to
receive one of the following
topicals twice daily for 10 wks.
Grading method of
Cook et al.7 was
also used.
Patients were
evaluated at each
visit by lesion count.
Acne severity was
evaluated by
counting open and
closed comedones,
pustules, papules,
Patients were evaluated at
and nodules. Acne
baseline and after 2, 4, and 8
severity grade by
weeks of treatment to assess the
Cook et al. 7 was
efficacy of both treatments.
also used.
Study Population/
Intervention
Author(s)/Date/
Study Design
Table 3d. Use of Other Topical Agents
CTG had a rapid effect
on the onset of
improvement
compared to CLN.
A single daily topical
application of 1%
clindamycin/0.025%
tretinoin gel formulation
was superior to 1%
clindamycin lotion
applied twice daily for
the reduction of acne.
Conclusions
Adverse effects were not reported.
There was no statistically significant
The combination of 3%
difference between the groups for the erythromycin/
first 8 weeks.
5% benzoyl peroxide
gel was more effective
At week 10, the active groups were
than the individual
statistically different.
constituents or
Mean comedonal and pustule counts placebo.
were reduced in all active treatment
The most dramatic
groups.
effect was on
combined inflammatory
Combination therapy consistently
lesions (papules and
improved papule and inflammatory
pustules).
lesion counts.
Both treatments were well tolerated.
50% reduction in total lesion count
was observed by day 60 in 77% of
patients on CTG compared with 56%
receiving CLN.
At week 12 there was significantly
greater reduction of inflamed lesions
from baseline to week 12 in the CTG
group compared to the CLN group.
Results
28
I
I
Level of
Evidence
Lookingbill et al., J Am
Acad Dermatol 1997; 37:
590-5.75
Multicenter, randomized,
double-blinded, placebo
controlled clinical trial to
determine the safety and
efficacy of combination
clindamycin/benzoyl
peroxide when compared
with clindamycin, benzoyl
peroxide or placebo
separately.
Safety and efficacy evaluations
were performed at baseline and
at 2, 5, 8 and 11 weeks.
1% clindamycin phosphate/5%
benzoyl peroxide gel;
1% clindamycin phosphate gel;
5% benzoyl peroxide gel;
placebo vehicle gel control.
334 subjects (ages 13-30 years)
were randomly assigned to
receive one of the following
topicals once daily:
Safety and efficacy was
evaluated at baseline and at 2,
4, 6, 8, and 10 weeks of
treatment.
(1) 5% benzoyl peroxide/1%
clindamycin phosphate gel
(n=95);
(2) 5% benzoyl peroxide gel
(n=95);
(3) 1% clindamycin phosphate
gel (n=49);
(4) placebo control (n=48).
The study evaluated
lesion counts,
assessed global
responses and
irritant effects.
Patients’ global
evaluations were
measured at week
10.
Total improvement
in lesion counts
from baseline was
monitored.
287 patients (ages13-30 years)
with moderately severe acne
were randomly selected to
receive one of the following
topicals twice daily for 10 weeks:
Tschen et al., Cutis 2001;
67: 165-9.73
Randomized, doubleblinded, parallel-group
clinical trial to evaluate the
effectiveness of benzoyl
peroxide and clindamycin
separately and in
combination.
Method of
Assessment
Study Population/
Intervention
Author(s)/Date/
Study Design
Topical clindamycin/
benzoyl peroxide
combination gel is welltolerated and superior
to the other treatments.
This has an advantage
over the combination of
erythromycin/benzoyl
peroxide gel because it
is not required to be
refrigerated.
The combination gel was significantly
superior to the two individual agents.
There was greater
efficacy obtained with
the combination
therapy and it was as
safe as the other
treatments.
Conclusions
All three active treatments were
significantly superior to the placebo
in global improvement and in
reducing both inflammatory and noninflammatory lesions.
Some patients reported adverse
effects.
The number of lesions was reduced
to a greater extent in patients treated
with the combination of 5% benzoyl
peroxide/1% clindamycin phosphate
gel compared to the other
treatments.
All study groups demonstrated
significant improvement from
baseline.
Results
29
Hjorth and Graupe, Acta
Derm Venereol Suppl
(Stockh) 1989; 143: 458.79
I
Multicenter, randomized,
double-blinded, placebocontrolled clinical trial to
compare the 20% azelaic
acid cream with its base
and compare it to oral
tetracycline treatment.
Author(s)/Date/
Study Design
Level of
Evidence
Patients with moderate acne
were treated for 5 months and
patients with severe acne were
treated for 6 months.
Second study had patients
receiving oral tetracycline
1-g/day for the first month,
0.75-g/day for the second month
and 0.5-g/day for the third month
(n-169); and cream base (n135).
20% azelaic acid cream (n-164);
placebo capsules (n-126).
Patients were randomized to
receive one of the following
topicals twice daily:
First study had subjects with
moderate to severe acne.
Study Population/
Intervention
Total lesion count
was monitored at
monthly intervals.
Method of
Assessment
No significant difference in either
treatment was observed after 5
months.
Both studies demonstrated significant
clinically relevant reduction in the
initial number of lesions during
therapy.
Results
20% azelaic acid
cream is an effective
treatment for
inflammatory acne and
is well tolerated.
Conclusions
30
31
IV.
The efficacy and safety of systemic antibacterial agents in the treatment of adult acne
and acne vulgaris in adolescents to adults
Oral antibiotic therapy has been used for the treatment of moderate and severe acne for many years.
Systemic antibiotics have been shown to be effective as monotherapy and also in combination with
other therapies. Many clinical trials have shown the effectiveness of antibiotics like tetracyclines,
erythromycin, doxycycline, minocycline, trimethoprim with or without sulfamethoxazole and
azithromycin. These systemic antibiotics suppress P. acnes growth, and because of this, there is a
decrease in the production of inflammatory factors. The prevalent and long-term use of antibiotics has
led to the emergence of resistance to P. acnes. To minimize the development of bacterial resistance,
antibiotics should be used for a short period of time and combination therapy should be used.
I
I
Level of
Evidence
A multicenter,
randomized, doubleblinded, placebocontrolled study to
compare oral tetracycline,
topical clindamycin and
placebo for treatment of
acne.
Gratton et al., J Am
Acad Dermatol 1982; 7:
50-3.91
Subjects were evaluated at
baseline and after 2, 4, 6, and
8 weeks.
(3) placebo (n=97).
(2) 1% topical clindamycin
phosphate solution (n=97);
(1) 250 mg oral tetracycline
hydrochloride (n=103);
305 patients (age range 18-35
years) with moderate to severe
acne were randomized to
receive one of the following
three groups twice daily for 8
weeks:
New topical tetracycline
consists of tetracycline
hydrochloride 0.22% with 4epi-tetracycline 0.28% and ndecylmethyl sulfoxide in
ethanol/water; this was applied
twice daily.
(3) new topical tetracycline and
oral placebo.
(2) topical placebo/systemic
tetracycline 0.5-gm/day;
(1) topical placebo and
systemic placebo treatment;
135 subjects (age 18-35 years)
with acne grade 2 and over,
according to Cooke et al., 7
were randomized to receive
one of the following:
Smith et al., South Med
J 1976; 69: 695-7.90
Randomized, doubleblinded study to evaluate
(1) patients treated with
topical and oral placebo;
(2) patients receiving
topical placebo and
systemic tetracycline
0.5-gm/day;
(3) patients treated with a
new topical tetracycline
preparation and an oral
placebo.
Study Population/
Intervention
Author(s)/Date/
Study Design
Table 4a. Use of Tetracyclines
Efficacy was
evaluated with
lesion count and
physicians’ overall
evaluation of
therapy.
Severity was
defined by papule,
pustule and
nodulocystic lesion
count.
All subjects were
evaluated with
visual grading and
photographs to
assure critical
evaluation.
Method of
Assessment
Conclusion
The most frequent side effect
reported in the patients was
diarrhea.
Both oral tetracycline and topical
clindamycin significantly reduced
the papule and pustule counts
compared to placebo.
Slight yellowish discoloration was
observed in 25% of subjects.
Oral and systemic groups both had
achieved statistically significant
improvement after 4, 7, 10, and 12
weeks of treatment compared to
placebo.
Both oral tetracycline
and topical
clindamycin are
effective in the
treatment of moderate
to severe acne.
This study confirms
that tetracycline in
oral dose of
0.5-gm/day is
effective treatment for
acne after 4 weeks of
The topical treatment was effective,
therapy.
but somewhat less than the oral
tetracycline, but significantly better
than the placebo after seven weeks
of treatment.
Results
32
I
Level of
Evidence
Study Population/
Intervention
Patients were evaluated at
baseline and after 2, 4, 6, 8
and 13 weeks of treatment.
(3) Topically applied placebo
liquid and orally administered
500 mg/day of tetracycline
hydrochloride capsules.
Blaney and Cook, Arch
75 patients (age range 11-25
Dermatol 1976; 112: 971- years) with moderate to severe
3.95
acne were randomized to
receive 1 of the following twice
Randomized, doubledaily for 13 weeks:
blinded, placebo(1) Topically applied mixture of
controlled study
tetracycline hydrochloride and
comparing the effect of
topical and oral
n-decylmethyl sulfoxide and
tetracycline to placebo in
orally administered lactose;
the treatment of acne.
(2) Topically applied placebo
liquid and orally administered
lactose;
Author(s)/Date/
Study Design
Blood chemistry
analysis was
performed.
All subjects were
evaluated with
visual grading
photographs to
assure critical
evaluation.
Method of
Assessment
The treatments were generally well
tolerated except for mild burning
and yellow tinted skin.
No significant difference was
apparent between the effects of
topical and oral administration of
tetracycline hydrochloride.
Both oral and topical tetracycline
showed significant improvement
compared to placebo.
Results
Larger numbers of
patients are required
to assess safety and
efficacy.
Both oral and topical
tetracyclines are
effective in the
treatment of moderate
to severe acne.
Conclusion
33
I
I
Author(s)/Date/
Study Design
Level of
Evidence
Double-blinded,
randomized study to
compare the efficacy of
systemic erythromycin
with systemic tetracycline
in the treatment of acne.
Gammon et al., J Am
Acad Dermatol 1986; 14:
108
183-6.
Multicenter, randomized,
double-blinded, placebocontrolled, parallel-group
clinical trial to determine
the effectiveness of
subantimicrobial-dose
(SD) doxycycline in the
treatment of acne.
Skidmore et al.,
Arch Dermatol 2003;
102
139: 459-64.
Use of Macrolides
Table 4b.
Patients were evaluated at
baseline and after 2, 4, 8, and
12 weeks of treatment.
Tetracycline 500 mg twice daily
for 4 weeks, then 500 mg once
daily for 8 weeks, plus
erythromycin placebo (n=100).
Erythromycin 333 mg 3 times
daily for 4 weeks, then 333 mg
once daily for 8 weeks, plus
tetracycline placebo (n=100);
200 patients (age 14-30 years)
with moderate to moderately
severe acne were randomized
to receive one of the following:
To evaluate safety
and efficacy,
papule, pustule,
and open and
closed comedo
counts were made.
Patients reported
adverse effects.
Some patients had gastrointestinal
discomfort. Some developed
Candida vaginitis.
Closed comedo counts decreased
more rapidly with tetracycline
treatment.
Erythromycin and tetracycline
treatment groups had significant
decreases in lesion counts starting
from the second week of treatment.
There was no
statistically significant
difference between
the two groups; both
drugs are effective.
20 mg doxycycline is
well tolerated.
Systemic 20 mg
doxycycline is
effective in the
treatment of moderate
acne.
At 6 months, the doxycycline group
had a significantly greater
percentage of reduction in the
number of comedones,
inflammatory and non-inflammatory
lesions than the placebo group.
Physician global assessment
scores showed greater
improvement in the treatment
group.
Conclusions
Results
Clinical laboratory
and microbiological
No significant difference was noted
samples were
in the microbial count between both
assessed at 6
groups.
months.
Efficacy was
measured by
noting change in
inflammatory, noninflammatory
lesions, and by
physician global
assessment
scores.
51 patients (age 18 years or
older) with moderate acne
were randomized to receive
20 mg doxycycline or placebo
twice daily for 6 months.
Patients were evaluated at
baseline and after 2, 4, and 6
months of treatment.
Method of
Assessment
Study Population/
Intervention
34
I
I
Level of
Evidence
Randomized, doubleblinded, placebocontrolled clinical trial to
determine the
effectiveness of
clindamycin and
tetracycline in the
treatment of acne.
Stoughton et al., Cutis
115
1980; 26: 424-5, 429
Christian and Krueger,
Arch Dermatol 1975;
111
111: 997-1000.
Randomized, doubleblinded, placebocontrolled clinical trial to
determine the
effectiveness of
clindamycin in the
treatment of acne.
Author(s)/Date/
Study Design
Open comedones
were analyzed for
the number of P.
acnes.
Topical 1% clindamycin
phosphate and placebo
capsules or oral tetracycline
250 mg twice daily and placebo
lotion for a 13-week course of
treatment.
At other times of the study, there
was no significant difference
between the two groups in the
number of pustules.
The use of topically
applied 1%
clindamycin is an
alternative to the use
of oral tetracycline.
Some patients receiving
clindamycin had severe diarrhea
and rash.
Improvement was
defined as at least
50% reduction in
the number of
papules or
pustules.
Topically applied 1% clindamycin
phosphate was found to be
superior to the oral tetracycline at 6
weeks, determined by the reduction
of papules and patient evaluation.
Clindamycin appears
to be effective in the
treatment of moderate
to severe acne.
Clindamycin treatment resulted in
significant reduction in comedones
and pustules compared to the
placebo group.
Efficacy was
measured by
noting change in
lesion count.
Evaluations
included counts of
all types of lesions
and severity rating.
Conclusions
Results
Method of
Assessment
50 patients (age 18-30 years)
with moderate acne were
randomized to receive one of
the following for 8 weeks:
Patients were evaluated at
baseline and after 1, 2, 4, 6, 10
and 13 weeks of treatment.
Patients were assigned 150 mg
st
clindamycin 4 times for the 1
nd
week, 3 times for the 2 week
and then 2 times for the rest of
the time (weeks 3-13).
91 patients (average age 20
years) with moderate acne
were randomized to receive
clindamycin or placebo for a
13-week course of treatment.
Study Population/
Intervention
35
I
Level of
Evidence
Randomized, doubleblinded, placebocontrolled cross-over
clinical trial to compare
the effectiveness of
systemic trimethoprimsulfamethoxazole or
placebo in the treatment
of acne.
Hersle, Dermatologica
117
1972; 145: 187-91.
Author(s)/Date/
Study Design
Patients were evaluated at 5
and 10 weeks.
43 patients (age 13-25 years)
with acne were randomized to
receive 80 mg trimethoprim
and 400 mg sulfamethoxazole
or placebo 1 time daily for 5
weeks. After 5 weeks, the
active preparation was given to
the placebo group and the
active treatment group
received the placebo.
Study Population/
Intervention
Table 4c. Use of Trimethoprim-Sulfamethoxazole
Overall
assessment was
made by lesion
count and
laboratory tests.
Method of
Assessment
Acne lesions had decreased from
100% to 38% in the active
treatment group compared to
100% to 91% (not significant) in the
placebo group.
Statistically significant improvement
was achieved with 80 mg
trimethoprim and 400 mg
sulfamethoxazole treatment
compared to the placebo.
Results
Trimethoprimsulfamethoxazole is
effective treatment for
acne compared to
placebo after 5 weeks
of treatment.
Conclusions
36
37
V.
The effectiveness and potential side effects of hormonal agents in the treatment of adult
acne and acne vulgaris in adolescents to adults
Androgenic hormones play an important role in the pathogenesis of acne vulgaris. Studies have
shown that hormonal overproduction can contribute to the development of acne. Androgenic
hormones stimulate the sebaceous glands, which can then increase sebum production. Many young
women with polycystic ovary syndrome (PCOS) first seek medical attention for acne. Indications for
hormonal abnormalities may include menstrual irregularities, other signs of virilization such as
hirsutism, androgenic alopecia, very early or very late onset acne, or failure to respond to
conventional therapy or relapse after isotretinoin. Hormonal treatment is an alternative treatment for
women with acne. Combined oral contraceptives have been evaluated and shown to be effective in
the treatment and management of acne in women especially with clinical signs of hyperandrogenism.
I
I
Level of
Evidence
A multicenter,
randomized, doubleblinded, placebocontrolled study to
evaluate the efficacy of a
low-dose oral
contraceptive in the
treatment of acne.
Thiboutot et al., Fertil
124
Steril 2001; 76: 461-8.
Lucky et al., J Am Acad
Dermatol 1997; 37: 746122
54.
A multicenter,
randomized, doubleblinded, placebocontrolled study to
evaluate the efficacy of
combination oral
contraceptive in the
treatment of acne.
Author(s)/Date/ Study
Design
Patients were evaluated at baseline
and at 1, 3, and 6 months.
350 women (age 14 and older) with
moderate facial acne and regular
menstrual cycles were randomized
to receive 100-g levonorgestrel and
20-g ethinyl estradiol contraceptive
tablets or placebo. Patients received
21 days of active drug followed by 7
days of placebo for 6 cycles.
Patients were evaluated at baseline
and monthly for 6 cycles, then 3
times during the last month.
Total lesion count,
inflammatory and noninflammatory lesion
count was performed,
using physician global
assessment and
patient selfassessment.
Efficacy was assessed
by facial lesion count,
investigator’s global
assessment, patient
self-assessment, and
analysis of within-cycle
variation (cycle 6) in
lesion counts.
257 women (age 15-49 years) with
moderate acne and without
hirsutism were randomized to
receive combination treatment listed
below for 3 weeks, followed by 1
week of inactive drug/placebo, each
month for 6 months:
Ethinyl estradiol 0.035 mg and
norgestimate 0.180/0.215/0.250 mg)
tablets, or placebo tablets.
Method of
Assessment
Study Population/
Intervention
Table 5a. Effectiveness of Contraceptive Agents
An oral contraceptive
containing 0.035 mg
ethinyl estradiol
combined with
triphasic regimen of
norgestimate is safe
and effective
treatment of
moderate acne
vulgaris in women.
Conclusions
Global assessment
showed that 57.9% of the
women in the treated group
were considered cleared
compared to 46.7% in the
placebo group.
Inflammatory, noninflammatory and total
lesion count was
significantly lower in the
treatment group compared
to the placebo group.
Low-dose oral
contraceptive
containing 20-g
ethinyl estradiol and
100-g levonorgestrel
is an effective and
safe treatment for
moderate acne.
Adverse events were
Physician global
minor.
assessment showed 93.7%
improvement in the
treatment group compared
to 65.4% in the placebo
group.
The mean total lesion
count decrease was 53.1%
in the treatment group
compared to 26.8% in the
placebo group.
The oral contraceptive
treatment group showed
statically significant greater
improvement than the
placebo group.
Results
38
I
Level of
Evidence
A multicenter randomized
double-blinded, placebocontrolled study to
compare the effect of 2
contraceptive
preparations in the
treatment of acne.
Leyden J et al.,
J Am Acad Dermatol
125
2002; 47: 399-409.
Author(s)/Date/ Study
Design
Patients were
evaluated by acne
lesion count, physician
global assessment and
patient selfassessment.
350 women (age 14 and older) with
moderate facial acne and regular
menstrual cycles were randomized
to receive 100-g levonorgestrel and
20-g ethinyl estradiol contraceptive
tablets or placebo tablets. Patients
received 21 days of active drug
followed by 7 days of placebo for 6
cycles.
Patients were evaluated at baseline
and once during each treatment
cycle.
Method of
Assessment
Study Population/
Intervention
There was 81.7%
improvement in the treated
group compared to 68.1%
in the placebo group by
using physician global
assessment and patient
self-assessment.
The inflammatory and noninflammatory lesion count
in the patient group
receiving ethinyl estradiol
was significantly lower
nd
starting from the 2 cycle
compared to the placebo
group.
Results
Low-dose oral
contraceptive
containing 20-g
ethinyl estradiol and
100-g levonorgestrel
is an effective and
safe treatment for
moderate acne.
Conclusions
39
II
Level of
Evidence
Muhlemann et al., Br J
Dermatol 1986; 115:
132
227-32.
A randomized, doubleblinded, placebocontrolled, cross-over
study to compare the
effectiveness of
spironolactone and
placebo in the treatment
of acne.
Author(s)/Date/
Study Design
Patients were evaluated at baseline
and after 12 weeks of treatment.
Acne severity was
assessed; inflamed
lesions were counted.
29 women with moderate to severe
acne were randomized to receive
either 200 mg spironolactone or
placebo for 3 months. After 3
months, patients were given placebo
for 1 month and crossed over for
further 3 months of placebo or
200 mg spironolactone.
Improvement was
defined as greater than
50% reduction in the
number of lesions.
Photographs were also
used to assess the
efficacy of the
treatment.
Method of
Assessment
Study Population/
Intervention
Table 5b. Effectiveness of Spironolactone
Spironolactone is a
useful alternative
therapy for women
with moderate acne.
Acne severity decreased
significantly with the use of
spironolactone in the
treatment group compared
to the placebo group.
The beneficial effect of
spironolactone was
observed by all assays.
86% of patients noted
improvement with
spironolactone compared
to 24% on placebo.
Conclusions
Results
40
II
II
Level of
Evidence
Miller et al., Br J
Dermatol 1986; 114:
135
705-16.
Randomized, doubleblinded, controlled trial to
compare the effect of
anti-androgen treatment
in women with acne.
A randomized, doubleblinded, placebocontrolled trial to
compare the effect of
systemic estrogen +
cyproterone acetate and
tetracycline in the
treatment of acne.
Greenwood et al., Br
Med J (Clin Res Ed)
134
1985; 291: 1231-5.
Author(s)/Date/
Study Design
Sebum secretion
rates and bacterial
counts were taken
before and during
treatment.
(1) Combination of 2 mg cyproterone
acetate + 50 µg ethinyl estradiol for 21
days with 500 mg tetracycline twice
daily;
Patients were evaluated at baseline
and every 2 months for 6 months.
All the treatments were taken daily from
days 5-25 of the cycle.
Group M (Minovlar): 1 mg of
norethisterone acetate and 50 µg
ethinyl estradiol.
Group C (high dose CPA): 50 mg
cyproterone acetate + 50 µg ethinyl
estradiol;
Group D (Diane): 2 mg cyproterone
acetate + 50 µg ethinyl estradiol;
90 women (age 16-36 years) were
randomized to receive one of the
following three treatments for 6 cycles:
Women were assessed at baseline and
every 2, 4 and 6 months.
(3) Placebo tablets for 3 weeks and
tetracycline 500 mg twice daily.
Sebum secretion
rates, photographic
assessment and
bacterial counts were
performed before and
during treatment for
anaerobes and
aerobes.
To assess efficacy,
lesion count was
performed on the
face, back and chest.
To assess efficacy,
grading and counting
of lesions was
performed.
Women (age range 16-30 years) with
acne were randomized to receive one
of the following treatments for 6
months:
(2) 2 mg cyproterone acetate + 50 µg
ethinyl estradiol for 3 weeks and
placebo tablets twice daily;
Method of
Assessment
Study Population/
Intervention
Table 5c. Effectiveness of Anti-Androgens
Anti-androgen and
estrogen
combination is more
effective than
standard estrogen
Adverse effects were
and progesterone
mild but difficult to asses.
contraceptives.
More rapid and complete
response was seen in
the groups receiving
CPA.
There was improvement
in all three groups in total
and in facial acne grades
during the 6-month
assessment period.
The addition of CPA
to estrogen adds
significantly to the
therapeutic effects in
acne.
Combination of 2 mg
cyproterone acetate
+ 50 µg ethinyl
estradiol is as
effective as oral
antibiotics treatment
for moderately
severe acne.
Combination of 2 mg
cyproterone acetate + 50
µg ethinyl estradiol with
500 mg tetracycline was
significantly better
(improvement 82%)
compared to tetracycline
alone (68%). The
estrogen + cyproterone
acetate treated group
had 74% improvement.
Sebum secretion rates
were reduced only in the
cyproterone acetate +
50 µg ethinyl estradiol
group.
Conclusions
Results
41
II
Level of
Evidence
Nader et al. J Am Acad
Dermatol 1984; 11: 256137
9.
This study was
conducted to determine if
lowering androgen levels
by treatment with
glucocorticoid would
clear acne.
Author(s)/Date/
Study Design
Method of
Assessment
Changes in acne and
testosterone
measurements were
performed.
Subjects were
categorized according
Changes in acne severity and serum
to whether their acne
testosterone levels were recorded
completely cleared,
periodically.
improved, or did not
improve.
158 women (age 16-40 years) who
had been identified as hyperandrogenic were treated with oral
prednisone (7.5-15 mg) twice daily
for at least 6 months.
Study Population/
Intervention
Table 5d. Effectiveness of Oral Corticosteroids
Conclusions
Pretreatment
testosterone levels
were significantly
higher in those
whose acne did not
clear.
Lowering the
androgen levels is
associated with
clearing acne.
Results
In 39.9% of patients, acne
completely cleared. In
50.6%, it was significantly
improved and in 9.5%,
there was no effect on
acne after treatment.
There were significant
differences between the
mean testosterone levels
for the patients whose
acne had cleared and
those whose did not clear.
42
43
VI.
The effectiveness and potential side effects of isotretinoin in the treatment of adult acne
and acne vulgaris in adolescents to adults
Isotretinoin is a member of the retinoid class of compounds related to retinol (vitamin A). The
effectiveness of systemic isotretinoin therapy in the treatment of acne has been demonstrated. Oral
isotretinoin is approved for the treatment of severe recalcitrant nodulocystic acne or for the treatment
of moderate acne that had failed to respond to conventional antibiotic therapies. Isotretinoin is the
only treatment that has an effect on all the factors involved in the pathogenesis. It suppresses sebum
production, which in turn reduces the bacterial population. Isotretinoin also normalizes desquamation
and is anti-inflammatory.
The approved dosage is 0.5-2.0 mg/kg/day, usually for a 20-week treatment period. Its absorption is
greater when the drug is taken with food because it is lipid soluble.
Isotretinoin has many side effects. Most of the side effects are temporary and resolve after reducing
or withdrawal of the drug. Side effects such as suicide and depression have been reported in studies
but a causal relationship has not been demonstrated. The treating physician should monitor for signs
and symptoms of psychiatric disturbance among acne patients before, during and after isotretinoin
therapy. Large, well designed, well implemented, and carefully analyzed epidemiological studies must
be conducted to evaluate the psychiatric side effects of isotretinoin for the treatment of acne.
Because of the teratogenic effects of isotretinoin on the fetus, the FDA and the manufacturers have
approved a new risk management program for isotretinoin. Prescribers, patients, pharmacies, drug
wholesalers and manufacturers in the U.S. are required to register and comply with the iPLEDGE
program. This program requires mandatory registration of all patients receiving this drug. Detailed
information can be found on the iPLEDGE web site (https://www.ipledgeprogram.com).
I
Level of
Evidence
Patients were evaluated at
baseline and at 2, 4, 8, 12, 16,
and 20 weeks and at 2-3
months after treatment was
discontinued.
Clinical side effects
were monitored.
Plasma cholesterol
and triglyceride
levels were
evaluated by
laboratory analysis.
150 patients (age 5-49 years)
with treatment-resistant
nodulocystic acne were
randomized to receive 0.1, 0.5,
or 1 mg/kg/day isotretinoin for
20 weeks. Therapy could be
stopped when 70-80%
reduction in lesions was
observed.
Strauss et al. J Am
Acad Dermatol 1984;
144
10: 490-6.
Multicenter,
randomized, doubleblinded study to
determine whether
there is a dosedependent clinical
response and doserelated incidence of
clinical and laboratory
side effects of
isotretinoin therapy.
Lesion counts for
face and trunk were
monitored.
Method of
Assessment
Study Population/
Intervention
Author(s)/Date/
Study Design
6. Use of Isotretinoin
Laboratory abnormalities were
greater than 10%. The most
frequent abnormality was in the
blood lipids, especially
triglycerides.
There was an increase in side
effects with higher doses of
isotretinoin.
Results
0.5, 1 mg/kg/day dose
of isotretinoin is
recommended for the
management of
nodulocystic acne.
10% of patients treated
with 1 mg/day required
a second course of
therapy.
There was no
significant difference in
clinical response
between dosages 0.1,
0.5, or 1 mg/kg/day of
isotretinoin.
Conclusions
44
I
Level of
Evidence
This study was
conducted to assess
the efficacy of
intermittent moderate
dose of systemic
isotretinoin as a
treatment for severe
acne.
Goulden et al., Br J
Dermatol 1997; 137:
150
106-8.
Author(s)/Date/
Study Design
Patients were evaluated at
baseline and every 3 months
during therapy and for 12
months following treatment.
80 consecutive patients (age
25 years and over) with
unresponsive acne or rapid
relapse after three or more
courses of conventional
antibiotic therapy were
randomized to receive
0.5 mg/kg of isotretinoin per
day for 1 week in every 4
weeks for 6 months.
Study Population/
Intervention
Side effects were
monitored at each
visit.
The study suggests
that intermittent doses
of isotretinoin may be a
cost-effective
alternative to full dose
isotretinoin therapy in
selected groups of
patients with acne.
Conclusions
This study did not have
4% of patients had relapse after 6
a control population.
months of treatment. 39% had
relapse after 12 months. There was
higher rate of relapse in patients
with truncal acne.
9% of patients who failed to
improve significantly were treated
with full dose regimen of
isotretinoin.
At the end of 6 months, total acne
grades and inflamed lesion count
were significantly reduced. Acne
had resolved in 88% of patients.
Results
Pregnancy test had
to be negative before
the start of the
Mild cheilitis was the principal side
treatment. Patients
effect.
were on
contraception
throughout the
treatment and for
one month following
treatment.
Acne severity was
assessed on the
face, chest and back
using the Leeds
9
objective technique.
Inflamed lesion count
and sebum excretion
rate were measured.
Fasting lipids and
liver functions were
compared during and
after therapy.
Method of
Assessment
45
I
Level of
Evidence
600 patients (≥12 yrs.) were
randomized to receive 1 of the
following for 20 weeks:
Group (1) 0.4 mg/kg
micronized isotretinoin once
daily without food and placebo
capsules twice daily with food
(n=300);
Strauss et al., J Am
Acad Dermatol 2001;
153
45: 196-207.
Multicenter, doubleblinded, randomized,
parallel-group clinical
study to compare the
safety of micronized
isotretinoin and
standard isotretinoin in
the treatment of
severe, recalcitrant,
nodular acne.
492 patients completed the
study.
All patients underwent lab
evaluation that included CBC,
LFTS and serum lipids profile.
All patients were evaluated at
baseline and at 8, 16, and 20
weeks after treatment.
Group (2) 1 mg/kg standard
isotretinoin in 2 divided doses
daily with food and 1 placebo
capsule daily without food
(n=300);
Study Population/
Intervention
Author(s)/Date/
Study Design
85.3%
80.3%
Mild
Moderate
Triglycerides were abnormally
elevated for 16-26%, and 2-3% had
abnormal liver enzymes. There was
a slight reduction in total white
blood cells, neutrophils or
lymphocytes.
85.3%
The authors conclude
that the psychiatric
adverse events in this
Severe
34.3 % 35.3%
study do not support a
causal relationship
Most adverse events were
Efficacy was
between the symptoms
measured by change mucocutaneous: (cheilitis, peeling
and isotretinoin use.
skin,
dry/bleeding
nose,
dry/irritated
in the nodular lesions
They are more likely to
eyes
and
facial
rash).
Headache
from baseline to
be due to underlying
was
also
seen
in
13-16%
of
week 20.
patients. Back pain was seen in 3- factors not assessed in
this trial.
Mood assessments
5% of patients.
were also performed.
This study did not have
Adverse events classified as
psychiatric disorders occurred in 1- a control placebo
group for comparison.
3.7% of patients.
87.3%
Both treatment groups had an
equivalent reduction in the number
of total nodules.
Lesion counts of
nodules, papules
and pustules were
performed.
Conclusions
Micronized one-daily
dose of isotretinoin
was equivalent to the
standard twice-daily
Adverse events occurred in 5.3% of
isotretinoin for the
patients who had to discontinue
treatment of
therapy.
recalcitrant nodular
Adverse events: Group 1 Group 2
acne.
Results
Photographs were
taken at baseline
and were used for
comparison in the
assessment of acne
severity by both
patient and
physician.
Method of
Assessment
46
I
I
Level of
Evidence
This population-based
cohort study was
conducted to
determine the
proposed association
between isotretinoin
therapy and the risk of
depression or
psychotic symptoms.
Jick et al. Arch
Dermatol 2000; 136:
163
1231-6.
Summary and
recommendations of
AAD consensus
conference on the safe
and optimal use of
isotretinoin treatment.
Goldsmith et al., J
Am Acad Dermatol
159
2004; 50: 900-6.
Author(s)/Date/
Study Design
Method of
Assessment
To determine the rates and
relative risk (RR) of psychotic
symptoms, data was analyzed
for history of 7,195/340
isotretinoin patients and
13,700/676 oral antibiotic (ages
10-29 years) patients from
Canada/ UK respectively.
(3) To develop
recommendations
regarding future research.
(2) To present the best data on
clinical use and adverse
effects;
Results were
expressed as relative
risk. RR was
estimated comparing
isotretinoin users,
oral antibiotic users
and non-users.
Three goals for the conference: Consensus
conferences of
(1) To bring scientific clarity to
experts in the field of
unresolved questions
acne.
regarding isotretinoin use;
Study Population/
Intervention
There were 1,777 patients with
depression or psychosis. 61% had
anxiety disorder, 29% had mood
disorders, 6% had affective
disorders and 3% had non-affective
disorders. The RR for current
isotretinoin use compared to the
non-exposed period was 1.0. The
RR for recent isotretinoin use,
current use and recent antibiotic
use was 0. 9, 1.3, and 0.9
respectively.
There is no dose of oral isotretinoin
that is safe from possible
teratogenic side effects during
pregnancy. The rate of
malformation of fetus with retinoid
exposure is about 20% compared
to 2% in the unexposed population.
Dr. Lookingbill recommended
starting isotretinoin at 0.5
mg/kg/day for the first 4 weeks to
avoid flares and then increase to
full dosage of 1.0 mg/kg/day.
Results
Depression can be
undiagnosed so it is
not possible to
definitively exclude all
subjects with a history
of major depression.
The authors in this
study do not provide
evidence that the use
of isotretinoin is
associated with an
increased risk for
depression, suicide, or
other psychiatric
disorders.
Individuals who have
risk factors for
depression or suicide
should be monitored
closely when being
treated with
isotretinoin.
The association
between isotretinoin
and depression or
suicide is not
determined.
Physicians prescribing
isotretinoin must
ensure that
contraceptive
counseling is provided.
Effective contraception
is essential in
minimizing the risk of
isotretinoin-associated
teratogenicity.
Conclusions
47
Marqueling and Zane,
Semin Cutan Med
Surg 2005; 24: 92164
102.
I
The aim of this paper
was to review the
published clinical
evidence assessing the
proposed association
between isotretinoin
use and the risk of
depression/suicide
among patients with
acne vulgaris treated
with isotretinoin.
Author(s)/Date/
Study Design
Level of
Evidence
A literature review was
performed. Data from articles
that met inclusion and
exclusion criteria were
reviewed for this study.
Study Population/
Intervention
Searches were done
using computerized
databases,
MEDLINE using
PubMed, EMBASE,
BIOSIS previews,
and PsychINFO.
Method of
Assessment
Some data supported the
possibility that isotretinoin therapy
may have a positive impact on
psychiatric well-being.
Nine articles were reviewed; 6
studies were conducted
prospectively and 3 retrospectively.
Results
The available data on
suicidal behavior
during isotretinoin
treatment are
insufficient to establish
a meaningful causative
association.
Factors like age,
gender and prior
psychiatric history
appear to be much
stronger predictors of
depression and
suicidal behavior.
The authors conclude
that although the
studies reviewed in this
article do not support a
causal association
between isotretinoin
use and an increased
risk of depression or
suicidal behavior, the
evidence may not be
sufficiently compelling
to rule out a weak
association.
Conclusions
48
I
Level of
Evidence
101 patients completed the
study and 31 patients were
unavailable for follow-up.
Depressive symptoms were
evaluated at baseline and 3-4
months after therapy.
Acne severity was
determined by
physician clinical
assessment.
Patients were
evaluated for
depressive
symptoms using the
Center for
Epidemiological
Studies Depression
Scale (CES-D).
Mean CES-D scores
were compared
between treatment
groups.
132 patients (age 12-19 years)
with moderate to severe acne
participated in the cohort study
comparing depressive
symptoms in adolescents
receiving isotretinoin therapy
(3-4 months) and those
receiving conservative therapy
(topical antibiotic, topical
retinoid and twice daily oral
antibiotic).
Chia et al., Arch
Dermatol 2005; 141:
165
557-60.
A cohort study,
controlled, comparing
depressive symptoms
in adolescents
receiving isotretinoin
therapy (3-4 months)
and those receiving
conservative therapy.
Method of
Assessment
Study Population/
Intervention
Author(s)/Date/
Study Design
Due to the small number of cases
with new-onset of depression, it
was not possible to perform a
multivariate analysis of incidence.
CES-D scores were no higher in
the isotretinoin group than in the
conservative therapy group.
Results
The participants were
from private practice
and university clinics.
Genetic factors and
environmental factors
of the subjects were
not taken into account.
The study had a very
small sample size and
was not randomized.
The authors conclude
that this cohort study
indicates that there is
no increase in the
prevalence of
depressive symptoms
in the isotretinoin
treated group
compared to the group
treated with maximal
conservative therapy.
The incidence of
suicidal ideation in the
isotretinoin and control
group was 0 and 1.4%
respectively. This
study showed that the
isotretinoin therapy
improved the
depressive symptoms.
Conclusions
49
50
VII.
The effectiveness and potential side effects of miscellaneous therapies in the treatment
of adult acne vulgaris in adolescents to adults
Intralesional corticosteroid injections are effective in the treatment of individual acne nodules.
Chemical peels have been used in dermatology for the treatment of acne scars. Chemical peel is a
nonsurgical procedure. Both glycolic acid-based and salicylic acid-based preparations have been
used in the treatment of acne. There is limited evidence from published clinical trials regarding the
efficacy and safety of peeling regimens and comedo removal for the treatment of acne.
III
This study evaluates
the use of
intralesional steroids
in the treatment of
acne.
Potter, J Invest
Dermatol 1971; 57:
169
364-70.
Patients were evaluated at baseline
and daily for up to 14 days after
treatment.
Patients were injected with
triamcinolone acetonide in numerous
inflammatory acne cysts.
9 patients (age 19-25 years) with
severe cystic acne were given
intralesional treatment with 15–50 mg
triamcinolone acetonide.
Patients were examined 1 week and 1
month after treatment
(2) 8 patients with cystic acne received
intralesional injections of saline placebo
control and betamethasone phosphate
in 3 different concentrations 3.0 mg/ml,
1.5 mg/ml and 0.75 mg/ml. This was
not blinded.
Blood samples
were analyzed
daily and plasma
cortisol was
measured by
laboratory
analysis to
evaluate adrenal
suppression.
III
Patients were evaluated at baseline, 3
and 7 days, and also 4 weeks after
treatment.
Flattening of cysts
was measured on
a 0-3 scale in
both treatments.
(1) 9 patients (age 16 – 35 years) with
cystic acne were randomly assigned to
receive intralesional injections of
triamcinolone acetonide in 3 different
concentrations of 0.63 mg/ml,
1.25 mg/ml and 2.5 mg/ml.
Levine and
Rasmussen, Arch
Dermatol 1983; 119:
168
480-1.
Randomized,
blinded, controlled
study to evaluate the
effectiveness of
intralesional steroid
injections of
corticosteroid in the
therapy of
nodulocystic acne.
Method of
Assessment
Study Population/
Intervention
Author(s)/Date/
Study Design
Level of
Evidence
Table 7a. Use of Intralesional Steroids
All patients were on
tetracycline, topical keratolytics
and dietary precautions.
Patients who received higher
doses of intralesional steroid
showed adrenal suppression,
with the duration related to the
dosage.
All patients were on
tetracycline, topical
medications.
Triamcinolone acetonide was
effective in reducing the
severity of nodulocystic acne.
None of the concentrations of
betamethasone had a
significant effect.
Results
A very small number of
patients were used to
show efficacy or safety.
Intralesional
triamcinolone
acetonide can produce
adrenal suppression
lasting for a prolonged
period of time.
To compare the
efficacy of two different
treatments, both
studies should have
been conducted in a
similar manner.
Triamcinolone
acetonide at
0.63 mg/ml was
effective.
Betamethasone
phosphate even at
3.0 mg/ml had no
effect on nodulocystic
acne lesions.
Conclusions
51
III
III
Level of
Evidence
Cunliffe’s grading
9
system (Leeds scale)
was used to grade
acne.
The improvements
were measured by
physician assessment
which included the
counting of facial
lesions.
26 patients (age 16-27 years) with mildto-moderate facial acne were treated
with each of the following
simultaneously three times every 2
weeks on opposing sides of the face for
6 weeks:
40 subjects with moderate to moderately
severe acne were treated with either
35% or 50% glycolic acid, depending
upon the degree of facial skin
greasiness.
Kim et al., Dermatol
Surg 1999; 25: 270170
3.
Wang et al.
Dermatol Surg
171
1997; 23: 23-9.
This study was
conducted to
evaluate the safety
and efficacy of serial
glycolic acid peels
for the treatment of
facial acne.
Subjects were evaluated at baseline and
after 2, 5, 8, and 11 weeks.
A series of 4 peels at 3-week intervals
were performed - at week 1, 4, 7, and
10.
Patient self-evaluation
was also used to
evaluate safety.
A split-face
Patient preference test
randomized clinical
trial to compare the
was given at the end of
efficacy and safety of (1) Jessner’s solution (resorcinol,
each study.
salicylic acid and lactic acid, in
70% glycolic acid
and Jessner’s
ethanol)
solution in the
(2) 70% glycolic acid
treatment of acne.
Patients were evaluated at baseline, and
bi-weekly.
Method of
Assessment
Study Population/
Intervention
Author(s)/Date/
Study Design
Table 7b. Use of Chemical Peels
Consistent and repetitive
treatment with glycolic
acid peels was required
for improvement.
Significant resolution of
comedones, papules and
pustules was observed in
the patients.
Some patients had
eczema with oozing and
crusting.
Redness was noted as a
common side effect.
There was no statistical
difference between the 2
treatment groups.
There was a decrease in
the mean acne grading
score in both treatments.
Results
Glycolic acid peels
have some potential
for the treatment of
moderate to
moderately severe
acne.
Both 70% glycolic acid
and Jessner’s solution
appear to be effective
in reducing mean acne
grading score but there
was no placebo group
in this study to
compare safety or
efficacy.
Conclusions
52
III
Level of
Evidence
Patients were evaluated at baseline,
after 2 weeks and many months after
treatments.
The procedure was repeated at 2-week
intervals.
14 patients (age 16-66 years) with large
(2-3 mm) whiteheads were treated with
light cautery using topical anesthesia
EMLA cream.
Pepall et al., Br J
Dermatol 1991; 125:
173
256-9.
This study describes
a simple treatment
for the ablation of
whiteheads by
cautery under local
anesthesia with
EMLA cream.
Study Population/
Intervention
Author(s)/Date/
Study Design
Table 7c. Use of Comedo Removal
Lesion counts and
photographs were
used to assess the
efficacy of the
treatment.
Method of
Assessment
95% of the whiteheads were
cleared.
This was confirmed by
photography and lesion counts.
All patients considered the
treatment to be beneficial.
Results
Whiteheads may
be treated with
cautery
technique using
topical
anesthesia.
Conclusions
53
54
VIII.
The effectiveness and potential side effects of complementary/alternative therapies in
the treatment of adult acne and acne vulgaris in adolescents to adults
There have been many clinical trials conducted studying the safety and efficacy of complementary
therapies for the treatment of acne. Some studies have suggested a correlation between increase in
stress and acne severity. This may be associated with increased sebum, free fatty acid and endocrine
activity, which are important for the pathogenesis of acne. Additional research is needed to
adequately assess the role of herbal therapy, hypnotherapy, and psychological approaches in the
treatment of acne.
II
II
Level of
Evidence
All patients were evaluated every 2
weeks.
Facial lesions were
counted and the
investigator
performed an
overall clinical
Randomized, double- (1) Sookshama Triphala: composed of
evaluation of
dried fruit and mineral (n=16);
blinded, placebopatients’ overall
controlled clinical trial
(2) Thiostanin: composed of dried fruit, change in facial
to compare the
acne. Photographs
mineral, and root (n=17);
efficacy of 4
were also used for
Ayurvedic
(3) Placebo tablets (n=15);
evaluating the
formulations and
patients.
(4)
Shankhabhasma
Vati:
composed
of
placebo in the
a
counch
shell
(n=14);
treatment of acne
vulgaris.
(5) Sunder Vati: composed of stem
bark, dried fruit, and rhizome (n=20).
82 patients (age 18–28 years) with
moderate facial acne were randomized
to receive 2 tablets of one of the
following, three times daily for 6 weeks:
Paranjpe and
Kulkarni, J
Ethnopharmacol
175
1995; 49: 127-32.
Skin tolerance was
also assessed.
The severity of acne
was assessed using
the lesion counting
technique described
by Burke and
9
Cunliffe. Efficacy
was measured by
monitoring the
changes in the total
inflamed and noninflamed lesion
counts during the
treatment.
124 subjects with mild to moderate
acne (age 12-35 years) were
randomized to receive either topical tea
tree oil in a 5% water-based gel (n=61)
or 5% topical benzoyl peroxide lotion
(n=63) for 3 months.
All subjects were evaluated at baseline
and every month for 3 months.
Method of
Assessment
Study Population/
Intervention
A randomized,
single-blinded study
to compare the
efficacy and safety of
topical tea tree oil
and topical benzoyl
peroxide.
Bassett et al.,
Med J Aust 1990;
174
153: 455-8.
Author(s)/Date/
Study Design
Table 8a. Use of Herbal Agents
2/3 patients in group 5
showed good to excellent
clinical response.
There was a significant.
reduction in the total number
of inflammatory lesions within
2 weeks and further
reduction during the 6 weeks
of treatment.
Significant reduction in lesion
count was seen only in the
Sunder Vati group 5 (60%).
The mechanism of
action of any of the
Ayurvedic
preparations is not
known at present.
A larger study group
and comparison to
other known systemic
therapies should be
evaluated to
determine the efficacy
and safety of the
Ayurvedic drugs.
This Ayurvedic
preparation Sunder
Vati may be of value in
the treatment of acne.
Tea tree oil may be
effective topical
treatment but studies
conducted doubleblinded and with
proper controls would
better determine the
safety and efficacy of
tea-tree oil for the
treatment of acne.
Both treatments were
effective in reducing the
number of inflamed lesions
but benzoyl peroxide was
significantly better than teatree oil.
Adverse effects were seen in
both groups.
Conclusions
Results
55
II
Level of
Evidence
Lalla et al., J
Ethnopharmacol
176
2001; 78: 99-102.
Randomized, doubleblinded, placebocontrolled clinical trial
to compare the
effectiveness of oral
and topical forms of
Ayurvedic
preparation to
placebo in the
treatment of acne.
Author(s)/Date/
Study Design
Global assessment
scale of Burke and
Cunliffe was used
9
for evaluation.
Overall change in
the facial acne from
baseline to the end
of the trial was
evaluated on a 4point scale: good to
excellent, slight to
fair, variable, no
change or worse.
53 patients (age 14-28 years) with mild
to moderately severe acne were
randomized to receive one of the
following for 4 weeks:
(1) Oral tablets containing active
ingredients and topical gel preparations
(n=23);
Patients were evaluated every week.
(4) Placebo tablets with placebo
topical preparation (n=2).
(3) Oral tablets containing active
ingredients and placebo topical
preparations (n=5);
(2) Oral tablets containing active
ingredients and topical cream
preparations (n=23);
Method of
Assessment
Study Population/
Intervention
Conclusions
Both combinations of
Group 1: 32% showed good
to excellent, 63% slight to fair oral and topical
preparations showed
improvement.
significant
Group 2: 58% good to
improvement of acne.
excellent, 26% slight to fair
The study had too
improvement.
small a number of
Group 3: 100% slight to fair
patients to evaluate
improvement
safety and efficacy.
Group 4: No improvement.
Results
56
III
Level of
Evidence
This study describes
the hypotheses
towards a unified
field theory of human
behavior with clinical
application to acne
vulgaris.
Ellerbroeck,
Perspect Biol Med
177
1973; 16: 240-62.
Author(s)/Date/
Study Design
Method of
Assessment
Patients were seen every 4-6 weeks,
for up to 2 1/2 years and followed up to
4 years.
38 patients (age 13-46 years) with acne The patient and
who refused to be evaluated by a
physician agreed
dermatologist.
upon severity of
acne.
Many patients in the trial had earlier
The presence and
pursued many different treatments.
degree of
improvement were
All patients received 1 mg tablet of
established by
trifluoperazine daily.
agreement of the
Patients also received staphylococcus
patients and the
toxoid at first twice weekly and then
opinion of their
every month for 6 months.
physician.
Good posture and a pleasant facial
expression were emphasized.
Study Population/
Intervention
Table 8b. Use of Psychological Approaches
No adverse effects were
reported.
The rest of the patients had
80-90% improvement.
At 16 weeks, 17 patients
were “cured” on the basis of
a clear skin.
Results
Control groups were
lacking in the study to
assess the efficacy of
this therapy.
The author used
psychotherapy for the
treatment of acne.
The author’s idea is
that a “disease” is
determined by all the
specific
psycholinguistic and
behavioral events in
the life history of the
patients.
Conclusions
57
Hughes, et al.
J Psychosom Res
1983; 27: 185178
91.
II
A randomized,
case-controlled
study to determine
if acne vulgaris can
be reduced by
psychological
treatment like
biofeedbackassisted relaxation
and cognitive
imagery treatments.
Author(s)/Date/
Study Design
Level of
Evidence
Study Population/
Intervention
All cases had a matched control group.
The treatment was for 12 sessions over
6 weeks.
Patients received relaxation and
cognitive imagery treatments, attentioncomparison training, or normal
dermatological care only.
Study involved 30 subjects with acne
who were receiving dermatological
treatment.
Table 8c. Use of Hypnosis/Biofeedback
Photographic method
of Cook et al. was
used to assess acne
7
severity.
Method of
Assessment
Biofeedback-assisted
relaxation and cognitive
imagery treatments
resulted in a significant
reduction in acne severity
compared to control
groups and
dermatological treatment
groups.
Results
Regular practice of
relaxation-imagery is
probably necessary in
order for patients to
maintain the improved
acne condition that was
observed at the end of
the treatment.
Biofeedback-assisted
relaxation and cognitive
imagery may be
effective in the treatment
of acne.
Conclusions
58
59
IX. The effectiveness of dietary restriction in the treatment of adult acne and acne vulgaris in
adolescents to adults
The role of diet in the development of acne and an association between diet and acne has not been
demonstrated. There are limited studies that directly evaluate the effectiveness of dietary restriction in
the treatment of acne in adolescents and adults. Various foods, including chocolate, fats, sugar, and
carbonated beverages have been thought to develop or worsen acne. Studies on diet and the
development of acne have been limited and inconclusive. It is difficult to conduct good clinical studies
because it is not possible to dissociate diet from genetic factors.
II
II
Level of
Evidence
Study Population/
Intervention
Fulton et al.,
JAMA 1969; 210:
180
2071-4.
65 adolescents and young adults with
mild to moderate acne were randomized
to receive an enriched chocolate bar
(ten times the amount of chocolate in a
Randomized,
typical bar) or a control bar (which
single-blinded,
appeared to be identical in size, shape,
controlled,
color and wrapping to the enriched
crossover study to
chocolate bar but contained no
determine the effect
chocolate) daily for 4 weeks. After 3
of consumption of
weeks of rest, patients crossed over to
high amounts of
the other group.
chocolate on acne.
Bett et al., Br Med 16 patients with acne (mean age
179
J 1967; 3: 153-5.
19.5years) were compared to 16
patients with other dermatologic
Cohort study to
diseases (mean age 20.0 years) and 16
evaluate the
healthy volunteers (mean age 19.7
influence of sugar
years).
consumption on the
development of
acne vulgaris.
Author(s)/Date/
Study Design
Table 9. Effectiveness of Dietary Restriction
Improvement was defined
as a 30% decrease in total
lesion count. Worsening
was defined as a 30%
increase in total lesion
count. Smaller differences
were reported as no
change.
Comedones, papules, and
pustules on the left side of
the face were counted
weekly.
Acne was diagnosed based
on the presence of
comedones, papules,
pustules, or cystic lesions of
the face, back, or chest.
Sugar intake was assessed
by self-reported
questionnaire.
Method of Assessment
Neither the
chocolate bar
nor the control
bar influenced
acne vulgaris.
There was no
difference in
severity of acne,
sebum secretion
rates, or sebum
composition
between the
treatment
groups.
No significant
difference in
sugar
consumption
was noted
among the acne
patients
compared to the
two control
groups.
Results
Larger double-blinded
studies with controlled
dietary factors should be
conducted.
Dietary chocolate had no
effect on acne severity.
Further studies are required
to test this possibility.
From this study it is not
possible to conclude that
diet is not involved in the
causation of acne or that
changes in diet would not
affect disease progress.
Patients with acne had a
similar amount of sugar
intake as the control
groups.
Conclusions
60
61
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