EVIDENCE BASED PHARMACY PRACTICE

Evidence

Evidence-based Pharmacy Practice (EBPP):

ACNE VULGARIS

Ilse Truter
Drug Utilization Research Unit (DURU), Department of Pharmacy, Nelson Mandela Metropolitan University

Acne is a disorder of the pilosebaceous follicles causing comedones, papules and pustules on the face, chest and
upper back.1 It affects virtually all adolescents, to varying degrees of severity, and usually appears at the time of
puberty.1 Although it may sometimes be unsightly and can persist for several years, it is not usually serious and
resolves in most patients by the age of 25 years.2 However, it can have a significant psychological impact as it affects
young people at a stage in their lives when they are especially sensitive about their appearance.2
Diagnosis is usually straightforward and most patients presenting in a community pharmacy will generally be seeking
appropriate advice on correct product selection rather than wanting someone to put a name on their rash. The
majority of cases seen in the pharmacy setting will be mild and can be managed appropriately without referral.
More persistent and severe cases need referral for more potent topical or systemic treatment. It is important to
note that all forms of acne can cause scarring.3

Definition of acne vulgaris

Acne vulgaris (acne) is the formation of comedones, papules,
pustules, nodules and/or cysts as a result of obstruction and
inflammation of pilosebaceous units (hair follicles and their
accompanying sebaceous gland).4

Epidemiology of acne vulgaris

Acne affects approximately 80% of people aged 11 to 30 years at

some time, with about 60% of those sufficiently affected to seek
treatment.2 Acne lesions typically develop at the onset of puberty.
Girls therefore tend to develop acne at an earlier age than boys.1
The peak incidence for girls is between 14 and 17 years, compared with 15 to 19 years for boys.1,2,5
There may be a familial tendency to acne and it is slightly
more common in boys, who also experience more severe
involvement.1 Acne is more common in males than females
during adolescence, but is more common in women than in men
during adulthood.6 In addition, white patients are more likely to
experience moderate to severe acne, although black skin is
prone to worse scarring.1
Acne usually resolves within 10 years of onset, although up to
five percent of women and one percent of men in their thirties can
have mild persistent acne.1,2,5 The incidence of acne appears to
have fallen in recent years, however the reasons are unknown.2

Aetiology/pathophysiology
The pathogenesis of acne vulgaris is multifactorial.6 The various
pathogenic factors represent specific targets for treatment and it
has been proven that treatment directed at different pathogenic
factors achieves better results than treatment methods aimed at
the same pathogenic factors.7
A cascade of events takes place at puberty resulting in the
formation of non-inflammatory and inflammatory lesions.

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Acne arises in the pilosebaceous units in the dermis,

which consist of a hair follicle and associated sebaceous gland. In response to increased testosterone
levels, the pilosebaceous gland produces sebum, a
mixture of fats and waxes that protect the skin and hair
by retarding water loss and forming a barrier against
external agents. The hair follicle is lined with epithelial
cells that become keratinised as they mature. During
puberty the production of androgenic hormones increases in both genders and testosterone levels rise. If
the sebaceous glands become oversensitive to testosterone, they produce excess oil and the skin becomes
greasy (a hallmark of acne). At the same time, keratin in
the follicular epithelial wall (the cells lining the follicle)
undergoes change. Prior to puberty, dead cells are
shed smoothly out of the ductal opening but at puberty
this process is disrupted and in patients with acne
these cells develop abnormal cohesion and partially
block the opening in the epidermis and effectively
reduce sebum outflow. Over time the opening of the
duct becomes blocked, trapping oil in the hair follicle.
Oil blocks the follicle openings in the epidermis and
causes them to dilate beneath the skin surface. If the
orifice of the follicular canal opens sufficiently, the
keratinous material extrudes through it and an open
comedone results. This is known as a blackhead as the
keratinous material darkens in contact with the air.
Because this material can escape, the comedone does
not become inflamed. If the follicular orifice does not
open sufficiently, a closed comedone (whitehead)
results, within which inflammation can occur. Most acne
sufferers have a combination of both open and closed
comedones .2

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Bacteria, particularly Propionibacterium acnes (P acnes),

cause the follicular wall of closed comedones to disrupt and
collapse, spilling their contents into the surrounding tissue
and provoking an inflammatory response. In addition,
bacterial enzymes decompose triglycerides in the sebum to
produce free fatty acids, which also cause inflammation.
This process leads to the formation of papules around the
follicular openings in the more common, milder form of acne
and to cyst formation in the deeper layers of the skin in the more
severe form. P acnes proliferate in the stagnant oil, stimulating
cytokine production, which produces the local inflammation
leading to the appearance of a spot. In response to the
proliferation of bacteria, white blood cells infiltrate the area and
kill the bacteria and in turn die leading to pus formation. The
pustule eventually bursts on the skin surface, carrying the
plug away. The whole process then starts again.
The main pathogenic factors involved in acne can
therefore be summarised as7:
Production of androgens in the body.
Excessive sebum production.
Abnormal desquamation of the follicular epithelium in the
duct of the sebaceous gland.
Proliferation of P acnes.
Inflammatory and immunological responses.

Diagnosis of acne vulgaris

Diagnosis is by examination. Differential diagnosis of acne is
routine and should not be difficult. The pharmacist will,
however, need to assess the severity of the acne. The
lesions usually occur on the forehead, nose and chin. The
periorbital area is usually spared.2 Acne, therefore, affects
the areas of the skin with the densest population of sebaceous glands. The scalp is rarely involved although it is
richly supplied with sebaceous glands.7 In severe cases, the
whole face, upper chest and back may be affected.2 Lesions
at different developmental stages often coexist.
Several rating scales have been developed with the aim
of trying to grade the severity of the individuals condition.
No method has yet gained universal acceptance and most
dermatology texts simply grade the severity of acne as mild,
moderate and severe (see Table 1).1 More complicated
grading systems rely heavily on the use of photographs or
diagrams, and the clinical appearance of the patient is
compared with a standard set of photographs and severity is
then decided on according to correspondence with a
particular photograph.7
Another classification is merely to describe these three
grades of acne1,5:
Mild acne
Patients with mild acne typically have predominantly open
and closed comedones (blackheads and whiteheads) with a
small number of active lesions normally confined to the face.
Mild acne should not cause permanent scarring. Any or all
of the following is present: small, tender, red papules;
pustules; and blackheads and/or whiteheads. Mild acne is
therefore characterised by the presence of a few to several
papules and pustules, but no nodules.

SA Pharmaceutical Journal April 2009

Table 1: Classification of acne severity4

Severity

Definition

Mild

< 20 comedones, or < 15 inflammatory lesions, or < 30 total lesions

Moderate

20 to 100 comedones, or 15 to 50 inflammatory lesions, or 30 to 125 total lesions

Severe

> 5 cysts, or total comedone count >100,

or total inflammatory count >5 0, or > 125
total lesions

Moderate acne
Similar to mild acne, but more papules and pustules.
Patients with moderate acne typically have a few to several
nodules. Lesions are often painful and there is a real
possibility of scarring.5
Severe acne
Similar to moderate acne but with nodular abscesses,
leading to extensive scarring. Patients with severe acne
have numerous or extensive lesions.
Another classification of acne severity is to grade acne as
follows7:
Grade 1: Comedones only.
Grade 2: Inflammatory papules present in addition to the
comedones.
Grade 3: Pustules present in addition to any of the
above.
Grade 4: Nodules, cysts, conglobate lesions or ulcers
present in addition to any of the above.
Acne can also be classified by the type of lesion comedonal, papulopustular, and nodulocystic (pustules and cysts
are considered inflammatory acne)3:
Comedonal acne
Comedonal acne presents with a tendency to greasiness
and the presence of enlarged pores, comedones and
occasionally papule and pustule formation. There may be
plenty of open or obstructed comedones, but with scant
inflammatory changes. Comedonal acne may cause scarring, requiring systemic therapy.

Inflammatory acne

Nodular cystic acne

This type of acne may reflect any or all of the above features
of acne, but also includes the presence of sub-epidermal
cysts and nodules. Nodulocystic acne consists of pustular
lesions larger than 0.5 cm.9 Cystic acne can be painful.
Finally, a distinction is also made between various acne
types10, for example acne conglobata, acne fulmicans, acne
keloidalis nuchae and acneiform eruptions.

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EVIDENCE BASED PHARMACY PRACTICE

Evidence

Conditions to eliminate

Acne may be triggered or worsened by external factors such

as mechanical obstruction (for example, helmets or shirt
collars), occupational exposure or certain medicine (see
below).9 Cosmetics and emollients may occlude follicles and
cause an acneiform eruption.9 Topical corticosteroids may
produce perioral dermatitis, a localised erythematous
papular or pustular eruption.9 Endocrine causes of acne
include Cushings disease or syndrome, polycystic ovarian
syndrome, and congenital adrenal hyperplasia.9 Clinical
clues to possible hyperandrogenism in women include
dysmenorrhoea, virilisation (for example, hirsutism,
clitoromegaly and temporal balding), and severe acne.9
Differential diagnosis typically includes perioral dermatitis, rosacea (in which no comedones are seen), corticosteroid-induced acne (which lack comedones and in which
pustules are usually in the same stage of development) and
acneiform drug eruptions.
Rosacea
Rosacea is an inflammatory condition of the skin follicles
causing acne-like papules and pustules. It is uncertain what
causes rosacea although successful treatment with antibiotics
suggests that bacterial pathogens play a significant role in the
disease.1 It is normally seen in patients over 40 years of age.1,5
It is characterised by recurrent flushing and blushing of the
central face especially the nose and medial cheeks.1 Crops of
inflammatory papules and pustules are also a common feature,
but comedones are not present in rosacea. Eye irritation and
blepharitis are present in approximately 20% of patients.
Medicines causing acne-like skin eruptions
Although an unlikely cause, certain medicines can produce
acne-like lesions. Examples of medicine that can trigger or
exacerbate acne are given in Table 2.1,5,9

Counselling approach to follow

The overall aim in the management of acne is to

clear skin lesions and to prevent scarring. The aim is also to
improve the patients quality of life by identifying, treating and/or
eliminating the underlying cause, and to use pharmacological
therapy when indicated. This should be accomplished without
adverse effects or with clinically acceptable adverse effects. A
list of symptom-specific questions to assist the pharmacist with
the patient assessment history is given in Table 3 and will also
help the pharmacist to determine if referral is needed.
Appropriate patient counselling is of the utmost importance in acne. Patients must know how to use their medicine, common side effects, likely timescale for improvement
and that treatment is long-term (and may be needed for
months or years). Patient involvement in the choice of
topical treatment is vital and products must be cosmetically
acceptable to the patient to ensure compliance. In general,
gels and solutions are good for oily skin but may sting
sensitive or dry skin.11 Creams are suitable for sensitive or
dry skin but may make oily skin more greasy.11 Lotions are
thinner than creams and are useful for large or hairy areas.11

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Table 2: Medicines that can trigger or exacerbate acne1,5,9

More commonly

Less commonly

Anabolic steroids (for example, danazol

and testosterone)
Bromides
Corticosteroids (for example, prednisone)
Corticotropin
Isoniazid
Lithium
Phenytoin
Rifampicin
Oral contraceptives (especially those with
high progestogen levels)

Azathioprine
Ciclosporin
Disulfiram
Phenobarbital
Quinidine
Tetracycline
Vitamins B1, B6, B12 and D2

When to refer
The following symptoms suggest the need for referral1,2,5,11,12:
Moderate or severe acne.
Development of severe complications (for example, deep
pustules, severe cases of nodular acne and/or pigmentation).
Suspected occupational causes.
Mild acne, if there is no improvement after two months
with over-the-counter (OTC) treatment or if treatment
response is poor.
Acne beginning or persisting outside the normal age
range for the condition or late onset acne.
Severe psychological stress.
Suspected medicine-induced acne.
Suspected rosacea.
Unpleasant side effects from current acne therapy.

Available treatment options for acne vulgaris

The main aims of acne management are to11,12:
Reduce the number of lesions and improve the skin
condition;
Eliminate pathogens;
Reduce the impact of psychological stress; and
Prevent scarring.
A structured approach to the management of acne requires
an understanding of the cause, the severity, the type of
lesions present and the treatment options available.
Therapy should be started at an early stage to prevent
scarring. The choice of medicine depends on previous
treatment, patient acceptability and the type of lesion
(comedonal or inflammatory). Ideally, an effective anti-acne
treatment should reduce the number of both types of lesions.
Treatment options are directed at reducing sebum
production, comedone formation, inflammation and infection.4 Selection of treatment is generally based on severity.
It is important to show understanding and empathy when
counselling patients since acne is predominantly a condition
that affects adolescents, a time when appearance is very
important.

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Table 3: Specific questions to ask the patient with acne when taking a dermatological history 1,5
Question

Relevance

Age of onset?

Acne is common in adolescence.

Patients with acne-like lesions who are outside the normal age range may be affected by
an adverse drug reaction or rosacea.

Where did the problem first appear?

Certain skin problems start in one particular location before spreading to other parts of
the body, for example impetigo usually starts on the face before spreading to the limbs.
Acne is typically confined to the face, chest and upper back.

Severity?

Moderate acne is not confined to the face, but also involves the back and chest. Lesions
are often painful and there is a real possibility of scarring.
Severe acne has all the characteristics of moderate acne plus the development of cysts.
Lesions are often widespread and scarring is frequent.

Are there any other symptoms?

Many dermatological conditions exhibit itch and/or pain, for example:

Mild itch is associated with psoriasis and medicine eruptions.
Severe itch is associated with scabies, atopic and contact dermatitis.
There is no itch associated with acne.

Occupational history (relevant to adults

only)

In some occupations, workers are exposed to irritants and chemicals (for example,
hairdressing) or to excessively hot and humid conditions causing sweating. Car mechanics, for example, are exposed to frequent or prolonged contact with grease and oils,
which can cause acne-like lesions.

General medical history

Skin disoders may be the first sign of internal disease. For example, diabetes can
manifest with pruritis and thyroid disease with hair loss and pruritis. Acne can be due to
a hormonal imbalance.

Foreign travel

Tropical skin conditions can be contracted when abroad but lesions do not appear until
the person has returned home.

Family and household contact history

Some skin conditions (such as scabies) can infect those with whom the patient is in close
contact.

The patients thoughts on the cause of

the problem

Ask for the patients opinion. This may help with the diagnosis or shed light on anxieties.

Temperature

The backs of the fingers can be used to identify generalised warmth or coolness of the
skin. Generalised warmth might indicate fever. Local warmth could indicate inflammation or cellulitis.

Distribution

The pattern of involvement of the skin may assist with diagnosis. Acne typically affects
the face, chest and upper back, whereas psoriasis typically affects elbows, knees, scalp
and the sacral area, adult seborrhoeic dermatitis affects the face and mid-chest.

Lesion shape

Are the lesions arciform (in an arc), linear, annular (in a ring) or clustered? Tinea
corporis (ringworm) usually presents as an annular rash.

Recent trauma

Have the lesions developed on a site of trauma or injury. This is seen in, for example,
psoriasis and warts.

Non-pharmacological management
The following non-pharmacological treatment advice can be
given to patients with acne2:
There is no evidence that poor hygiene causes acne, but
cleansing the affected areas two to three times daily is
recommended. An antibacterial soap or a mild cleanser
to degrease the skin and to remove bacteria can be used,
and can help to reduce the severity of the condition,
although extra washing, the use of antibacterial soaps
and scrubbing have, according to evidence, no added
benefit.4 Sweat should not be allowed to remain on the
skin, but should be washed off as soon as possible.
Patients should be advised to avoid hairstyles in which
the hair is constantly touching the face, and to shampoo

SA Pharmaceutical Journal April 2009

the hair regularly.

Herbal and various alternative therapies have been used
to treat acne. Although these products appear to be well
tolerated, limited data exist regarding the safety and
efficacy of these agents.13,14
Pimples and blackheads should not be squeezed or
pinched with the fingers. Comedone expressors (blackhead removers) can be used, with removal aided by
exposing the skin to steam first.
There is limited evidence regarding the benefit of
physical modalities including glycolic acid peels and
salicylic acid peels.13,14
Natural sunlight is thought to be helpful in reducing acne,
but overexposure should be avoided.

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EVIDENCE BASED PHARMACY PRACTICE

Evidence

Patients should avoid greasy cosmetics and rather use

water-based moisturisers. They should also avoid using
hairspray.
Dietary restriction (either specific foods or food classes)
has not been demonstrated to be of benefit in the
treatment of acne.3,13,14 There is, for example, no evidence that fatty foods and chocolate cause acne, although no harm is done by testing if excluding them from
the diet has a beneficial effect.
A healthy, balanced diet with plenty of water, and regular
exercise, is always good advice.
Psychological approaches, hypnosis and biofeedback
have also been used.13,14

Pharmacological treatment
The pharmacological treatment of acne can be divided into
topical and systemic treatment. The different medicines used
in the treatment of acne are illustrated in Figure 1.4
Topical treatments
Non-prescription topical treatment is usually the first line of
treatment for mild to moderate acne. Topical OTC acne
treatments typically contain benzoyl peroxide, azelaic acid,
salicylic acid, sulphur or an antibacterial.
The overall aim of topical therapy is to remove follicular
plugs, allowing sebum to flow freely, and to minimise
bacterial colonisation of the skin. Treatment must be used
regularly for up to three months to produce benefits.2 Approximately 60% of patients should see an improvement in
their symptoms after eight to 12 weeks.5 If symptoms fail to
improve after this time period, referral is necessary. Four
types of preparations are available2:

Figure 1: Medicines used in the treatment of acne4

Obstruction of pilosebaceous duct by cohesive
keratinocytes, sebum and hyperkerotosis

Drugs that normalise pattern of follicular

keratinisation
Adapalene
Isotretinoin
Tazarotene
Tretinoin

Drugs with anti-inflammatory effects

Antibiotics (by preventing neutrophil chemotaxis)
Corticosteroids (intralesional and oral)
NSAIDs
Rupture of follicular wall

Compacted cells, keratin

and sebum

Inflammation
Increased sebum
production

Proliferation of
Propionibacterium acnes

Drugs with antibacterial effects

Antibiotics (topical and oral)
Benzoyl peroxide
Isotretinoin (indirect effect)

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Keratolytics (also known as comedolytics in relation to

acne, or peeling agents) promote shedding of the keratinised
epithelial cells on the skin surface, although the compounds
used may do this via different mechanisms. They prevent
closure of the pilosebaceous orifice and the formation of
follicular plugs and facilitate sebum flow. They also possess
varying levels of antimicrobial activity, which contribute to
their effectiveness. Examples include benzoyl peroxide,
salicylic acid, sulphur and resorcinol.
Antimicrobials. Two of the contributory factors to acne
are increased sebum production and P acnes. Therefore,
one approach to treatment is to remove excess sebum from
the skin and reduce the bacterial count. Several products
are formulated as astringent lotions and detergent-based
washes containing antibacterial or antiseptic ingredients,
and there are some antimicrobial creams. Examples of
antimicrobial active ingredients include cetrimide,
chlorhexidine, povidone-iodine, triclocarban and triclosan.
Topical antibiotics should never be used as monotherapy,
and should preferably be combined with topical nonantibiotic antimicrobials such as benzoyl peroxide.7
Anti-inflammatory agents. An example includes topical
nicotinamide. It appears to be effective. It may produce sideeffects of dryness, peeling and irritation similar to those of
benzoyl peroxide.
Abrasive products contain small, gritty particles in a skin
wash, intended to remove follicular plugs mechanically. They
typically contain aluminium oxide particles or polyethylene
granules.3 Abrasives are contraindicated in the presence of
superficial capillaries (telangiectasia), and overenthusiastic use
can cause irritation. Abrasive cleansers and vigorous scrubbing may worsen acne by provoking inflammation. There is
little evidence for the use of abrasive preparations in acne.

Hair

Drugs that inhibit sebaceous

gland function
Antiandrogens (e.g. spironolactone)
Corticosteroids (oral, in very low doses)
Oestrogens (oral contraceptives)
Isotretinoin

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Benzoyl peroxide
Benzoyl peroxide is generally accepted as the first-line
topical treatment for mild to moderate acne.2 It exerts its
main effect by having a mild but significant keratolytic effect
(therefore acting in a comedolytic fashion), but it is also a
broad-spectrum antimicrobial, acting in a non-antibiotic
fashion.7 It has potent antimicrobial effects but is sloweracting than systemic antibiotics.7 It reduces the concentration of P acnes., has slight anti-inflammatory and mild
anticomedogenic effects. Many studies have investigated
the efficacy of benzoyl peroxide. No resistance has been
reported to date.7 It is applied once or twice daily to the
entire affected area.7 There is no evidence to suggest that
10% benzoyl peroxide is more effective than 5%.5 Therefore,
because of its potential to cause erythema and irritation,
concentrations of 10% should probably be avoided.5 Lower
strengths should be used in persons with sensitive skin and
in very young or anxious patients.7 Higher concentrations
and washes can be used on the chest, shoulders and back.7
Benzoyl peroxide can be used alone in mild acne or in
combination with topical retinoids in severe comedonal and
early inflammatory acne. It may be used in combination with
systemic antibiotics when prolonged or repeated courses of
the latter are necessary. A variety of other agents (for
example, miconazole and hydrocortisone) have been used
in combination with benzoyl peroxide but none has proved to
be significantly better than benzoyl peroxide alone.5
Benzoyl peroxide can cause drying, burning and peeling
on initial application.1,5 If patients experience these side
effects, they should stop using the product for a day or two
before starting again. Patients should start on the lowest
strength available, especially if they have a sensitive or fair
skin.1,5

most forms of acne vulgaris. They should be used early for

best results, and antimicrobial therapy should be added for
inflammatory lesions if present.7 They are an essential part of
maintenance therapy.
Salicylic acid
Salicylic acid is used in concentrations of up to two percent
for acne.2 It exerts a keratolytic effect by increasing the
hydration of epithelial cells. It may also have some bacteriostatic activity and a direct anti-inflammatory effect on lesions.2
It is believed to enhance penetration of other medicines into
the skin, and is combined with sulphur in some preparations.2 Salicylic acid is a mild irritant and similar precautions
should be adopted as for benzoyl peroxide. Preparations
are applied twice or three times a day. It is readily absorbed
through the skin and excreted slowly. Salicylate poisoning
can occur if preparations are applied frequently, in large
amounts and over large areas.2 Patients who are sensitive to
aspirin should avoid these preparations.
Sulphur and recorcinol
Sulphur and resorcinol are claimed to possess keratolytic
and antiseptic properties, but there is little evidence of their
effectiveness. Sulphur may be used on its own or in combination preparations with other keratolytic agents, such as
resorcinol, salicylic acid or benzoyl peroxide, or with calamine.3 Both sulphur and resorcinol can cause skin irritation
and sensitisation. These agents are now infrequently used.2
Salicylic acid and sulphur have been used for many years on
the basis of their keratolytic action but based on evidence
they are probably best avoided.5

Prescription treatment

Azelaic acid
Azelaic acid is a suitable topical agent for mild to moderate
acne due to its antimicrobial effect on P acnes and its
influence on follicular hyperkeratosis.3 It is usually applied
twice daily. Its safety and efficacy have not been proven for
use for more than six months.3

Prescription treatment includes the following2:

Topical comedolytic, antibacterial and combined
comedolytic/antimicrobial preparations.
Oral antibiotics.
Hormonal agents.
Isotretinoin.
Other medicines.

Retinoids
Topical retinoids target the microcomedo, which forms the
earliest precursor of visible acne lesions.7 They have
multiple anti-acne actions, namely to inhibit/reduce the
number of microcomedones, reduce mature comedones,
reduce inflammatory lesions, promote normal desquamation
of follicular epithelium, have an anti-inflammatory effect,
enhance the penetration of other medicines and maintain
remission by inhibiting microcomedones.7 Different topical
retinoids are available, namely tretinoin, adapalene,
isotretinoin and tazarotene.3,7 They have similar efficacy but
share a common side effect namely initial irritation on
application.7 The topical retinoids should be applied to the
whole affected area and not only on visible lesions.
According to the Global Alliance recommendations,7 the
topical retinoids should be the primary form of treatment for

Oral antibiotics
Oral antibiotics are indicated for moderate to severe acne
(Grades 2 to 4).7 Examples are tetracyclines (especially
doxycycline, lymecycline, minocycline, and the older firstgeneration tetracyclines such as oxytetracycline), erythromycin, clindamycin and co-trimoxazole.7 Penicillins are not
considered to be effective in the management of acne.
Minocycline, doxycycline and lymecycline have similar
efficacy and pharmacoeconomically there is very little
difference between them.7 The Standard Treatment Guidelines and Essential Drugs List for South Africa: Primary
Health Care12 recommends benzoyl peroxide 5% gel applied
at night, as well as oral doxycycline 100 mg daily for three
months, if there are many pustules.
Oral antibiotics induce improvement within the first three
or four months of treatment, with little improvement thereafter,

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EVIDENCE BASED PHARMACY PRACTICE

Evidence

while antibiotic resistance usually becomes apparent after

four months of treatment.7 It is therefore suggested that
courses of antibiotics for acne should be limited to a maximum of four months.7 Oral antibiotics should therefore be
prescribed for three months, and an additional month can be
considered if total clearance has not been achieved. Compliance should be checked in patients who do not respond
well. Oral antibiotics should be used in combination regimens and never as monotherapy.7
Female patients must be counselled that some antimicrobials can impair the efficacy of oral contraceptives and that
additional non-hormonal contraceptive measures may be
required.12
The Global Alliance recommends the following with
respect to oral antibiotics for acne7:
Oral cyclines should be considered first-line agents when
treating moderate to severe acne.
Lymecycline should be considered first. The optimal
dosage is 300 mg to 600 mg per day.
Doxycycline or minocycline can be prescribed as secondline agents. The optimal dosage for both active ingredients is 100 mg to 200 mg per day, respectively.
First-generation tetracyclines such as oxytetracycline
should be considered as third-line agents.
Erythromycin can be used in children under 12 years old
or during pregnancy.
Co-trimoxazole can be considered in selected cases.
Hormonal agents
The mainstay of hormonal therapy for acne includes oral
contraceptives, cyproterone acetate, drospirenone and spironolactone.7 Hormonal therapy is useful in androgen-driven acne.
They are an excellent choice for women who need oral
contraception for gynaecological reasons. They should be
used early for patients with moderate to severe acne who also
have signs of androgen over-activity (Seborrhoea, Acne,
Hirsutism, Androgenic alopecia (SAHA)).7 They should also be
used early in female patients with clinical signs of
hyperandrogenism (endocrine evaluation dehydroepiandrosterone (DHEA), testosterone, luteinising hormone/folliclestimulating hormone (LH/FSH) ratio).7 They can be considered
in women with normal serum androgens with persistent
inflammatory papules and nodules on the lower face, or with
prominent acne flare at menstruation.7 They are also useful in
combination treatment and in women with late-onset acne.
Isotretinoin
Oral isotretinoin is the standard of care for severe acne.7 It
targets all the pathophysiological factors involved in acne. It
may achieve dramatic results even in severe disease, and
may be used in moderate and unresponsive disease.7 Side
effects are common but usually manageable. The rate of
recurrence is variable, and retreatment may be needed.7
Isotretinoin, a naturally occurring metabolite of vitamin A,
inhibits sebaceous gland differentiation and proliferation,
reduces sebaceous gland size, suppresses sebum production, and normalises follicular epithelial desquamation.

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Isotretinoin is indicated in severe nodular acne and acne

unresponsive to other therapies. It is used at a dosage of 0.5
to 1 mg/kg per day with a cumulative dosage of 120 to 150
mg/kg over a four to six-month treatment period.7,8 Coadministration with steroids at the onset of therapy may be
useful in severe cases to prevent initial worsening.6
Oral isotretinoin is highly effective at reducing sebum
secretion and a 16 to 20 week course leads to remission in
most patients.11 There may be an indication for the so-called
pulse-dosage regimen, where 0.5 mg/kg is taken daily on the
first seven days of each month.13 This usually reduces side
effects, except for the teratogenic effect, and has proved to
be highly effective for patients who relapsed after a previous
full course of oral isotretinoin, as well as for older patients
with chronic, indolent, resistant acne.7
Oral isotretinoin should only be prescribed by a dermatologist or specialist because it may cause serious adverse
effects. It is highly teratogenic (classified as Category X in
pregnancy3 and should be avoided) and women of childbearing age should use effective contraception for one
month before starting treatment, during treatment and for at
least one month after stopping isotretinoin.3 A United States
of America Food and Drug Administration-mandated registry
(called iPLEDGE) is in place for all individuals prescribing,
dispensing and taking isotretinoin.6 The aim of this registry is
to further decrease the risk of pregnancy and other unwanted
and potentially dangerous adverse effects during a course of
isotretinoin therapy.6 Special investigations during therapy
should include serum lipids and liver function (before and
after one month of therapy, relative to risks), blood glucose,
haematology and uric acid (as indicated).3 Depression is a
known complication of acne, and may be exacerbated by
isotretinoin.3 Psychological evaluation of acne patients is
therefore an important aspect of acne management.
Patients with nodulocystic acne are at greatest risk of
scarring and should be referred for oral isotretinoin treatment.
Also, patients with inflammatory acne with scarring, moderate to
severe acne unresponsive to treatment, acne with severe
psychological distress (dysmorphophobic patients), gramnegative folliculitis, and frequently relapsing acne where
repeated or prolonged courses of systemic antibiotics are
needed, should be referred for oral isotretinoin therapy.7
Other medicines that may be used in acne treatment
Intralesional corticosteroid injections are effective in the
treatment of individual acne nodules.13,14 For patients who
may not have access to expensive treatments for severe
inflammatory acne, a combination of co-trimoxazole and low
dosage prednisone for a few weeks may give excellent
results.7 Another useful drug is dapsone, which at a dosage
of 50 mg to 150 mg per day, can bring about complete
clearance of nodular inflammatory acne.7 The condition can
be controlled with long-term maintenance treatment, with low
dosage dapsone being relatively safe, provided that the
patient has a normal glucose-6-phosphate dehydrogenase
(G6PD) level and that full blood counts are done regularly to
detect any resulting anaemia.7 High-dose vitamin A used to

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EVIDENCE BASED PHARMACY PRACTICE 

be a popular treatment for acne in the past, but evidence for

its effectiveness is lacking and because of its potential for
severe toxicity, its use in acne should be discouraged.7

Treatment of scars
Small scars can be treated with chemabrasion (which uses
chemicals to peel away top layers of skin), laser resurfacing
(which uses a carefully controlled laser to burn away scar
tissue) or dermabrasion (which uses a whirling wire brush to
skim off scar tissue) under the supervision of a trained
professional.4,15 Deeper, discrete scars can be excised.4
Wide, shallow depressions can be treated with subcision or
collagen injection.4 Collagen implants are temporary and
must be repeated every few years.4

Management of the different grades of acne

vulgaris
The management of the different grades of acne as it is
stated in the South African Acne Guideline 2005 Update is
summarised in Table 4.7

Conclusion
The management of acne vulgaris by non-dermatologists is
increasing.8 Pharmacists have a definite role to play in the less
severe forms of acne and especially with respect to the counselling of patients with any form or severity of acne. Acne can be
extremely distressing and can impact severely on the quality of
life of a person. Initially mild acne should be treated with topical
agents. The choice of treatment depends on whether
comedonal or inflammatory lesions predominate. In more
severe disease, addition of systemic drugs to topical therapy is
required. Oral antibiotics are the mainstay of treatment for
moderate to severe acne. Early referral of those with severe
acne may prevent scarring. Acne responses to treatment vary
considerably. Frequently more than one treatment modality is
used concomitantly. Best results are seen when treatments are
individualised on the basis of clinical presentation.
The reader is strongly encouraged to consult the following sources for more detailed evidence-based information on
acne:

Acne Guideline 2005 Update has been developed and

published in an attempt to improve the outcomes of acne
treatment in South Africa (see Reference 7).
Guidelines of Care for Acne Vulgaris Management published by the National Guideline Clearinghouse (levels of
evidence are also indicated) (see Reference 13). The
guidelines can also be consulted in the Journal of the
American Academy of Dermatology (see Reference 14).
Summary of Recommended Guideline: Acne Management of the Guidelines Advisory Committee (GAC)
these EBM guidelines indicate different levels of evidence (see Reference 10).

References:
1.
Rutter P. 2004. Community Pharmacy: Symptoms, Diagnosis and
Treatment. Edinburgh: Churchill Livingstone.
2.
Nathan A. 2008. FASTtrack: Managing Symptoms in the Pharmacy.
London: Pharmaceutical Press.
3.
South African Medicines Formulary (SAMF). 2008. 8th Edition. Edited by
CJ Gibbon. Claremont: Health and Medical Publishing Group of the
South African Medical Association.
4.
The Merck Manual of Diagnosis and Therapy. 2006. 18th Edition. Edited
by MH Beers. Whitehouse Station: Merck Research Laboratories.
5.
Rutter P. 2005. Symptoms, Diagnosis and Treatment: A Guide for
Pharmacists and Nurses. Edinburgh: Elsevier Churchill Livingstone.
6.
Harper JC & Fulton J. 2008. Acne Vulgaris. eMedicine, 15 July.
Available on the web: http://emedicine.medscape.com/article/1069804print (date accessed: 15 December 2008).
7.
Acne Guideline 2005 Update. 2005. Compiled by W Sinclair & HF
Jordaan. South African Medical Journal, 95 (11): 883-892.
8.
Haider A & Shaw JC. 2004. Treatment of Acne. Journal of the American
Medical Association, 292: 726-735.
9.
Feldman S, Careccia RE, Barham KL & Hancox J. 2004. Diagnosis and
Treatment of Acne. American Family Physician, 69: 2123-2130, 2135-2136.
10. Lauharanta J. 2007. Guidelines Advisory Committee (GAC). Summary
of Recommended Guideline: Acne Management. (EBM guidelines.) April.
Available on the web: www.gacguidelines.ca (date accessed: 15
December 2008).
11. MeReC Bulletin. 1999. The Treatment of Acne Vulgaris: An Update. 10
(8). Liverpool: National Prescribing Centre.
12. Standard Treatment Guidelines and Essential Drugs List for South Africa:
Primary Health Care. 2003. Pretoria: The National Department of Health.
13. Strauss JS, Krowchuk DP, Leyden JJ, Lucky AW, Shalita AR, Siegfried EC,
Thiboutot DM, Van Voorhees AS, Beutner KA, Sieck CK & Bhushan R.
2007. Guidelines of Care for Acne Vulgaris Management. National Guideline
Clearinghouse. Available on the web: http://www.guideline.gov/summary/
summary.aspx?doc_id=10797 (date accessed: 12 December 2008).
14. Strauss JS, Krowchuk DP, Leyden JJ, Lucky AW, Shalita AR, Siegfried
EC, Thiboutot DM, Van Voorhees AS, Beutner KA, Sieck CK & Bhushan
R. 2007. Guidelines of Care for Acne Vulgaris Management. Journal of
the American Academy of Dermatology, 56 (4): 651-663.
15. Acne Vulgaris Treatment Overview. 2007. Acne Health Centre. WebMD.
Available on the web: http://www.webmd.com/skin-problems-and-treatments/
acne/acne-vulgaris-treatment-overview (date accessed: 15 December 2008).

Table 4: Management of the different grades of acne7

Grade

Recommended treatment

Grade 1

This degree of acne should be managed topically. A topical retinoid will suffice in most cases, but the addition of benzoyl
peroxide or azelaic acid may be necessary in resistant cases.

Grade 2

In milder cases with superficial inflammatory papules, the same treatment as above can be followed. However, where the
papules are more deeply situated, a systemic antibiotic is indicated.

Grade 3

In these cases there is always a severe, deep inflammatory process present with a marked influx of neutrophils, necessitating systemic antibiotics. These should always be used in combination with a topical retinoid and, if the systemic treatment
needs to go on for longer than three months, topical benzoyl peroxide should be added. Hormonal treatment can be used with
good success at this stage in female patients who desire contraception or who have other gynaecological indications for this
treatment.

Grade 4

Systemic isotretinoin represents the treatment of choice in these patients. In females, an oral contraceptive combined with
anti-androgens can sometimes be effective. Systemic antibiotics can bring about excellent improvement in these cases, but
the improvement is of short duration and these medicines do not represent a long-term solution for this type of acne.
Unacceptably long courses of antibiotics are usually necessary.

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