US Pharm. 2013;38(5):43-46.
ABSTRACT: Acne is no longer considered a health problem strictly of
adolescence, as its prevalence in adults has significantly increased.
Acne vulgaris and acne rosacea are diagnosed based on the clinical
presentation of the patient’s skin and are classified primarily
according to severity. The treatment of acne should be approached in a
stepwise fashion. Successful outcomes generally involve combination
therapy with different drug mechanisms. Although acne vulgaris and acne
rosacea may be considered minor issues from a medical standpoint, either
form can have a significant psychosocial impact on the patient’s
quality of life. Health care providers involved in the care of patients
with acne should be extremely sensitive not only to acne’s physical
manifestations, but also to the emotional burdens resulting from it.
Acne, once viewed as strictly an adolescent health problem, now
affects an increasing number of adults. The exact cause of this
dermatologic disorder is unclear. Both acne vulgaris and acne rosacea
are discussed in this article.
An estimated 17 to 28 million Americans suffer from acne vulgaris.1
Although up to 85% to 90% of all teenagers report having some degree of
acne, this dermatologic disorder also can affect adults aged 20 to 40
years. Pubescent acne is more common in males than in females. In
contrast, between 30% and 50% of adult women are diagnosed with acne.1-3
This shift in the incidence of acne from adolescence to an older age
group has produced a much more demanding and articulate set of patients
with high expectations of improvement.4
The underlying cause of acne is usually multifactorial, and the
precise cause remains unknown. There are numerous precipitating factors,
however, and these should be identified during the initial health
history. Certain pharmacologic agents, including isoniazid, phenytoin,
and lithium, have been associated with drug-induced acneiform eruptions.
Personal care products such as moisturizers and cosmetics should be
water based, noncomedogenic, and fragrance free. Hair products should be
water based and should not come in contact with the forehead and
temporal regions of the face. Although the ingestion of specific foods
(e.g., chocolate, colas, greasy foods) does not cause acne, some studies
have found that exposure to the cooking oils used in establishments
such as fast-food restaurants may exacerbate the condition. This
correlation has been debated, however. Hormonal imbalances such as
androgen excess should be evaluated in women who present with
Acne is believed to be caused by an abnormality in the structure or
function of the pilosebaceous follicle, most likely because of the
increased production of adrenogenic hormone. As a result, the follicular
canal widens and cell production or keratinization increases. The
sebaceous glands eventually atrophy, and sebum mixes with the loose
cells to form a keratinous plug appearing as a blackhead (open comedo).
Trauma or inflammatory changes may lead to the formation of a whitehead
(closed comedo). If the follicular canal is damaged, the contents of the
follicle may extrude into the dermis and initiate an inflammatory
response. If the inflammation is close to the surface, a papule or
pustule forms. If the inflammation is deeper in the dermis, a nodule or
cyst develops; permanent scarring is possible.3
The anaerobic gram-positive bacterium Propionibacterium acnes,
part of the normal flora colonization in the pilosebaceous follicle,
plays an important role in the initial development and maintenance of
acne. Although P acnes itself is not a cause of infection, the
bacterium converts triglycerides in the sebum into free fatty acids that
attract inflammatory cells, including polymorphonuclear leukocytes and
Acne vulgaris is diagnosed based on the clinical presentation of the
patient’s skin, with classification primarily made according to
severity. The mildest form is comedonal (open or closed comedones). Mild
inflammatory acne is manifested by papules. Moderate inflammatory acne
consists of pustules and some cysts. Severe cystic acne manifests as
cysts, nodules, and scarring.3,4
The main goals of pharmacotherapy for acne vulgaris are to prevent
new lesions and reduce the number and severity of existing lesions;
prevent scarring and hyperpigmentation; and limit the duration of
disease.7 The patient should be counseled that improvement is
seen approximately 4 to 6 weeks after initiation of therapy. Some forms
of acne may require continuous treatment throughout adolescence into
early adulthood. Nonpharmacologic measures should include a gentle,
nondrying skin cleanser used no more than twice daily. Skin scrubbing
and excessive face washing do not necessarily open or cleanse pores, and
these practices may lead to irritation and acne exacerbation.3,4
The treatment of acne should be approached in a stepwise fashion.7
If the acne is mild or moderate and involves primarily comedonal
lesions with an occasional small inflamed papule or pustule, the
preferred products are benzoyl peroxide, azelaic or salicylic acid, and
topical retinoids. These topical agents improve the defect in
keratinization by promoting effective skin exfoliation. Currently,
successful treatment outcomes generally involve combination therapy with
different drug mechanisms.8-10 TABLES 1, 2, and 3 summarize the various topical and oral preparations for acne vulgaris.
Topical treatment forms include creams, lotions, solutions, gels, and
disposable wipes in various concentrations. The patient’s response to
these formulations varies depending upon individual skin type. Many gels
and solutions contain considerable amounts of alcohol. If a patient is
experiencing significant dryness despite a low concentration of active
drug component, the provider should consider switching to a preparation
that does not contain alcohol, such as a cream or aqueous gel.3
For moderate-to-severe acne with predominantly inflammatory lesions, it is important to reduce the growth of P acnes in
the follicular canal and the generation of its extracellular products
and inflammatory effects. A combined topical retinoid with benzoyl
peroxide, azelaic acid, or a topical antibiotic is recommended. If no
considerable improvement is seen after approximately 6 weeks, or if the
condition worsens, combination topical therapy is generally initiated
before adding an oral antibiotic such as tetracycline, doxycycline, or
minocycline.11 Other antimicrobials, including erythromycin
and trimethoprim-sulfamethoxazole, may be used, but they may be less
effective. Antimicrobial resistance, a growing concern, should be
suspected in patients who do not respond within 8 to 16 weeks of
For severe recalcitrant acne with inflammatory lesions, extensive
nodules, cysts, or scars, drugs that decrease sebaceous activity, such
as selected oral contraceptives, antiandrogens, or isotretinoin, may be
added to the regimen.12-14 Local corticosteroid injections are another effective option for large inflammatory lesions.7
The algorithm in FIGURE 1 summarizes the pharmacologic management of acne vulgaris.
Women of childbearing age who are using isotretinoin or tazarotene,
which are teratogenic and classified as Pregnancy Category X, should be
counseled to avoid becoming pregnant. Tetracycline, doxycycline, and
minocycline, which also are contraindicated during pregnancy, may
decrease the effectiveness of oral contraceptives. Women taking this
antibiotic class should use a long-acting contraceptive, such as
Depo-Provera, or a barrier method to prevent pregnancy. Retinoic acid,
adapalene, and salicylic acid are Pregnancy Category C and should be
avoided in women of childbearing age. Topical application of benzoyl
peroxide is also Pregnancy Category C, but is generally considered safe
for use during pregnancy.3,11,15
All patients receiving isotretinoin must participate in the iPLEDGE
program, a pregnancy-prevention system designed to enhance safe and
appropriate use of the drug through patient education.15,16
All female patients must have two negative urine or serum pregnancy
tests before the initial isotretinoin prescription is written. In
addition, for each month of therapy, a negative pregnancy test result
must be obtained before the patient receives the next prescription,
regardless of whether she is sexually active. Female patients who are or
might become sexually active with a male partner must use two forms of
effective contraception simultaneously for at least 1 month before
initiation of therapy, throughout treatment, and for up to 4 months
following discontinuation of therapy. The patient should be given
patient information and a consent form detailing the association between
isotretinoin and birth defects and other potentially serious
Although the iPLEDGE program is beneficial and effective, criticisms
abound. For many patients, the system has caused numerous delays in
receiving isotretinoin therapy. The provider may not prescribe more than
a 30-day supply, and a new prescription may not be written for at least
30 days.16 Moreover, pharmacists are under similar
restrictions, and no more than a 30-day supply may be filled and
dispensed to the patient. In addition, both the provider and the
pharmacist must verify these written prescriptions in the online system
before filling, and phone-in orders are not permitted.
There is also a 7-day window during which the medication must be
picked up at the pharmacy once the prescription is dated by the
prescriber. If the original prescription is lost or the prescription is
not picked up during the 7-day window, the patient must wait 30 days to
receive the drug. This strict sequence of requirements can make it
extremely difficult for patients to receive and take isotretinoin
according to the prescribed schedule. Recently, iPLEDGE procedures
regarding nonchildbearing patients have been relaxed. However, these
patients must still answer online questions monthly (as must their
physician) and obtain regular blood tests (including CBC, chemistry
profile, and fasting triglyceride and cholesterol levels), and they are
subject to the 7-day window requirement.16,17
Sometimes mistaken for acne vulgaris, acne rosacea is a dermatologic
disorder that usually develops in middle-aged patients (30-50 years). It
is characterized as a chronic inflammatory condition that primarily
affects the central portion of the face. Rosacea is more likely to occur
in women, although men may have more severe manifestations of the
The etiology of rosacea is unclear, but various theories suggest
nonspecific bacterial or fungal infections, accumulation of the Demodex folliculorum
mite in the hair follicle, and menopausal changes. Easy flushing and
blushing of the face and exacerbation of the disorder is often
associated with the ingestion of alcohol, spicy foods, or
caffeine-containing products and exposure to sun, strong winds,
strenuous exercise, and stress.3,18
Early vascular rosacea usually presents after exposure to cold
weather environments. In response, increased blood flow to the
superficial dermis results in erythema, with persistent telangiectasia
occurring later in this stage. During this period, approximately 50% of
patients report ocular involvement, from mild conjunctivitis,
blepharitis, and dry eye syndrome to more severe cases of keratitis and
corneal ulceration. Patients diagnosed with second-stage rosacea often
present with telangiectasia and persistent papules and pustules
superimposed on the existing erythemic rash. Hyperplasia of the
sebaceous glands and connective tissue can lead to development of a
large, red, bulbous nose (rhinophyma), which is almost
exclusively seen in males older than 40 years and is treatable only by
surgery. Late-stage rosacea also presents with persistent edema.3,18
The main goal of therapy for acne rosacea is patient recognition of
the specific triggers that potentiate the condition and cause flare-ups.
As with acne vulgaris, patients should be advised to avoid harsh
cleansers and to use only fragrance-free, hypoallergenic skin care and
makeup products in order to reduce the risk of skin irritation.18
First-line treatment should include a topical agent. Cases that
involve ocular symptoms should be treated with oral antibiotics.
Metronidazole, sodium sulfacetamide with sulfur, and azelaic acid are
treatment options. Topical clindamycin is an effective alternative for
patients who cannot tolerate metronidazole. The mechanism by which
topical metronidazole works to improve the inflammation is unknown, but
it is most likely related to the drug’s antibacterial effect. Sodium
sulfacetamide with sulfur and azelaic acid also exhibit
anti-inflammatory properties and have been shown to be effective in
treating mild-to-moderate rosacea.3,18
If no improvement is seen after 6 weeks, second-line therapy should
be initiated. This involves adding an oral antibiotic mainly for its
anti-inflammatory effect, rather than for its antibacterial properties.
After 2 weeks, the dosage should be decreased by 50% and discontinued
after 6 weeks while continuing the topical agent indefinitely.3,18
Third-line treatment consists of isotretinoin.3,18 Precautions and laboratory monitoring similar to those for acne vulgaris should be followed. TABLES 4 and 5 (available at www.uspharmacist.com) summarize the various topical and oral preparations for acne rosacea. The algorithm in FIGURE 2 summarizes the pharmacologic management of rosacea.
Although both acne vulgaris and rosacea may be considered minor
clinical issues, numerous studies have determined that these disorders
can have a significant psychosocial impact on the patient’s quality of
life.19 Adolescents, who are already self-conscious and can
be highly sensitive to physical imperfections no matter how little
perceived by others, are generally stereotyped as being the most
affected by acne. However, studies have demonstrated a direct
correlation between the patient’s age and the negative impact on
quality-of-life scores, regardless of severity. The patient’s concerns
about personal appearance must be identified early in the course of
treatment, as many patients experience psychological stress or
depression secondary to the physical effects of the disorder.19,20
Health care providers should be extremely sensitive not only to acne’s
physical manifestations, but also to the emotional burdens resulting
from the condition.
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3. Poole Arcangelo V, Peterson A. Pharmacotherapeutics for Advanced Practice: A Practical Approach. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:183-193.
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estradiol in treating acne vulgaris: a randomized, placebo-controlled
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acne in women: a retrospective analysis of 85 consecutively treated
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16. iPLEDGE. www.ipledgeprogram.com. Accessed April 8, 2013.
17. Barth JH, MacDonald-Hull SP, Mark J, et al. Isotretinoin therapy
for acne vulgaris: a re-evaluation of the need for measurements of
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20. Aktan S, Ozmen E, Sanli B. Anxiety, depression, and nature of acne vulgaris in adolescents. Int J Dermatol. 2000;39:354-357.
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