Authors: Hguyen, Quan
H.; Kim, Y. Alyssa; Schwartz, Robert A
Family Physician, July 1994 v50 n1 p89(10)
Subjects: Acne Care and
Reference #: A15597728
COPYRIGHT American Academy of Family Physicians 1994
Acne vulgaris can affect
both adolescents and adults. The pathogenesis of acne is multifactorial
and involves overproduction of sebum, an abnormal follicular
keratinization process, proliferation of Propionibacterium acnes, and
hormonal and immunologic factors. Clinical manifestations of acne range
from noninflammatory comedones to inflammatory papules, pustules and
cysts. Current therapy allows the physician to select a variety of
topical and/or systemic antibiotics, retinoids, and hormone agents aimed
at specific pathogenic factors. Most treatment regimens require several
weeks of consistent use to be effective. Sound patient education, a
strong therapeutic alliance and modification of lifestyle factors are
powerful adjuncts to medical management.
Full Text COPYRIGHT
American Academy of Family Physicians 1994
Acne vulgaris is a common
disorder involving the sebaceous follicles. It is usually first noted
during the teenage years. Some degree of acne develops in as many as 80
percent of adolescents.[1-3] Acne usually develops at an earlier age in
girls than in boys, but the disorder affects boys more frequently and
more severely. Acne can persist into mid-adulthood in some persons,
and can also present initially in adulthood. It is estimated that 40 to
50 percent of adult women are affected by a low-grade persistent form of
Although acne is usually
considered to be self-limited, it should not be ignored. If untreated,
acne can leave emotional and physical scars that last a lifetime. The
psychosocial impact on teenagers may be devastating. Most patients with
acne present to primary care physicians for treatment. Only a small
proportion of patients with acne are referred to a dermatologist.
A rational approach to
the treatment of acne requires a clear understanding of the
multifactorial basis of the disorder.[4-6] The normal pilosebaceous unit
is composed of large, multilobulated sebaceous glands, a rudimentary
hair and a wide follicular canal lined with stratified squamous
epithelium. During the regular turnover process of the skin, desquamated
cells from the follicular epithelium are carried up the follicular canal
by sebum secreted from the sebaceous glands. If the pilosebaceous unit
becomes plugged, the trapped sebum causes bacterial proliferation and
inflammation, resulting in the development of acne vulgaris (Figure
Stimulation of the
sebaceous follicle by a surge of androgenic hormones appears to be an
important factor in the development of acne. Acne usually does not occur
until puberty, when hormone changes begin, androgen-sensitive sebaceous
follicles enlarge and sebum production increases.
An abnormal desquamation
process is required to produce clinical acne vulgaris. This process
consists of increased sloughing of the epithelium, which becomes more
cohesive and blocks the follicular orifice with the accumulation of dead
cells. Within the blocked follicle, the impacted sebum favors the
proliferation of Propionibacterium acnes, an anaerobic diphtheroid
organism that normally resides in the pilosebaceous unit. One
nutritional requirement of this bacterium is glycerol, obtained through
lipolysis of the triglycerides in the sebum, which releases free fatty
acids as byproducts. P. acnes also releases various chemotactic
products, which attract neutrophils to the area. These neutrophils
secrete hydrolytic enzymes that cause secondary damage to the follicular
wall. The irritating free fatty acids and other bacterial enzymes can
then leak into the dermis, creating intense inflammation.[1-3]
The hallmark of acne
vulgaris is a micro-comedo formed by a sebum-plugged pilosebaceous
follicle. Accumulation of sebum results in a visible closed comedo, or
whitehead. Continuing distention of the closed comedo causes protrusion
from the follicular orifice, forming an opened comedo, or blackhead. The
dark color of a blackhead is due to oxidized lipids, melanin and densely
packed keratinocytes. It is not dirt, as commonly assumed.
develop when the compacted follicular contents rupture, releasing
bacteria and bacterial products, including free fatty acids, into the
dermis. When the inflammatory response occurs at a deeper level in the
dermis, a papule develops. Unusually intense inflammation can lead to a
fluctuant and painful acne cyst, which heals with post-inflammatory
pigment changes and scar formation.
Comedones can occur
anywhere on the body, but are usually found on the forehead and upper
cheeks in adolescent patients. Comedones may progress to inflammatory
lesions on the lower cheeks, chin, chest, upper back and shoulders,
where many pilosebaceous follicles are found. Acne conglobata, an
atypical and severe form of acne, is characterized by numerous inflamed
cystic lesions, sinuses and extensive scarring over the face and upper
When choosing a treatment
regimen and evaluating the response to treatment, it is sometimes
helpful to grade acne in a particular patient on the basis of the
following severity scale.
Type 1: comedonal, few lesions (fewer than
10) on face only, without scarring.
Type 2: papular, moderate number of lesions
(10 to 25) on face and trunk, with mild scarring.
Type 3: pustular, many lesions (more than
25), moderate scarring.
Type 4: nodulocystic, extensive scarring.
Course and Prognosis
While many cases of mild
to moderately severe acne resolve over time, most comedones do not
usually resolve spontaneously. Larger inflammatory papules and pustules
may take several weeks to resolve and the post-inflammatory
hyperpigmentation can last for months. Inflammatory cystic lesions can
result in acne scars, which may appear as hypotrophic pitted scars or,
less commonly, as hypertrophic scars and keloids.
A complete history should
be obtained and important points about the etiology and treatment of
acne should be discussed with the patient prior to the initiation of
treatment.[1-4,8] The more the patient knows about acne, the more
compliant he or she will be. Important issues to discuss are the
Acne may flare up
premenstrually because the sebaceous duct orifice may become more
obstructed at this time in the cycle. In females, the possibility of
androgenic disorders, such as polycystic ovarian disease and Cushing’s
syndrome, should be considered; the patient should be asked about
menstrual irregularities and evidence of hirsutism should be looked for
on physical examination. In young women with acne that does not respond
to therapy, hormone testing may reveal an androgen excess, even in the
absence of symptoms such as menstrual abnormality, male-pattern hair
loss or hirsutism. An endocrinology consultation may be warranted in
Although clinical studies
have not demonstrated any causal relationship between certain foods and
acne, patients should be advised to eat a well-balanced diet and avoid
those foods which consistently result in acne flare-ups.
The development of acne
is not related to dirt. Patients should be advised that excessive
scrubbing, especially with abrasive cleaning lotions and facial sponges,
may actually worsen the condition. Patients who have oily skin should
wash their faces using a mild, unscented soap (i.e., Dial, Ivory,
Lever-2000) and water.
Although sunshine can be
beneficial in some patients, very humid environments and heavy sweating
can worsen acne in other patients. Exposure to pollution and
hydrogenated hydrocarbons may aggravate acne.
rubbing and humidity from tight or occlusive clothing can aggravate
acne. In addition, patients should be warned that repeatedly picking the
lesions can result in more inflammation, scarring and pigmentary
Comedogenic agents such
as heavy oils, greases or dyes in cosmetic creams and hairsprays can
exacerbate acne. Patients who use cosmetics should be advised to use
water-based products instead of occlusive, oil-based products.
Certain drugs, including
corticosteroids, adrenocorticotropic hormone (ACTH), androgens,
phenytoin, barbiturates, lithium, isoniazid, cyclosporine, iodides and
bromides, are now known to cause acne. Although some oral contraceptives
may provide excellent therapy for acne, those with androgenic and
antiestrogenic progesterones may actually promote acne eruptions. Also,
gram-negative folliculitis can occur as a complication of chronic
broadspectrum antibiotic therapy.
Strong rapport between
the patient and the physician is necessary in the treatment of acne
vulgaris. During the initial visit, sufficient time should be spent
explaining the causes of acne, its aggravating factors and the rationale
for therapy. The patient should be advised that medication may take
weeks to have its full effect and that therapy can only control acne,
not cure it. Patients need to understand that therapy may be continued
and modified according to response.[9-12]
Mild noninflammatory acne
can be treated with topical antibacterial agents such as benzoyl
peroxide or comedolytic agents such as tretinoin (Retin-A) and salicylic
acid (Table 1). These agents can unplug the blocked follicles with their
exfoliative effects. The combination of benzoyl peroxide in the morning
and tretinoin at night may be effective when either agent alone has
failed. Comedone extraction can accelerate resolution when it is used in
addition to topical medications.
Topical Agents for the Treatment of Acne Vulgaris
Benzoyl peroxide gel, cream, lotion, soap
Erythromycin ointment, lotion, swab or gel
Clindamycin solution, lotion or gel (Cleocin T)
Meclocycline cream (Meclan)
Tretinoin cream, gel or liquid (Retin-A)
Astringents, soaps, cleansers
Benzoyl Peroxide. Benzoyl
peroxide is the most commonly used acne medication available without a
prescription. It is a potent anti-bacterial oxidizing agent that can
decrease the number of P. acnes organisms and, consequently, the amount
of free fatty acids. Its mild comedolytic and exfoliant properties can
also unplug obstructed follicles.
Benzoyl peroxide is the
first-line monotherapy for mild acne, and it may be used in combination
with other agents in more severe acne. Benzoyl peroxide is available in
over-the-counter preparations of 2.5 percent, 5 percent, and 10 percent
gels, creams, lotions or soaps. All concentrations seem to be
therapeutically equivalent. The liquid and cream formulations (Benoxyl,
Oxy-10) are less irritating and may be useful in patients with dry skin.
The gel formulation (Benzagel, Persa-Gel, Desquam-X) is more irritating
but more effective for patients with oily skin.
Benzoyl peroxide should
be applied once or twice daily Patients should expect mild redness and
scaling of the skin during the first week of use. Contact sensitivity is
reported in a small percentage of patients.
all-trans-retinoic acid is the most effective topical comedolytic agent;
it can normalize the desquamation process[7,9,10] Tretinoin decreases
the cohesiveness of follicular epithelial cells, thus inhibiting the
formation of microcomedones, and increases cell turnover, resulting in
the expulsion of existing comedones. The agent also decreases the
thickness of the stratum corneum and potentiates the penetration of
other topical antibiotic agents.
Tretinoin is available as
Retin-A cream (0.025 percent, 0.05 percent, 0.1 percent), Retin-A gel
(0.01 percent, 0.025 percent), and Retin-A liquid (0.05 percent).
Tretinoin therapy should usually be started with the lower strength
cream or gel. If no response occurs after a few weeks of treatment, then
the higher-concentration liquid formulation can be used. The lubricating
cream is favored in patients with dry skin, and the drying gel is best
for patients with oily skin.
Tretinoin is applied once
daily before bedtime to the affected areas. Mild redness and peeling are
part of the therapeutic effect of the medication but can decrease
compliance. Patients should be aware that improvement may take six to 12
weeks, and that flare-ups of acne can occur during the first few weeks
of therapy due to surfacing of the lesions onto the skin. It is
extremely important that patients avoid excessive sun exposure and use
Exfoliants. These agents
include salicylic acid, glycolic acid, trichloroacetic acid, elemental
sulfur and resorcinol. They are not effective in removing deep comedones
and can cause irritation of the skin.
Mild inflammatory lesions
can be treated effectively with topical antibiotics.[7,9,10,14] The main
action of topical antibiotics is to eliminate R acnes from the sebaceous
follicles and thereby suppress free fatty acid production. Some topical
antibiotics have anti-inflammatory effects through the inhibition of
chemotactic factors. The effectiveness of topical antibiotics in the
treatment of acne is limited by their low lipid solubility and
consequent difficulty in penetrating sebum-filled follicles. All topical
antibiotics are applied twice daily.
is available in a 1 percent concentration prepared as a solution, lotion
or gel formulation (Cleocin-T). Clindamycin is as effective in the
treatment of acne as erythromycin.[15-18] Rare cases of pseudomembranous
colitis have been reported with clindamycin use.
Erythromycin. This agent
is available in a 2 percent solution (Eryderm, A/T/S), gel (Erygel,
Emgel) or pledgets (Erycette, T-Stat). Topical erythromycin is
considered to be the safest antibiotic for use during pregnancy. It is
also available in a 3 percent gel formulation combined with 5 percent
benzoyl peroxide (Benzamycin). This new formulation is probably the most
effective current topical antibiotic and may be as effective as systemic
antibiotics in some patients. This product has not been fully evaluated
in pregnant or lactating women.
Meclocycline is available in a topical cream (Meclan). It is less drying
but may be less effective than other topical agents.
Patients with moderate or
severe inflammatory acne win require oral antibiotics in addition to
topical therapy (Table 2). Systemic antibiotics are favored over topical
preparations because of the more rapid clinical improvement achieved
(two to six weeks). The side effects of oral antibiotics are
gastrointestinal distress and vaginal candidiasis.
Oral Agents for the Treatments of Acne Vulgaris
Trimethorprin-sulfamethoxazole (Bactrim, Spetra)
Tetracycline. Due to its
effectiveness and low cost, tetracycline is the first-choice oral
antibiotic in the treatment of pustular acne. The usual starting
dosage is 250 mg four times daily or 500 mg twice daily one hour before
or two hours after meals. Metallic ions in antacids or dairy products
can interfere with absorption of tetracycline. Because tetracycline can
cause enamel hyperplasia and tooth discoloration, it should not be used
in pregnant women or in children younger than 12 years of age.
Erythromycin. The usual
dosage of erythromycin is the same as that for tetracycline. P. acnes is
more resistant to erythromycin than to tetracycline, and the
gastrointestinal side effects of erythromycin often limit its use.
antibiotic is highly effective because of its lipid solubility and
ability to penetrate the sebaceous follicle. Minocycline (Minocin) is
used in patients with tetracycline-resistant acne. The drug has good
absorption with food. A drawback is its cost. Side effects of
minocycline include dizziness and, rarely, color changes in the acne
scar. The usual starting dose is 50 mg twice daily or 100 mg once daily.
Doxycycline. This drug is
less expensive than minocycline and, due to its high lipid solubility,
is also very effective. The usual dosage is 100 mg once daily.
Photosensitivity and gastrointestinal distress are the most common side
Trimethoprim-Sulfamethoxazole. This drug is used for severe cases of
acne that are refractory to other antibiotics and for gram-negative
folliculitis. Therapy is initiated with one double-strength tablet of
trimethoprim-sulfamethoxazole (Bactrim DS, Cotrim DS, Septra DS) each
day. Potential side effects include a severe eruption reaction.
Patients with severe
inflammatory acne unresponsive to conventional therapy may require
referral to a dermatologist. Treatment options include isotretinoin,
steroid injections and hormone therapy Isotretinoin. Oral
13-cis-retinoic acid is a derivative of vitamin A. It is the only
systemic drug that decreases sebum production and reverses the abnormal
epithelial desquamation process.[20,21] It also can decrease the
population of P acnes in the sebaceous follicle. These actions make it
the treatment of choice for patients with severe nodulocystic acne.
The initial dose of isotretinoin (Accutane) is 0.5 to 1.0 mg per kg, or
40 to 80 mg per day. The usual duration of therapy is four to five
months, and the satisfactory response rate can be as high as 90 percent.
Transient exacerbation of acne may occur during the initial month of
therapy, but most patients will respond well over time.
Side effects of
isotretinoin include cheilitis, dry skin, pruritus, epistaxis and
photosensitivity. It can also cause decreased night vision,
hypertriglyceridemia, abnormal liver function tests, electrolyte
imbalance and elevated platelet count. Pseudotumor cerebri can occur if
isotretinoin is taken in combination with tetracycline. These side
effects are usually reversible once therapy is discontinued.
Women of child-bearing
age must receive counseling about the possibility of teratogenicity, the
most serious side effect of isotretinoin, before beginning treatment and
must have received a written warning as well. They must not be pregnant
(determined by a serum pregnancy test) and must use appropriate
contraception one month before the initiation of therapy, during the
entire course of therapy, and two months after cessation of therapy.
Intralesional injection of triamcinolone acetonide (Kenalog), 1.0 to 2.5
mg per mL of solution, will lead to rapid resolution of most cystic
lesions in two to three days. Stock solutions should be diluted in
normal saline or 1 percent lidocaine (Xylocaine) to appropriate
concentrations. The corticosteroid is injected into the cyst with a 27-
to 30-gauge needle. It is important to inject a minimal amount and to do
so superficially to avoid local steroid atrophy.
Hormone therapy should be limited to female patients with severe acne
that is unresponsive to medications. Oral contraceptives are useful
sources of low-dose estrogen (0.035 to 0.1 mg per day), which can
suppress ovarian androgen production. Acne improvement may take three to
four months. Combination oral contraceptives that contain androgenic
progesterone-like norgestrel should be avoided since these can actually
Other less commonly used
hormones include prednisone (5 mg per day), which suppresses adrenal
overproduction of androgen, and spironolactone (150 to 200 mg per day),
which reduces sebum production by sebaceous follicles. These
hormones should be administered with caution because of their potential
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