EPIDEMIOLOGY

ACNE VULGARIS
Acne vulgaris is a self-limited disorder of the pilosebaceous unit that is seen primarily in adolescents. Most cases
of acne present with a pleomorphic array of lesions, consisting of comedones, papules, pustules, and nodules
with varying extent and severity. While the course of acne may be self-limiting, the sequelae can be lifelong,Acne
is sufficiently common that it often has been termed physiologic. Mild degrees of acne are frequently seen at
birth, probably resulting from follicular stimulation by adrenal androgens, and may continue into the neonatal
period. However, in the vast majority of cases it is not until puberty that acne becomes a more significant
problem. Acne often heralds the onset of puberty. In girls, the occurrence of acne may precede menarche by more
than a year. In these very young patients, the predominant lesions are comedones. Acne prevalence hits its peak
during the middle-to-late teenage period, with more than 85% of adolescents affected, and then steadily
decreases. However, acne may persist through the third decade or even later, particularly in women. One study
demonstrated a prevalence of facial acne in women between ages 26 and 44 to be 14%. 1 Acne severity seems to be
familial. The prevalence of high school students with moderate-to-severe acne was 19.9% in those students with a
family history of acne and 9.8% in those students without a family history of acne. 2 In twin studies, 81% of the
population variance in acne was found due to genetic factors (vs. 19% environmental factors).3 Nodulocystic acne
has been reported to be more common in white males than in black males, and one group of investigators has
found that acne is more severe in patients with the XYY genotype. 4,5
ETIOLOGY AND PATHOGENESIS
Understanding the underlying basis for acne, and the mechanisms of action of the multitude of therapeutic
options in treating acne will assure better therapeutic results. The pathogenesis of acne is multifaceted,
but four basic steps have been identified. These key elements (Fig. 80-1) are: (1) follicular epidermal
hyperproliferation, (2) excess sebum production, (3) inflammation, and (4) the presence and activity of
Propionibacterium acnes. Each of these processes are interrelated and under hormonal and immune influence.
Follicular epidermal hyperproliferation results in the formation of a microcomedo. The epithelium of the
upper hair follicle, the infundibulum, becomes hyperkeratotic with increased cohesion of the keratinocytes.
The excess cells and their tackiness result in a plug in the follicular ostium. This plug then causes downstream
concretions of keratin, sebum, and bacteria to ccumulate in the follicle. These packed concretions
cause dilation of the upper hair follicle producing a microcomedo. The stimulus for keratinocyte
hyperproliferation and increased adhesion is unknown. However, several proposed factors in keratinocyte
hyperproliferation include: androgen stimulation, decreased linoleic acid, increased interleukin-1 (IL-1) activity,
and effects of P. acnes. Dihydrotestosterone (DHT) is a potent androgen that may play a role in acne. Fig. 80-2
demonstrates the physiologic pathway for dehydroepiandrosterone sulfate (DHEA-S) conversion to the
androgen DHT. 17-hydroxysteroid dehydrogenase (HSD) and 5- reductase are enzymes responsible for
converting DHEA-S to DHT. When compared to epidermal keratinocytes, follicular keratinocytes have increased
17- HSD and 5-reductase, thus enhancing DHT production. 6,7 DHT may stimulate follicular keratinocyte
proliferation. Also supporting the role of androgens in acne pathogenesis is the evidence that individuals
with complete androgen insensitivity do not develop acne. 8 Follicular keratinocyte proliferation may also be
regulated by linoleic acid. Linoleic acid is an essential fatty acid in the skin that is decreased in subjects with
acne. The quantity of linoleic acid normalizes after successful treatment with isotretinoin. Subnormal levels
of linoleic acid may induce follicular keratinocyte hyperproliferation and produce proinflammatory cytokines.
It has also been suggested that regular quantities of linoleic acid are actually produced but are simply diluted by
increased sebum production.9 In addition to androgens and linoleic acid, IL-1 may also contribute to
keratinocyte hyperproliferation. Human follicular keratinocytes demonstrate hyperproliferation and
microcomedone formation when IL-1 is added. IL-1 receptor antagonists inhibit microcomedone formation
providing additional support for the cytokine’s role in acne pathogenesis.10,11 Fibroblast growth factor receptor
(FGFR)-2 signaling may also be involved in hyperkeratinization. There is a long established relationship between
acne and Apert syndrome, a complex bony malformation syndrome, due to a gain in function mutation in the
gene encoding FGFR-2. Mutations in FGFR-2 in a mosaic distribution underlie a nevus comedonicus- like
lesion.12 The FGFR-2 pathway is androgen dependent and proposed mechanisms in acne include an increased
production of IL-1 and 5-reductase. The second key feature in the pathogenesis of acne is excess sebum
production from the sebaceous gland. Patients with acne produce more sebum than those without acne, although
the quality of sebum is the same between the two groups.15 Components of sebum— triglycerides and
lipoperoxides—may play a role in acne pathogenesis. Triglycerides are broken down into free fatty acids by P.
acnes, normal flora of the pilosebaceous unit. These free fatty acids promote further bacterial clumping and
colonization of P. acnes, incite
inflammation, and may be comedogenic.16 Lipoperoxides also produce proinflammatory cytokines and activate
the peroxisome proliferator-activated receptors (PPAR) pathway, resulting in increased sebum. 17,18 Androgenic
hormones also influence sebum production through actions on sebocyte proliferation and differentiation. Similar
to their action on the follicular infundibular keratinocytes, androgen hormones bind to and influence sebocyte
activity.19 Those with acne have higher average serum androgen levels (although still within normal range) than
unaffected controls.20,21 5-reductase, the enzyme responsible for converting testosterone to the potent DHT, has
greatest activity in areas of skin prone to acne, the face chest and back.14 The role of estrogen on sebum
production is not well defined. The dose of estrogen required to decrease sebum production is greater than the
dose required to inhibit ovulation.22 The mechanisms by which estrogens may work include: (1) directly
opposing the effects of androgens within the sebaceous gland; (2) inhibiting the production of androgens by
gonadal tissue via a negative feedback loop on pituitary gonadotropin release; and (3) regulating genes that
suppress sebaceous gland growth or lipid production.23 Corticotropin-releasing hormone may also play a
role. It is released by the hypothalamus and increased in response to stress. Corticotropin-releasing hormone
receptors are present on a vast number of cells, including keratinocytes and sebocytes, and are upregulated
in the sebocytes of patients with acne.24 The microcomedo will continue to expand with densely packed keratin,
sebum, and bacteria. Eventually this distension will cause follicular wall rupture. The extrusion of the keratin,
sebum, and bacteria into the dermis results in a brisk inflammatory response. The predominant cell type within
24 hours of comedo rupture is the lymphocyte. CD4lymphocytes are found around the pilosebaceous unit, while
CD8cells are found perivascularly. One to two days after comedo rupture, the neutrophil becomes the
predominant cell type surrounding the burst microcomedo.25 It was originally thought that inflammation follows
comedo formation, but there is evidence that dermal inflammation may actually precede comedo formation.
Biopsies taken from comedo-free acne-prone skin, demonstrate increased dermal inflammation compared to
normal skin. Biopsies of newly formed comedos demonstrate even greater inflammation. 26 This may suggest that
inflammation actually precedes comedo formation, again emphasizing the interplay between all of the
pathogenic factors. As mentioned above, P. acnes also plays an active role in the proces of inflammation. P. acnes
is a Gram-positive, anaerobic, and microaerobic bacterium found in the sebaceous follicle. Adolescents with acne
have higher concentrations of P. acnes compared to nonacne controls. However, there is no correlation between
the raw number of P. acnes organisms present in a sebaceous follicle and the severity of the acne.27 Sebocyte
differentiation and proinflammatory cytokine/chemokine responses are varied depending on the strain of P.
acnes predominating within the follicle.28 The cell wall of P. acnes contains a carbohydrate
antigen that stimulates antibody development. Those patients with the most severe acne have the highest
titers of antibodies.29 The antipropionobacterium antibody enhances the inflammatory response by activating
complement initiating a cascade of proinflammatory events. 30 P. acnes also facilitates inflammation by eliciting
a delayed type hypersensitivity response and by producing lipases, proteases, hyaluronidases, and chemotactic
factors.31,32 Reactive oxygen species and lysosomal enzymes are released by neutrophils and levels may correlate
with severity.33 Additionally, P. acnes has been shown to stimulate expression of cytokines by binding to toll-like
receptor 2 (TLR-2) on monocytes and polymorphonuclear cells surrounding the sebaceous follicle.34 After binding
TLR-2, proinflammatory cytokines such as IL-1, IL-8, IL-12, and TNF-are released.35,36 The antimicrobial
peptides, histone H4 and cathelicidin, are also secreted locally in response to P. acnes. Histone H4 exerts direct
microbial killing, while cathelicidin interacts with components of the innate immune system, such as defensins
and psoriasin, in response to P. acnes.37,38 Another indicator of the role of innate immunity in the pathogenesis of
acne is the differentiation of peripheral blood monocytes to CD209macrophages and CD1bdendritic cells in
response to P. acnes.39 The impact of diet on acne is an emerging area of interest, particularly relating to glycemic
index and dairy consumption. Both are thought to increase insulin- like growth factor (IGF)-1 with possible
proacne effects and an increase in androgen activity.40,41
CLINICAL FINDINGS
HISTORY. Most patients with acne vulgaris report gradual onset of lesions around puberty. In other cases,
acne can be seen in the neonatal or infantile age. Neonatal acne appears at about 2 weeks of age and infantile
acne develops at 3–6 months of age (see Chapter 107). Since classic acne vulgaris is usually gradual in onset,
patients describing an abrupt onset of acne should be questioned to possibly discover an underlying etiology,
such as an androgen-secreting tumor. Hyperandrogenism should be considered in the female patient whose acne
is severe, sudden in its onset, or associated with hirsutism or irregular menstrual periods. The patient should be
asked about the frequency and character of her menstrual periods and whether her acne flares with changes in
her menstrual cycle. Hyperandrogenism can also result in deepening of the voice, an increase in libido and
hirsutism. A complete medication history is important, as some medications can cause an abrupt onset of a
monomorphous acneiform eruption. Drug-induced acne may be caused by: anabolic steroids, corticosteroids,
corticotropin, phenytoin, lithium, isoniazid, vitamin B complexes, halogenated compounds, and certain
chemotherapy medications, particularly with epidermal growth factor receptor (EGFR) inhibitors.
CUTANEOUS LESIONS. The primary site of acne is the face and to a lesser degree the back, chest, and
shoulders. On the trunk, lesions tend to be concentrated near the midline. The disease is characterized
by several clinical lesion types (Fig. 80-3). Although one type of lesion may predominate, close inspection
usually reveals the presence of several types of lesions. The lesions may be either noninflammatory or
inflammatory. The noninflammatory lesions are comedos, which may be either closed (whiteheads; Fig. 80-3A)
or open (blackheads; Fig. 80-3B). The open comedo appears as a flat or slightly raised lesion with a central dark-
colored follicular impaction of keratin and lipid (Fig. 80-4). Closed comedones, in contrast to the open
comedones, may be difficult to visualize. They appear as pale, slightly elevated, small papules, and do not
have a clinically visible orifice (Fig. 80-3A). Stretching of the skin is an aid in detecting the lesions. The
inflammatory lesions vary from small papules with a red border to pustules and large, tender, fluctuant nodules
(see Figs. 80-3C and 80-3D and Figs. 80-4–80-6). Some of the large nodules were previously called “cysts” and the
term nodulocystic has been used to describe severe cases of inflammatory acne. True cysts are rarely found in
acne; this term should be abandoned and substituted with severe nodular acne (see Figs. 80-3D and 80-6). Whether
the lesion appears as a papule, pustule, or nodule depends on the extent and location of the inflammatory
infiltrate in the dermis. Scarring can be a complication of both noninflammatory and inflammatory acne. There
are four general types of acne scars: (1) ice pick, (2) rolling, (3) boxcar, and (4) hypertrophic42 (Fig. 80-7). Ice pick
scars are narrow,deep scars that are widest at the surface of the skin and taper to a point in the dermis. Rolling
scars are shallow, wide scars that have an undulating appearance. Boxcar scars are wide sharply
demarcatedscars. Unlike ice pick scars, the width of boxcar scars is similar at the surface and base. In rare
instances, especially on the trunk, the scars may be hypertrophic. Acne vulgaris is usually an isolated cutaneous
finding, other than in the presence of hyperandrogenism. Such cases may have associated hirsutism, precocious
puberty, and other signs of hyperandrogenism.
LABORATORY TESTS
In general, laboratory workup is not indicated for patients with acne unless hyperandrogenism is suspected.
There are numerous clinical studies relating acne to elevated serum levels of androgens in both adolescents and
adults. Among 623 prepubertal girls, girls with acne had increased levels of DHEAS as compared to age-matched
controls without acne.43 DHEAS can serve as a precursor for testosterone and DHT. Elevated serum levels of
androgens have been found in cases of severe cystic acne and in acne associated with a variety of endocrine
conditions, including congenital adrenal hyperplasia (11- and 21-hydroxylase deficiencies), ovarian or
adrenal tumors, and polycystic ovarian disease. However, in the majority of acne patients serum androgens are
within the normal range. Excess androgens may be produced by either the adrenal gland or ovary. The
laboratory workup should include measurement of serum DHEAS, total testosterone, and free testosterone.
Additional tests to consider include the luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio or
serum 17-hydroxyprogesterone to identify an adrenal source of androgens in cases where testing does not clearly
indicate an adrenal or ovarian source of androgens. Testing should be obtained just prior to or during the
menstrual period, not midcycle at the time of ovulation. Patients on contraceptives that prevent ovulation
will need to discontinue their medication for at least 1 month prior to testing. Values of DHEAS in the range of
4,000–8,000 ng/mL (units may vary at different laboratories) may be associated with congenital
adrenal hyperplasia. Patients with a serum level of DHEAS 8,000 ng/mL could have an adrenal tumor and
should be referred to an endocrinologist for further evaluation. An ovarian source of excess androgens can be
suspected in cases where the serum total testosterone is 150 ng/dL. Serum total testosterone in the range of 150–
200 ng/dL or an increased LH/ FSH ratio (2.0) can be found in cases of polycystic ovary disease. Greater
elevations in serum testosterone may indicate an ovarian tumor, and appropriate referral should be made. There
is a significant amount of variability in individual serum androgen levels. In cases in which abnormal results are
obtained, it may be wise to repeat the test before proceeding with therapy or additional testing. Many patients
report that their acne flares during periods of stress. Although objective data are limited, stress is known to
increase the output of adrenal steroids, which may affect the sebaceous gland.46 It has been shown that patients
with acne have a greater increase in urinary glucocorticoid levels after corticotropin
administration.47
DIFFERENTIAL DIAGNOSIS
Although one type of lesion may predominate, acne vulgaris is diagnosed by a variety of acne lesions
(comedones, pustules, papules, and nodules) on the face, back, or chest (see Box 80-1). Diagnosis is usually easy,
but inflammatory acne may be confused with folliculitis, rosacea, or perioral dermatitis. Patients with tuberous
sclerosis and facial angiofibromas have been misdiagnosed as having recalcitrant midfacial acne. Facial flat warts
or milia are occasionally confused with closed comedones. Acne can be seen in association with endocrinologic
abnormalities. Patients with hyperandrogenism may have acne plus other stigmata of increased androgen levels
(i.e., hirsutism, deepened voice, irregular menses). Endocrinologic disorders such as polycystic ovarian
syndrome (including HAIR-AN syndrome), congenital adrenal hyperplasia, and adrenal and ovarian
neoplasms often have accompanying acne. Variants of acne must also be differentiated from typical acne vulgaris
in order to guide treatment. These types of acne include: neonatal acne, infantile acne, acne fulminans, acne
conglobata, acne with solid facial edema, and acne excoriée des jeunes filles. These variants are discussed in
detail later in the chapter. There are several less common acneiform eruptions that can be confused with acne
vulgaris. These mimickers include: medication-induced acne, halogen acne, chloracne, acne mechanica, tropical
acne, radiation acne, and other various miscellaneous acneiform disorders that are discussed subsequently.
COMPLICATIONS
All types of acne lesions have the potential to resolve with sequelae. Almost all acne lesions leave a transient
macular erythema after resolution. In darker skin types, postinflammatory hyperpigmentation may persist
months after resolution of acne lesions. In some individuals, acne lesions may result in permanent scarring. Acne
vulgaris may also take a psychological toll on many patients. It is estimated that 30%–50% of adolescents
experience psychiatric disturbances due to acne.48 Studies have shown that patients with acne have similar levels
of social, psychological, and emotional impairment as those with asthma and epilepsy. 49 Additional studies have
also shown that unemployment rates are higher among adults with acne than those without. 50 When appropriate,
patients should be referred for psychiatric counseling.
PROGNOSIS AND CLINICAL COURSE
The age of onset of acne varies considerably. It may start as early as 6–8 years of age or it may not appear until
the age of 20 or later. The course is one of several years’ duration followed by spontaneous remission in the
majority of cases. While most patients will clear by their early twenties, some have acne extending well into the
third or fourth decades. The extent of involvement varies, and spontaneous fluctuations in the degree of
involvement are the rule rather than the exception. In women there is often a fluctuation in association with
menses, with a flare just before the onset of menstruation. This flare is not due to a change in sebaceous gland
activity as there is no increase in sebum production in the luteal phase of the menstrual cycle. It has been shown
that prepubescent females with comedonal acne and those females with high DHEAS levels are predictors of
severe or long-standing nodulocystic acne.51
TREATMENT
Tailoring a patient’s acne regimen with the knowledge of the pathogenesis of acne and the mechanism of action
of the available acne treatments will ensure maximum therapeutic response. Treatment regimens
should be initiated early and be sufficiently aggressive to prevent permanent sequelae. Often multiple treatments
are used in combination so as to combat many factors in the pathogenesis of acne (Table 80-1). The
mechanism of action of the most common treatments for acne can be categorized in the following categories as
they relate to the pathophysiology:
1. Correct the altered pattern of follicular
keratinization.
2. Decrease sebaceous gland activity.
3. Decrease the follicular bacterial population,
particularly P. acnes.
4. Exert an anti-inflammatory effect.
LOCAL THERAPY
Cleansing. The importance of cleansing in the treatment of acne is generally intuitive. Twice daily washing
with a gentle cleanser followed by the application of acne treatments may encourage a routine
and therefore better compliance. Overcleansing or using harsh alkaline soaps are likely to increase the skin’s pH,
disrupt the cutaneous lipid barrier, and compound the irritancy potential of many topical acne treatments. Use of
a syndet (synthetic detergent) will allow cleansing without disruption of the skin’s normal pH. Antibacterial
soaps, containing agents such as triclosan, inhibit Gram-positive cocci but may increase Gram-negative rods;
their overall affect on acne is unclear. Medicated cleansers, containing benzoyl peroxide or salicylic acid, offer
convenience as a wash and are excellent for hard to reach areas like the back.
Topical Agents. (See Table 80-2)
Sulfur/Sodium Sulfacetamide/Resorcinol. Products containing sulfur, sodium sulfacetamide, and resorcinol,
once favored treatments for acne, are still found in several over-the-counter and prescription niche formulations.
Sulfonamides are thought to have antibacterial properties through their inhibition of para-aminobenzoic acid
(PABA), an essential substance for P. acnes growth.52 Sulfur also inhibits the formation of free fatty acids and has
presumptive keratolytic properties. It is often combined with sodium sulfacetamide to enhance its cosmetic
tolerability due to sulfur’s distinctive odor. Resorcinol is also indicated for use in acne for its antimicrobial
properties. It is generally found in 2% concentration in combination with 5% sulfur.
Salicylic Acid. Salicylic acid is a ubiquitous ingredient found in over-the-counter acne preparations in
concentrations ranging from 0.5% to 2%. This lipid soluble -hydroxy acid has comedolytic properties, though
somewhat weaker than those of a retinoid. Salicylic acid also causes exfoliation of the stratum corneum though
decreased cohesion of the keratinocytes. Mild irritant reactions may result.
Azelaic Acid. Azelaic acid is available by prescription in a 20% cream or 15% gel. This dicarboxcylic acid has
both antimicrobial and comedolytic properties.53 It is also a competitive inhibitor of tyrosinase and thus may
decrease postinflammatory hyperpigmentation.54 It is generally well tolerated, though transient burning can
occur, and is safe in pregnancy.
Benzoyl Peroxide. Benzoyl peroxide preparations are among the most common topical medications prescribed
by dermatologists and are also readily available over-the-counter. Benzoyl peroxide is a powerful antimicrobial
agent through decreasing both the bacterial population and the hydrolysis of triglycerides. Benzoyl peroxide
preparations are available in creams, lotion, gels, washes, and pledgets. Products that are left on the skin, such as
a gel, are generally considered more effective. Benzoyl peroxide can produce significant dryness and irritation.
Allergic contact dermatitis has been uncommonly reported. Of significance, bacteria are unable to develop
resistance to benzoyl peroxide, making it the ideal agent for combination therapy.55
Topical Antibiotics. (See Chapter 218). Erythromycin and clindamycin are the most commonly used topical
antibiotics for the treatment of acne. These two agents have also been used in combination preparations with
benzoyl peroxide. Increased levels of P. acnes resistance have been reported in patients who are being treated
with antibiotics. However, the development of resistance is less likely in patients who are treated with a
combination of benzoyl peroxide/erythromycin or clindamycin.56 Therefore, the combination of these two
products is preferable over monotherapy with topical antibiotics. Topical dapsone is the most recently
approved topical antibiotic for acne. With twice daily application topical dapsone has shown better efficacy in
controlling inflammatory lesions (58%) versus noninflammatory lesions (19%).57,58 Unlike oral dapsone,
topical dapsone is safe for use even in patients with a G6PD deficiency.59 It is generally well tolerated but should
not be applied concomitantly with benzoyl peroxide or it may impart an orange color on the skin. 60
Retinoids. (See Chapter 217). Retinoids are defined by their ability to bind to and activate retinoic acid receptors
(RAR) and in turn activate specific gene transcription resulting in a biologic response. Some have chemical
structures similar to tretinoin (all-trans-retinoic acid), but they may be entirely dissimilar, such as adapalene or
tazarotene, and still potentiate a retinoid effect. In general, the binding of these agents to nuclear RAR affects the
expression of genes involved in cell proliferation, differentiation, melanogenesis, and inflammation.61,62 The result
is modification of corneocyte accumulation and cohesion, and inflammation. Thus, retinoids have both
comedolytic and antiinflammatory properties.62 Tretinoin is commercially available in several strengths and
formulations. Having both potent comedolytic and anti-inflammatory properties, it is widely used. In general, all
retinoids can be contact irritants, with alcohol-based gels and solutions having the greatest irritancy potential.
Some newer formulations utilize a microsphere delayed-delivery technology (Retin A Micro® 0.04% or 0.1% gel)
or are incorporated within a polyolprepolymer (PP-2) (Avita® cream) to decrease the irritancy potential of
tretinoin while allowing greater concentration of medication. Advising patients to apply tretinoin on alternate
nights during the first few weeks of treatment can help ensure greater tolerability. Patients must also be
cautioned about sun exposure due to thinning of the stratum corneum, especially those with any irritant reaction.
Regular use of a sunscreen should be advised. The comedolytic and anti-inflammatory properties of topical
retinoids make them ideal for maintenance therapy of acne. Generic tretinoin is inactivated by concomitant use
of benzoyl peroxide and is photolabile. Therefore, patients should be counseled to apply tretinoin at bedtime.
Adapalene is a synthetic retinoid widely marketed for its greater tolerability. It specifically targets the
RARreceptor. It is both photostable and can be used in conjunction with benzoyl peroxide without
degradation. Adapalene 0.1% gel has been shown in clinical trials to have greater or equal efficacy to tretinoin
0.025% gel with greater tolerability.63,64 It is available at a 0.1% concentration in both a nonalcohol gel and cream
and as a 0.3% gel. The 0.3% adapalene gel has been shown to have similar efficacy to tazarotene 0.1% gel with
increased tolerability.65 A combination topical agent containing 0.1% adapalene and 2.5% benzoyl
peroxide is also available.66,67 Tazarotene, also a synthetic retinoid, exerts is action through its metabolite,
tazarotenic acid, which in turn inhibits the RARreceptor. It is a potent comedolytic agent and has been show to
be more effective than tretinoin 0.025% gel and tretinoin 0.1% microsphere gel.68,69 Both the 0.1% cream and gel
formulations are approved for the treatment of acne. The irritant properties of tazarotene can be minimized by
the use of short-term contact therapy. In this regimen, the medication is applied for 5 minutes then washed off
with a gentle cleanser. Tazarotene has been given a pregnancy category X rating and female patients of
childbearing age should be adequately counseled. An overview of topical agents for acne treatment is outlined in
Table 80-2.
SYSTEMIC THERAPY
Antibiotics and Antibacterial Agents. (See Chapter 230).
Tetracyclines. Broad-spectrum antibiotics are widely used in the treatment of inflammatory acne. The
tetracyclines are the most commonly used antibiotics in the treatment of acne. Although the oral administration
of tetracyclines does not alter sebum production, it does decrease the concentration of free fatty acids while the
esterified fatty acid content increases. Decreases in free fatty acid formation also have been reported
with erythromycin, demethylchlortetracycline, clindamycin, and minocycline. The free fatty acids are probably
not the major irritants in sebum, but their level is an indication of the metabolic activity of the P. acnes
bacteria and its secretion of other proinflammatory products. The decrease in free fatty acids may take
several weeks to become evident. This, in turn, is reflected in the clinical course of the disease during antibiotic
therapy, as several weeks are often required for maximal clinical benefit. The effect, then, is one of
prevention; the individual lesions require their usual time to undergo resolution. However, the fact that a
decrease in free fatty acids does occur strengthens the rationale for the use of tetracycline. Tetracycline may also
act through direct suppression of the number of P. acnes, but part of its action may be due to its antiinflammatory
activity. In clinical practice, tetracycline is usually given initially in dosages of 500–1,000 mg/day. Higher doses of
up to 3,500 mg/day have been used in severe cases, but prudent monitoring of liver functions is warranted.
Tetracycline should be taken on an empty stomach, 1 hour before or 2 hours after meals, to promote absorption;
thus, compliance by adolescents with its administration can be challenging. Gastrointestinal (GI) upset is the
most common side effect, with esophagitis and pancreatitis possible. Uncommon side effects include
hepatotoxicity, hypersensitivity reactions, leukocytosis, thrombocytopenic purpura, and pseudotumor cerebri.
Tetracyclines should be used with caution in patients with renal disease as they may increase uremia.
Tetracyclines have an affinity for rapidly mineralizing tissues and are deposited in developing teeth, where they
may cause irreversible yellow–brown staining; also, tetracyclines have been reported to inhibit skeletal growth in
the fetus. Therefore, they should not be administered to pregnant women, especially after the fourth month of
gestation and are not recommend for use in children younger than 9 years of age in the treatment of acne.
The tetracycline derivatives, doxycycline and minocycline, are also commonly used in the treatment
of acne. They have the distinct advantage of being able to be taken with food without impaired
absorption. Doxycycline is administered in dosages of 50–100 mg twice daily. Its major disadvantage is the
potential risk of photosensitivity reactions, including photo-onycholysis, and patients may need
to be switched to another antibiotic during summer months. Minocycline is given in divided dosages at
a level of 100–200 mg/day. Patients on minocycline should be monitored carefully, as the drug can cause
blue–black pigmentation, especially in the acne scars, as well as the hard palate, alveolar ridge, and anterior
shins. Vertigo has occasionally been described. Minocycline-induced autoimmune hepatitis and a
systemic lupus erythematosus-like syndrome have been reported during minocycline therapy, but these
side effects are very rare.70,71 Of note, patients who develop lupus-like reactions can be safely switched to
an alternative tetracycline. Serum sickness-like reactions and drug reaction with eosinophilia and systemic
symptoms (DRESS) syndrome have also been reported with minocycline use.
Macrolides. Due to the prevalence of erythromycinresistant strains of P. acnes, the use of oral erythromycin is
generally limited to pregnant women or children. Azithromycin has been used more often for acne, typically at
dosages of 250–500 mg orally three times weekly.72 Azithromycin undergoes hepatic metabolism with GI upset
and diarrhea as the most common side effects.
Trimethoprim–Sulfamethoxazole. Trimethoprim–sulfamethoxazole combinations are also effective in acne.
In general, because the potential for side effects is greater with their use, they should be used only in
patients with severe acne who do not respond to other antibiotics. GI upset and cutaneous hypersensitivity
reactions are common. Serious adverse reactions, including the Stevens–Johnson syndrome-toxic
epidermal necrolysis spectrum (see Chapter 40) and aplastic anemia, have been described. If trimethoprim–
sulfamethoxazole is used, the patient must be monitored for potential hematologic suppression approximately
monthly.
Cephalexin. Cephalexin, a first generation cephalosporin, has been shown in vitro to kill P. acnes. However,
because it is hydrophilic and not lipophilic it penetrates poorly into the pilosebaceous unit. Success with oral
cephalexin73 is most likely due to its anti-inflammatory rather than antimicrobial properties. Due to the risk of
promoting the development of bacterial resistance particularly to Staphylococcus, the authors discourage
the use of cephalexin for acne.
Clindamycin and Dapsone. Less commonly used antibiotics include clindamycin and dapsone. Oral
clindamycin had been used more readily in the past, but because of the risk of pseudomembranous colitis, it
is now rarely used systemically for acne. It is still commonly used topically, however, often in combination
with benzozyl peroxide. Dapsone (see Chapter 225), a sulfone often used for cutaneous neutrophilic disorders,
may be beneficial in severe markedly inflammatory acne and select cases of resistant acne. It is used
at doses of 50–100 mg daily for 3 months. G6PD levels should be examined prior to initiation of therapy and
regular monitoring for hemolysis and liver function abnormalities is warranted. While not as reliably effective
as isotretinoin, it is relatively low cost and should be considered in severe cases where isotretinoin is not an
option.
Antibiotics and Bacterial Resistance. Antibiotic resistance is a growing concern worldwide
and should be suspected in patients unresponsive to appropriate antibiotic therapy after 6 weeks of treatment.
Increasing propionobacterium resistance has been documented to all macrolides and tetracyclines
commonly used in the treatment of acne. A prevalence rate of 65% was documented in one study performed in
the United Kingdom.74 Overall, resistance is highest with erythromycin and lowest with the lipophilic
tetracyclines, doxycycline, and minocycline.75 The least resistance is noted with minocycline. To prevent
resistance, prescribers should avoid antibiotic monotherapy, limit long-term use of antibiotics and combine
usage with benzoyl peroxide whenever possible.55
HORMONAL THERAPY OF ACNE. The goal of hormonal therapy is to counteract the effects of androgens
on the sebaceous gland. This can be accomplished with the antiandrogens, or agents designed to decrease
the endogenous production of androgens by the ovary or adrenal gland, including oral contraceptives,
glucocorticoids, or gonadotropin-releasing hormone (GnRH) agonists.
Oral Contraceptives. Oral contraceptives can improve acne by four main mechanisms. Firstly, they decrease
the amount of gonadal androgen production by suppressing LH production. Secondly, they decrease the amount
of free testosterone by increasing the production of sex hormone binding globulin.
Thirdly, they inhibit the activity of 5-reductase activity, so as to prevent the conversion of testosterone to the
more potent DHT. Lastly, progestins that have an antiandrogenic effect can block the androgen receptors on
keratinocytes and sebocytes. The third-generation progestins—gestodene (not available in the
United States), desogestrel, and norgestimate, have the lowest intrinsic androgenic activity.76 Two progestins
have demonstrated antiandrogenic properties: (1) cyproterone acetate (not available in the United States) and (2)
drospirenone. There are three oral con traceptives currently Food and Drug Administration
(FDA) approved for the treatment of acne: (1) Ortho Tri-Cyclen, (2) Estrostep, and (3) Yaz. Ortho Tri-Cyclen
is a triphasic oral contraceptive comprised of a norgestimate (180, 215, 250 mg)–ethinyl estradiol (35 g)
combination.77 In an effort to reduce the estrogenic side effects of oral contraceptives, preparations with lower
doses of estrogen (20 g) have been developed for the treatment of acne. Estrostep contains a graduated dose of
ethinyl estradiol (20–35 g) in combination with norethindrone acetate (1 mg). 78 Yaz contains ethinyl estradiol (20
ug) and the antiandrogen drospirenone (3 mg). Drospirenone is a 17 -spironolactone derivative that has both
antimineralocorticoid and antiandrogenic properties, which may improve estrogen-related weight gain and
bloating.78 An oral contraceptive containing a low dose of estrogen (20 g) in combination with levonorgestrel
(Alesse) has also demonstrated efficacy in acne.79 Side effects from oral contraceptives include nausea, vomiting,
abnormal menses, weight gain, and breast tenderness. Rare but more serious complications include
thrombophlebitis, pulmonary embolism, and hypertension. With the use of estrogen–progestin-containing oral
contraceptives rather than estrogen alone, side effects such as delayed menses, menorrhagia, and premenstrual
cramps are uncommon. However, other side effects such as nausea, weight gain, spotting, breast tenderness,
amenorrhea, and melasma can occur.
Glucocorticoids. Because of their anti-inflammatory activity, high-dose systemic glucocorticoids may be of
benefit in the treatment of acne. In practice, their use is usually restricted to the severely involved patient, often
overlapping with isotretinoin to limit any potential flaring from at the start of treatment. Furthermore, because of
the potential side effects, these drugs are ordinarily used for limited periods of time, and recurrences after
treatment are common. Prolonged use may result in the appearance of steroid acne. Glucocorticoids in low
dosages are also indicated in those female patients who have an elevation in serum DHEAS associated with an
11- or 21-hydroxylase deficiency or in other individuals with demonstrated androgen excess. Low-dose
prednisone (2.5 mg or 5 mg) or dexamethasone can be given orally at bedtime to suppress adrenal androgen
production.44 The combined use of glucocorticoids and estrogens has been used in recalcitrant acne in women,
based upon the inhibition of sebum production by this combination.80 The mechanism of action is probably
related to a greater reduction of plasma androgen levels by combined therapy than is produced by either drug
alone.
Gonadotropin-Releasing Hormone Agonists. GnRH agonists, such as leuprolide (Lupron),
act on the pituitary gland to disrupt its cyclic release of gonadotropins. The net effect is suppression of ovarian
steroidogenesis in women. These agents are used in the treatment of ovarian hyperandrogenism. GnRH
agonists have demonstrated efficacy in the treatment of acne and hirsutism in females both with and without
endocrine disturbance.81 However, their use is limited by their side effect profile, which includes menopausal
symptoms and bone loss.
Antiandrogens. Spironolactone is an aldosterone antagonist and functions in acne as both an androgenrecepto
blocker and inhibitor of 5-reductase. In doses of 50–100 mg twice a day, it has been shown to reduce sebum
production and to improve acne.82 Side effects include: diuresis, potential hyperkalemia, irregular menstrual
periods, breast tenderness, headache, and fatigue. Combining spironolactone treatment with an oral
contraceptive can alleviate the symptoms of irregular menstrual bleeding. Although hyperkalemia is a risk of
spironolactone, this risk has shown to be minimal, even when spironolactone is administered with other
aldosterone antagonists (such as drospirenone containing oral contraceptives). 83 As an antiandrogen, there is a
risk of feminization of a male fetus if a pregnant female takes this medication. Long-term studies in rats receiving
high doses of spironolactone demonstrated an increased incidence of adenomas on endocrine organs and the
liver. These findings recently led to a black box warning by the FDA. 84 Cyproterone acetate is a progestational
antiandrogen that blocks the androgen receptor. It is combined with ethinyl estradiol in an oral contraceptive
formulation that is widely used in Europe for the treatment of acne. Cyproterone acetate is not available in the
United States. Flutamide, an androgen receptor blocker, has been used at doses of 250 mg twice a day in
combination with oral contraceptives for treatment of acne or hirsutism in females. 85 Liver function tests should
be monitored, as cases of fatal hepatitis have been reported. 86 Pregnancy should be avoided. Use of flutamide
in the treatment of acne may be limited by its side effect profile.
Isotretinoin. (See Chapter 228). The use of the oral retinoid, isotretinoin, has revolutionized the management
of treatment-resistant acne.87 It is approved for use in patients with severe recalcitrant nodular acne. However, it
is commonly used in many other acne scenarios, including any significant acne that is unresponsive to treatment
with oral antibiotics and acne that results in significant physical or emotional scarring.
Isotretinoin is also effective in the treatment of Gramnegative folliculitis, pyoderma faciale, and acne fulminans.
88 The remarkable aspects of isotretinoin therapy are the complete remission in almost all cases and the longevity

of the remission, which lasts for months to years in the great majority of patients. However, due to its
teratogenicity its use has become highly regulated in the United States with the initiation of the iPledge
program in March 2006 to insure that pregnancy-prevention procedures are followed.
The mechanism of action of isotretinoin is not completely known. The drug produces profound inhibition
of sebaceous gland activity, and this undoubtedly is of great importance in the initial clearing. 89,90 In some
patients, sebaceous gland inhibition continues for at least a year, but in the majority of patients, sebum
production returns to normal after 2–4 months.89 Thus, this action of the drug cannot be used to explain
the long-term remissions. The P. acnes population is also decreased during isotretinoin therapy, but this
decrease is generally transient.90,91 Isotretinoin has no inhibitory effect on P. acnes in vitro. Therefore, the
effect on the bacterial population is probably indirect, resulting from the decrease in intrafollicular lipids
necessary for organism growth. Isotretinoin also has anti-inflammatory activity and probably has an effect
on the pattern of follicular keratinization. These effects also are temporary, and the explanation for long-term
remissions remains obscure. Given the ubiquitous distribution of RAR, isotretinoin almost always causes side
effects, mimicking those seen in the chronic hypervitaminosis A syndrome. 92 In general, the severity of side
effects tends to be dose dependent. The most common side effects are related to the skin and mucous
membranes. Cheilitis of varying degrees is found in virtually all cases. Other side effects that are likely to be seen
in over 50% of patients are dryness of the mucous membranes and skin. An eczematous dermatitis is occasionally
seen, particularly in cold, dry weather. Thinning of hair and granulomatous paronychial lesions are less
common. Ophthalmologic findings include xerophthalmia, night blindness, conjunctivitis, keratitis, and optic
neuritis. Corneal opacities and hearing loss (both transient and persistent) have also been reported with
isotretinoin use. Pseudotumor cerebri, also known as benign intracranial hypertension, is evidenced by severe
headache, nausea, and visual changes. The risk of pseudotumor cerebri may be increased with concomitant use
of tetracyclines and isotretinoin; therefore, these two medications should not be used together without careful
prior consideration. If symptoms suggest benign intracranial hypertension, prompt neurological evaluation
for evidence of papilledema is required. Vague complaints of headache, fatigue, and lethargy are also not
infrequent. The relationship between isotretinoin use and psychiatric effects is currently being examined. Risk of
depression, suicide, psychosis, and aggressive and/or violent behavior are all listed as possible side effects.
While no clear mechanism of action has been established, some evidence for biologic plausibility does exist.
Psychiatric adverse events are described with high-dose vitamin A and etretinate. Also, retinoids
have the demonstrated ability to enter the central nervous system (CNS) of rats and mice. And finally,
there are documented case reports and studies linking isotretinoin use to depression in certain individuals.93
A meta-analysis of nine studies looking at the possible link between isotretinoin and depression found
that the incidence of depression in patients on isotretinoin ranged from 1%–11%.94 The authors importantly
pointed out that this range is similar to control group patients on oral antibiotics. Another author examining
case-control studies on isotretinoin and depression found the relative risk to range from 0.9 to 2.7 with
wide confidence intervals.95 Some studies demonstrate that those on isotretinoin have an overall improvement
in mood.96 Retinoids have not been shown to activate genes to induce behavioral/psychiatric changes. Nor is
there evidence demonstrating functionality of retinoid signaling pathways in the mature CNS. Large
population-based studies have not supported causality As dermatologists are often on the front line seeing
adolescents at risk for depression, careful screening of adolescents is particularly needed, since the risk of
depression in this population is 10%–20%. GI symptoms are generally uncommon, but nausea,
esophagitis, gastritis, and colitis can occur. Acute hepatitis is rare but liver function studies should be
regularly monitored, as elevation in liver enzymes can occur in 15% of patients, sometimes necessitating dose
adjustments. Elevated levels of serum triglycerides occur in approximately 25% of patients on isotretinoin.
This elevation, which is dose-related, typically occurs within the first 4 weeks of treatment and is
often accompanied by an overall increase in cholesterol with a decrease in the high-density lipoprotein
levels. The effect of this transient alteration on overall coronary artery health is unclear. Acute pancreatitis is
a rare complication that may or may not be related to triglyceride levels. There are case reports documenting
a potential link between isotretinoin and new-onset or flared inflammatory bowel disease. However, a study
that critically examined these case reports found no grounds for a causal relationship between isotretinoin
use and inflammatory bowel disease.98 A recent population- based case-control study found that patients
with inflammatory bowel disease were no more likely to have used isotretinoin than those without inflammatory
bowel disease.99 Patients with a family history of inflammatory bowel disease, or those with a preexisting
inflammatory bowel disease, should be counseled regarding the possibility of isotretinoin-induced
inflammatory bowel disease. Isotretinoin has effects on bone mineralization as well. A single course of
isotretinoin was not shown to have a significant effect on bone density. 100 However, chronic or repeated courses
may result in significant osteopenia. Osteoporosis, bone fractures, and delayed healing of bone fractures have
also been reported. The significance of reported hyperostosis is unclear, but the development of bony
hyperostoses after isotretinoin therapy is more likely in patients who receive the drug for longer periods of time
and in higher dosages, such as for disorders of keratinization. 101 Serial bone densitometry
should be done in any patient on long-term isotretinoin. Myalgias are the most common musculoskeletal
complain, seen in 15% of patients. In severe cases, creatine phosphokinase levels should be evaluated
for possible rhabdomyolysis. Other laboratory abnormalities that have been reported with isotretinoin use are an
elevated erythrocyte sedimentation rate and platelet count. Alterations in the red blood cell parameters with
decreased white cell counts can occur. White blood cells in the urine have rarely been linked to isotretinoin use.
Most laboratory changes are mild and spontaneously resolve upon discontinuation of medication use.
The greatest concern during isotretinoin therapy is the risk of the drug being administered during pregnancy
and thereby inducing teratogenic effects in the fetus.102,103 The drug is not mutagenic; its effect is on
organogenesis. Therefore, the production of retinoic embryopathy occurs very early in pregnancy, with a
peak near the third week of gestation.102,103 A significant number of fetal abnormalities have been reported
after the use of isotretinoin. For this reason, it should be emphasized that isotretinoin should be given only
to patients who have not responded to other therapy. Furthermore, women who are of childbearing age
must be fully informed of the risk of pregnancy. The patient must employ two highly effective contraception
techniques such as the use of an oral contraceptive and condoms with a spermicidal jelly. Contraception
must be started at least 1 month before isotretinoin therapy. Female patients must be thoroughly counseled
and demonstrate an understanding of contraception techniques before starting isotretinoin. Two
forms of contraception should be used throughout the course of isotretinoin and for 1 month after stopping
treatment. No more than 1 month’s supply of isotretinoin should be given to a female patient so that she
can be counseled on a monthly basis on the hazards of pregnancy during isotretinoin therapy. A pregnancy
test must be repeated monthly. Abstinence as a form of birth control should only be allowed in special
instances. Because the drug is not mutagenic, there is no risk to a fetus conceived by a male who is taking
isotretinoin. Although it may seem obvious, it is important to remind men who are taking isotretinoin
not to give any of their medication to female companions under any circumstances.
The recommended daily dosage of isotretinoin is in the range of 0.5–1 mg/kg/day. A cumulative
weight-based dosing formula may also be used with a total dose of 120–150 mg/kg of isotretinoin during
a course of therapy.104 This dosing regimen is of particular use in patients who have variable dosages
or interrupted periods of treatment as achieving the total dose will ensure the greatest chance of longterm
remission. Because back and chest lesions show less of a response than facial lesions, dosages as high
as 2 mg/kg/day may be necessary in those patients who have very severe truncal involvement. Patients
with severe acne, particularly those with granulomatous lesions, will often develop marked flares of
their disease when isotretinoin is started. Therefore, the initial dosing should be low, even below 0.5 mg/
kg/day. These patients often need pretreatment for 1–2 weeks with prednisone (40–60 mg/day), which
may have to be continued for the first 2 weeks of therapy. A typical course of isotretinoin is 20 weeks,
but the length of the course of treatment is not absolute; in patients who have not shown an adequate
response, therapy can be extended. Additional improvement may be seen for 1–2 months after discontinuation,
so that complete clearance may not be a necessary endpoint for determining when to discontinue
therapy. Low-dose regimens, 0.1–0.4 mg/ kg/day, have shown efficacy. However, with such
dosages, the incidence of relapses after therapy is greater. Approximately 10% of patients treated with
isotretinoin require a second course of the drug. The likelihood for repeat therapy is increased in patients
younger than 16–17 years of age. It is standard practice to allow at least 2–3 months between courses
of isotretinoin. Furthermore, laboratory monitoring is indicated. It is appropriate to obtain a baseline complete
blood count and liver function tests, but the greatest attention should be paid to following serum triglyceride
levels. Baseline values for serum triglycerides should be obtained and repeated at 3–4 weeks and 6–8 weeks
of therapy. If the values are normal at 6–8 weeks, there is no need to repeat the test during the remaining
course of therapy unless there are risk factors. If serum triglycerides increase above 500 mg/dL, the levels
should be monitored frequently. Levels above 700 to 800 mg/dL are a reason for interrupting therapy or
treating the patient with a lipid-lowering drug. Eruptive exanthemas or pancreatitis can occur at higher
serum triglyceride levels.
DIET. Several articles suggesting a role for diet in acne exist.105,106 A recent review of these studies concluded
that there may be some link between milk and acne as well as between high-glycemic index foods and
acne.107 Yet, overall the implications of these studies is not clear and the role of chocolate, sweets, milk,
highglycemic index foods, and fatty foods in patients with acne requires further study. There is no evidence to
support the value of elimination of these foods. However, restricting a food firmly thought by the patient
to be a trigger is not harmful, as long as the patient’s nutritional well-being is not compromised.
ACNE SURGERY. Acne surgery, a mainstay of therapy in the past used for the removal of comedones and
superficial pustules, aids in bringing about involution of individual acne lesions. However, with the advent
of comedolytic agents, such as topical retinoids, its use is primarily restricted to those patients who do not
respond to comedolytic agents. Even in those patients, the comedones are removed with greater ease and
less trauma if the patient is pretreated with a topical retinoid for 3–4 weeks. Acne surgery should not be
performed at home, as inaccurate placement of the comedo extractor may rupture the follicle and incite
an inflammatory reaction. The Unna type of comedo extractor, which has a broad flat plate and no narrow
sharp edges, is preferable. The removal of open comedones is desirable for cosmetic purposes, but does
not significantly influence the course of the disease. In contrast, closed comedones should be removed to prevent
their rupture. Unfortunately, the orifice of closed comedones is often very small, and usually the material
contained within the comedo can be removed only after the orifice is gently enlarged with a no. 25 needle
or other suitable sharply pointed instrument.
INTRALESIONAL GLUCOCORTICOIDS. Intralesional injection of glucocorticoids can dramatically
decrease the size of deep nodular lesions. The injection of 0.05–0.25 mL per lesion of a triamcinolone acetate
suspension (2.5–10 mg/mL) is recommended as the anti-inflammatory agent. This is a very useful form of
therapy in the patient with nodular acne, but it often has to be repeated every few weeks. A major advantage
is that it can be done without incising or draining the lesions, thus avoiding the possibility of scar
formation. Hypopigmentation, particularly in darker skinned patients, and atrophy are risks.
PHOTOTHERAPY AND LASERS. Various forms of phototherapy are under investigation for their use
in treating acne vulgaris. Ultraviolet (UV) light has long been thought to be beneficial in the treatment
of acne. Up to 70% of patients report that sun exposure improves their acne.108 This reported benefit
may be due to camouflage by UV radiation induced erythema and pigmentation, although it is likely that
the sunlight has a biologic effect on the pilosebaceous unit and P. acnes. Although ultraviolet B (UVB) can
also kill P. acnes in vitro, UVB penetrates poorly to the dermal follicle and only high doses causing sunburn
have be shown to improve acne.109,110 UV radiation may have anti-inflammatory effects by inhibiting cytokine
action.111 Twice-weekly phototherapy sessions are needed for any clinical improvement. The therapeutic utility of
UV radiation in acne is superseded by its carcinogenic potential Other types of phototherapy for acne treatment
utilize porphyrins. Treatment of acne with phototherapy works either by activating the endogenous
porphyrins of P. acnes or by applying exogenous porphyrins. Coproporphyrin III is the major endogenous
porphyrin of P. acnes. Coproporphyrin III can absorb light at the near-UV and blue light spectrum of
415 nm.117 Irradiation of P. acnes with blue light leads to photoexcitation of endogenous bacterial porphyrins,
singlet oxygen production, and subsequent bacterial destruction. 118 A visible light source, either blue
or red, or both may be used to excite the endogenous porphyrins. The high intensity, enhanced, narrowband
(407–420 nm) blue light known as ClearLight (Lumenis) is currently FDA approved for the treatment
of moderate inflammatory acne.116 Red light too may be beneficial, as it penetrates deeper into the
dermis and has greater anti-inflammatory properties, but causes less photoactivation of the porphyrins.
Therefore, the combination of blue and red light may prove the most beneficial. Treatments should
be given twice weekly for 15-minute sessions for the face alone, and 45 minutes for the face, chest, and
back. A multicenter study has shown that 80% of patients treated with the ClearLight for 4 weeks had
a 60% reduction in acne lesions. There was a gradual return of lesions over 3–6 months
The most consistent improvement in acne after light treatment has been demonstrated with photodynamic
therapy.120 Photodynamic therapy involves the topical application of aminolevulinic acid (ALA) 1 hour prior
to exposure to a low-power light source. These sources include the pulsed dye laser, intense pulsed light, or a
broadband red light source. The topical ALA is taken up by the pilosebaceous unit and metabolized to
protoporphyrin IX.121 The protoporphyrin IX is targeted by the light and produces singlet oxygen species, which
then damage the sebaceous glands.122 Several studies utilizing ALA-PDT maintained Although lasers are
beginning to find a role in the treatment of acne, the authors consider them inferior to the traditional medical
treatments. They work by emitting minimally divergent, coherent light that can be focused over a small area of
tissue. The pulsed KTP laser (532 nm) has demonstrated a 35.9% decrease in acne lesions when used twice
weekly for 2 weeks. Although there was no significant decrease in P. acnes, there was significantly lower sebum
production even at 1 month.125 The pulsed dye laser (585 nm) can also be used at lower fluences to treat acne.
Instead of ablating blood vessels and causing purpura, a lower fluence can stimulate procollagen production by
heating dermal perivascular tissue.122 The beneficial effects of a single treatment can last 12 weeks. 126 Some of the
nonablative infrared lasers, such as the 1,450 nm and 1,320 nm laser, have shown to be helpful in improving
acne.127,128 These lasers work by causing thermal damage to the sebaceous glands. The concurrent
use of a cryogen spray device protects the epidermis while the laser causes necrosis of the sebaceous
gland.129 In a pilot study, 14 out of 15 patients treated with the 1,450 nm laser had a significant reduction in
inflammatory lesions that persisted for 6 months. The 1,320 nm Nd:Yag and the 1,540 erbium glass lasers
have also been demonstrated to improve acne Multiple treatments are needed with either of these
lasers to lessen acne lesions. These treatments tend to be painful and show a gradual modest improvement,
limiting their utility. One of the newer uses of light for treating acne is with a photopneumatic device (Isolaz,
Solta Medical). This photopneumatic device has a handpiece that applies negative pressure (i.e., suction) to the
skin and then delivers a broadband-pulsed light (400–1,200 nm). The suction is employed to unplug the
infundibulum of the pilsebaceous unit and the light is delivered to activate the P. acnes porphyrins, thus releasing
singlet oxygen species. Patients treated with this device may experience some posttreatment erythema or
purpura. Results are modest and temporary and the device is best for inflammatory lesions. 132,133 Although the
lightbased treatments are beneficial in that they avoid some of the side effects of the oral medications, the cost of
these light and laser treatments tends to be prohibitive