Beruflich Dokumente
Kultur Dokumente
that have been described—one in Papua New Guinea matory lesions (red papules, pustules, or nodules)
and the other in Paraguay—that do not develop acne.6 (Fig. 78-1). Although one type of lesion may predomi-
Although this may be genetically determined, envi- nate, close inspection usually reveals the presence of
ronmental factors may also be at play because these several types of lesions. Closed comedones are known
::
groups have not been exposed to a westernized diet. as “whiteheads” (Fig. 78-1A), and open comedones are
Acneiform Disorders
C D
Figure 78-1 Clinicopathologic correlation of acne lesions. A, Closed comedone. The follicular infundibulum is distended,
filled with keratin and sebum, and the follicular epithelium is attenuated. The follicular ostium is narrow. B, Open com-
edone. Resembles the closed comedone with the exception of a patulous follicular ostium. C, Inflammatory papule. Acute
and chronic inflammatory cells surround and infiltrate the follicle, which shows infundibular hyperkeratosis. D, Nodule.
The follicle is filled with acute inflammatory cells. With the rupture of the distended follicle, there is a foreign body granu-
lomatous response.
A B
Figure 78-2 Mild acne vulgaris. A, A 13-year-old girl with mild acne vulgaris. Scattered comedones or inflammatory lesions
(or both) are seen, usually limited to less than half of the face. The T-zone of the face is commonly involved. No nodules are 1393
present. B, An adult female with primarily inflammatory acne. Note the typical involvement of the jawline.
A B
Figure 78-3 Moderate acne vulgaris. A, A 15-year-old male patient with moderate acne. Typically, more than half of the
face is involved with increasing numbers of lesions, usually a mix of lesions is seen: papules, pustules, and comedones.
Infrequent and limited nodules may be present. Chest and back involvement may also be moderately affected. B, A
16-year-old female patient with open and deep closed comedones. Scarring and postinflammatory changes are possible
sequelae.
types, postinflammatory hyperpigmentation may per- acne are more likely to be passed over by prospective
sist for months after resolution of acne lesions. In some employers.29 A cross-sectional study found that 14% of
individuals, acne lesions may result in permanent students reported “problem acne,” which was associ-
scarring. Acne scars can be atrophic or hypertrophic.25 ated with an increased risk of depressive symptoms as
Atrophic scars can be further categorized based on size well as suicidal thoughts and attempts.32,33 One study
and shape: ice pick, boxcar, or rolling26 (Fig. 78-5). Ice has estimated the prevalence of suicidal ideation in
pick scars are narrow, deep scars that are widest at the patients with acne as 7%.34 In adolescents, two large
surface of the skin and taper to a point in the dermis, studies have shown that anxiety, depression, and sui-
typically less than 2 mm in diameter. Boxcar scars are cidal ideation are higher in those with self-described
wide sharply demarcated scars that do not taper to a “problem acne” or “substantial acne.” These findings
point at the base and range in size from 1.5 to 4 mm. highlight the importance of appropriate psychiatric
Rolling scars are shallow, wide scars (often >4–5 mm) screening and referral. Importantly, the impact of acne
that have an undulating appearance. Perifollicular on patients’ lives was often independent of severity,
elastolysis is another type of scar, which typically pres- such that some patients with only minimal acne expe-
ents as atrophic soft papules on the upper part of the rience psychological and psychosocial distress.35 Thus,
trunk.27 Hypertrophic and keloidal scars, in addition to although some consider acne “cosmetic,” its impact on
sinus tracts, can also form. one’s well-being can be significant.
Although not life threatening, acne leads to signifi-
cant morbidity, including depression, anxiety, and psy-
chosocial stress, and is a major cause of psychosocial
ETIOLOGY AND
and psychological impairment for young people,28,29
triggering anxiety and mood disorders and affecting
PATHOGENESIS
self-esteem.30,31 It is ranked third among chronic skin Current understanding of acne is that it is a com-
diseases for causing disability, as measured by equiva- plex and multifactorial inflammatory disease. Recent
lent years of “healthy” life lost by virtue of being in studies are better defining the cellular and molecular
states of poor health or disability.3 Patients experience mechanisms involved in acne and the importance of
social isolation and are reluctant to participate in group inflammation and the immune response. The patho-
activities. Unemployment rates are higher among genesis of acne is multifaceted, and at least four factors
adults with acne than those without. Self-esteem issues have been identified. These key elements (Fig. 78-6) are
are also likely to be the driving force behind higher (1) follicular epidermal hyperproliferation, (2) sebum
1394 rates of unemployment in people with acne; however, production, (3) Propionibacterium acnes, and (4) inflam-
there is also an existing bias whereby patients with mation and immune response. Each of these processes
Figure 78-4 Severe acne vulgaris. A, A 17-year-old female patient with extensive acne. Numerous pustules and nodular
lesions admixed with comedones and smaller papules cover the entire face. B, Deep, friable nodules that coalesce into
pseudocysts in acne conglobata. C, Chest and back involvement can be extensive and severe. Scarring is a common com-
plication in severe acne.
are interrelated and under hormonal and immune sulfate (DHEA-S) by 17-β hydroxysteroid dehydro-
influence. genase (HSD) and 5-α reductase enzymes (Fig. 78-7).
It is thought that all clinical lesions begin with the Compared with epidermal keratinocytes, follicular
microcomedo and develop into clinical lesions— keratinocytes have increased 17-β HSD and 5-α reduc-
comedones, inflammatory lesions, and scarring. Fol- tase, thus enhancing DHT production.36,37 DHT may
licular epidermal hyperproliferation results in the stimulate follicular keratinocyte proliferation. Also sup-
formation of a microcomedo. The epithelium of the porting the role of androgens in acne pathogenesis is
upper hair follicle, the infundibulum, becomes hyper- the evidence that individuals with complete androgen
keratotic with increased cohesion of the keratinocytes, insensitivity do not develop acne.38
resulting in the obstruction of the follicular ostium, Follicular keratinocyte proliferation is also regu-
where keratin, sebum, and bacteria begin to accumulate lated by linoleic acid, an essential fatty acid in the skin.
in the follicle and cause dilation of the upper hair fol- Low levels of linoleic acid induce follicular keratino-
licle, producing a microcomedo. Exactly what initiates cyte hyperproliferation and the production of proin-
and stimulates the hyperproliferation and increased flammatory cytokines. The levels of linoleic acid are
adhesion of keratinocytes is unknown. Several pro- decreased in individuals with acne and normalize after
posed factors in keratinocyte hyperproliferation include successful treatment with isotretinoin.39
androgen stimulation, decreased linoleic acid, increased In addition to androgens and linoleic acid, IL-1 α
IL-1-α activity, and effects of P. acnes. Dihydrotestoster- has been shown to contribute to keratinocyte hyper-
one (DHT) is a potent androgen that may play a role in proliferation. IL-1α induces follicular keratinocyte 1395
acne. DHT is converted from dehydroepiandrosterone hyperproliferation and microcomedone formation,
A
Part 14
::
Acneiform Disorders
B C
Figure 78-5 Acne vulgaris, scarring. A, Honeycomb scarring in a young girl with mild to moderate inflammatory acne.
B, Extensive keloidal scarring occurring as sequelae of acne fulminans. C. Rolling scars.
Acne pathogenesis
Inflammatory Nodule
Microcomedone Comedone papule or pustule
Hyperkeratotic Accumulation of Further expansion Rupture of follicular
infundibulum shed corneocytes of follicular unit wall
Cohesive and sebum Proliferation of Marked perifollicular
corneocytes Dilation of follicular Proprionibacterium inflammation
Sebum secretion ostium acnes Scarring
Perifollicular
inflammation
A B C D
1396
Figure 78-6 A–D Acne pathogenesis.
DHEAS
FSH LH ACTH 3β-HSD
Androstenedione
17β-HSD
Testosterone
17 Preg DHT
A A E
17 Prog DHEA
T T
A DOC
T Cortisol
Skin
Figure 78-7 Pathways of steroid metabolism. Dehydroepiandrosterone (DHEA) is a weak androgen that is converted to
the more potent testosterone by 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD. 5-α Reductase then converts
testosterone to dihydrotestosterone (DHT), the predominant hormonal effector on the sebaceous gland. The sebaceous
gland expresses each of these enzymes. A, androstenedione; ACTH, adrenocorticotropin-stimulating hormone; DHEAS,
dehydroepiandrosterone sulfate; DOC, deoxycortisol E, estrogen; FSH, follicle-stimulating hormone; LH, luteinizing
hormone; T, testosterone.
and IL-1 receptor antagonists inhibit microcomedone fatty acids promote P. acnes colonization and induction
formation.40,41 The initial event that upregulates the of inflammation.47 Lipoperoxides also found in sebum
production of IL-1α has not been determined. Fibro- induce proinflammatory cytokines and activate the
blast growth factor receptor (FGFR)-2 signaling is peroxisome proliferator-activated receptors (PPAR)
also involved in follicular hyperkeratinization. There pathway, resulting in increased sebum.48,49
is a long-established relationship between acne and Androgenic hormones activate sebocyte prolifera-
Apert syndrome, a complex bony malformation syn- tion and differentiation and the induction of sebum
drome, caused by a gain-of-function mutation in the production. Similar to their action on the follicular
gene encoding FGFR-2. Mutations in FGFR-2 in a infundibular keratinocytes, androgen hormones bind
mosaic distribution underlie a nevus comedonicus- to and influence sebocyte activity.50 Those with acne
like lesion.42 The FGFR-2 pathway is androgen depen- have higher average serum androgen levels (although
dent, and proposed mechanisms in acne include an still within normal range) than unaffected control par-
increased production of IL-1α and 5-α reductase.43,44 ticipants.51,52 5-α Reductase, the enzyme responsible
The second and key feature in the pathogenesis of for converting testosterone to the potent DHT, has
acne is the production of sebum from the sebaceous greatest activity in areas of skin prone to acne, face,
gland. Human sebum are composed mainly of triglyc- chest, and back.44
erides found ubiquitously and of unique lipids, such The role of estrogen on sebum production is not well
as squalene and wax esters not found anywhere else in defined. The dose of estrogen required to decrease
the body, including the surface of the skin.45 Increased sebum production is greater than the dose required
sebum secretion has been associated with acne. On aver- to inhibit ovulation.53 The mechanisms by which
age, people with acne excrete more sebum than those estrogens may work include (1) directly opposing the
without acne, and secretion rates have been shown to effects of androgens within the sebaceous gland, (2)
correlate with the severity of clinical manifestations, inhibiting the production of androgens by gonadal tis-
although the quality of sebum is the same between the sue via a negative feedback loop on pituitary gonado-
two groups.46 The main component of sebum, triglyc- tropin release, and (3) regulating genes that suppress
erides, is important in acne pathogenesis. Triglycerides sebaceous gland growth or lipid production.54
are broken down into free fatty acids by P. acnes, nor- Corticotropin-releasing hormone may also play a 1397
mal flora of the pilosebaceous unit. In return, these free role. It is released by the hypothalamus and increased
rounding the burst microcomedo.56 of human immune response.59,68 Moreover, the levels
It was originally thought that inflammation follows of porphyrin production and vitamin B12 regulation
comedo formation, but there is evidence that dermal were recently shown to be different between acne- and
inflammation may actually precede comedo forma- health-associated strains, suggesting a potential molec-
::
tion. Biopsies taken from comedo-free acne-prone skin ular mechanism for disease-associated strains in acne
Acneiform Disorders
demonstrate increased dermal inflammation com- pathogenesis and for health-associated strains in skin
pared with normal skin. Biopsies of newly formed health.69 Metabolite-mediated interactions between the
comedos demonstrate even greater inflammation.57 host and the skin microbiota may also play an essential
This may suggest that inflammation actually precedes role in acne development.70
comedo formation, again emphasizing the interplay Sebocyte differentiation and proinflammatory cyto-
between all of the pathogenic factors. kine and chemokine responses are varied depending
P. acnes is one of the key factors involved in acne on the strain of P. acnes predominating within the fol-
pathogenesis. P. acnes is a gram-positive, anaerobic, licle.35 Certain strains of P. acnes induce a differential
microaerophilic bacterium found in the sebaceous fol- host immune response. P. acnes ribotypes associated
licle and is the dominant bacterial inhabitant of the with acne induced distinct T helper 1 (Th1) and Th17
human sebaceous gland,58 accounting for almost 90% responses, which potentially contribute to inflamma-
of the bacterial 16S transcripts.59 P. acnes is generally tion in acne, but P. acnes ribotypes associated with
believed to play a major role in the pathogenesis of health-induced high levels of IL-10, which presumably
acne vulgaris, in part by eliciting a host inflamma- regulate and inhibit inflammatory responses.71
tory response.60 S. epidermidis is also present in follicles P. acnes directly induces inflammation through vari-
but is located near the surface, suggesting that it does ous mechanisms. The cell wall of P. acnes contains a
not contribute to the deeper inflammatory process.58 carbohydrate antigen that stimulates antibody devel-
There is a significant increase in P. acnes colonization opment. Patients with the most severe acne have been
at puberty, the time when acne commonly develops, shown to have the highest titers of antibodies.72 The
and teenagers with acne can have as many as 100- antipropionobacterium antibody enhances the inflam-
fold more P. acnes bacteria present on their skin than matory response by activating complement initiating a
healthy age-matched counterparts.61 However, there cascade of proinflammatory events.73 P. acnes also facili-
are no consistent data correlating the raw number of tates inflammation by eliciting a delayed-type hypersen-
P. acnes organisms present in a sebaceous follicle and sitivity response and by producing lipases, proteases,
the severity of the acne.61 hyaluronidases, and chemotactic factors.72,74 Reactive
Previously, a shotgun approach to target all P. acnes oxygen species (ROS) and lysosomal enzymes are
with antibiotics has been used, which has led to sig- released by neutrophils and levels may correlate with
nificant bacterial resistance in up to 60% clinical iso- severity.75 Additionally, P. acnes stimulates host innate
lates, directly correlating with antibiotic treatment responses via secretion of proinflammatory cytokines
failure.61-63 and chemokines from peripheral blood mononuclear
The recent association of specific P. acnes strains with cells (PBMCs) and monocytes60,76 and inflammatory
acne versus healthy skin supports the concept that P. cytokines and antimicrobial peptides such as human
acnes is an etiologic agent in the pathogenesis of acne. β-defensin-2 (hBD2) from KC77,78 and sebocytes.35
Certain P. acnes strains, as identified by multilocus The mechanisms by which P. acnes triggers the innate
sequence typing, were found to be associated with immune response has been studied and includes the
acne, designated as type IA1 or IC strains.64-67 Acne- activation of pattern recognition receptors (PRRs),
associated types were further investigated using full which recognize conserved pathogen-associated
genome sequencing in conjunction with ribotyping.59,68 molecular patterns (PAMPs) and activate specific sig-
Specifically, phylotype IB-1 was associated with acne, naling cascades, resulting in the induction of immune
as were the ribotype 4 and 5 subgroups of phylo- response genes. P. acnes-induced secretion of proinflam-
type IA-2. The ribotype 1 subgroup of phylotype matory cytokines IL-8, IL-12, and TNF-α in monocytes
1398 IA-2, together with phylotypes IA-1, IB-2, and IB-3, has been shown to involve TLR2,60 which is expressed
was found evenly distributed in acne patients and on macrophages surrounding the sebaceous follicles of
TABLE 78-2
Treatment Algorithm for Acne Vulgaris
MILD MODERATE SEVERE
PAPULAR OR PAPULAR OR CONGLOBATA OR
COMEDONAL PUSTULAR PUSTULAR NODULAR FULMINANS
First Topical retinoid or Topical retinoid + Oral antibiotic + Oral antibiotic + topical Oral isotretinoin ± oral
combinationa topical antimicrobial topical retinoid ± retinoid ± BPO corticosteroids
or combinationa BPO or combinationa
Second Topical dapsone Topical dapsone or Oral antibiotic + Oral isotretinoin or oral High-dose oral
or azelaic acid or azelaic acid or salicylic topical retinoid ± antibiotic + topical antibiotic + topical
salicylic acid acid BPO or combinationa retinoid ± BPO–azelaic retinoid + BPO or
acid or combinationa combinationa
Female — — + Oral contraceptive– + Oral contraceptive– + Oral contraceptive–
antiandrogen antiandrogen antiandrogen
Additional Comedone Comedone extraction, Comedone extraction, Comedone extraction; Intralesional cortico-
options extraction Laser or light therapy, laser or light ther- intralesional cortico- steroid, laser or light
photodynamic apy, photodynamic steroid, laser or light therapy, photody-
therapy therapy therapy, photodynamic namic therapy
therapy
Refractory to Check compliance Check compliance
treatment Exclude gram-negative
folliculitis
Females: exclude PCOS,
adrenal or ovarian
tumors, CAH
Males: exclude ECAH
Maintenance Topical retinoid Topical retinoid ± BPO, Topical retinoid ± BPO, Topical retinoid ± BPO, or
± BPO, or or combinationa or combinationa combinationa
combinationa
a
Manufactured combination products include benzoyl peroxide (BPO)–erythromycin, BPO–clindamycin, adapalene–BPO, and tretinoin–clindamycin.
CAH, congenital adrenal hyperplasia; PCOS, polycystic ovarian syndrome.
Adapted from Gollnick H, Cunliffe W, Berson D, et al. Management of acne: a report from a Global Alliance to improve outcomes in acne. J Am Acad Dermatol. 1401
2003;49(1Suppl):S1.
tion of the skin’s normal pH. Medicated cleansers, to decrease the irritancy potential of tretinoin while
containing benzoyl peroxide, salicylic acid, or sulfur, allowing greater concentration of medication. Advis-
offer convenience as a wash and are excellent for hard- ing patients to apply tretinoin on alternate nights dur-
to-reach areas such as the back. ing the first few weeks of treatment can help ensure
::
TABLE 78-3
Commonly Available Prescription Acne Preparations—Topical
GENERIC TRADE VEHICLE CONCENTRATION SIZE
Retinoids—Topical
Tretinoin Retin-A Cream 0.025%, 0.05%, 0.1% 20 g, 45 g
Gel 0.01%, 0.025% 15 g, 45 g (0.025% only)
Liquid 0.05% 28 mL
Retin-A micro Gel with microsponge 0.04%, 0.1% 20 g, 45 g
50-g pump
Avita Cream 0.025% 20 g, 45 g
Gel 0.025% 20 g, 45 g
Refissa Cream 0.05% 40 g
Tretin-X Cream 0.025%, 0.05%, 0.1% 35 g (kit with cleanser)
Gel 0.025%, 0.1% 35 g (kit with cleanser)
Generic Cream 0.025%, 0.05%, 0.1% 20 g, 45 g
Gel 0.01%, 0.025%, 0.05% 15 g, 45 g
Adapalene Differin Cream 0.1% 15 g, 45 g
Gel 0.1%, 0.3% 15 g, 45 g
Lotion 0.1% 2 oz
Generic Gel 0.1% 45 g
Tazarotene Tazorac Cream 0.1% 30 g, 60 g
Gel 0.1% 30 g, 60 g
Fabior Foam 0.1% 50 g, 100 g
Retinoid Combinations—Topical
Tretinoin–clindamycin Ziana Gel 0.025%/1.2% 30 g, 60 g
Veltin Gel 0.025%/1.2% 30 g, 60 g
1402
Adapalene–benzoyl peroxide Epiduo Gel 2.5%/0.1%, 2.5%/0.3% 45 g
(Continued)
Antimicrobials—Topical
Benzoyl peroxide Benzac AC Gel 2.5%, 5%, 10% 60 g
Wash 2.5%, 5%, 10% 240 mL (2.5%), 226 mL
Benzac W Gel 2.5%, 5%, 10% 60 g
Wash 5%, 10% 226 mL
Benzashave Cream 5%, 10% 113.4 g
Benziq LS Gel 5.25% 50 g
Wash 5.25% 175 g
Brevoxyl Gel 4%, 8% 42.5 g
Creamy wash 4%, 8% 170 g (kit with cleanser)
Tazarotene, also a synthetic retinoid, exerts its action phase II clinical trial with topical minocycline 1% and
through its metabolite, tazarotenic acid, which in turn 4% foam for the treatment of moderate to severe acne
inhibits the RARγ receptor. It is a potent comedolytic has been published and shows promising results.128
agent and has been shown to be more effective than
Salicylic Acid:
::
tretinoin 0.025% gel and tretinoin 0.1% microsphere Salicylic acid is a ubiquitous ingre-
dient found in OTC acne preparations (gels and washes)
Acneiform Disorders
The goal of hormonal therapy is to counteract the such as nausea, weight gain, spotting, breast tender-
Acneiform Disorders
effects of androgens on the sebaceous gland. This ness, amenorrhea, and melasma can occur.
can be accomplished with antiandrogens, or agents Glucocorticoids: Because of their antiinflamma-
designed to decrease the endogenous production of tory activity, high-dose systemic glucocorticoids may
androgens by the ovary or adrenal gland, including be of benefit in the treatment of acne. In practice, their
oral contraceptives, glucocorticoids, or gonadotropin- use is usually restricted to severely involved patients,
releasing hormone (GnRH) agonists. often overlapping with isotretinoin to limit any poten-
Oral Contraceptives: Oral contraceptives can tial flaring from at the start of treatment. Furthermore,
improve acne by four main mechanisms. First, they because of the potential side effects, these drugs are
decrease the amount of gonadal androgen produc- ordinarily used for limited periods of time, and recur-
tion by suppressing LH production. Second, they rences after treatment are common. Prolonged use
decrease the amount of free testosterone by increas- may result in the appearance of steroid acne. Gluco-
ing the production of sex hormone binding globu- corticoids in low dosages are also indicated in female
lin. Third, they inhibit the activity of 5-α reductase patients who have an elevation in serum DHEAS
activity, preventing the conversion of testosterone associated with an 11- or 21-hydroxylase deficiency
to the more potent DHT. Last, progestins that have or in other individuals with demonstrated androgen
an antiandrogenic effect can block the androgen excess. Low-dose prednisone (2.5 mg or 5 mg) or dexa-
receptors on keratinocytes and sebocytes. The third- methasone can be given orally at bedtime to suppress
generation progestins—gestodene (not available in adrenal androgen production.106 The combined use of
the United States), desogestrel, and norgestimate— glucocorticoids and estrogens has been used in recalci-
have the lowest intrinsic androgenic activity.139 Two trant acne in women based on the inhibition of sebum
progestins have demonstrated antiandrogenic prop- production by this combination.143 The mechanism
erties: (1) cyproterone acetate (not available in the of action is probably related to a greater reduction of
United States) and (2) drospirenone. There are three plasma androgen levels by combined therapy than is
oral contraceptives currently FDA approved for the produced by either drug alone.
treatment of acne: (1) Ortho Tri-Cyclen, (2) Estrostep, Gonadotropin-Releasing Hormone Ago-
and (3) Yaz (Table 78-4). Ortho Tri-Cyclen is a tripha- nists: GnRH agonists, such as leuprolide (Lupron),
sic oral contraceptive comprised of a norgestimate act on the pituitary gland to disrupt its cyclic release of
(180, 215, 250 mg)–ethinyl estradiol (35 µg) combina- gonadotropins. The net effect is suppression of ovar-
tion.140 In an effort to reduce the estrogenic side effects ian steroidogenesis in women. These agents are used
of oral contraceptives, preparations with lower doses in the treatment of ovarian hyperandrogenism. GnRH
of estrogen (20 µg) have been developed for the treat- agonists have demonstrated efficacy in the treatment
ment of acne. Estrostep contains a graduated dose of acne and hirsutism in female patients both with and
without endocrine disturbance.144 However, their use
is limited by their side effect profile, which includes
menopausal symptoms and bone loss.
TABLE 78-4
U.S. Food and Drug Administration–Approved Antiandrogens: Spironolactone is an aldo-
Oral Contraceptives for Acne in Women sterone antagonist and functions in acne as both an
androgen-receptor blocker and inhibitor of 5-α reduc-
Ortho Tri-Cyclen (norgestimate + ethinyl estradiol) tase. In dosages of 50–100 mg twice a day, it has been
Estrostep (norethindrone acetate + ethinyl estradiol)
1406 shown to reduce sebum production and to improve
Yaz (drospirenone + ethinyl estradiol)
acne.145 Side effects include diuresis, potential
supported causality. As dermatologists are often on therapy. If the values are normal at 8 weeks, there is no
the front line seeing adolescents at risk for depression, need to repeat the test during the remaining course of
careful screening of adolescents is particularly needed therapy unless there are risk factors. If serum triglyc-
because the risk of depression in this population is 10% erides increase above 500 mg/dL, the levels should be
::
GI symptoms are generally uncommon, but nau- are a reason for interrupting therapy or treating the
sea, esophagitis, gastritis, and colitis can occur. Acute patient with a lipid-lowering drug. Eruptive xantho-
hepatitis is rare, but liver function studies should mas or pancreatitis can occur at higher serum triglyc-
be regularly monitored because elevations in liver eride levels.
enzymes can occur in 15% of patients, sometimes A recent study evaluating the characteristics of lab
necessitating dose adjustments. Elevated levels of abnormalities in 515 patients who underwent isotret-
serum triglycerides occur in approximately 25% of inoin therapy for acne reported clinically insignifi-
patients taking isotretinoin. This elevation, which is cant leukopenia (1.4%) or thrombocytopenia (0.9%),
dose related, typically occurs within the first 4 weeks infrequent transaminitis (1.9%) with the most signifi-
of treatment and is often accompanied by an overall cant elevations occurring with triglyceride (19.3%)
increase in cholesterol with a decrease in the high- and cholesterol (22.8%) levels. Recommendations
density lipoprotein levels. The effect of this transient for otherwise healthy patients with normal baseline
alteration on overall coronary artery health is unclear. labs are to repeat laboratory studies after 2 months
Acute pancreatitis is a rare complication that may or taking isotretinoin therapy, and if results are normal,
may not be related to triglyceride levels. There are no further testing may be required. Routine com-
case reports documenting a potential link between plete blood count monitoring was also found to be
isotretinoin and new-onset or flared inflammatory unnecessary.167
bowel disease (IBD). However, a study that critically The greatest concern during isotretinoin therapy
examined these case reports found no grounds for is the risk of the drug being administered dur-
a causal relationship between isotretinoin use and ing pregnancy and thereby inducing teratogenic
IBD.163 A recent population-based case-control study effects in the fetus.168,169 The drug is not mutagenic;
found that patients with IBD were no more likely its effect is on organogenesis. Therefore, the pro-
to have used isotretinoin than those without IBD.164 duction of retinoic embryopathy occurs very early
Patients with a family history of IBD and those with in pregnancy, with a peak near the third week of
a preexisting IBD should be counseled regarding the gestation.168,169 A significant number of fetal abnor-
possibility of isotretinoin-induced IBD. malities have been reported after the use of isotreti-
Isotretinoin has effects on bone mineralization as noin. For this reason, it should be emphasized that
well. A single course of isotretinoin was not shown isotretinoin should be given only to patients who
to have a significant effect on bone density.165 How- have not responded to other therapy. Furthermore,
ever, chronic or repeated courses may result in sig- women who are of childbearing age must be fully
nificant osteopenia. Osteoporosis, bone fractures, informed of the risk of pregnancy. The patient must
and delayed healing of bone fractures have also been use two highly effective contraception techniques
reported. The significance of reported hyperostosis is such as the use of an oral contraceptive and con-
unclear, but the development of bony hyperostoses doms with a spermicidal jelly. Contraception must
after isotretinoin therapy is more likely in patients be started at least 1 month before isotretinoin ther-
who receive the drug for longer periods of time and apy. Female patients must be thoroughly counseled
in higher dosages, such as for disorders of keratini- and demonstrate an understanding of contraception
zation.166 Serial bone densitometry should be done in techniques before starting isotretinoin. Two forms of
any patient on long-term isotretinoin. Myalgias are contraception should be used throughout the course
the most common musculoskeletal complaint, seen of isotretinoin and for 1 month after stopping treat-
in 15% of patients. In severe cases, creatine phos- ment. No more than 1 month’s supply of isotretinoin
1408 phokinase levels should be evaluated for possible should be given to a female patient so that she can
rhabdomyolysis. be counseled on a monthly basis on the hazards of
desquamation and epidermolysis at higher concen- The most consistent improvement in acne after light
trations,176 with one study of 80 patients reporting treatment has been demonstrated with photodynamic
glycolic acid peels effective at improving comedonal, therapy.191 Photodynamic therapy involves the topical
papulopustular, and nodulocystic acne variants.177 application of aminolevulinic acid (ALA) 1 hour before
::
Salicylic acid is a lipophilic agent that also decreases exposure to a low-power light source. These sources
Acneiform Disorders
corneocyte cohesion and promotes desquamation of include the pulsed-dye laser, intense pulsed light, or a
the stratum corneum. Whereas low concentrations broadband red light source. The topical ALA is taken
of salicylic acid are found in daily acne cleansers, up by the pilosebaceous unit and metabolized to proto-
concentrations of 20% to 30% are typically used for porphyrin IX.192 The protoporphyrin IX is targeted by
superficial peels, and similar to glycolic acid, have the light and produces singlet oxygen species, which
been reported to reduce the number of inflamma- then damage the sebaceous glands.193 Several studies
tory and noninflammatory acne lesions.178 The most using ALA-PDT maintained clinical improvement for
common side effects of chemical peels include ery- up to 20 weeks.194,195
thema, xerosis, exfoliation, burning, and increase in Although lasers are beginning to find a role in the
photosensitivity. treatment of acne, the authors consider them inferior
to the traditional medical treatments. They work by
emitting minimally divergent, coherent light that can
PHOTOTHERAPY AND LASERS be focused over a small area of tissue. The pulsed KTP
laser (532 nm) has demonstrated a 35.9% decrease in
Various forms of phototherapy are under investiga- acne lesions when used twice weekly for 2 weeks.
tion for their use in treating acne vulgaris.179 Ultravio- Although there was no significant decrease in P. acnes,
let (UV) light has long been thought to be beneficial there was significantly lower sebum production even
in the treatment of acne. Up to 70% of patients report at 1 month.196 The pulsed-dye laser (585 nm) can
that sun exposure improves their acne.180 This reported also be used at lower fluences to treat acne. Instead
benefit may be attributable to camouflage by UV radi- of ablating blood vessels and causing purpura, a
ation–induced erythema and pigmentation, although lower fluence can stimulate procollagen production
it is likely that the sunlight has a biologic effect on the by heating dermal perivascular tissue.193 The benefi-
pilosebaceous unit and P. acnes. Although UVB can cial effects of a single treatment can last 12 weeks.197
also kill P. acnes in vitro, UVB penetrates poorly to the Some of the nonablative infrared lasers, such as the
dermal follicle, and only high doses causing sunburn 1450- and 1320-nm laser, have shown to be helpful
have be shown to improve acne.181,182 UV radiation in improving acne.198,199 These lasers work by causing
may have antiinflammatory effects by inhibiting cyto- thermal damage to the sebaceous glands. The concur-
kine action.183 Twice-weekly phototherapy sessions are rent use of a cryogen spray device protects the epider-
needed for any clinical improvement. The therapeutic mis while the laser causes necrosis of the sebaceous
utility of UV radiation in acne is superseded by its car- gland.200 In a pilot study, 14 of 15 patients treated
cinogenic potential.179,184-187 with the 1450-nm laser had a significant reduction in
Other types of phototherapy for acne treatment inflammatory lesions that persisted for 6 months. The
use porphyrins. Treatment of acne with phototherapy 1320-nm Nd:YAG (neodymium-doped yttrium alu-
works either by activating the endogenous porphyrins minum garnet) and the 1540 erbium glass lasers have
of P. acnes or by applying exogenous porphyrins. Cop- also been demonstrated to improve acne.201 Multiple
roporphyrin III is the major endogenous porphyrin treatments are needed with either of these lasers to
of P. acnes. Coproporphyrin III can absorb light at the lessen acne lesions. These treatments tend to be pain-
near-UV and blue light spectrum of 415 nm.188 Irradia- ful and show a gradual modest improvement, limit-
tion of P. acnes with blue light leads to photoexcitation ing their utility.
of endogenous bacterial porphyrins, singlet oxygen One of the newer uses of light for treating acne is
production, and subsequent bacterial destruction.189 A with a photopneumatic device (Isolaz, Solta Medical).
1410 visible light source—blue, red, or both—may be used to This photopneumatic device has a handpiece that
excite the endogenous porphyrins. The high-intensity, applies negative pressure (ie, suction) to the skin and
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