Lippincott Williams & Wilkins; 2014. (6)
assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70:338. (21)
treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71:116. (22)
Lee NP, Arriola ER. Topical corticosteroids: back to basics. West J Med. 1999;171:351. (10)
Tadicherla S et al. Topical corticosteroids in dermatology. J Drugs Dermatol. 2009;8:1093. (13)
American Academy of Dermatology Atopic Dermatitis Clinical Guidelines.
https://www.aad.org/education/clinical-guidelines/atopic-dermatitis-guideline.
National Eczema Association. https://nationaleczema.org/.
COMPLETE REFERENCES CHAPTER 39
DERMATOTHERAPY AND DRUG-INDUCED SKIN
PA: Lippincott Williams & Wilkins; 2014.
Berger TG et al. Pruritus in the older patient: a clinical review. JAMA. 2013;310:2443.
Morley KW, Dinulos JG. Update on glucocorticoid use in children. Curr Opin Pediatr. 2012;24:121.
Lee NP, Arriola ER. Topical corticosteroids: back to basics. West J Med. 1999;171:351.
Giannotti B, Pimpinelli N. Topical corticosteroids. Which drug and when? Drugs. 1992;44:65.
Fisher D. Adverse effects of topical corticosteroid use [published correction appears in West J Med.
1995;162:476]. West J Med. 1995;162:123.
Tadicherla S et al. Topical corticosteroids in dermatology. J Drugs Dermatol. 2009;8:1093.
to use topical corticosteroids. Br J Dermatol. 2008;158:917.
Long CC, Finlay AY. The finger-tip unit—a new practical measure. Clin Exp Dermatol. 1991;16:444.
Long CC et al. A practical guide to topical therapy in children. Br J Dermatol. 1998;138:293.
assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70:338.
treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71:116.
Tollefson MM, Brucker AL. Atopic dermatitis:skin directed management. Pediatrics. 2014;134:e1735.
general population. Arch Dermatol. 1979;115:959.
Herman SM, Vender RB. Antihistamines in the treatment of dermatitis. J Cutan Med Surg. 2003;7:467.
Gupta MA, Guptat AK. The use of antidepressant drugs in dermatology. J Eur Acad Dermatol Venereol.
Lio PA. Non-pharmacologic therapies for atopic dermatitis. Curr Allergy Asthma Rep. 2013;13:528.
psoriasis. J Am Acad Dermatol. 1999;41:546.
Ahmed AM et al. A review of cutaneous drug eruptions. Clin Geriatr Med. 2013;29:527.
Song JE, Sidbury R. An update on pediatric cutaneous drug eruptions. Clin Dermatol. 2014;32:516.
antibiotics. Contact Dermatitis. 1998;39:148.
ear surgery. Clin Otolaryngol Allied Sci. 2002;27:365.
Heine A. Diphenhydramine: a forgotten allergen? Contact Dermatitis. 1996;35:311.
epidermal necrolysis. Dent Clin North Am. 2005;49:67.
Acne is a condition in which the pilosebaceous units of the skin become
plugged and distended, presenting as comedones, papules, pustules, or
Drug therapies work by reducing sebum production, normalizing
keratinization in the pilosebaceous units, reducing Propionibacterium
acnes, or reducing inflammation.
Patients must be counseled that pharmacotherapy works best to prevent
future lesions, not to resolve current ones. Therefore, topical therapies
should be applied regularly to the entire acne-prone area(s), not just to
lesions. Full treatment effect takes time from weeks to months for most
Appropriate choice of vehicle ensures efficacy and tolerability of topical
therapy. Gels should be used in patients with normal to oily skin, and
lotions and creams should be reserved for those with dryer skin types.
Topical retinoids are first-line monotherapy for comedonal acne. They
are also key components of combination therapies in maculopustular
acne and preferred agents to continue for maintenance therapy once
acne is under control. If comedonal acne cannot be controlled with
topical retinoids alone, then salicylic acid or azelaic acid may be used as
Initial treatment for maculopustular acne is a topical retinoid in
combination with topical or oral antibiotics. If treatment with topical
antibiotics is selected, the regimen should also include topical benzoyl
peroxide to reduce the development of antibiotic resistance. Antibiotic
duration should be limited to the period needed to obtain control of acne;
then the retinoid, with or without benzoyl peroxide, should be continued
Antiandrogenic therapies, such as combined oral contraceptives or
spironolactone, are useful alternative treatment options for
maculopustular acne in nonpregnant women.
Oral isotretinoin monotherapy should be used to treat nodular acne. Case 40-5 (Questions 1–6),
Isotretinoin is extremely effective and can induce a lengthy remission of
acne, but the adverse effect profile and the need for laboratory
monitoring preclude use in comedonal or maculopustular acne. The
iPLEDGE risk management program controls isotretinoin distribution to
prevent accidental prescription of this severe teratogen to pregnant
Zits, pimples, whiteheads, and blackheads are all terms commonly used for acne
vulgaris, or simply acne. Acne is a condition in which the pilosebaceous units of the
skin become plugged and distended, presenting as comedones, papules, pustules, or
nodules. Unless otherwise stated, all references to acne in this chapter refer to acne
Acne affects an estimated 9.4% of the world population, including greater than
90% of all adolescents in the United States.
1,2 While teenagers and young adults are
typically afflicted by acne, it can occur at any age. Acne often begins when sebaceous
gland activity increases in association with puberty. Because the onset of puberty has
decreased in recent years, so has the age of acne onset. Acne is now seen as early as
8 to 9 years of age, with peak onset occurring between 16 and 20 years.
to dissipate in most patients by their 30s; however, up to 20% of the patients have
acne persisting into adulthood.
5 There is no known cure for acne, but treatment can
reduce its severity and minimize scarring.
There are four primary mechanisms responsible for acne: (1) increased sebum
production, (2) hyperkeratinization, (3) colonization of Propionibacterium acnes (P.
acnes), and (4) release of inflammatory mediators to the skin. Acne begins with the
overproduction of sebum, often secondary to an increase in androgen levels.
Androgens such as dehydroepiandrosterone sulfate (DHEAS) are metabolized to
dihydrotestosterone (DHT) in the skin, which in turn stimulates sebum biosynthesis.
DHEAS levels rise before puberty and begin to decline in early adulthood.
increase in sebum production triggers keratinization which is the proliferation of
keratinocytes in the follicular epithelial lining. Keratinization increases cell-to-cell
adhesion, interfering with normal desquamation. The cellular debris from
keratinization, in addition to excess sebum accumulation, causes sebaceous follicles
to plug and form undetectable microcomedones. If the superficial portion of the
follicular opening dilates from the pressure of the impaction, an open comedo
(blackhead) forms. The dark color of open comedones is caused by light refraction,
not by dirt; comedo contents are white when expressed.
further inflamed, because as pressure builds from further sebum production and
cellular accumulation, follicular contents can escape to the skin surface.
follicular opening remains narrow and a closed comedo (whitehead) forms,
increased pressure can rupture the follicular wall, with infiltration of foreign matter
into the dermis inciting a marked local inflammatory response. The depth and extent
of this occurrence determine whether a papule, pustule, or nodule results.
Distension in the follicle and increased sebum production allow the gram-positive
anaerobe, P. acnes, to colonize and proliferate. The occupation of P. acnes in the
follicle stimulates the upregulation of cytokines and releases proteases,
hyaluronidases, lipases, and chemotactic factors that attract neutrophils, T cells, and
10 Hydrolytic enzymes released by macrophages may contribute to
weakening of the follicular wall, hastening rupture, and resulting progression of
comedo to inflammatory lesion.
Inflammatory mediators traverse the follicular wall
into the dermis and intensify the inflammatory process even before wall rupture.
Acne presents as comedones or inflammatory papules, pustules, or nodules. (See
Chapter 39, Dermatotherapy and Drug-Induced Skin Disorders.) In severe cases
(acne conglobata), multiple lesions coalesce into abscesses with draining sinus
tracts. Acne lesions generally appear in areas with the highest density of
pilosebaceous units including the face, neck, upper chest, shoulders, and back.
Sunlight and diet may be risk factors for worsening acne, but are controversial.
Ultraviolet light may make sebum more comedogenic, but some of the visible
wavelengths may reduce the follicular bacterial population.
have investigated lower-milk-intake and lower-glycemic-load diets for potential
13 but research on dietary modifications is not yet sufficiently robust to
Risk factors for acne include a family history and increased body mass index.
Worsening of acne has been associated with times of increased stress.
The differential diagnosis of acneiform eruptions includes (a) acne vulgaris, (b)
rosacea, (c) folliculitis caused by gram-negative bacteria, Pityrosporum, or
mechanical irritation, (d) drug-induced acne (acne medicamentosa) such as that
caused by topical or systemic corticosteroids, or by anabolic steroids, and (e)
9,14 Detailed discussions of severe acne variants, such as acne
conglobata and acne fulminans, are beyond the scope of this chapter. In addition,
acne may be secondary to systemic diseases, such as SAPHO (synovitis, acne,
pustulosis, hyperostosis, osteitis) and Apert syndromes.
There is no standard for the grading of acne severity. Initial treatment should be
selected based on patient-specific factors including the presence of comedonal,
maculopustular and nodular acne, which are used in order to guide treatment
decisions. Clinicians may choose to adopt an acne severity scale to assist in the
Treatment is individualized and depends on the clinical presentation of the patient.
The goals of the treatment are to relieve discomfort, improve skin appearance,
prevent scarring, and minimize the psychosocial impact of the condition.
Treatment is largely preventive because little can be done for existing lesions.
Slow improvement over the course of weeks to months is expected for all treatments.
Therefore, treatment regimens should not be modified more often than every 6 to 8
weeks. Although some acne may resolve without residual changes, it is important to
counsel patients that inflammatory acne may result in scaring or hyperpigmentation,
which, while reversible, may take several months to fully resolve. Recognition of the
duration of improvement of these secondary symptoms is important when considering
the efficacy of a medication because patients may not recognize the improvement.
Patients should be counseled on the basic pathophysiology of acne, proper drug
administration or application technique, delay in onset of therapeutic effect, potential
adverse effects of any recommended therapy, and steps to take if adverse effects
occur. Clinical practice guidelines are available. Table 40-1 outlines a general
approach to the treatment of acne.
Nonpharmacologic therapy plays a minimal role in the management of acne. There is
no good evidence to support that acne can be caused or cured by poor hygiene.
Twice-daily washing with warm water and mild facial cleanser may suffice;
however, excessive washing and scrubbing should be avoided. Using harsh cleaners
disrupts the skin barrier encouraging bacterial colonization and the removal of oil
from the skin, which further stimulates its production.
patients must resist squeezing or picking at acne lesions. Drugs known to cause acne,
such as corticosteroids, androgens, and anabolic steroids, should be avoided when
In addition, oil-based cosmetics and other known precipitants should be
avoided. Oil-free, noncomedogenic moisturizers formulated for facial skin can
improve the penetration and tolerability of many topical acne drugs by improving the
skin’s hydration, especially in patients with sensitive skin.
Treatment Selection by Acne Type
Comedonal acne Topical retinoid, azelaic acid
Maculopapular acne Topical retinoid + topical antimicrobial (antibiotic or benzoyl peroxide)
Topical retinoid + oral antibiotic + benzoyl peroxide
Or (additional options for female patients)
Combination oral contraceptive
Dermatologists may use procedures such as surgical comedo extraction, chemical
peels, and microdermabrasion as adjunct therapy to improve cosmetic appearance.
Current guidelines prefer drug therapy to light and laser therapies because there are
less stringent clinical testing for devices versus drugs, concern about long-term
effects of therapies aimed at sebaceous gland function, and the inadequate research
done on light and laser therapies to date.
10 Acne scarring is treated with various
microsurgical techniques such as dermabrasion, laser therapy, chemical peels, and
Available drug therapies exhibit one or more of the following mechanisms: (a)
normalizing follicular keratinization (e.g., retinoids, benzoyl peroxide to some
degree, azelaic acid); (b) decreasing sebum production (e.g., isotretinoin, hormonal
therapies); (c) suppressing P. acnes (e.g., antibiotics, benzoyl peroxide, azelaic acid,
systemic isotretinoin); and (d) reducing inflammation (e.g., antibiotics, retinoids).
examination, you can see several closed comedones on her nose and chin and open comedones dispersed
could be contributing to her acne?
There are several factors that may be contributing to L.Y.’s acne. Mechanical
irritation caused by the sweatband may cause acne mechanica. Increased sweat and
humid conditions encountered while running track can lead to favorable conditions
for the colonization of P. acnes. Finally, it is important to ask L.Y. whether her
makeup is oil based, because oil-based products can be comedogenic.
CASE 40-1, QUESTION 2: What are the treatment options for L.Y.’s acne?
Topical therapies are the most appropriate first-line treatment for comedonal acne.
Options include retinoids, azelaic acid, and salicylic acid.
Retinoids, analogs of vitamin A, normalize keratinization by decreasing horny cell
cohesiveness and stimulating epidermal cell turnover. These actions combine to
unplug follicles and prevent microcomedo formation. Retinoids reduce inflammation
by inhibiting the production of inflammatory mediators. It is important to note that
topical retinoids have no antibacterial properties.
As the most potent comedolytic agents, topical retinoids are preferred therapy in
18 They are also a core component of combination therapies for
maculopapular/pustule acne and a first-line treatment to maintain remission of acne
once it is controlled. Tretinoin, all-trans-retinoic acid, is the naturally occurring form
of vitamin A acid and is a first-generation topical retinoid. It is generally well
tolerated, although it can cause retinoid dermatitis leading to further
hyperpigmentation if used too aggressively in patients with darker skin tones. Starting
at a low dose or using creams over gels can minimize the risk of worsening
22 Alternatively, adapalene, a retinoid-like product, that binds to
specific retinoic acid nuclear receptors can be used. It is generally well tolerated
available and, although effective, is the least tolerated agent in this class.
Topical retinoids and retinoid-like products should be applied once daily at
bedtime to avoid degradation in ultraviolet light.
24 Common adverse effects of this
class include skin irritation, peeling, erythema, and dryness.
depends on the drug concentration and vehicle used. Patients should be counseled to
apply daily sunscreen and gentle moisturizing cream while using these agents.
Patients should be aware that acne might initially worsen during treatment because
Azelaic acid is a dicarboxylic acid that works to normalize keratinization and
indirectly reduces inflammation through suppression of P. acnes.
the 20% strength are indicated for the treatment of acne, whereas the 15% gel,
Finacea, is indicated for rosacea. Although azelaic acid hits several of the pathways
leading to acne formation, the evidence for use is not as robust as other topical
It is applied twice daily to the skin and could be an option for patients who
are unable to tolerate other topical therapies.
Topical salicylic acid works as a concentration-dependent keratolytic agent. It is
commonly reserved for patients with comedonal acne
who cannot tolerate other comedolytic therapies or as augmentation to other therapies
as studies have demonstrated that their effectiveness is less than either topical
retinoids or benzoyl peroxide.
It is typically applied twice daily and is not effective
if soly used as needed. Patients should be cautioned regarding chronic use over large
body surfaces because it increases the risk of percutaneous absorption that could lead
to systemic salicylate toxicity.
CASE 40-1, QUESTION 3: What treatment option is most appropriate for L.Y.?
Topical retinoids are first-line agents for her type of acne. Selection of the specific
topical retinoid is provider-specific and generally depends on what is most
affordable for the patient. Adapalene should be considered for patients with darker
skin tones secondary to the reduced risk for hyperpigmentation. She should be
instructed to apply the product to her entire face every other day for the first 2 weeks
and then advance to daily as tolerated. It is important to let L.Y. know that this is for
routine and not as needed use in order to be effective and that she will need to wait
several weeks before judging its effectiveness. She should apply the product at
bedtime, ideally 30 minutes after washing her face with a mild cleanser, and wash it
off in the morning (or after several hours, if excessive skin dryness or peeling
CASE 40-1, QUESTION 4: What vehicle would you recommend for L.Y.?
L.Y. has slightly oily skin. Therefore using a gel is the vehicle of choice because it
has more drying effects compared to lotions of creams.
QUESTION 1: M.G. is a 27-year-old female who presents to the dermatology clinic with open and closed
manage her acne. What would you recommend M.G. to better manage her acne?
Although topical retinoids are first-line treatment for comedonal acne, some
patients require additional agents to achieve satisfactory results. M.G. should be
instructed to continue adapalene and initiate salicylic acid wash daily. This wash
should be used on her entire face, not just areas with active breakouts, twice daily. It
is important to remind her that it may take several weeks before she sees an effect.
Although P. acnes is part of the skin’s normal flora, under the conditions leading to
acne, it helps transform comedones into inflammatory pustules or papules.
Antibiotics do not resolve existing lesions, but they can prevent future lesions by
decreasing both P. acnes colonization and inflammation. The antibiotics that are most
effective in acne have antioxidant properties. In addition, antibiotics inhibit the
release of reactive oxygen species by P. acnes, which in turn reduces leukocyte
10 Due to this multifactorial mechanism of action, clinical efficacy does
not correlate perfectly with reductions in bacterial load; successful antibiotic courses
do not necessarily eradicate P. acnes.
Topically applied antibiotics avoid systemic exposure and achieve high follicular
concentrations. They can augment topical retinoids when initiating therapy for
comedonal and papular acne cases involving inflammatory lesions, or they can be
added to regimens for patients failing monotherapy. Topical antibiotics alone in acne
treatment should be avoided due to concerns for bacterial resistance.
Topical antibiotics are usually applied once or twice daily for 3 months. Although
rare reports of systemic adverse effects exist, topical effects, such as stinging and
tingling, are the most common adverse effects, and even these occur less frequently
with topical antibiotics compared to other topical therapies.
Doxycycline is most convenient and effective; tetracycline is an alternative.
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