Manual of Dermatologic Therapeutics
7th Edition
© 2007 Lippincott Williams & Wilkins
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1
Acne
R. Sonia Batra
I. Definition and Pathophysiology
Acne vulgaris is a very common, chronic disorder, involving inflammation of the pilosebaceous units that can be varied in presentation and difficult to treat. Acne lesions include comedones, inflamed papules, pustules, and nodules. Acne typically involves areas with the largest number of pilosebaceous glands: the face, chest, and back (1). Most adolescents (80%) experience some acne; however, it may linger into adulthood, particularly in women with hormonal acne flares during the menstrual cycle. Lesions may begin as early as ages 8 to 10 at adrenarche, when androgens of adrenal origin begin to stimulate pilosebaceous units on the face (2). In girls, this may precede menarche by more than a year. Prevalence increases steadily throughout adolescence and then decreases in adulthood. Although girls often develop acne at a younger age than boys, severe disease affects boys 10 times more frequently (up to 15% are involved). Patients with severe cystic acne often have a family history of the same (3).
Neonatal acne or cephalic pustulosis is self-limited with an onset around 2 to 3 weeks of age. Almost one in five newborns is affected by at least mild neonatal acne characterized by erythematous nonscarring papules on the face and neck, most commonly on the cheeks and nasal bridge. This disorder spontaneously resolves within 1 to 3 months. Recent data implicates Malassezia spp. in its pathogenesis (4). Topical 2% ketoconazole cream as well as benzoyl peroxide have been shown to be effective treatments, although parental reassurance alone is often sufficient, given the transient and benign nature of the eruption. Infantile acne (usually at age 3 to 6 months) includes persistent comedones and inflammatory lesions with an increased risk of scarring. Immature infantile adrenal glands lead to elevated dehydroepiandrosterone (DHEAS) levels until the age of 12 months. Boys are more often affected than girls because of additional high testosterone levels between the ages of 6 to 12 months. Infantile acne usually resolves within 1 to 2 years; however, individuals with infantile acne may have more severe teenage acne than their peers. Some of these infants may eventually require systemic isotretinoin. Acne in midchildhood may be a marker for adrenal or gonadal tumors.
A significant increase in adult acne has been observed over the last several decades. A study by Goulden found the prevalence of acne in a group aged 25 to 58 years to be 3% of men and 12% of women. Eighty-two percent of the affected individuals had experienced acne since teenage years and most did not see a decrease until after age 45 (5). In another study by Goulden, 50% of patients with adult acne had a first-degree relative with postadolescent acne; one third of the women had at least one symptom of hyperandrogenism and 37% of the entire group had failed a course of Accutane (6).
The principal factors involved in the pathogenesis of acne are androgen-mediated stimulation of sebaceous glands, abnormal keratinization of the follicular epithelium leading to follicular plugging, proliferation and activity of Propionibacterium acnes within the follicle, and inflammation (7). Severity of involvement often corresponds to the amount of sebum secreted; patients with severe acne will usually have large and active sebaceous glands with prominent follicular openings (“pores”) and oily skin (“seborrhea”). Altered follicular growth and differentiation fosters an environment in which P. acnes proliferates, and the resultant host-immune response to the bacterium with proinflammatory cytokines results in inflamed lesions.
Early-onset acne may be the first sign of an underlying hormonal abnormality, especially if there is an associated advanced bone age and early pubic hair development. Early comedonal acne development is predictive of later, more severe disease. At puberty, hormonal stimuli lead to increased growth and development of sebaceous
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follicles. Female patients with severe acne or evidence of virilization often have abnormally high levels of circulating androgens. Several studies have demonstrated that many female patients with milder forms of acne and no evidence of virilization may still have ovarian and/or adrenal overproduction of androgens. In those patients with normal circulating levels of androgens, there is some evidence that suggests a heightened end-organ responsiveness of the sebaceous glands to androgenic stimulation. This heightened end-organ response may result in increased conversion of testosterone to dihydrotestosterone (DHT) and other 5-α-reduced metabolites or suppressed follicular testosterone metabolism. Male acne patients tend to have higher levels of androstenedione, testosterone, free androgen index, and 11-deoxycortisol (8).
The enlarged gland secretes sebum into a dilated follicle that contains an elevated number of normal cutaneous bacteria. Sebum contains free and esterified fatty acids as well as unsaponifiable lipid components. The anaerobic diphtheroid P. acnes enzymatically produces free fatty acid (FFA) from sebum in the follicle. These FFAs are the primary irritating substances in inflammatory acne. As triglyceride levels rise, so does the population of P. acnes. The bacterium also produces low-molecular-weight peptides, which act as chemoattractants for polymorphonuclear leukocytes. Patients with severe acne demonstrate cell-mediated immunity directed toward P. acnes, and the severity of inflammation is proportional to the anti-P. acnes immunity. In addition, toll-like receptor 2 (TLR-2) has been implicated in acne pathogenesis. TLR-2 is a pattern recognition receptor activated by P. acnes. TLR-2 activates a transcription factor to upregulate the production and release of proinflammatory cytokines including interleukin-12 (IL-12) and IL-8 from monocytes. TLR-2 is expressed on inflammatory cells around the pilosebaceous unit in patients with acne, and its expression increases as the acne lesion becomes older and more inflamed (9). Attraction and killing of leukocytes by comedonal components, the resultant inflammatory cascade, and specific immunologic events probably contribute to the final appearance of an inflammatory acne lesion.
Disordered shedding of the cells that line sebaceous follicles is another factor in the pathogenesis of acne lesions. Sticky desquamating horny cells are retained in the follicular orifice, and the dilated opening becomes plugged by entrapped sebum forming a closed comedo (“whitehead”). If this comedonal mass protrudes from the follicle, it is recognized as an open comedo (“blackhead”). The dark color is due to oxidized lipid, melanin, or densely packed keratinocytes and bacteria, and not dirt. As hydrolytic enzymes released from polymorphonuclear leukocytes induce follicle walls to leak or rupture, sebum (with its irritant and chemoattractant factors), keratin, bacteria, and hair are released into the dermis and result in an inflammatory mass (papule, “pimple,” pustule, nodule, cyst, and/or abscess). Activation of the classic and alternative pathways of complement by P. acnes enhances the inflammation. Experimentally, follicular hyperkeratosis is induced by IL-1 α and epidermal growth factors; isotretinoin inhibits this process.
Most acne papules or pustules result from the rupture of an intrafollicular microcomedo rather than a visible one. Patients with large numbers of comedones usually have only small numbers of inflammatory lesions, whereas patients with severe cystic acne usually have few comedones. In adult life, the cells lining the follicle presumably become less susceptible to comedogenic materials. Spontaneous resolution of acne may also be related to a decreased dermal reactivity to irritant substances.
As many as one third of adult women are affected by a low-grade acneiform eruption that may start de novo or merge imperceptibly with preexisting adolescent acne. The eruption may be induced by chronic exposure to comedogenic substances such as isopropyl myristate, cocoa butter, and fatty acids present in some creams and moisturizers, by androgenic stimuli from progestins present in some oral contraceptives, by recent cessation of oral contraceptives, or by unknown causes.
Inflammatory acne may yield both scarring and pigmentary changes. Early treatment is essential to prevent and minimize the cosmetic disfigurement associated with acne scarring. Adequate therapy will, in all cases, decrease its severity and may entirely suppress this disease. However, if left alone, most inflammatory acne tends to disappear slowly in the early twenties in men and somewhat later in women. Permanent pitted or nodular hypertrophic scars may result.
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II. Subjective Data
  • Acne has a significant impact on the patient’s self-image and quality of life, and the psychological toll of acne may be comparable to that of asthma or epilepsy (10). Even clinically mild acne may cause considerable social embarrassment to the patient. As with all medical and psychological conditions, the patient’s perception of the severity of the problem is an important factor in choosing treatment. Decisions by the physician about the severity of objective disease and therapeutic plans must be evaluated in this context.
    A quality of life scale has been developed specifically for the patient with acne (11). Respondents answer on a grade of 0 to 3 to what extent they have experienced each item. The scale may be used to help the clinician evaluate the relationship between acne severity and psychosocial impact and morbidity, especially among mild to moderately affected patients for whom quality of life issues are often a major consideration in deciding whether to institute therapy.
    • Feeling self-conscious in the presence of others.
    • Decrease in your socialization with others.
    • Difficulties in your relationships with your spouse or partner.
    • Difficulties in your relationships with your close friends.
    • Difficulties in your relationships with your immediate family.
    • Feeling like an “outcast” most of the time because of the effect of acne upon your appearance.
    • People making fun of your appearance.
    • Feeling rejected in a romantic relationship because of the effect of acne upon your appearance.
    • Feeling rejected by your friends because of the effect of acne upon your appearance.
  • Inflammatory lesions of acne may itch as they erupt and may be very painful or tender.
III. Objective Data (See color insert)
  • Noninflammatory lesions. The initial lesion is the closed comedo; visible as a 1- to 2-mm white bump (whitehead) most easily seen when the skin is stretched. If follicle contents extrude, a 2- to 5-mm, dark-topped, open comedo (blackhead) results.
  • Inflammatory lesions. Erythematous papules, pustules, cysts, and abscesses may be seen. Patients with cystic acne also tend to show “double,” or polyporous comedones, which result from prior inflammation during which epithelial scarring caused fistulous links between neighboring sebaceous units. Acne lesions are seen primarily on the face, but the neck, chest, shoulders, and back may be involved. One or more anatomic areas may be involved in any given patient, and the pattern of involvement, once present, tends to remain constant.
  • The skin, scalp, and hair are frequently oily.
  • Pustules and cysts often rupture spontaneously and drain a purulent and/or a bloody but odorless discharge.
IV. Assessment
Several points regarding etiology or therapy should be considered with each patient:
  • Are endocrine factors important in this patient? Sudden onset of acne, treatment-resistant acne, and acne associated with signs of androgenism should lead one to suspect an endocrine abnormality.
    • Is the acne accompanied by irregular menstrual periods or concomitant hirsutism? Stein–Leventhal syndrome, Cushing’s syndrome, 21-hydroxylase deficiency, and other endocrinopathies are frequently accompanied by acne. Polycystic ovarian syndrome is defined by menstrual irregularities, acne, pelvic ultrasound imaging of subcapsular ovarian cysts, and an elevated luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio (a level greater than 2 to 3 is suggestive). The testosterone elevations are modest in the range of 80 to 150 ng/dL.
      Men and women with mild to severe cystic acne, especially those who do not respond to conventional therapy, may have elevated plasma-free testosterone and/or DHEAS levels. Hyperandrogenism is associated with acne, hirsutism, alopecia, and menstrual irregularities; other possible findings include infertility,
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      deepening of the voice, increased libido, acanthosis nigricans, insulin resistance, type 2 diabetes mellitus and dyslipidemia. DHEAS elevations above 8,000 ng/mL suggest the presence of an adrenal tumor; a range of 4,000 to 8,000 ng/mL is indicative of congenital adrenal hyperplasia. Testosterone elevations point to an ovarian dysfunction, with levels of 150 to 200 ng/dL suggesting an ovarian tumor. Oral contraceptives can mask an underlying endocrine disorder, so testing should be done 1 month after the discontinuation of exogenous hormones. Women may have high normal levels of DHEAS and testosterone and may benefit from hormonal therapy. Postmenopausal acne occurs in dark-complexioned women with previously oily skin, with the development of small closed comedones at the periphery of the face; unopposed adrenal androgens are the presumed cause.
    • Is there a premenstrual flare-up? Premenstrual flares of acne are associated with a narrowing of the sebaceous duct orifice between days 15 and 20 of the menstrual cycle. This can lead to duct obstruction and resistance to the flow of sebum. Many women tend to do well on anovulatory drugs.
    • Is the patient on oral contraceptives, or has she stopped taking these pills within the past few months? When were the pills started? Which ones? Acne may be associated with oral contraceptive pills if recently started or discontinued and if composed of an androgenic progesterone. During the first two or three cycles on oral contraceptives, acne may worsen. Post-pill acne may continue for as long as a year after birth control pills are stopped. Although anovulatory drugs may provide excellent therapy for acne, the various pills differ enormously in their effect on the sebaceous gland (see sec. V.C.2). Oral contraceptives that contain the androgenic and antiestrogenic progestogens norgestrel and norethindrone acetate may actually provoke an acneiform eruption.
  • What is the effect of seasonal changes? Is sunlight beneficial? Has the patient recently been in a hot and humid environment? Most patients find that summer sunlight will diminish the activity of their acne. However, very humid environments or heavy sweating will lead to keratin hydration, swelling, decrease in the size of the sebaceous follicle orifice, and partial or total duct obstruction. Therefore, it is not always good advice to “get out into the sun,” except in a dry climate. A small number of people with excessive sunlight exposure will develop an acneiform papular eruption related to abnormal follicular keratinization (“Mallorca,” miliary, actinic acne). In addition, many sunscreens are comedogenic; facial formula and gel-based sunscreens are recommended.
  • Does the patient have occupational or other exposure to chemicals? Exposure to heavy oils, greases, polyvinyl chloride, chlorinated aromatic hydrocarbons, and tars can cause acne. These occlusive comedogenic agents will initiate lesions, as can some greasy substances used for hair care (pomade acne). Certain oily or greasy cosmetics and creams can also exacerbate acne.
  • Does the patient wear occlusive or tight clothing or have any habits that will initiate or aggravate the disease? Mechanical trauma (pressure, friction, rubbing, squeezing) from clothing or athletic wear or from behavioral habits will also cause lesions. For example, an individual with the habit of cradling the chin in his or her hand may develop unilateral lesions at that site.
  • Has the patient been on any medications known to cause acne? The most prominent among these are corticosteroids, adrenocorticotropic hormone (ACTH), phenytoin, androgens, anabolic steroids (danazol and testosterone), iodides, and bromides. Other possible stimuli include trimethadione, isoniazid, lithium, halothane, vitamin B12, cobalt irradiation, and hyperalimentation therapy. Drug-induced acne often presents as an abrupt, monomorphous eruption of inflammatory papules (12).
  • Is the acne of rapid onset and associated with fever and leukocytosis (acne fulminans)? Is a destructive arthropathy present, resembling rheumatoid arthritis (acne arthropathy)? SAPHO syndrome consists of synovitis, acne, pustulosis (palmar-plantar, pustular psoriasis), hyperostoses, and osteitis; this is considered one of the spondylarthropathies and has been reported with inflammatory bowel disease and pyoderma gangrenosum. The PAPA syndrome, an autosomal dominant disorder, consists of pyogenic sterile arthritis, pyoderma gangrenosum, and acne (13).
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  • How has the patient’s acne been treated in the past? Have antibiotics been used? If so, what were the instructions, dosage, duration, and effect of these therapies? Was tetracycline inadvertently taken with meals instead of on an empty stomach? Was the dosage adequate? (see sec. V.C.1.)
    There is an increased incidence of bacterial resistance of both P. acnes and coagulase-negative Staphylococcus aureus noted after long-term antibiotic use. These resistant bacteria are found in both the patients and their close contacts. P. acnes resistance to antibiotics should be considered in treatment failures. This is seen particularly with erythromycin; but cross-resistance can occur with clindamycin. Multiple antibiotics should not be used at the same time and benzoyl peroxides should be added as a second agent to help minimize this possibility. The highest possible dose of an oral antibiotic should be started for as short a course as possible. Oral minocycline has the lowest risk for bacterial resistance over time. Oral isotretinoin reduces the total number of resistant P. acnes.
    An unusual complication of chronic broad-spectrum antibiotic therapy is the development of a gram-negative folliculitis. Such patients will notice a sudden change in their acne, with the appearance of pustules or large inflammatory cysts that, on culture, usually grow Proteus, Pseudomonas, or Klebsiella species. Because acne cysts are sterile on routine bacteriologic culture, a sudden change in morphology warrants Gram’s stain and culture of cyst/abscess contents (see Chap. 4). This condition is treated with the appropriate antibiotic or systemic isotretinoin. Gram-negative folliculitis can develop in individuals who have not been on oral antibiotics and may be associated with impaired immune function.
  • Is there any effect from stress or emotional upsets on acne activity? An acutely stressful situation may cause acne to flare (14). Are there shallow erosions covered by a serous crust? Excoriated acne (acne excoriee), especially in young women, may be confused with impetigo.
  • The number and type of lesions should be roughly quantified to assess further therapeutic responses.
V. Therapy
  • Mild involvement (few to many comedones)
    • Bacteriostatics are thought to improve acne by decreasing the formation of harmful by-products, but not necessarily the actual number, of P. acnes bacteria. These agents can be applied twice daily to the point of mild dryness and erythema but not discomfort.
      • Benzoyl peroxide (see also Chap. 40, Acne Preparations, sec. II.F) has a potent bacteriostatic effect with a reduction of P. acnes within 2 days and a reduction in lesion count after 4 days of application. Benzoyl peroxides decrease the likelihood of bacterial resistance and should be a mainstay of every acne program, if tolerated. It is hypothesized that this agent is decomposed by the cysteine present in skin, after which free-radical oxygen is capable of oxidizing proteins in its vicinity. These proteins include the bacterial proteins of the sebaceous follicles, thereby decreasing the number of P. acnes and consequently the amount of FFAs. Topical 5% benzoyl peroxide lowers FFAs 50% to 60% after daily application for 14 days and decreases aerobic bacteria by 84% and anaerobic bacteria (primarily P. acnes) by 98%. Benzoyl peroxide will also reduce the size and number of comedones present and may inhibit sebum secretion. Contact sensitivity is observed in 1% to 3% of patients. Benzoyl peroxides can bleach the color out of clothing.
        • Benzoyl peroxide products include preparations such as clear aqueous gel (Desquam-X Desquam-E); clear alcohol gel (Benzagel, PanOxyl); clear oil-based lotion (Benoxyl); Brevoxyl in a regular and creamy base; and a glycerin and glycolic acid containing product (Triaz). Numerous other prescriptions and over-the-counter benzoyl peroxide products, ranging in strength from 2.5% to 10.0%, are also available. The 2.5% formulation is therapeutically equivalent to the 5% and 10% concentrations and induces less irritation. Patients with lesions of the chest and back may find the use
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          of a benzoyl peroxide wash easier (Desquam-X, 5% and 10%; Benzac A-C, 5% and 10%; Brevoxyl, 4% and 8%; Triaz, 3%, 6%, and 9%).
      • Topical antibiotics (see also Chap. 40, Acne Preparations, sec. II.G) may affect acne lesions by their bacteriostatic action or because of suppressive effects on the inflammatory response. Papular and pustular lesions respond best; the activity of comedonal or cystic acne may not be altered. Resistant organisms may emerge after continued therapy; combination therapy with benzoyl peroxide minimizes this risk. All topical antibiotics are applied twice daily.
        • Clindamycin phosphate is available in 1% concentration in a hydroalcoholic vehicle (30 or 60 mL) as a gel or lotion. Although the drug has not been detected in the blood after topical use, its detection in the urine suggests that 4% to 5% of topically applied clindamycin is absorbed. There have been two reports of pseudomembranous colitis after topical use of clindamycin hydrochloride. Patients with inflammatory bowel disease should avoid topical clindamycin use, and all patients should be warned to discontinue therapy if intestinal symptoms occur. Products that combine clindamycin with benzoyl peroxide include Benzaclin and Duac.
        • Erythromycin base applied topically is effective and nonsensitizing. It is available as 1.5% solution (Staticin, 60 mL); 2.0% solution (EryDerm, 60 mL, A/T/S, 60 mL, Emgel, 60 mL); 2% pledgets (Erycette, T-Stat pads); 2% ointment (Akne-Mycin); or a combination 3% erythromycin and 5% benzoyl peroxide gel (Benzamycin).
        • Sulfacet R and Novacet have a combination of sodium sulfacetamide (an antibacterial agent) and sulfur (a comedolytic agent). These products can help decrease the redness of skin lesions, and Sulfacet comes with a skin tint to help cosmetically cover lesions.
        • Klaron lotion contains sodium sulfacetamide without sulfur. The solution is a water-based gel, and it is a good choice for sensitive skin. All sulfur-based products are contraindicated in patients with a sulfonamide allergy.
      • Salicylic acid is a β-hydroxy acid that penetrates into the sebaceous gland and has comedolytic and anti-inflammatory properties. It can be used as an adjunctive therapy and is found in cleansers, toners, masks, and peels. Its side effects include erythema and scaling.
      • Aluminum chloride hexahydrate (6.25% Xerac A-C) is an effective antiperspirant that has also an antibacterial effect. It may be useful in cases of acne in which sweating is prominent or appears to be aggravating the disease, but its effects have not been well studied.
      • Azelaic acid is a dicarboxcylic acid that has antimicrobial, anti-inflammatory, and comedolytic activity, and it is relatively nonirritating. It is available as a cream (Azelex) or gel (Finacea) formulation. Azelaic acid may help lighten postinflammatory hyperpigmentation and is a good choice for ethnic or pigmented skin. It is not a photosensitizer and so far shows minimal tendency for bacterial resistance. This drug works best when combined with other topical preparations, for example, benzoyl peroxides or retinoids.
      • Clinac OC, indicated for oily skin, is an over-the-counter copolymer that absorbs 20 times its volume of sebum. It is applied one to three times per day, depending on the degree of oiliness. Clinac is also available in combination with benzoyl peroxide, Clinac-BPO.
      • Although the administration of systemic antibiotics will reduce comedo formation in experimental animal systems, these drugs play no role in the therapy of the usual patient with comedonal acne.
    • Exfoliants. These agents, such as elemental sulfur, resorcinol, and abrasives, produce irritation and consequent peeling and exfoliation. Not all topical irritants have the property of decreasing the presence or formation of new comedones. Most of these are a source of additional injury to already inflamed skin and may be ineffective in removing deeply rooted comedones.
      • Topical exfoliants and irritants. Clear gels or lotions (Novacet); tinted creams (Sulforcin); tinted lotions (Liquimat).
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  • Mild or moderate involvement (few to many comedones, some papules and/or pustules)
    • Benzoyl peroxide gel.
    • Retinoids are one of the most effective groups of drugs for acne that help in correcting the abnormal desquamation of the follicles that leads to the formation of microcomedones. There are now three topical retinoids available in the United States. A small percentage of patients may experience a pustular flare of their acne in the first few weeks of topical retinoid therapy, a transient effect that is indicative of the effectiveness of therapy. The risk of teratogenicity with topical retinoid application is minimal. Tazarotene is labeled as Category X, on the basis of its indication for psoriasis when larger areas with an altered skin barrier are treated. Tretinoin and adapalene are Category C. All the three drugs recommend minimizing exposure to sunlight and sunlamps because of an increased susceptibility to burning, likely secondary to the thinning of the stratum corneum.
      • Tretinoin (trans-retinoic acid; vitamin A acid) first became available 25 years ago. The irritant effects of tretinoin sometimes limit its usefulness, but these can be minimized by the correct method of application. Tretinoin, which does not function as a vitamin in its therapeutic applications, increases epidermal cell turnover and decreases the cohesiveness (“stickiness”) of horny cells, thereby inhibiting the formation of comedones while helping existing comedones to loosen and be expelled. Tretinoin not only changes follicular keratinization but also decreases the number of normal cell layers of the stratum corneum from 14 to 5. This decrease in the thickness of the barrier layer may potentiate the penetration of other topical agents.
        • Tretinoin products. Retin-A cream, 0.1%, 0.05%, or 0.025%; Retin-A liquid, 0.05%; Retin-A gel, 0.01% or 0.025%; Retin-A micro gel, 0.1% or 0.04%; Avita, 0.025% cream or gel. Retin-A micro, a viscous yellow gel, contains porous microspheres that release tretinoin more slowly over time, thereby making it less irritating while having the same efficacy. Patients may notice a fine white residue if they overapply this product.
          Avita uses a large polymer compound, polyolprepolymer-2 (PP-2), to create a reservoir of the drug in the upper layers of the skin and the sebaceous glands delivering the drug over 12 to 24 hours.
      • Adapalene (Differin 0.1% cream, gel, solution, and pledgets) is a derivative of naphthoic acid and a selective retinoic acid analog. This product is not degraded by sunlight, is not phototoxic, and is compatible with benzoyl peroxide application at the same time. When compared with topical tretinoin 0.025% gel, there is a lower incidence of cutaneous irritation and it compares favorably in the reduction of both inflammatory and noninflammatory lesions. This effect may be secondary to its more selective binding, increased lipophilic properties, and follicular penetration. This is a good first-line therapy in colder climates or in patients with sensitive skin.
      • Tazarotene (Tazorac gel/cream, 0.05%, 0.1%, Avage Cream, 0.1%) is a potent selective retinoid that binds to the retinoic acid receptors, RAR-β and RAR-γ. This drug is converted in the epidermis to its active metabolite tazarotenic acid and was originally developed for the treatment of psoriasis. Tazorac is a category X drug and must be avoided in pregnancy. This drug can be irritating and should be avoided in patients with sensitive skin or seborrheic dermatitis. The 0.1% gel is more effective than the 0.05% concentration; however, starting with the 0.05% concentration may decrease the irritation. Some investigators advocate short-contact therapy, such as 1- to 5-minute exposures every other night, especially for patients with resistant comedones. Treatment time can be gradually increased to overnight. Twice-daily short-contact therapy can be tolerated in the individual with an oilier complexion. This product is not degraded by sunlight.
    • Instructions for use—Retinoids. The cream base is preferred for dry skin and the gels are preferred for oily skin. Easily irritated skin should be started with adapalene (Differin) cream 0.1%, tretinoin 0.025% cream or 0.01% gel, Retin-A
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      Micro 0.04% gel or Avita; others may start at higher strengths. The strength of the product may be gradually increased once the patient has become tolerant of the weaker formulation.
      • Apply sparingly every other night to the entire face except around the eyes, lips, and neck. After 2 to 3 weeks, if no excess irritation, erythema, dryness or scaling is noted, increase to every night. For tretinoin, apply before bedtime on thoroughly dry skin—wait for at least 45 minutes after the face has been washed. Tazarotene is best applied over or several minutes after the application of a moisturizer at bedtime.
      • Use mild, gentle soaps not more than twice daily.
      • Avoid excessive exposure to sun. Use sunscreens.
      • Use water-based cosmetics if necessary.
      • Expect mild redness and peeling within a week, lasting 3 to 4 weeks, and a flare-up in the acne during the first 2 to 4 weeks. This is explained as the surfacing of lesions onto the skin.
      • Clearing requires approximately 3 months. Inflammatory lesions improve more rapidly, but comedones take longer. Effectiveness cannot be judged before 8 weeks and is best assessed at 12 weeks.
      • Continue retinoid application after the lesions clear.
      • Apply less frequently if the daily use of the retinoid cannot be tolerated—for example, every other night or skipping every third night.
      • Although there is negligible systemic absorption of topical retinoids, this agent should be discontinued if pregnancy is suspected. Cases of neurologic toxicity and ear malformation have been reported.
    • Combined retinoid-bacteriostatic therapy. With this mode of therapy, the retinoid prevents or removes comedones, whereas benzoyl peroxide or topical antibiotic eradicates P. acnes. The retinoid also enhances absorption of the other product. Irritation reactions limit the use of this combination therapy.
      • Instructions for use.
        • Apply retinoid cream or solution in the evening/bedtime, as with retinoid alone.
        • Apply benzoyl peroxide gel or topical antibiotic in the morning.
        • After clearing, decrease frequency of therapy and concentration of medication.
        • If using tretinoin, apply the agents at different times, not simultaneously. Mixing the highly unsaturated tretinoin with reactive oxidants such as benzoyl peroxide destroys both chemicals.
  • Moderate or severe involvement (inflammatory papules, pustules, cysts, abscesses, and/or scarring). Use topical therapy as discussed previously, plus antibiotics.
    • Antibiotics. Some systemic antimicrobials suppress the growth of normal cutaneous flora (primarily P. acnes). As bacteria are decreased and the FFA level slowly diminishes, inflammatory lesions decrease and new lesions stop appearing within 2 to 6 weeks. The beneficial effects of antibiotics may be multifold. Not only are the number of bacteria and FFA levels decreased but antibiotics useful in acne therapy also directly interfere with local chemical and cellular inflammatory mechanisms. Tetracycline, erythromycin, and clindamycin have been shown to inhibit leukocyte chemotaxis and other neutrophil inflammatory functions and may also directly inhibit extracellular lipases responsible for the generation of inflammatory compounds. Antibiotic therapy cannot be truly evaluated until 6 to 8 weeks after starting. Antibiotic levels in sebum are not detectable until approximately 7 days after treatment has started, and, in addition, lipid formed in basal cells of sebaceous follicles may require 1 month to reach the skin surface. Although sebum composition changes, the rate of secretion remains constant; therefore, skin may remain oily. Therapy may need to be continued for several months. The overall incidence of bacterial resistance has increased from 20% noted 20 years ago, to 62% in 1996 (15). The full antibiotic dose should be utilized, and it is controversial whether to taper the oral antibiotics or to stop with no taper. Tapering may allow resistant organisms to grow more
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      readily. Long-term use of antibiotics likely contributes to the pool of resistant organisms.
      Female patients should be counseled that oral antibiotics might decrease the effectiveness of oral contraceptives, although one study showed a failure rate of only 1% to 3% with the combination of oral antibiotics and oral contraceptives (16). In addition, a recent report found that increasing cumulative days of antibiotic use may be associated with an increased risk of breast cancer in women (17). The risk was highest in women on macrolide, tetracycline, and cephalosporin classes of antibiotics, and for durations >500 days. Although the data is limited, this finding indicates that reliance on systemic antibiotics should be limited and long-term maintenance therapy should focus on topical regimens or other medications.
      • Tetracycline is often the first antibiotic prescribed. It is the least expensive, has few side effects, and is well tolerated for longer periods of time. Tetracycline is effective in low doses because high concentrations are achieved within sebaceous follicles, especially when inflammation is present.
        Apart from minor gastrointestinal tract irritation, Candida vaginitis is a common complication. Although tetracycline can cause enamel hyperplasia and hence tooth discoloration, by age 12, growth of teeth is essentially complete. Tetracycline should neither be used in younger children nor be administered during pregnancy. There is drug interaction with the metallic ions Al3+, Mg2+, and Ca2+ present in antacid preparations and dairy products; these products should never be taken at the same time as tetracycline. Pseudotumor cerebri is an uncommon adverse reaction from tetracycline. The duration of treatment can be from 2 weeks to 10 months. The presenting symptoms are usually headache, nausea, vomiting, and double vision. With a timely diagnosis, the increased intracranial pressure will resolve.
        Initiate therapy at 250 mg q.i.d. (or 500 mg b.i.d.) taken on an empty stomach (half hour before meals or 2 hours after) until there is clear improvement; then, decrease the dosage to a maintenance level (250 to 500 mg/day) or eliminate it. If inflammatory lesions have not subsided after 4 to 6 weeks, increase the dose to 1.5 g/day for 2 weeks, and if necessary to 2 g/day for several weeks to induce remission in otherwise unresponsive patients. Once remission is achieved, it is almost always possible to decrease the dosage to a lower level.
      • Erythromycin, 1 g/day, is also effective in the treatment of acne. The same dose and time responses noted for tetracycline also apply for this drug. Forty percent of P. acnes organisms are resistant to erythromycin. Combination with topical benzoyl peroxide helps decrease the bacterial resistance. Elevated liver function tests (LFTs) and reversible hepatotoxicity have infrequently been reported.
      • Minocycline (Minocin, Dynacin, Vectrin) is a useful but expensive antibiotic in patients unresponsive to other antibiotics. It is overall the most effective antibiotic available to treat acne, but it can have serious side effects. This antibiotic is very lipid soluble and penetrates the sebaceous follicle more effectively; it is well absorbed, even with meals. Owing to its highly lipophilic nature, it crosses the blood–brain barrier and can precipitate pseudotumor cerebri syndrome. The duration of therapy can be a week to a year, with the most common presenting symptoms being headache, visual disturbances, diplopia, pulsatile tinnitus, nausea, and vomiting.
        Because minimal amounts of minocycline remain in the gut, the frequency of Candida vaginitis is less than in those taking tetracycline. Most tetracycline-resistant bacteria are sensitive to minocycline at a dose of 100 mg b.i.d. Dizziness, nausea, and vomiting may be a problem if full doses are administered initially. Start at 50 mg/day and slowly increase to as much as 100 mg b.i.d. Some patients may eventually achieve complete control on 50 mg/day.
        Minocycline may cause a blue discoloration of acne cysts or sites of trauma; this discoloration usually does not appear until 8 months of therapy with a total cumulative dose of 70 g and is usually reversible after
        P.12

        discontinuation of the drug. Once a cumulative dose of 100 g is reached, alternative therapies should be considered. Cases of autoimmune hepatitis, serum sickness-like reactions, pulmonary infiltrates with eosinophilia, and a syndrome similar to drug-induced lupus (DIL) have been reported secondary to minocycline. For DIL, the duration of time ranged from 6 weeks to 2 years after starting antibiotics; patients had a positive antinuclear antibody (ANA) but negative antibodies to DNA. All symptoms resolve with discontinuation of the drug. The estimated risk is an 8.5-fold increase from controls, an absolute risk of 52.8 cases/100,000 prescriptions (18). If long-term minocycline is taken (i.e., >2 years) periodic LFTs and ANA levels may be warranted. A personal or family history of systemic lupus erythematosus (SLE) or underlying liver and/or kidney disease may be relative contraindications to the use of this drug.
      • Doxycycline (Vibramycin, Monodox) has similar absorption and duration-of-activity characteristics. Its effectiveness in acne approaches that of minocycline, when used in the same fashion with similar dosages. Early data suggests that subantimicrobial doses of doxycycline, 20 mg (Periostat), may play a therapeutic role in acne by reducing inflammation through anticollagenolytic, antimatrix-degrading metalloproteinase, and cytokine downregulating properties (19). Patients taking doxycycline must be warned to avoid excessive exposure to sunlight because of the photosensitivity that accompanies the use of this drug.
      • Clindamycin (Cleocin), 300 to 450 mg/day, is an extremely effective agent for acne. However, the risk of pseudomembranous colitis limits its systemic use to only very severe cases that are unresponsive to all other modes of therapy.
      • Trimethoprim-sulfamethoxazole (Bactrim, Septra) has also been shown to decrease FFA levels and inhibit inflammatory acne. Trimethoprim is very lipophilic, which enhances follicle penetration. Start with one double-strength tablet at bedtime; up to two tablets/day may be used. A high rate of allergic reactions limit its use. Neutropenia may occur on long-term therapy, and a baseline complete blood count (CBC) with intermittent monitoring is recommended. Toxic epidermal necrolysis (TEN) is unlikely to occur after the first month of therapy. Cases of hepatic necrosis and aplastic anemia have also been associated with this drug.
      • Trimethoprim (Proloprim, Trimpex), 300 mg b.i.d., used alone, is an effective alternative therapy.
      • Cephalosporins may be useful in patients resistant to other antibiotics.
      • Ampicillin may also be helpful in certain patients, particularly pregnant women with acne, for whom the use of tetracycline, erythromycin, and minocycline should be avoided. In resistant acne patients, culture may reveal a gram-negative bacteria responsive to ampicillin.
      • Azithromycin in a 500-mg dose three times a week has been shown to yield a 60% reduction in inflammatory papules in 83% of patients enrolled in a 12-week study (20). There is no associated pseudotumor cerebri and, therefore, it can be used for an acne flare during early Accutane therapy.
      • Some reports suggest that nonsteroidal anti-inflammatory agents such as indomethacin or ibuprofen may exert an additive beneficial effect when given with oral antibiotics.
    • Sebaceous gland suppression
      • Oral contraceptives (estrogen given as an anovulatory agent) may be of use in unresponsive cases in young women after more conventional regimens have failed. If a patient with acne is already taking anovulatory agents for contraception, an effort should be made to use a formulation known to alleviate, rather than exacerbate, acne. Most or all the estrogen effect is the result of adrenal and androgen inhibition rather than local suppression at the gland site; small doses of androgen can overcome the sebum-suppressive effects of large doses of estrogen in women as well as in men. There is a direct correlation between the degree of sebaceous gland inhibition and acne
        P.13

        improvement. The gland, however, responds variably to estrogen suppression. On average, there will be a decrease of 25% in sebum production on administration of 0.1 mg ethinyl estradiol. This drug and its 3-methyl ether, mestranol (which has two thirds the potency of ethinyl estradiol), are the estrogens present in oral contraceptives. All combination birth control pills are antiandrogenic because they reduce free testosterone, testosterone conversion to 5-α-androstanediol, and sex hormone–binding globulin. With combination therapy, it is important to use a pill with adequate estrogenic effect linked with nonandrogenic progesterones such as drospirenone, desogestrel, norgestimate, northindrone, and ethynodiol diacetate. Drospirenone is a new progestogen with antimineralocorticoid, progestogenic, and antiandrogenic activity. Patients may exhibit a difference in the tolerability of side effects between the various progestational agents. If a patient has been taking an oral contraceptive with minimal side effects, the clinician does not need to change the pill unless there appears to be a correlation with worsening of acne.
        • The preferable pills are Yasmin (3 mg drospirenone, 0.03 mg ethinyl estradiol), Desogen and OrthoCept (0.15 mg desogestrel, 0.03 mg ethinyl estradiol), Orthocyclen, or Ortho Tri-cyclen (0.25 mg norgestimate, 0.035 mg ethinyl estradiol), Alesse (0.1 mg levonorgestrel, 0.02 mg ethinyl estradiol), Ovcon 35 (0.4 mg norethindrone, 0.035 mg ethinyl estradiol), Brevicon (0.5 mg norethindrone, 0.35 mg ethinyl estradiol), Modicon (0.5 mg northindrone, 0.035 mg ethinyl estradiol), or Demulen (0.05 mg ethinyl estradiol, 1.0 mg ethynodiol diacetate), in decreasing order of effectiveness.
          Decrease in acne should be noted within 3 months and marked improvement should be noted within 4 months of administration. The progestational agent norgestrel and norethindrone acetate should be avoided (Ovral, Ovrette, Lo-ovral, Loestrin). Estrogen therapy is rarely needed before age 16, after which time there will be no problem with growth retardation.
        • Prednisone 2.5 to 7.5 mg, administered at night or dexamethasone 0.25 to 0.75 mg are useful in female patients, with severe acne unresponsive to conventional therapy, who suffer from adrenal gland overproduction of androgens such as congenital adrenal hyperplasia. Dexamethasone has a higher risk of causing adrenal suppression. For individuals with an acute acne flare, Prednisone can also be used in a dose of 20 mg/day for 1 week before an important occasion such as a wedding.
        • Concomitant administration of estrogen and prednisone may act synergistically in suppressing sebum production by inhibiting both adrenal and ovarian androgen production.
        • Spironolactone (Aldactone), used for many years as a diuretic, is also an antiandrogen that blocks the binding of androgens to androgen receptors. It is useful in treating recalcitrant acne in women with adult acne. Menstrual irregularities and breast tenderness are common side effects, and the drug may be easier to use in women taking birth control pills. The drug should not be used during pregnancy, because it may block the normal development of male genitalia. Most clinicians recommend combined use of this drug with oral contraceptives. Spironolactone alters potassium excretion (usually only at higher doses and in only 10% of patients). Serum electrolytes should be monitored during initial institution of therapy. Nausea, vomiting, and anorexia are also common (21).
          Spironolactone has been shown to promote breast tumors in rats fed with doses 25 to 100 times higher than human doses. There have been no data to support this association in women on long-term therapy, although caution should be used if there is a strong family history of breast cancer.
          Good candidates for this drug are individuals with a premenstrual flare-up of their acne, acne onset after the age of 25, oily skin, coexistent hirsutism, and acne that has a predilection for the lower face, especially
          P.14

          the chin and mandible. Start patients on 50 to 100 mg/day taken with meals. If no clinical response is seen in 1 to 3 months, adjust the dose up to 200 mg/day if necessary. Once maintenance has been achieved, try to lower the dose to the lowest effective daily dose. Keep in mind that hirsutism requires higher doses and longer treatment schedules. A topical 5% gel may be developed in the future.
        • Oral cyproterone acetate is available in Europe and Canada usually in combination with ethinyl estradiol for treatment of hirsutism and acne. Topical cyproterone acetate (a sexual steroid, antiandrogen) in combination with liposomes has been shown to improve acne.
        • Flutamide, an androgen receptor blocker, has been shown to have benefit in doses of 250 mg b.i.d. However, the risks of fatal hepatitis and lipid abnormalities make this an expensive and high-risk choice of therapy.
        • Gonadotropin-releasing hormone agonists (GnRHas) block ovarian androgen production and are widely used in the treatment of infertility disorders. This category of drugs includes buserelin, leuprolide, and nafarelin and, theoretically, they may be used to treat acne. They are very expensive, decrease the levels of estrogen, and, therefore, increase the risk of bone loss. Endocrinologists or reproductive endocrinologists are usually involved in the care of patients with these drugs.
        • Sebaceous glands have type 1 5-α reductase activity. Inhibitors that block this enzyme and, therefore, the conversion of testosterone to DHT may have a place in acne therapy.
      • Patients with severe recalcitrant cystic acne should be considered for treatment with isotretinoin (13-cis-retinoic acid, Accutane, Amnesteem, Claravis, Sotret). The emergence of increased bacterial resistance of P. acnes has resulted in an increase in the number of cases of treatment-resistant acne. Criteria for treatment with isotretinoin include less than 50% improvement after 6 months of oral and topical therapy, scarring, associated psychological distress, or acne that relapses quickly once conventional therapy is discontinued.
        The beneficial effects of this synthetic retinoid are indisputable, although its mode of action remains unclear. Isotretinoin is sebostatic, inducing a decrease in sebum production rates to as low as 10% of pretreatment values. However, given that sebum production approaches pretreatment rates after therapy is completed without a concomitant return of acne, other mechanisms, such as an anti-inflammatory effect or correction of altered keratinization, may be equally important. Isotretinoin therapy causes a 2.6-fold decrease in androgen site–binding capacity (22).
        The initial dose of isotretinoin is 0.5 to 1.0 mg/kg of the patient’s body weight. Many of the problems with this drug come from starting at too high a dose. For the first month, a patient may be started at 20 mg daily. This allows for monitoring of any adverse effects and allows the patient to become accustomed to or more comfortable with the drug. The daily dose may be increased each month by an additional 20 mg (e.g., 20 mg first month, 40 mg second month, 60 mg third month, etc.) to a dose of approximately 1 mg/kg. Most physicians plan a course of therapy that reaches a total dose of 100 to 120 mg/kg, which may take up to 6 months to achieve. Some practitioners administer the drug until 2 months after complete healing, with an average treatment of 7 months. Although lower doses may achieve the same initial response rates, they are associated with a much higher recurrence rate on discontinuation of the drug.
        There appears to be no advantage to single versus divided dose, but isotretinoin absorption is enhanced by taking it with meals. Because the skin will often continue to clear after drug administration has been stopped, at least a 2-month waiting period and preferably a 6-month period is advised before one commits a patient to a second course of therapy. Any woman who fails to respond to isotretinoin should be evaluated for hyperandrogenism. The response rate may be as high as 90% with one to two courses
        P.15

        of treatment, and with adequate dosing, most patients experience prolonged remissions from their disease. In a 10-year follow-up study, 61% of patients were free from acne. Of those who relapsed, 23% required a second course of Accutane. Ninety-six percent had relapsed within 3 years of therapy; truncal acne had a higher relapse rate. Patients given a cumulative dose of 120 mg/kg overall were less likely to relapse (22).
        Intermittent isotretinoin at lower doses may benefit some patients with adult acne or stubborn isotretinoin treatment failures. In one study, with isotretinoin 0.5 mg/kg/day for 1 week every 4 weeks for a total of 6 months, the acne resolved in 88% of patients, and at 1 year, 39% had a relapse of their acne (73% relapse with truncal acne) (6).
        Isotretinoin is teratogenic in humans. A pregnancy prevention program was initiated in 1988. Since that time, 0.3% of treated female patients have become pregnant; 38% of live born infants had retinoid embryopathic defects. Women of childbearing age must have a negative pretreatment pregnancy test and continue adequate contraception for the duration of therapy. Because of the short half-life of isotretinoin, the current recommendation is that conception may be attempted 1 month after the cessation of treatment. Men may take isotretinoin without concern for its teratogenic effects.
        The U.S. Food and Drug Administration (FDA) had received 20 spontaneous reports, over a 15-year period, of depression associated with isotretinoin use, leading to a change in the Accutane package insert in early 1998 warning of the association with psychiatric disorders including suicide. More than 50% of these reported patients had a significant personal or family history of depression. These cases may reflect an idiosyncratic response to the medication because larger, controlled studies have failed to find a causal association (23,24). Acne by itself can be associated with depression, but an increased awareness of this potential side effect of isotretinoin should be kept in mind before prescribing this drug and during follow-up.
        Xerosis, cheilitis, alopecia, dry eyes, muscle and bone aches, and hypertriglyceridemia are frequent side effects, but all are reversible on discontinuation of therapy. Although patients may experience a temporary flare-up of their acne when treatment is started, this does not affect their ultimate response to isotretinoin. Excessive granulation tissue, giving a pyogenic granuloma-like picture, is a less common problem. Because of delayed or poor wound healing, incisional surgery including attempts at cosmetic scar revision should be delayed for 12 months after the completion of isotretinoin therapy.
        Another concerning side effect of isotretinoin therapy is the development of vertebral hyperostoses. This finding was recognized initially in patients being treated for various disorders of keratinization who had received isotretinoin at higher dosages and for longer periods than is recommended for acne. Diffuse interstitial skeletal hyperostoses (DISH) would commonly affect the spine and is often asymptomatic. However, asymptomatic vertebral hyperostoses have since been found in patients with acne who had been treated according to the current recommendations. Only long-term follow-up will determine whether these vertebral changes will cause symptomatic disease or become a contraindication to therapy. A single course of isotretinoin may slightly decrease bone density and bone mineralization, but it is not known whether these changes are reversible or increase a patient’s risk for osteoporosis and fractures when older. Baseline vertebral x-rays and bone density studies may be considered in individuals who receive three or more courses of isotretinoin.
      • Vitamin A (Aquasol A), in doses ranging from 50,000 to 500,000 units/day in divided doses, has been advocated for the treatment of severe nodulocystic acne that does not respond to other modalities. This treatment has yet to be evaluated in an adequately controlled, prospective clinical trial and is not an approved indication for the drug. However, vitamin A is available without prescription, and patients may take it on the advice of friends or the lay
        P.16

        press. The toxic dose for adults is usually at least 50,000 IU/day over a period of a year or longer. Normal diets contain approximately 7,500 to 10,000 IU/day. Physicians should be aware of the signs and symptoms of chronic hypervitaminosis A, because patients may take an excess of the vitamin without their knowledge or approval. Signs and symptoms include dry, coarse, scaly skin, hair loss, fissures of the lips, pruritus, sore tongue or mouth, and low-grade fever. Normal serum vitamin A levels do not rule out a diagnosis of hypervitaminosis A.
  • Adjunctive therapy
    • Intralesional corticosteroids. The therapy of choice for cystic lesions and acne abscesses is the intralesional injection of small amounts of corticosteroid preparations (triamcinolone acetonide or diacetate, 0.63 to 2.5 mg/mL). The high local concentration of corticosteroid injected leads to rapid involution of these nonpyogenic, sterile, inflammatory lesions.
      The stock 10-, 25-, or 40-mg/mL steroid suspension should be diluted with lidocaine or bacteriostatic normal saline and only enough injected through a 1-mL syringe with a 27- or 30-gauge needle to distend the cyst slightly (usually 0.025 to 0.1 mL). Use of undiluted solutions or injections of too large an amount may lead to temporary atrophic depressions in the skin (see Chap. 40, Antiinflammatory Agents, sec. I). Most lesions, particularly early ones, will flatten and disappear within 48 hours of injection.
    • Acne surgery
      • Comedo expression. Gentle removal of comedones by pressing over the lesion with a comedo extractor or the opening of an eyedropper not only relieves the patient of unsightly lesions but may also prevent progression to more inflammatory lesions. Occasionally, it may be necessary to incise the follicular opening carefully with a No. 11 scalpel blade or a 25-, 27-, or 30-gauge needle. Over-rigorous attempts to express comedones may result in an increased inflammatory response. Retinoid-resistant comedones can be treated with 30% to 50% trichloroacetic acid on the wooden end of a Q-tip.
        Recurrence of comedones after removal is common. Open comedones have been shown to recur within 24 to 40 days and closed comedones, within 30 to 50 days. Fewer than 10% of comedo extractions are a complete success. Nevertheless, this mode of therapy, carefully done, is useful in the appropriate case.
      • Draining of cysts. Careful and judicious incision and drainage of cysts and/or abscesses may initiate healing and shorten the duration of lesions.
      • Microdermabrasion, with aluminum oxide crystals or other abrasive substances is a newly developed technique that is advocated for treatment of acne and acne scars. Early data indicate that this modality may be a useful adjunct to other topical therapies (25).
    • Laser and light therapies
      • Blue light or photodynamic therapy (420 nm). These light sources cause an overproduction of porphyrins that are toxic to P. acnes. Pulsed green light (532 nm) is also approved for the treatment of acne and presumably works in the same way. Light treatments can be performed alone or with prior application of aminolevulinic acid 20% for 10 minutes to 2 hours. Protocols vary, but one standard treatment is every 3 weeks in a 3-month course. This may be performed in conjunction with other acne therapies.
      • Nonablative lasers in the infrared range rely on selective photothermolysis to target the follicle. Through transient thermal effects, P. acnes is reduced and sebaceous glands are heated and decreased in size. The 1320-nm Nd:YAG, 1450-nm diode, and 1540-nm Er:glass lasers show promise in the treatment of inflammatory acne and clinical improvement in acne scars (26). Treatments are typically performed monthly for 4 to 6 months. Other therapies may be continued concomitantly. The limiting factors are patient discomfort and expense.
        • P.17

      • Pulsed dye lasers in the visible light range (585 to 595 nm) can be used to minimize erythema of active acne lesions and acne scars (27). However, data is inconsistent as to whether this laser decreases acne lesion counts (28,29).
      • Ultraviolet light (UVL). Exposure to sunlight or UVB sunlamps may be moderately effective in some patients. Patients using tretinoin may show a heightened sensitivity to UVL. However, this method carries the potential for photodamage and carcinogenesis in the long term.
    • α-Hydroxy acids (glycolic, lactic, pyruvic, and citric acids) and β-hydroxy acids (salicylic acid) are available in topical cream formulations or as peeling agents. These acids reduce corneocyte cohesion.
  • Acne scars
    • Laser skin resurfacing. Ablative CO2/Er:YAG laser skin resurfacing can improve the appearance of acne scars of all types but requires significant postoperative wound care and recovery time. A newer fractional resurfacing device, Fraxel, shows promise for remodeling acne scars through a series of treatments with less downtime. Nonablative lasers (see preceding text) are thought to stimulate collagen production and, thereby, gradually improve the appearance of pitted acne scars.
    • Dermabrasion using high-speed diamond buffing drills can remove small and superficial scars and sometimes deep scars. However, this method is highly dependent on practitioner technique and can result in scarring in untrained hands.
    • Fillers. Fat transfer and injection of filler substances can be used to elevate acne scars.
    • Surgical techniques. Punch excision, punch elevation, and elliptical excision can be used to remove isolated ice-pick or deep boxcar scars.
  • Patient education about long-standing misconceptions. A number of myths circulate with regard to the relationship between habits, diet, hygiene, and acne. Patients should be counseled that if certain exposures aggravate their individual case of acne, these should be avoided. However, strict or fad diets and regimens are unlikely to affect sebaceous gland function or acne activity. Detailed information and instructions should be emphasized. Moreover, shared, realistic expectations between the physician and patient of any acne treatment regimen or therapeutic approach are essential to achieve the desired improvement.
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