 Management
General Principles Treatment of acne should be individualized and frequently involves a trial-and-error approach that begins with those agents that are known to be most effective, least expensive, and have the fewest side effects. Acne is a multifactorial disease; therefore, appropriate therapy often involves the use of more than one agent, each of which targets a different pathogenic factor. Mild acne can often be managed successfully by topical treatments, including over-the-counter (OTC) remedies. More severe, widespread acne often requires systemic treatment in combination with topical therapy. Oral medications should be tapered or discontinued as soon as control is achieved. A patient should be advised not to squeeze or pick lesions.
Topical Therapies Despite the testimonials seen on infomercials, no “one-size-fits-all” treatment for acne exists. In fact, the active ingredients in most advertised preparations can be obtained less expensively in many OTC products. Benzoyl Peroxide Benzoyl peroxide is a potent antibacterial agent that has comedolytic properties and is effective against both inflammatory (papules/pustules) and noninflammatory lesions (comedones) (see Table 12.1). Benzoyl peroxide may be used alone to treat mild acne, but it is most effective when used in conjunction with other topical and systemic therapies. Benzoyl peroxide is available OTC in many different strengths and formulations including bar soaps, washes, gels, lotions, creams, foams, and pads. Clearasil, Oxy, Pan-Oxyl, and Clean & Clear are several brands that make benzoyl peroxide-containing products. Benzoyl peroxide is also available by prescription in combination with clindamycin, erythromycin, and adapalene. Lower-strength (e.g., 2.5%) preparations are less irritating and probably as effective as the higher 5% and 10% concentrations.
How to Use Benzoyl Peroxide Beginning with a lower-strength preparation, benzoyl peroxide is applied sparingly once or twice daily, in a thin layer on acne-prone areas. Side effects: Irritation and burning are not uncommon but usually resolve in 2 to 3 weeks; bleaching of colored clothing and bedding.
Topical Retinoids Topical retinoids are primarily comedolytic (i.e., they treat comedones) but they also have potent anti-inflammatory effects (see Tables 12.2A and 12.2B). In addition, retinoids facilitate the penetration of other topical antiacne agents such as benzoyl peroxide. These agents help “plump up” the skin and make enlarged pores (follicular prominence) less obvious. They should not be used during pregnancy or breastfeeding (although no studies have shown them to be harmful to the fetus). Topical retinoids used for acne include (listed in increasing potency) the following: Adapalene (Differin), available as 0.1% cream or gel, or 0.3% gel Tretinoin (Retin-A Micro), available as 0.025%, 0.04%, 0.05%, or 0.1% in cream or gel Tazarotene (Tazorac), available as 0.05% or 0.1% cream or gel, or 0.1% foam
Newer products that combine topical retinoids with topical antibiotics, can help simplify treatment regimens. Examples include Ziana (tretinoin 0.025% and clindamycin 1.2% gel), Veltin (tretinoin 0.025% and clindamycin 1.2% gel), and Epiduo (benzoyl peroxide 2.5% and adapalene 0.1% gel).
How to Use Topical Retinoids Topical retinoids are applied once daily, as a thin layer to acne-prone areas at bedtime. Patients who exhibit sensitivity may use it every other day, or less frequently, until they develop a tolerance to it. The area of application should first be washed and thoroughly dried. Side effects: May include erythema, dryness, and peeling—these usually resolve after 3 weeks; photosensitivity (or “sun sensitivity”) in some patients, thus concurrent daily use of sunscreen should be advised.
Topical Antibiotics Preparations that contain the topical antibiotics, clindamycin and erythromycin, are active against P. acnes and have anti-inflammatory action against papules and pustules (see Table 12.3). Topical clindamycin and erythromycin are considered equally effective. Drug resistance has been reported with these antibiotics so monotherapy with these agents should be avoided.
How to Use Topical Antibiotics These agents are applied once or twice daily, in a thin layer across the acne-prone areas. Side effects: Irritation and burning are uncommon and may be avoided by using an ointment-based erythromycin such as Akne-Mycin or clindamycin (Cleocin) in a lotion preparation. Topical antibiotics are available in a variety of vehicles, including creams, lotions, ointments, gels, and solutions.
Combination of Topical Antibiotic and Benzoyl Peroxide The combination of erythromycin or clindamycin with benzoyl peroxide helps prevent bacterial resistance and has a synergistic effect (the combination appears to be more effective than either drug used alone) (see Table 12.4). Benzamycin (Benzoyl peroxide 5% and erythromycin 3%), BenzaClin (benzoyl peroxide 5% and clindamycin 1%), Duac (benzoyl peroxide 5% and clindamycin 1.2%), and Acanya (benzoyl peroxide 2.5% and clindamycin 1.2%) are the most commonly prescribed formulations.
How to Use Combination of Topical Antibiotics and Benzoyl Peroxide These agents are applied sparingly once daily to acne-prone areas. Side effects: The same cautions apply as for benzoyl peroxide. Dryness, erythema, and pruritus are the most common side effects.
Alternative Topical Prescription Drugs Azelaic acid: antibacterial and anticomedone, available as a 20% cream (Azelex) or 15% gel (Finacea). Sulfur and sodium sulfacetamide preparations: antibacterial and keratolytic properties, available as 10% sodium sulfacetamide in lotion, cream, or wash (Ovace, Klaron) and together with 5% sulfur as a cleanser, cream, or lotion (Avar Cleanser, Clenia, Plexion, Sulfacet-R, Novacet). Dapsone: antibacterial and antineutrophil, available as 5% gel (Aczone).
Topical Nonprescription Agents Alpha- and Beta-Hydroxy Acids Many OTC products contain ingredients that have been used for acne for many generations without great success. For children just beginning to develop acne or for patients with very mild acne, gentle OTC washes or creams containing the topical peeling agents salicylic acid or glycolic acid; or the anti-inflammatory agents resorcinol or sulfur, may be helpful.
Systemic Therapies Systemic therapy is added to topical treatment, in patients with moderate to severe acne, moderate acne unresponsive to topical treatment, acne that tends to scar, or those with significant acne on the chest and back. Systemic therapy results in a more rapid improvement, which may serve to enhance patient compliance. However, side effects, drug allergy/intolerance, drug interactions, and fetal exposure in women who are, or may become pregnant, must be carefully considered before initiating systemic treatment. Systemic agents for acne include oral antibiotics, hormonal agents, such as oral contraceptives and antiandrogenic drugs and oral retinoids (isotretinoin or “Accutane”) which is usually reserved for more severe, recalcitrant disease (see discussion below).
Oral Antibiotics Tetracyclines The tetracycline derivatives—minocycline and doxycycline—are the mainstay and the first-line antibiotic drugs of choice for moderate to severe acne (see Table 12.5). Tetracycline derivatives inhibit the growth of P. acnes, which decreases free fatty acid production and pustule formation and have a significant anti-inflammatory action via inhibition of the neutrophil chemotactic response. The use of any of the tetracyclines during a child's tooth development (before 8 years of age) may cause a permanent discoloration of the teeth. Unborn fetuses and nursing children are also at risk.
Tetracycline Tetracycline is not readily available in the United States and is less commonly used today. The following dosing is advised where it is available: 250 to 500 mg twice a day and taken on an empty stomach (1 hour before or 2 hours after a meal). Dairy products such as milk or divalent cations that contain iron, magnesium, zinc, or calcium may interfere with tetracycline's absorption from the stomach.
Minocycline Dosing: 50 mg twice a day, 75 mg once or twice a day, or 100 mg once or twice a day. An extended-release formulation of minocycline tablets, Solodyn, is available in doses ranging from 45 to 135 mg, given in a weight-based dosage of 1 mg/kg daily (see Table 12.5). It has been shown to have anti-inflammatory effects without acting on P acnes, the bacteria involved in causing acne. This approach is intended to prevent bacterial resistance. The drug's excellent absorption allows it to be taken with food. It causes few, if any, phototoxic problems and appears to be less likely to induce candidal vulvovaginitis than tetracycline. Side effects: Nausea, vomiting, and, in high doses (those that approach 200 mg/day), dizziness owing to vestibular dysfunction (dizziness usually diminishes after a few days or when the dosage is lowered). Reversible discoloration of the skin—muddy brown in sun-exposed areas, bluish color in scars or normal skin (usually the shins), and a grayish-blue discoloration of the oral or ocular mucosa can occur. It can also lead to blue gray staining of adult teeth. Risk of discoloration increases with prolonged treatment. In rare cases, minocycline is associated with benign intracranial hypertension, hepatitis, and a lupus-like syndrome that is antinuclear antibody positive. This syndrome, which occurs most often in young women, usually develops late in the course of therapy.
Doxycycline Dosing: ranges from 50 mg twice a day, 75 mg once or twice a day, or 100 mg once or twice a day. Doxycycline is absorbed well and may be taken with food. Its main disadvantage is its phototoxic potential—the highest of the tetracyclines. Patients should be advised regarding careful sun protection. Side effects: Higher incidence of gastrointestinal upset—patients should be advised not to swallow without liquid and not to take right before lying down. Vestibular dysfunction, hyperpigmentation, and the lupus-like syndrome associated with minocycline have not been reported.
Alternative Antibiotics Azithromycin, clarithromycin, trimethoprim-sulfamethoxazole, or amoxicillin are used as second- line alternatives when a tetracycline derivative fails or is not tolerated.
Oral Retinoids (Isotretinoin) Isotretinoin (13-cis-retinoic acid) is an oral synthetic derivative of vitamin A that promotes long-term remissions in severe acne and is used for patients with severe, recalcitrant nodulocystic acne. Isotretinoin is also highly effective in patients with moderate to severe acne that was previously unresponsive to topical and systemic acne therapies. While isotretinoin is still commonly referenced by its original trade name in the United States, Accutane, it is currently only sold under several generic brand names Amnesteem, Claravis, Absorica, and Sotret. It is available as Roaccutane outside of the United States.
Mechanism of Action Dramatically reduces the size and output of sebaceous glands. Normalizes the shedding dead skin cells (stabilizes keratinization), the process through which keratinocytes (epidermal cells) produce the protein keratin. Consequently, the keratinocytes are less likely to clog pores (comedogenesis).
Dosage Oral isotretinoin is available as capsules in strengths of 10, 20, 30, and 40 mg. Absorica (isotretinoin-Lidose) is a formulation which enhances absorption of isotretinoin in the absence of dietary fat. It is available in strengths of 10, 20, 25, 30, 35, and 40 mg. Patients are dosed based on weight and usually given 0.5 to 1 mg/kg/day until a total dosage of 120 to 150 mg/kg is reached (which equates to 4 to 6 months of treatment). There is some evidence that longer courses with lower doses (0.25 to 0.4 mg/kg/day) can also be effective while minimizing the dose-related side effects.
Side Effects General Isotretinoin can cause severe birth defects in pregnant women or a woman who becomes pregnant while taking the drug, even if for a short time. Teratogenic birth defects include skull abnormalities, heart defects, deafness, cleft palate, and central nervous system defects. Because the drug remains in the body for a long time, it can cause birth defects for 1 month after a woman has stopped taking it. It also carries an increased risk of miscarriage when used during pregnancy or up to 1 month prior to pregnancy. Many prescribers require that women use oral contraceptives before starting treatment, during treatment, and for 1 month after isotretinoin treatment is completed. Isotretinoin's ability to shut down the oil production in the body accounts for some of its less serious side effects, such as cheilitis (dryness and inflammation of the lips), conjunctivitis, dry skin, nose bleeds, dry eyes, increased sun sensitivity, and itching. In general, these reactions are well tolerated because the drug is so effective that patients want to continue taking it despite these mild side effects. Approximately 25% of patients experience serum triglyceride elevations, and 15% experience decreases in high-density lipoprotein levels. Less commonly, a patient may experience musculoskeletal and joint pains, or hair thinning (usually reversible upon drug discontinuation). Allergic reactions, decreased night vision, persistent headaches, benign intracranial hypertension, and hearing impairments, are rare findings. Skeletal hyperostosis is limited to those who take a high dosage (much higher than is used to treat acne), and those undergoing long-term isotretinoin therapy. Studies performed in men taking isotretinoin showed no significant effects on their sperm and no long-term damage to a man's ability to have healthy children. Isotretinoin has also been under scrutiny for a possible link to inflammatory bowel disease (IBD). A case-control study showed that this drug may be associated with a very small risk of developing ulcerative colitis, but no connection to Crohn disease was found.
Depression and Suicide In the United States, the Food and Drug Administration (FDA) has received reports of depression and suicide in patients who take isotretinoin, and there is concern about a possible link between the drug, psychiatric disorders, and suicide. Depression is unfortunately a common problem and the onset tends to occur between 12 and 24 years of age when acne is most prevalent. Increased incidence of emotional problems in adolescence coupled with the stress of having severe acne makes it difficult to determine whether isotretinoin can trigger depression and suicide or whether successful treatment may thwart such problems. Because suicide is a major cause of death in teenagers, particularly in boys, it has been difficult to determine a causal relationship between isotretinoin and these events, there is a great need for further study.
| ALERT | If a patient taking isotretinoin is showing signs of moodiness, depression, or psychosis, the drug should be discontinued and the patient should be evaluated! |
| THE iPLEDGE PROGRAM |
Due to isotretinoin's potential for serious toxicity during pregnancy, the Federal Drug Administration established an isotretinoin federal registry program called iPLEDGE. The registry keeps tabs on all isotretinoin prescriptions in the United States. Manufacturers, wholesalers, pharmacists, prescribers, and patients are linked through a centralized computer registry. The registry also connects to the laboratories that perform the required pregnancy testing in this system.
|
| PROCEDURES ALL iPLEDGE PATIENTS MUST FOLLOW |
Everyone in the United States who is prescribed isotretinoin must register with iPLEDGE. After registration, a female patient of childbearing potential must receive ongoing counseling and pregnancy testing each month while taking the drug. All patients, male or female, are allowed only a 30-day supply of isotretinoin at each office visit. These prescriptions are only valid for 7 days after they are prescribed (unless the patient is unable to become pregnant).
|
Adjuvant Therapeutic Modalities Manual extraction of comedones with a comedone extractor can quickly improve the appearance of acne. Comedones may be removed more easily if the patient is pretreated with a topical retinoid for 3 to 4 weeks before comedo removal.
Intralesional Corticosteroid Injection Intralesional injections of glucocorticosteroids, introduced with a 30-gauge needle, can reduce the inflammatory response and decrease the size of nodular inflammatory lesions. The recommended dose of intralesional triamcinolone acetate suspension is a concentration of 2.5 mg/mL to avoid local steroid atrophy. For patients with severe disease and considerable hypertrophic scarring, the concentration can be increased to 5 or 10 mg/mL.
Office-Based Chemical Peels Chemical peels have become popular as antiaging facial rejuvenation procedures; however, they are sometimes used to treat acne as well. In this procedure, a chemical acid solution is applied to the skin, causing the skin to peel off so that new skin can regenerate. Chemical peels are probably not effective for the treatment of inflammatory lesions of acne. They seem to work best in the elimination of comedonal acne and postinflammatory hyperpigmentation. Deeper peels, with stronger concentrations of acids, are sometimes used to treat acne scars. The two most commonly used chemicals for peels are the alpha-hydroxy acids (glycolic, lactic, and mandelic acids) and the beta-hydroxy acids (salicylic acid).
Lasers, Lights, and Other New Technologies Laser and light therapies offer a promising, noninvasive treatment alternative and are most effective when used in combination with traditional acne medication treatments. They improve inflammatory acne and acne scarring.
Photodynamic Therapy Photodynamic therapy (PDT) involves applying a photosensitizing agent (aminolevulinic acid—ALA) to the skin, which accumulates in the sebaceous glands, followed by exposure to a high-intensity light source. Light sources used in PDT include visible (nonlaser, e.g., blue, red, intense pulsed) or laser light (e.g., 585 to 595 nm pulsed dye, 635 nm red diode). The P. acnes that reside in sebaceous glands produce porphyrins as a by-product of their metabolism. The light activates these porphyrins and kills the bacterial cells.
Lasers Lasers that are used in dermatology are devices that produce light at a specific wavelength to target and destroy specific chromophores in the skin (hemoglobin, water, melanin, etc.). Lasers and light devices used for acne target blood vessels, and sebaceous glands; and fractionated laser devices are beneficial for treatment of acne scarring. Below is a list of some laser and light devices that have been used for acne: Intense pulsed light (IPL): These devices emit a wider range of wavelengths (500 to 1,200 nm). Selective UV filters allow for versatility and customization to reach the specific targets such as blood vessels and sebaceous glands. Pulsed dye laser (PDL): This laser is “tuned” to a specific wavelength of light (585 to 95 nm) and is effective at removing redness and telangiectasias in acne, acne scars, and rosacea. Pulsed light and heat energy (LHE) therapy: This treatment combines pulses of light and heat, which may target both P. acnes and sebaceous glands. Diode laser: This laser uses longer infrared wavelengths (1,450 nm) and targets water and the sebaceous glands. It appears to be effective for acne and acne scars.
|
Differential Diagnosis 
Helpful Hints 
Points to Remember 
SEE PATIENT HANDOUTS,