Tht NEW ENGLAND JOURNAL ofMEOICINE
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`l~l _________ c_L_1_N_1_c_A_ L_P_RA __ c_T_1_c_E ________ _.II
`
`Acne
`
`William D.James, M.D.
`
`This Journal feature begins with a case vignttte highlighting a common clinical problem.
`Evidence supporting various strategies is then presented,followed by a review of formal guidelines,
`when they exist. The article ends with the author's clinical recommendations.
`
`A 17-year-old boy with a six-month history of acne presents for initial evaluation and
`treatment Physical examination reveals closed and open comedones and a large num(cid:173)
`ber of erythematous papules and pustules (50 or more) of the face and upper trunk.
`How should he be treated?
`
`THE CLINICAL PROBLEM
`
`Acne affects more than 85 percent of teenagers but frequently continues into adult(cid:173)
`hood.1 Although there are more than 2 million visits to office-based physicians per
`year for patients in the age range of15 to 19 years, the mean age at presentation fur
`treatment is 24 years, with 10 percent of visits taking place when patients are between
`the ages of35 and 44 years. 2 The social, psychological, and emotionalimpairment that
`can result from acne bas been reported to be similar to that associated with epilepsy,
`asthma, diabetes, and arthritis. 3 Patients evaluated at tertiary care centers are prone to
`depression, social withdrawal, anxiety, and anger and are more likely to be unemployed
`than persons without acne. 4•5 Scarring can lead to lifelong problems in regard to self..
`esteem. The directcostofacne in the United States is estimated to exceed $1 billion per
`year, with $100 million spent on over-the-counter acne products. 6
`Acne is a follicular disease, the principal abnormality of which is impaction and dis(cid:173)
`tention of the pilosebaceous unit. The cause of the hyperproliferation ofkeratinocytes
`and the abnormalities of differentiation and desquamation are unknown. Itis likely that
`hyperresponsiveness to the stimulation of sebocytes and follicular keratinocytes by
`androgens leads to the hyperplasia of the sebaceous glands and the seborrhea that
`characterize acne. 7--9
`Propionibacterium acnes colonizes the follicular duct and proliferates in teenagers with
`acne. 10This organism probably contributes to the developmentofinflammation. With
`this combination of factors present, the follicular epithelium is invaded by lymphocytes;
`it ruptures, and sebum, microorganisms, and keratin are released into the dermis.11
`Neutrophils, lymphocytes, and foreign-body giant cells accumulate and produce the
`erythematous papules, pustules, and nodular swellings characteristic of inflamma(cid:173)
`tory acne.
`
`STRATEGIES AND EVIDENCE
`
`D IAG N OS IS
`The diagnosis of acne is usually readily made. Acne is characterized by open and closed
`comedones (blackheads and whiteheads), which are present either alone or, more
`commonly, with pustules and erythematous papules concentrated on the face and
`upper trunk. Many systems fur grading the severity of disease have been used. The se(cid:173)
`verity of acne is generally assessed by the number, type, and distribution of lesions.
`
`From the Department of Dermatology,
`University of Pennsylvania, Philadelphia.
`
`N EnglJ Med 2005;352:1463 -72.
`CoPf"f!,t © 2005 Mossochusdn I.I odicd Sod,ty.
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`Almirall EXHIBIT 2018
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`Tht NEW ENGLAND JOURNAL ofMEOI CIN E
`
`From a therapeutic standpoint, the presence of
`scarring may lead to a more aggressive approach
`than normally pursued. Table 1 gives a narrative de(cid:173)
`scription of acne, accompanied by representative
`photographs that illustrate a simplified classifica(cid:173)
`tion of severity (Fig. 1 to 4).
`
`THERAPY
`Topical and oral agents for the treatment of acne
`are listed in Table 2.
`
`Topical Treatment
`Topical medications are active only where and when
`they are applied; their main action is the prevention
`of new lesions. Thus, they should be used daily on
`all areas of the skin that are prone to acne. Mainte(cid:173)
`nance therapy is needed to prevent recurrence. The
`main side effect of topical products that limits their
`use is irritation; this is a consideration primarily for
`patients for whom multiple medications are pre(cid:173)
`scribed and who use over-the-counter skin prod(cid:173)
`ucts. Patients should be discouraged from applying
`anything to the fuce other than what is recommend(cid:173)
`ed so that irritation may be avoided. Most of the
`topical preparations are available in a variety of
`strengths and delivery systems. Gels, pledgets,
`washes, and solutions are most drying and are par(cid:173)
`ticularly suited for oily skin, whereas creams, lo(cid:173)
`tions, and ointments are preferable for patients with
`dry, easily irritated skin.
`
`Fieure 1. Mild Acne.
`Multiple open and closed comedones are present,
`with few inflammatory papules.
`
`Table 1. Classification of Acne.*
`
`Severity
`
`Description
`
`Mild
`
`Comedones (noninflammatory lesions) are the main lesions.
`Papules and pustules (Fig. l) may be present but are small
`and few in number (generally <10).
`Moderate Moderate numbers of papules and pustules (l~0) and come-
`dones (l~0) are present (Fig. 2). Mild disease of the
`trunk may also be present.
`
`Moderately Numerous papules and pustules are present (40-100), usually
`severe
`with many comedones (40-100) and occasional larger,
`deeper nodular inflamed lesions (up to 5). Widespread af.
`fected areas usually involve the face, chest, and back (Fig. 3).
`
`Severe
`
`Nodulocystic acne and acne congtobata with many large, pain(cid:173)
`ful nodular or pustular lesions are present, along with many
`smaller papules, pustules, and comedones (Fig. 4A).
`
`* The information is from Cunliffe et al.12
`
`Fieure 2. Moderate Acne.
`Erythematous papules and pustules are the predomi(cid:173)
`nant lesions, and disease is limited to the face.
`
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`CLINICAL PRACTICE
`
`Topical Retinoids
`Topical retinoids work to correct abnormalities in
`the follicular keratinocyte. They are effective in both
`the treatment and prevention of the primary lesion
`of acne, the comedo, and thereby limit the forma(cid:173)
`tion of inflammatory lesions.19 Some types also
`reduce inflammation by interfering with the inter(cid:173)
`action between toll-like receptor 2 and external
`products of P. acnes on the surfuce of antigen-pre(cid:173)
`senting cells. 20 In addition, topical retinoids im(cid:173)
`prove the penetration of other topical medications
`and may help to improve the hyperpigmentation
`that is left in dark skin types after the resolution of
`22
`inflammatory lesions. 21
`•
`For the mild, primarily comedonal, types of acne
`(Fig. 1), topical retinoids may be used alone, where-
`
`Fieure 3. Moderately Severe Acne.
`Erythematous papules, pustules, and nodules are
`present on the face.
`
`Fieure 4. Severe Acne.
`Multiple painful nodules are present on the back (Panel A) in spite of aggressive topical and oral interventions. (Similar
`lesions appear on the patient's chest and face.) Panel B shows the response after treatment with isotretinoin.
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`Tht NEW ENG LANO JOURNAL of MEDICINE
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`Table 2. Medications for the Treatment af Acne.
`
`Drue
`
`Topical qents
`
`Retinoids
`Tretinoin
`
`Adapalene
`
`Dose
`
`Side Effects
`
`Other Consideratio ns
`
`Applied once nightly;
`strengths of0.025-
`0.1% available
`
`Applied once daily,
`at night or in the
`morning
`
`Irritation (redness and scaling)
`
`Generics available
`
`Minimal irritation13
`
`Tazarotene*
`
`Applied once nightly
`
`Irritation
`
`Antimicrobials
`
`Benz~I peroxide,
`alone or with zinc,
`2.5- 10%
`
`Applied once or twice
`daily
`
`Benz~I peroxide can bleach clothing
`and bedding
`
`Clindamycin, erythro(cid:173)
`mycint
`
`Applied once or twice
`daily
`
`Propensity to resistance
`
`Combination benzoyl
`peroxide and
`clindamycin or
`erythromycin
`
`Applied once or twice
`daily
`
`Limited data suggest tazarotene
`more effective than
`alternatives•4,ts
`
`Available over the counter; 2.5-5%
`concentrations as effective as
`and less drying than 10% con(cid:173)
`centration
`
`Most effective for inflammatory le(cid:173)
`sions (ratherthancomedones);
`resistance a concern when
`used alone
`
`Combination more effective than
`topical antibiotics alone; limits
`development of resistance; use
`of individual products in com•
`bi nation less expensive and
`appears similarly eflective16
`
`Other topical qents
`Azelaic acid, sodium
`sulfacetamide(cid:173)
`sulfur, salicylic acidt
`
`Applied once or twice
`daily
`
`Well tolerated
`
`Good adjunctive or alternative
`t reatments
`
`as for patients with more severe acne, the use of
`these products in combination with topical or
`
`oral antimicrobial agents is appropriate. 12•23 Ran(cid:173)
`domized, double-blind, multicenter comparative
`studies have shown a reduction of 38 to 71 per(cid:173)
`cent in noninflammatory and inflammatory lesion
`counts. Direct comparisons of topical retinoids have
`indicated that tazarotene in a 0.1 percent gel is
`more efficacious than 0.1 percent tretinoin or 0.1
`15 although tazarotene also
`percent adapalene, 14
`•
`tends to be the most irritating. The maximum ther(cid:173)
`apeutic response to topical retinoids occurs over
`approximatelyU weeks.
`
`Topical Antimicrobials
`Topical antimicrobial agents are effective in the
`treatment of inflammatory disease.24 Benzoyl per(cid:173)
`oxide is a bactericide and is an excellent first-line
`medication. The response to this agent is rapid,
`with improvement noted as early as fNe days after
`
`treatment has begun, but irritation is common.
`Water-based products, as compared with alcohol(cid:173)
`based products, when used at low peroxide con(cid:173)
`centrations (2.5 to 5 percent) will help to limit this
`problem and have an efficacy similar to that of other
`products in this class. 25
`Topical clindamycin or erythromycin also may be
`useful, but, as documented in many randomized,
`clinical trials, these agents are most effective when
`used in combination with benzoyl peroxide or
`topical retinoids.16026-28 Randomized trials have
`demonstrated a reduction in total lesion counts of
`50 to 70 percent when combination therapy is
`used.16,26-28 Moreover, the topical antibiotics clin(cid:173)
`damycin and erythromycin rapidly induce bacterial
`resistance when used as monotherapy, and this re(cid:173)
`sistance correlates with decreased clinical effica(cid:173)
`cy. 29,30 Benzoyl peroxide does not induce resistance;
`when used with topical or oral antibiotics, it pro(cid:173)
`tects against the development of this problem,29
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`Table 2. (Continued.)
`
`Drue
`
`Oral antibiotics:!:
`Tetracyclinei
`
`Doxycyclinei
`
`MinocyclineS
`
`Trimethoprim-sulfameth(cid:173)
`oxazole
`
`Erythrornycini"
`
`Hormonal qents1
`
`Spironolactonej
`
`Estrogen-containing oral
`contraceptives
`Oral retinoid
`lsotretinoin I
`
`CLINICAL PRACTICE
`
`Dose
`
`Side Effects
`
`Other Considerations
`
`250-500 mg once or
`twice daily
`
`50-100 mg once or
`twice daily
`
`50-100 mg once or
`twice daily
`
`One dose (160 mg tri(cid:173)
`methoprim, 800 mg
`sulfamethoxazole)
`twice daily
`
`250-500 mg two to
`lour times daily
`
`50-200 mg in divided
`doses
`
`Gastrointestinal upset
`
`Photo toxicity
`
`Hyperpigmentation of teeth, oral mucosa,
`and skin; lupus-like reactions with long(cid:173)
`term treatment
`
`Inexpensive; dosing limited by
`need to take on empty stomach
`
`20-mg dose antiinflammatory
`only; limited data on efficacy17
`
`Toxic epidermal necrolysis and allergic eruptions Trimethoprim may be used alone
`in 300-mg dose twice daily;
`limited data available18
`
`Gastrointestinal upset
`
`Menstrual irregularities, breast tenderness
`
`Resistance problematic; consen(cid:173)
`sus is that efficacy is limited
`
`Higher doses more effective but
`cause more side effects; best
`given in combination with oral
`contraceptives
`
`Daily
`
`Potential side effects include thromboembolism
`
`0.5-1.0 mg/kg/day in
`divided doses
`
`Relapse rate higher if patient is
`<16 yr at initial treatment, if
`acne is of high severity and
`involves the trunk, or if drug
`is used in adult women
`
`Birth delects; adherence to pregnancy-
`prevention program outlined by drug manu(cid:173)
`facturer, including two initial negative preg(cid:173)
`nancy tests, is essential; hypertriglyceridemia,
`elevated results on liver-function tests, abnor(cid:173)
`mal night vision, benign intracranial hyperten(cid:173)
`sion, dryness of the lips, ocular, nasal, and oral
`mucosa and skin, secondary staphylococcal
`infections, and arthralgias are possible com(cid:173)
`mon or important side effects; perform labora(cid:173)
`tory testing of lipid profiles and liver-function
`tests monthly until dose is stabilized
`
`* Tazarotene is in pregnancy category X: contraindicated in pregnancy.
`i" Clindarnycin, erythrornycin, and azelaic acid are in pregnancy category B: no evidence of risk in humans.
`:j: Oral antibiotics are indicated for moderate-to-severe disease; for the treatment of acne on the chest, back, or shoulders; and in patients with
`inflammatory disease in whom topical combinations have failed or are not tolerated.
`i This drug is in pregnancy category D: positive evidence of risk in humans.
`,i Hormonal agents are for use in women only.
`I lsotretinoin is in pregnancy category X: contraindicated in pregnancy. It should be used only in patients with severe acne that does not clear
`with combined oral and topical therapy.
`
`and its use has been recommended if treatment Other Topical Medications
`with antibiotics is continued for longer than three Azelaic acid, products containing sodium sulfuceta(cid:173)
`months. In a recent trial,16 the effects of benzoyl mide and sulfur, and salicylic acid preparations are
`peroxide alone were similar to those of a more ex- generally well tolerated, but clinical experience in(cid:173)
`pensive combined benzoyl peroxide-erythromycin dicates that they are less effective than the agents
`product However, these comparators were used discussed above. Studies involving these products
`twice daily without the concomitant use of topical are few, and most have had limitations in their
`retinoids. There is no role for topical clindamycin or methods. These medications are best used as ad(cid:173)
`erythromycin if oral antibiotics are administered.
`juncts or when other medications are not tolerated.
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`Finally, the avoidance of potentially irritating over(cid:173)
`the-counter astringents, harsh cleansers, or anti(cid:173)
`bacterial soaps should be emphasized.
`
`ORAL THERAPY
`Oral Antibiotics
`Oral antibiotics are indicated for moderate-to(cid:173)
`severe disease, for the treatment of acne on the
`chest, back, or shoulders, and in patients with in(cid:173)
`flammatory disease in whom topical combinations
`have failed or are not tolerated.
`When oral therapy is warranted, tetracycline is
`inexpensive and often effective in previously un(cid:173)
`treated cases. Results from randomized clinical tri(cid:173)
`als indicate that a 50 to 60 percent rate ofimprove(cid:173)
`ment in inflammatory lesions can be expected.31
`However, gastrointestinal side effects and the need
`to take tetracycline on an empty stomach are disad(cid:173)
`vantages. Clinical experience and limited data have
`suggested that doxycycline, minocycline, and tri(cid:173)
`methoprim-sulfamethoxazole are more effective
`than tetracycline. 32•34 Doxycyline and minocycline
`are both preferred over trimethoprim-sulfameth(cid:173)
`oxazole because of the side-effect profile.
`Starting the therapy at higher doses is recom(cid:173)
`mended, since the response cannot be judged for at
`least six weeks and full efficacy is not apparent for
`three months. Iflittle response is seen at six weeks,
`adjustments to the treatment plan such as adding
`topical medication or switching oral antibiotics are
`justified.
`After control of the acne is achieved and main(cid:173)
`tained for at least two months, a reduction in the
`dose can be attempted. Oral antibiotic therapy gen(cid:173)
`erally is taken over a three-to-six-month course.
`Eventual discontinuance is the goal, followed by
`long-term topical therapy (typically with topical reti(cid:173)
`noids alone or in combination with benzoyl perox(cid:173)
`ide). Controversy exists as to the need for a second
`form of contraception in women using both oral
`contraceptives and oral antibiotics, but a panel of
`experts has recommended a conseIVative approach
`i.e., two forms of contraception -given that in(cid:173)
`-
`dividual patients show large decreases in plasma
`ethinyl estradiol levels when taking antibiotics, in(cid:173)
`cluding tetracycline. 35
`
`Lack of Response
`Reasons that acne may have a poor response to
`treatment with antibiotics include inadequate po(cid:173)
`tency (e.g., the use of topical therapy for severe dis(cid:173)
`ease), an inadequate duration of treatment (at least
`
`Fq:ure 5. Gram-Neptive Folliculitis.
`Pustules are centered around the anterior nares.
`
`a month is needed to see a response), improper pa(cid:173)
`tient education, poor compliance with the use of
`medication, or the development of resistance to
`antibiotics. 36 Resistance is an increasing problem,
`since 60 percent of P. ames isolates are resistant to
`at least one antibiotic; resistance is most common
`with the use of erythyromycin (50 percent of cases),
`clindamycin (35 percent), and tetracycline (25 per(cid:173)
`37 Resistance to antibiotics should be sus(cid:173)
`cent). 36
`•
`pected in patients who do not have a response to
`treatment or who have a relapse during treatment,
`especially those who have been on multiple cours(cid:173)
`es of oral and topical antibiotics or have a history of
`variable compliance. Because resistance to erythro(cid:173)
`mycin and clindamycin are often present simulta(cid:173)
`neously, the occurrence of a flare of acne while one
`of these antibiotics is being used should prompt a
`switch to tetracycline or doxycycline. Tetracycline(cid:173)
`resistant strains of P. ames are usually also resistant
`to doxycycline, so a switch to minocycline is recom(cid:173)
`mended if resistance to tetracycline is suspected. 38
`The implications associated with the development
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`CLINICAL PRACTICE
`
`of resistant organisms, including Staphylococrus
`aureus in the nares, streptococci in the oropharynx,
`and enterobacteria, are currently uncertain. 39
`Infection with gram-negative organisms may
`also complicate long-term antibiotic therapy. The
`overgrowth of gram-negative organisms in the an(cid:173)
`terior nares has been reported to occur in 85 per(cid:173)
`cent of patients treated with oral antibiotics for six
`months or longer. 40 In 4 percent of such patients,
`pustules may develop, primarily on the central and
`lower face (Fig. 5); a culture ofone of the pustules
`will yield a gram-negative organism identical to
`that present in the anterior nares. Such superin(cid:173)
`rected acne is best treated with isotretinoin. 40
`
`Hormonal Therapy
`In women who have signs of hyperandrogenism
`(e.g., irregular menses, androgenic alopecia typified
`by decreased hair density from the vertex to the an(cid:173)
`terior scalp, or hirsutism), who have acne that is re(cid:173)
`sistant to conventional therapy, who q uicldy have a
`relapse after a course ofisotretinoin, or who have
`a sudden onset of severe acne, an evaluation for an(cid:173)
`drogen excess is indicated; this should minimally
`include serum dehydroepiandrosterone and free
`testosterone levels. 41 If these levels are elevated, fur(cid:173)
`ther evaluation for specific disorders (e.g., virilizing
`tumors, congenital adrenal hyperplasia, or poly(cid:173)
`cystic ovary syndrome) may allow for targeted ther(cid:173)
`apies, although a discussion of these therapies is
`beyond the scope of this review.
`Therapy with oral contraceptives containing es(cid:173)
`trogen or with spironolactone, an androgen antag(cid:173)
`onist, is often useful in women with hyperandro(cid:173)
`genism and in women with normal serum androgen
`levels.4 2-47 Norgestimate-ethinyl estradiol (Ortho
`Tri-cyclen) and norethindrone acetate-ethinyl es(cid:173)
`tradiol (Estrostep) are approved by the Food and
`Drug Administration fur the treatment of acne,
`and studies indicate that drospirenone-ethinyl
`estradiol (Yasmin) and levonorgestrel-ethinyl es(cid:173)
`tradiol (Alesse) are also effective. Studies generally
`indicate that after six to nine months of use, there
`is a reduction in inflammatory-lesion counts of30
`to 60 percent, with improvement occurring in 50 to
`90 percent of patients. 43-46 Any oral contraceptive
`that contains estrogen is likely to have similar pos(cid:173)
`itive effects. The effects on acne of injectable
`progestins and patch systems have not been evaluat(cid:173)
`ed, and progesterone-only contraceptives may make
`acne worse.
`Clinical obse1Vation indicates that women with
`
`deep-seated nodules of the lower fuce and neck
`(Fig. 6) are part of a subset of patients in whom
`hormonal treatment may be especially useful.9 A
`response to hormonal inte1Vention may be seen
`after one menstrual cycle, but three to six months
`are needed to judge the full effect Usually, oral con(cid:173)
`traceptives are tried first; if these are ineffective
`after several months, spironolactone, 50 to 100 mg,
`is added. This sequence is sensible, since contra(cid:173)
`ception is warranted when spironolactone is used,
`because of the potential teratogenic effects of this
`drug. Hormonal treatment is especially useful in
`women who desire contraception or have other
`manifestations ofhyperandrogenism, such as irreg(cid:173)
`ular menstrual cycles or hirsutism. Oral antibiotics
`and topical therapy may be used in combination
`with hormonal treatments.48,4 9
`
`lsotretinoin
`Patients with severe acne that does not clear with
`combined oral and topical therapy are candidates
`for treatment with oral isotretinoin. When the use
`of this agent is being considered, an assessment of
`the severity of disease should include the effect of
`the acne on the patient, such as the potential for
`scarring. 50 Isotretinoin reduces the size and secre(cid:173)
`tions of sebaceous glands, secondarily inhibits the
`growth of P. ames and the resulting inflammation,
`and prevents comedogenesis through normaliza(cid:173)
`tion of the differentiation of follicular keratinocytes.
`Isotretinoin thus affects all four pathogenic factors
`of acne, which explains its nearly universal efficacy
`during active therapy. 9•51 In addition, it is the only
`treatment that leads to remission that may be per(cid:173)
`manent. 52
`Approximately40 percent of patients remain free
`of acne after one course of treatment, 40 percent
`have a recurrence oflow severity that responds to
`medications to which the acne had previously been
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`resistant, and 20 percent will need repeated treat(cid:173)
`ment with isotretinoin at a future time. 53 Patients
`younger than 16 years, those with severe acne on
`the trunk, and aduh women are more likely than
`others to have a relapse. 52•5"'57 These first two
`groups may require muhiple courses ofisotretinoin
`over the duration of their acne-prone years, whereas
`the third group is best treated with hormonal ther(cid:173)
`apy. The chance of a prolonged remission is greater
`when a total dose ofU0 to 150 mg per kilogram of
`body weight is achieved. 53 Most patients can be
`started on 20 to 40 mg per day, with an increase
`to 40 to 80 mg over several months. Side effects of
`therapy are dose-dependent and may be limited
`by treatment with reduced doses over an extended
`period.
`Isotretinoinis teratogenic; embryopathy (includ(cid:173)
`ing, characteristically, ear defects combined with
`either central nervous system defects, cardiovascu(cid:173)
`lar defects, or both) has been reported to be caused
`after a single dose. Women of childbearing age
`must closely follow the pregnancy-prevention pro(cid:173)
`gram outlined by the drug's manufacturer. The psy(cid:173)
`cliological status of the patient should also be
`monitored carefully. Ahhough population-based
`studies have not confirmed an association between
`the use ofisotretinoin and the risk of suicide or de(cid:173)
`pression, 50,58,59 there have been case reports of de(cid:173)
`pression that occurred in the first two months after
`the start of treatment, cleared after the cessation of
`therapy, and recurred with the resumption of ther(cid:173)
`apy. 60 Acne is known to be associated with anxiety,
`depression, and a negative self.image, and success(cid:173)
`ful treatment with isotretinoin improves these fac(cid:173)
`tors. Thus, the potential for depression or suicide
`that may accompany treatment with isotretinoin
`must be balanced with the psycliological benefits
`ofeffectivetreatment61
`Isotretinoin may cause hypertriglyceridemia and,
`to a lesser extent, can affect cholesterol levels. Aher(cid:173)
`ations in dosing or dietary interventions usually
`allow for the continuation of treatment. Drying of
`the nasal mucosa may occur, which can lead to col-
`
`onizationofS. aureus, the potential complications of
`which include abscesses, conjunctivitis, impetigo,
`cellulitis, and folliculitis. These complications may
`be prevented with the use ofintranasal bacitracin. 62
`
`Other Forms of Therapy
`The physical removal of comedones and the direct
`injection of steroids into inflamed cysts are two
`tecliniques that have been clinically shown to resuh
`in the rapid relief of acne.63 Other methods such as
`cliemical peels, microdermabrasion, and treatment
`irwolving light, lasers, or radiofrequencies require
`more investigation in order to clarify their role in
`therapy.
`
`AREAS OF UNCERTAINTY
`
`Randomized, controlled trials are needed to define
`the relative efficacies of various therapies and to
`guide the optimal sequence of alternative therapies,
`with attention to long-term efficacy, quality oflife,
`and costs.
`
`GUIDELINES
`
`There are currently no formal up-to-date, evidence(cid:173)
`based guidelines available.
`
`CONCLUSIONS
`AND RE COMMENDATIONS
`
`The management of acne depends on its severity.
`For the patient in the vignette, in whom moderately
`severe acne is present (based on the large number
`of papules and pustules, and their distribution), I
`would prescribe both topical and oral therapy. For
`the face, I would initially prescribe 0.025 percent
`tretinoin for nighttime use, in combination with
`5 percent benzoyl peroxide, in an aqueous vehicle,
`in the morning. I would also prescribe 500 mg of
`tetracycline twice daily. I would see the patient in six
`to eight weeks to assess efficacy, irritation, and com(cid:173)
`pliance and to adjust the regimen accordingly.
`
`REFERENCE S
`
`l. Kraning 1(1(, Odland GF. Prtvalen~,
`mod>idicy and cost of dermatologicdiseases.
`J Invest Dermatol 1979;73:Suppl:395-401.
`2. McConnell RC, Fleischer AB )r, Willi(cid:173)
`ford PM, Feldman SR. Most topical tretinoin
`treatment is for acne vulgaris through the
`age of 44 years, an analysis of the National
`Ambulatory Medical Care Survey, 1990-1994.
`J Am Acad Dermatol 1998;38:221-<'i.
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`3. Mallon E, Newt0nJN, Klassen A, Stew(cid:173)
`art-Brown SL, Ryan 1J, Finlay AY. The
`quality oflife in acne, a comparison with
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`questionnaires. Br J Dermatol 1999;140:
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`4- KooJ. Thepsychosocialimpactofacne:
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`5. Cunliffe W). Acne and unemployment
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`de~ r<!pOrt/teChnology assessment No. V.
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`publication no. 01-E018.)
`7. Thiboutot D, Harris G, lles V, Cimis G,
`Gilliland K, Hagari S. Activity of the type 1
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`1470
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`N ENCLJ MED 352;14 www. NEJM .O RC APRIL7,2005
`
`The New England Journal of Medicine as published by New England Journal of Medicine
`Downloaded from www nejm org at ALLERGAN INC on August 10, 2010 For personal use only No other uses without permission
`Copyright © 2005 Massachusetls Medical Society
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