The NEW ENGLAND JOURNAL of MEDICINE
`
`CLINICAL PRACTICE
`
`Acne
`
`William D.James, M.D.
`
`This Journal feature begins with a case vignette highlighting a common clinical problem.
`Evidence supporting various strategies is then presented,followed by a review offormaI guideIines,
`when they exist. The article ends with the author’s clinical recommendations.
`
`A 17-year-old boy with a six-month history ofacne presents for initial evaluation and
`treatment. Physical examination reveals closed and open comedones and a large num-
`ber oferythematous 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-
`From the Department of Dermatology,
`hood.z Although there are more than 2 million visits to office-based physicians per University of Pennsylvania, Philadelphia.
`year for patients in the age range of 15 to 19 years, the mean age at presentation for N EnglJ Med 2005;352:1463-72.
`treatment is 24 years, with 10 percent of visits taking place when patients are between
`copyr~gh¢ © 2005 Ma~ach~se¢¢s Med~cat So~¢y
`the ages of 35 and 44 years.2 The social, psychological, and emotional impairment that
`can result from acne has been reported to be similar to that associated with epilepsy,
`asthma, diabetes, and arthritis) 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,s Scarring can lead to lifelong problems in regard to self-
`esteem. The direct cost ofacne in the United States is estimated to exceed $1 billion per
`year, with $100 million spent on over-the-counter acne products.°
`Acne is a follicular disease, the principal abnormality of which is impaction and dis-
`tention of the pilosebaceous unit. The cause of the hyperproliferation ofkeratinocytes
`and the abnormalities of differentiation and desquamation are unknown. It is likely that
`hyperresponsiveness to the stimulation ofsebocytes and follicular keratinocytes by
`androgens leads to the hyperplasia of the sebaceous glands and the seborrhea that
`characterize acne.7-9
`Propionibaaerium aches colonizes the follicular duct and proliferates in teenagers with
`acne.~° This organism probably contributes to the development of inflammation. 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.~
`Neutrophils, lymphocytes, and foreign-body giant cells accumulate and produce the
`erythematous papules, pustules, and nodular swellings characteristic of inflamma-
`tory acne.
`
`STRATEGIES AND EVIDENCE
`
`DIAGNOSIS
`
`The diagnosis ofacne 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 for grading the severity of disease have been used. The se-
`verity ofacne is generally assessed by the number, type, and distribution of lesions.
`
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`Copyright © 2005 Massachusetts Medical Society. All rights reserved.
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`The NEW ENGLAND JOURNAL 0fMEDICINE
`
`From a therapeutic standpoint, the presence of
`scarring may lead to a more aggressive approach
`than normally pursued. Table i gives a narrative de-
`scription of acne, accompanied by representative
`photographs that illustrate a simplified classifica-
`tion of severity (Fig. i to 4).
`
`THERAPY .,~.~
`Topical and oral agents for the treatment ofacne
`are listed in Table 2.
`
`P.
`
`Topical Treatment
`
`Topical medications are active onlywhere andwhen
`theyare applied; their main actionis the prevention
`of new lesions. Thus, they should be used daily on
`all areas of the skin that are prone to acne. Mainte-
`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-
`scribed and who use over-the-counter skin prod-
`ucts. Patients should be discouraged from applying
`anything to the face other than what is recommend-
`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-
`ticularly suited for oily skin, whereas creams, lo-
`tions, and ointments are preferable for patients with
`dry, easily irritated skin.
`
`Figure 1. Mild Ache.
`
`Multiple open and closed comedones are present,
`with few inflammatory papules.
`
`. :-i,i: :.
`~- .-
`
`:-~
`
`,.
`
`¢.~. ,.~
`
`Table 1. Classification of Ache.~
`
`Severity
`
`Mild
`
`Description
`
`Comedones (noninflammatory lesions) are the main lesions.
`Papules and pustules (Fig. 1) may be present but are small
`and few in number (generally <10).
`
`Moderate Moderate numbers of papules and pustules (10-40) and come-
`dones (10-40) 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 ache and ache conglobata with many large, pain-
`ful nodular or pustular lesions are present, alongwith many
`smaller papules, pustules, and comedones (Fig. 4A).
`
`a
`
`~
`"
`
`~ ~’
`
`8
`’~
`
`3
`
`d~
`
`.i~__
`
`~"
`
`Figure 2. Moderate Ache.
`
`Erythematous papules and pustules are the predomi-
`
`12
`* The information is from Cunliffe et al. nant lesions, and disease is limited to the face.
`
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`N ENGLJ MED 352;14 WWW, N EJ M,ORG APRIL 7, 2OO5
`
`The New England Journal of Medicine as published by New England Journal of Medicine.
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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
`ofacne, the comedo, and thereby limit the forma-
`tion of inflammatory lesions?9 Some types also
`reduce inflammation by interfering with the inter-
`action between toll-like receptor 2 and external
`products of P. aches on the surface of antigen-pre-
`senting cells.2° In addition, topical retinoids im-
`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
`inflammat°rylesi°nsy’22
`For the mild, primarily comedonal, types ofacne
`(Fig. 1), topical retinoids may be used alone, where-
`
`B
`
`Figure 3. Moderately Severe Acne.
`Erythematous papules, pustules, and nodules are
`present on the face.
`
`Figure 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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`The New England Journal of Medicine as published by New England Journal of Medicine.
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`Copyright © 2005 Massachusetts Medical Society. All rights reserved.
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`The NEW ENGLAND JOURNAL 0fMEDICINE
`
`Table 2. Medications for the Treatment of Acne.
`
`Drug
`
`Topical agents
`
`Retinoids
`
`Tretinoin
`
`Adapalene
`
`Dose
`
`Side Effects
`
`Other Considerations
`
`Applied once nightly;
`strengths of 0.025-
`0.1% available
`
`Applied once daily,
`at night or in the
`morning
`
`Irritation (redness and scaling)
`
`Generics available
`
`Minimal irritation~3
`
`Tazarotene*
`
`Applied once nightly
`
`Irritation
`
`Antimicrobials
`
`Benzoyl peroxide,
`alone or with zinc,
`2.5-10%
`
`Applied once or twice
`daily
`
`Benzoyl peroxide can bleach clothing
`and bedding
`
`Clindamycin, erythro-
`mycin"i"
`
`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,~s
`
`Available over thecounter; 2.5-5%
`concentrations as effective as
`and less drying than 10% con-
`centration
`
`Most effective for inflammatory le-
`sions (rather than comedones);
`resistance a concern when
`used alone
`
`Combination more effective than
`topical antibiotics alone; limits
`development of resistance; use
`of individual products in com-
`bination less expensive and
`appears similarly effective~6
`
`Other topical agents
`
`Azelaic acid, sodium
`sulfacetamide-
`sulfur, salicylic acid"i"
`
`Applied once or twice Well tolerated
`daily
`
`Good adjunctive or alternative
`treatments
`
`as for patients with more severe acne, the use of treatment has begun, but irritation is common.
`these products in combination with topical or Water-based products, as compared with alcohol-
`oral antimicrobial agents is appropriate?2,23 Ran- based products, when used at low peroxide con-
`domized, double-blind, multicenter comparative centrations (2.5 to 5 percent) will help to limit this
`studies have shown a reduction of 38 to 71 per- problem and have an efficacy similar to that of other
`cent in noninflammatory and inflammatory lesion products in this class.2s
`counts. Direct comparisons of topical retinoids have
`Topical clindamycin or erythromycin also may be
`indicated that tazarotene in a 0.1 percent gel is useful, but, as documented in many randomized,
`more efficacious than 0.1 percent tretinoin or 0.1 clinical trials, these agents are most effective when
`percent adapalene,~4,~s although tazarotene also used in combination with benzoyl peroxide or
`tends to be the mostirritating. The maximum ther-
`topical retinoids.i6,26-28 Randomized trials have
`apeutic response to topical retinoids occurs over demonstrated a reduction in total lesion counts of
`approximately 12 weeks.
`50 to 70 percent when combination therapy is
`used.i6,26-28 Moreover, the topical antibiotics din-
`Topical Antimicrobials
`damycin and erythromycin rapidly induce bacterial
`resistance when used as monotherapy, and this re-
`Topical antimicrobial agents are effective in the
`treatment of inflammatory disease.24 Benzoyl per- sistance correlates with decreased clinical effica-
`cy.29,3° Benzoyl peroxide does not induce resistance;
`oxide is a bactericide and is an excellent first-line
`medication. The response to this agent is rapid, when used with topical or oral antibiotics, it pro-
`with improvement noted as early as five days after
`tects against the development of this problem,29
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`N ENGLJ MED 352;14 WWW,N EJ M,ORG APRIL 7, 2OO5
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`CLINICAL PRACTICE
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`Table 2. (Continued.)
`
`Drug
`
`Dose
`
`Side Effects
`
`Other Considerations
`
`Oral antibiotics’,;."
`
`Tetracycline~
`
`Doxycycline~
`
`Minocycline~
`
`Inexpensive; dosing limited by
`Gastrointestinal upset
`250-500 mg once or
`twice daily need to take on empty stomach
`
`50-100 mg once or
`twice daily
`
`50-100 mg once or
`twice daily
`
`Phototoxicity
`
`20-rag dose antiinflammatory
`only; limited data on efficacy~7
`
`Hyperpigmentation of-teeth, oral mucosa,
`and skin; lupus-like reactions with long-
`term treatment
`
`Toxic epidermal necrolysis and allergic eruptions Trimethoprim may be used alone
`One dose (160 mg tri-
`Trimethoprim-sulf-ameth-
`oxazole methoprim, 800 mg in 300-rag dose twice daily;
`limited data available~8
`
`sulf-amethoxazole)
`twice daily
`
`Erythromycin"i"
`
`Hormonal agents¶
`
`Spironolactone~
`
`250-500 mg two to
`four times daily
`
`Gastrointestinal upset
`
`Resistance problematic; consen-
`sus is that efficacy is limited
`
`Higher doses more effective but
`Menstrual irregularities, breast tenderness
`50-200 mg in divided
`doses cause more side effects; best
`given in combination with oral
`contraceptives
`
`Estrogen-containing oral
`contraceptives
`
`Daily
`
`Potential side effects include thromboembolism
`
`Oral retinoid
`
`Isotretinoinll
`
`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 defects; adherence to pregnancy-
`prevention program outlined by drug manu-
`f-acturer, including two initial negative preg-
`nancy tests, is essential; hypertriglyceridemia,
`elevated results on liver-f-unction tests, abnor-
`mal night vision, benign intracranial hyperten-
`sion, dryness of-the lips, ocular, nasal, and oral
`mucosa and skin, secondary staphylococcal
`infections, and arthralgias are possible com-
`mon or important side effects; perform labora-
`tory testing of-lipid profiles and liver-f-unction
`tests monthly until dose is stabilized
`
`* Tazarotene is in pregnancy category X: contraindicated in pregnancy.
`"i" Clindamycin, erythromycin, and azelaic acid are in pregnancy category B: no evidence of-risk in humans.
`:~" 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.
`This drug is in pregnancy category D: positive evidence of-risk in humans.
`¶ Hormonal agents are for use in women only.
`II Isotretinoin 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 sulfaceta-
`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-
`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-
`erythromycin if oral antibiotics are administered,
`juncts or when other medications are not tolerated.
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`N ENGL J MED 352;14 WWW. NEJM.ORG APRIL 7, 2OO5
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`The NEW ENGLAND JOURNAL of MEDICINE
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`Finally, the avoidance of potentially irritating over-
`the-counter astringents, harsh cleansers, or anti-
`bacterial soaps should be emphasized.
`
`.!
`
`",
`
`" :":
`
`" ? :’ -
`
`:.7:- i.i :"]-,~7
`
`i’
`
`q o .’
`
`ORAL THERAPY
`Oral Antibiotics
`Oral antibiotics are indicated for moderate-to-
`severe disease, for the treatment of acne on the
`chest, back, or shoulders, and in patients with in-
`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-
`treated cases. Results from randomized clinical tri-
`als indicate that a 50 to 60 percent rate of improve-
`ment in inflammatory lesions can be expected?~
`However, gastrointestinal side effects and the need
`to tal<e tetracycline on an empty stomach are disad-
`vantages. Clinical experience and limited data have
`suggested that doxycycline, minocycline, and tri-
`methoprim-sulfamethoxazole are more effective
`than tetracycline?2-34 Doxycyline and minocycline
`are both preferred over trimethoprim-sulfameth-
`oxazole because of the side-effect profile.
`Starting the therapy at higher doses is recom-
`mended, since the response cannot be judged for at
`least six weeks and full efficacy is not apparent for
`three months. If little response is seen at six weeks,
`adjustments to the treatment plan such as adding
`topical medication or switching oral antibiotics are
`a month is needed to see a response), improper pa-
`justified,
`tient education, poor compliance with the use of
`After control of the acne is achieved and main-
`rained for at least two months, a reduction in the medication, or the development of resistance to
`dose can be attempted. Oral antibiotic therapy gen- antibiotics ?6 Resistance is an increasing problem,
`erally is taken over a three-to-six-month course,
`since 60 percent of P. aches isolates are resistant to
`Eventual discontinuance is the goal, followed by at least one antibiotic; resistance is most common
`long-term topical therapy (typically with topical reti- with the use oferythyromycin (50 percent ofcases),
`noids alone or in combination with benzoyl perox- clindamycin (35 percent), and tetracycline (25 per-
`36 37
`ide). Controversy exists as to the need for a second cent). , Resistance to antibiotics should be sus-
`form of contraception in women using both oral pected in patients who do not have a response to
`contraceptives and oral antibiotics, but a panel of
`treatment or who have a relapse during treatment,
`experts has recommended a conservative approach especially those who have been on multiple cours-
`-- i.e., two forms of contraception-- given that in- es of oral and topical antibiotics or have a history of
`dividual patients show large decreases in plasma variable compliance. Because resistance to erythro-
`ethinyl estradiol levels when taking antibiotics, in- mycin and clindamycin are often present simulta-
`35
`cluding tetracycline,
`neously, the occurrence of a flare ofacne while one
`of these antibiotics is being used should prompt a
`switch to tetracycline or doxycycline. Tetracycline-
`Lack of Response
`resistant strains ofP. acnes are usually also resistant
`Reasons that acne may have a poor response to
`to doxycycline, so a switch to minocycline is recom-
`treatment with antibiotics include inadequate po-
`tency (e.g., the use of topical therapy for severe dis- mended if resistance to tetracycline is suspected?8
`ease), an inadequate duration of treatment (at least The implications associated with the development
`
`Figure 5. Gram-Negative Folliculitis.
`pustules are centered around the anterior nares.
`
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`N ENGL J MED 352;14 WWW.NEJM.ORG APRIL 7, 2005
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`CLINICAL PRACTICE
`
`of resistant organisms, including Staphylococcus
`aureusin the nares, streptococci in the oropharynx,
`and enterobacteria, are currently uncertain.~9
`Infection with gram-negative organisms may
`also complicate long-term antibiotic therapy. The
`overgrowth of gram-negative organisms in the an-
`terior nares has been reported to occur in 85 per-
`cent of patients treated with oral antibiotics for six
`months or longer.4° In 4 percent of such patients,
`pustules may develop, primarily on the central and
`lower face (Fig. 5); a culture of one of the pustules
`will yield a gram-negative organism identical to
`that present in the anterior nares. Such superin-
`fected acne is best treated with isotretinoin.4°
`
`~..~_~ .
`’
`
`[:~-~- :
`
`/
`
`_~’
`
`Figure 6. Ache on the Lower Face of a Woman.
`
`deep-seated nodules of the lower face and neck
`(Fig. 6) are part of a subset of patients in whom
`hormonal treatment may be especially useful.9 A
`Hormonal Therapy
`response to hormonal intervention may be seen
`In women who have signs of hyperandrogenism
`(e.g., irregular menses, androgenic alopecia typified after one menstrual cycle, but three to six months
`by decreased hair density from the vertex to the an- are needed tojudge the full effect. Usually, oral con-
`terior scalp, or hirsutism), who have acne that is re-
`traceptives are tried first; if these are ineffective
`sistant to conventional therapy, who quickly have a after several months, spironolactone, 50 to 100 rag,
`relapse after a course ofisotretinoin, or who have
`is added. This sequence is sensible, since contra-
`a sudden onset of severe acne, an evaluation for an- ception is warranted when spironolactone is used,
`drogen excess is indicated; this should minimally because of the potential teratogenic effects of this
`include serum dehydroepiandrosterone and free drug. Hormonal treatment is especially useful in
`testosterone levels.4~ If these levels are elevated, fur- women who desire contraception or have other
`ther evaluation for specific disorders (e.g., virilizing manifestations ofhyperandrogenism, such as irreg-
`tumors, congenital adrenal hyperplasia, or poly- ular menstrual cycles or hirsutism. Oral antibiotics
`cystic ovary syndrome) may allow for targeted ther- and topical therapy may be used in combination
`apies, although a discussion of these therapies is with hormonal treatments.48,49
`beyond the scope of this review.
`Isotretinoin
`Therapy with oral contraceptives containing es-
`trogen or with spironolactone, an androgen antag- Patients with severe acne that does not clear with
`onist, is often useful in women with hyperandro- combined oral and topical therapy are candidates
`genism and in women with normal serum androgen
`for treatment with oral isotretinoin. When the use
`levels.42-47 Norgestimate-ethinyl estradiol (Ortho ofthis agent is being considered, an assessment of
`Tri-cyclen) and norethindrone acetate-ethinyl es-
`the severity of disease should include the effect of
`tradiol (Estrostep) are approved by the Food and
`the acne on the patient, such as the potential for
`Drug Administration for the treatment of acne,
`scarring,s° Isotretinoin reduces the size and secre-
`and studies indicate that drospirenone-ethinyl
`tions of sebaceous glands, secondarily inhibits the
`estradiol (Yasmin) and levonorgestrel-ethinyl es- growth of P. aches and the resulting inflammation,
`tradiol (Alesse) are also effective. Studies generally and prevents comedogenesis through normaliza-
`tion of the differentiation of follicular keratinocytes.
`indicate that after six to nine months of use, there
`is a reduction in inflammatory-lesion counts of 30
`Isotretinoin thus affects all four pathogenic factors
`to 60 percent, with improvement occurring in 50 to ofacne, which explains its nearly universal efficacy
`90 percent of patients.43-46 Any oral contraceptive during active therapy.9,s~ In addition, it is the only
`that contains estrogen is likely to have similar pos-
`treatment that leads to remission that may be per-
`itive effects. The effects on acne of injectable manent,s2
`progestins and patch systems have not been evaluat-
`Approximately 40 percent of patients remain free
`ed, and progesterone-only contraceptives may make of acne after one course of treatment, 40 percent
`have a recurrence of low severity that responds to
`acne worse,
`Clinical observation indicates that women with medications to which the acne had previously been
`
`N ENGLJ MED 352;14 WWW,N EJ M,ORG APRIL 7, 2OO5
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`The NEW ENGLAND JOURNAL of MEDICINE
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`AREAS OF UNCERTAINTY
`
`resistant, and 20 percent will need repeated treat- onization ofS. aureus, the potential complications of
`ment with isotretinoin at a future time.ss Patients which include abscesses, conjunctivitis, impetigo,
`younger than 16 years, those with severe acne on cellulitis, and folliculitis. These complications may
`the trunk, and adult women are more likely than be prevented with the use ofintranasal bacitracin.62
`others to have a relapse,s2,s4-s7 These first two
`groups may require multiple courses ofisotretinoin Other Forms of Therapy
`over the duration of their acne-prone years, whereas The physical removal ofcomedones and the direct
`the third group is best treated with hormonal ther-
`injection of steroids into inflamed cysts are two
`apy. The chance of a prolonged remission is greater
`techniques that have been clinically shown to result
`when a total dose of 120 to 150 mg per kilogram of in the rapid reliefofacne.6s Other methods such as
`body weight is achieved,ss Most patients can be chemical peels, microdermabrasion, and treatment
`started on 20 to 40 mg per day, with an increase
`involving light, lasers, or radiofrequencies require
`to 40 to 80 mg over several months. Side effects of more investigation in order to clarify their role in
`therapy are dose-dependent and may be limited
`therapy.
`by treatment with reduced doses over an extended
`period.
`Isotretinoin is teratogenic; embryopathy (includ-
`ing, characteristically, ear defects combined with Randomized, controlled trials are needed to define
`either central nervous system defects, cardiovascu-
`the relative efficacies of various therapies and to
`lar defects, or both) has been reported to be caused guide the optimal sequence of alternative therapies,
`after a single dose. Women of childbearing age with attention to long-term efficacy, quality of life,
`must closely follow the pregnancy-prevention pro- and costs.
`gram outlined by the drug’s manufacturer. The psy-
`chological status of the patient should also be
`monitored carefully. Although population-based
`studies have not confirmed an association between There are currently no formal up-to-date, evidence-
`the use ofisotretinoin and the risk of suicide or de- based guidelines available.
`pression,s°,sS,s9 there have been case reports of de-
`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-
`apy.6° Acne is known to be associated with anxiety, The management of acne depends on its severity.
`depression, and a negative self-image, and success- For the patient in the vignette, in whom moderately
`ful treatment with isotretinoin improves these fac-
`severe acne is present (based on the large number
`tors. Thus, the potential for depression or suicide of papules and pustules, and their distribution), I
`that may accompany treatment with isotretinoin would prescribe both topical and oral therapy. For
`must be balanced with the psychological benefits
`the face, I would initially prescribe 0.025 percent
`tretinoin for nighttime use, in combination with
`of effective treatment.6~
`Isotretinoin may cause hypertriglyceridemia and, 5 percent benzoyl peroxide, in an aqueous vehicle,
`in the morning. I would also prescribe 500 mg of
`to alesser extent, can affect cholesterol levels. Alter-
`ations in dosing or dietary interventions usually
`tetracycline twice daily. I would see the patient in six
`allow for the continuation oftreatment. Drying of
`to eight weeks to assess efficacy, irritation, and corn-
`the nasal mucosa may occur, which can lead to col- pliance and to adjust the regimen accordingly.
`
`GUIDELINES
`
`CONCLUSIONS
`A N D R E C O M M E N D AT I O N S
`
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`Copyright © 2005 Massachusetts Medical Society. M1 rights reserved.
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