Drug Information

Treatment of acne vulgaris

Treatment of acne vulgaris
Treatment of acne vulgaris
Treatment of acne vulgaris
Author
Emmy Graber, MD
Section Editors
Robert P Dellavalle, MD, PhD, MSPH
Moise L Levy, MD
Mark V Dahl, MD
Deputy Editor
Abena O Ofori, MD

INTRODUCTION — Although acne is not physically disabling, its psychological impact can be striking, contributing to lower self-esteem, depression, and anxiety [1-3] . As a result, there is a significant demand for effective acne therapies. In 2001, the global market for prescription acne products was estimated to be two billion dollars; the non-prescription market was estimated at two to four times that size [4] .

A variety of medications are available for the treatment of acne. The lack of standardization for grading acne severity and measuring treatment outcomes has made systematic interpretation of the literature difficult [5] . However, quality evidence-based literature in the field of acne is growing [6] .

The clinical findings and therapeutic principles that support the selection of specific treatment regimens will be discussed here. A table summarizing the treatment recommendations for patients with acne vulgaris is provided (figure 1).

In addition, the anti-acne products will be reviewed, including topical retinoids, topical antimicrobials, azelaic acid, oral antibiotics, and hormonal therapies (table 1). Adjunctive therapies and over-the-counter regimens, oral isotretinoin, hormonal therapies, and the pathogenesis and diagnosis of acne vulgaris are reviewed separately. (See "Light-based, adjunctive, and other therapies for acne vulgaris" and "Oral isotretinoin therapy for acne vulgaris" and "Hormonal therapy for women with acne vulgaris" and "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris".)

PATIENT ASSESSMENT — The treatment of acne includes a number of topical and systemic therapies and is guided by several clinical features (table 1) [6] . Deciding on the appropriate course of treatment for an individual patient requires a comprehensive assessment that includes:

  • Clinical type of acne (eg, comedonal, inflammatory, nodular)
  • Severity of acne
  • Skin type (dry, oily)
  • Presence of acne scarring or postinflammatory hyperpigmentation
  • Menstrual history and history of signs of hyperandrogenism in women
  • History of prior successful and failed treatments
  • History of acne-promoting medications
  • Psychological impact of acne on the patient

The presence or absence of acne scarring should be assessed. Patients with acne who are experiencing scarring may warrant more aggressive initial therapy. In addition, acne-related postinflammatory hyperpigmentation can be distressing for patients. Patients with postinflammatory hyperpigmentation can benefit from the use of medications or procedures that accelerate resolution. (See 'Therapy for postinflammatory hyperpigmentation' below.)

Women with irregular menses or signs of hyperandrogenism may warrant laboratory work-up and anti-androgenic therapies. (See "Hormonal therapy for women with acne vulgaris" and "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris", section on 'Hyperandrogenism'.)

Certain medications can cause acne. If medication-induced acne is suspected, the risks and benefits of discontinuing the medication should be addressed (table 2). (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris", section on 'Drug-induced acne'.)

OVERVIEW OF TREATMENT

General approach to treatment — Four key factors promote the development of acne lesions (figure 2). These factors are targeted during therapy, and include [7] :

  • Follicular hyperproliferation and abnormal desquamation
  • Increased sebum production
  • Propionibacterium acnes (P. acnes) proliferation
  • Inflammation

Follicular hyperkeratinization and abnormal corneocyte desquamation lead to follicular obstruction. This, in combination with the androgen-stimulated increase in sebum production, promotes the formation of the microcomedo, the earliest lesion of acne. The microcomedo enlarges to form a comedo as lipids, bacteria, and desquamated corneocytes accumulate (picture 1A-B). P. acnes can proliferate in this environment. Follicular rupture may occur, leading to a host inflammatory response, with the appearance of papules and pustules consistent with inflammatory acne (picture 2). (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris".)

Effective management of acne involves the use of therapeutic agents that combat these factors (table 1). A global panel of experts has recommended a comprehensive treatment plan for patients with acne vulgaris (figure 1) [8] . Patients should be given realistic expectations regarding timelines for improvement. It takes approximately eight weeks for a microcomedo to mature. Thus, therapy must be continued beyond this duration in order to assess efficacy.

Topical retinoids are effective in the treatment of comedonal acne due to their ability to normalize follicular hyperkeratosis and prevent formation of the microcomedo [9] . Topical retinoids also improve inflammatory acne [8,10] . This may be due to a combination of intrinsic anti-inflammatory properties of topical retinoids and their ability to prevent the formation of microcomedones. (See 'Topical retinoids' below.)

Topical retinoids can be used as monotherapy in individuals with exclusively comedonal acne. However, patients with an inflammatory component often benefit from the addition of concomitant antimicrobial therapies (eg, benzoyl peroxide or topical antibiotics) that reduce the number of proinflammatory P. acnes colonizing the skin. (See 'Topical antimicrobials' below.)

Patients with moderate to severe inflammatory acne often warrant more aggressive treatment with oral antibiotics [7] . Antibiotics in the tetracycline class are most frequently used, and appear to have both antibacterial and anti-inflammatory properties. The use of benzoyl peroxide with topical or oral antibiotics decreases the emergence of antibiotic resistant bacteria. (See 'Oral antibiotics' below.)

Acne typically recurs over years and maintenance therapy is an important component of acne management. The preventive effect of topical retinoids and the concern for antibiotic resistance make topical retinoids ideal candidates. If clinical improvement cannot be maintained with topical retinoid monotherapy, an antimicrobial agent containing benzoyl peroxide can be added [11] . (See 'Maintenance therapy' below.)

Androgens stimulate increased sebum production, which contributes to the formation of acne [9] . Hormonal therapy may benefit women with moderate to severe acne, even in the absence of a hyperandrogenic state. (See "Hormonal therapy for women with acne vulgaris".)

Oral isotretinoin, a retinoid, decreases sebum production, reduces P. acnes colonization, and normalizes follicular keratinization. It is an option for patients with severe acne that essentially cures or significantly improves acne in the majority of patients who complete a full course of treatment [12] . Oral isotretinoin is used as monotherapy; a typical treatment course is approximately 20 weeks. This drug has multiple side effects and is US Food and Drug Administration (FDA) approved only for use in patients with severe, recalcitrant, nodular acne [13] . Oral isotretinoin is teratogenic and female patients who are potentially childbearing should utilize two forms of contraception. (See "Oral isotretinoin therapy for acne vulgaris".)

Adjunctive therapies, such as light-based and laser therapies, chemical peels, comedo extraction, and intralesional glucocorticoids have also been used for acne management. (See "Light-based, adjunctive, and other therapies for acne vulgaris".)

Choice of vehicles for topical treatments — The choice of delivery system for topical acne medications depends upon the patient's skin type (dry versus oily) and preference. Gels have a drying effect; they may be preferred by patients with oily skin. Creams and lotions tend to be moisturizing. Solutions are drying but they cover large areas more easily than other preparations, and foams are easy to apply to hair-bearing areas. Pledgets are single-use absorbent pads impregnated with medication. They are convenient to use, and facilitate the spreading of medication over large areas.

Further modifications to the vehicle of a drug may also affect characteristics such as efficacy, tolerability, or stability. As an example, the microsphere formulation of tretinoin consists of tretinoin contained in microscopic biodegradeable spherical particles. As the microspheres are degraded, tretinoin is slowly and progressively delivered to the skin. This formulation is associated with improved drug stability and decreased irritation [14,15] . (See 'Topical retinoids' below.)

TOPICAL RETINOIDS — Topical retinoids are used for the treatment of both noninflammatory and inflammatory acne, and should be included in the initial management of most patients.

Topical retinoids are vitamin A derivatives that act by binding to two nuclear receptor families within keratinocytes: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR) [16] . The retinoid-receptor complexes are transported into the nucleus where they activate specific regulatory DNA sequences called retinoid hormone response elements, thereby stimulating the transcription of target genes. These events contribute to the normalization of follicular keratinization and decreased cohesiveness of keratinocytes, resulting in reduced follicular occlusion and microcomedone formation [17] .

In addition to this direct effect of retinoids on comedogenesis, retinoids may also improve inflammatory acne through other mechanisms. The retinoid-receptor complex competes for coactivator proteins of AP-1, a key transcription factor involved in inflammation [16,18] . Retinoids also down-regulate expression of toll-like receptor (TLR)-2, which has been implicated in the inflammatory response in acne [19,20] .

The first topical retinoid for the treatment of acne, all-trans retinoic acid (tretinoin), is still extensively used. Adapalene and tazarotene are other effective topical retinoids. Topical isotretinoin is not available in the United States, but is utilized in other countries. Properties of the individual preparations and comparisons of the available drugs are discussed below (table 1). (See 'Comparative studies' below.)

Combination gels containing a retinoid and an antimicrobial are available (table 3). (See 'Combination therapy' below.)

Evidence for efficacy — Multiple studies support the efficacy of topical retinoids in the treatment of acne vulgaris [10,21-30] . Representative trials of topical retinoids versus placebo include:

  • A 12-week randomized trial of 60 patients with acne vulgaris treated with tretinoin 0.05% solution, tretinoin 0.025% solution, or placebo showed greater reductions in acne lesions with the tretinoin formulations than with placebo [21] .
  • In a 12-week randomized controlled trial, 200 patients were given either adapalene 0.1% gel or vehicle. Treatment with adapalene led to significantly greater reductions in total, inflammatory, and noninflammatory lesions [29] . The mean percent reduction in total lesion counts at the end of therapy was 63.2 percent for patients who received adapalene gel versus 36.9 percent for patients treated with vehicle.
  • A 12-week trial involved 653 patients who were randomly assigned to treatment with adapalene 0.3% gel, adapalene 0.1% gel, or vehicle [25] . Adapalene 0.3% gel, adapalene 0.1% gel, and vehicle gel yielded 55.6, 48.2, and 36.4 percent reductions in total lesion counts, respectively. Thus, adapalene products were more effective than vehicle alone.
  • Pooled results of two randomized controlled trials of a total of 847 patients with acne vulgaris treated with tazarotene 0.1% cream or vehicle for 12 weeks showed a significantly greater reduction in noninflammatory, inflammatory, and total lesion counts in patients treated with tazarotene compared with patients who received the vehicle [28] . The median percent reduction in total lesion counts for patients treated with tazarotene was 43 percent compared with 23 percent for patients treated with vehicle.

In addition to treating active acne, retinoids accelerate the resolution of acne-induced post-inflammatory hyperpigmentation [16] . This complication occurs more frequently in patients with darker skin pigmentation, and is often a significant concern. (See 'Therapy for postinflammatory hyperpigmentation' below.)

Topical retinoids are also useful as maintenance therapy for patients who have responded to initial treatment [31-34] . The use of retinoids as maintenance therapy can diminish the prolonged use of antibiotics [9] . (See 'Maintenance therapy' below.)

In addition, topical retinoids may enhance the penetration of other topical acne medications [9,35] .

Salicylic acid and azelaic acid are alternative comedolytic therapies for patients who are unable to tolerate topical retinoids, but may be less effective. (See "Light-based, adjunctive, and other therapies for acne vulgaris" and 'Azelaic acid' below.)

Instructions for application — The topical retinoids are applied once daily and traditionally at night due to photolability reported with tretinoin [36] . Adapalene is more light-stable [37] . In addition, a newer formulation of tretinoin, tretinoin gel microsphere (Retin-A Micro®), is less affected by light exposure than its precursors. In a study in which tretinoin gel microsphere 0.1% and tretinoin 0.025% gel were exposed to simulated solar ultraviolet radiation, 94 percent of tretinoin in the microsphere formulation remained stable after two hours, compared to only 19 percent of tretinoin in the 0.025% gel [38] .

Tretinoin should not be applied at the same time as benzoyl peroxide. Tretinoin is less stable when exposed to benzoyl peroxide due to oxidation, an effect magnified during light exposure [36,38] . Adapalene and tretinoin gel microsphere remain more stable than tretinoin in the presence of benzoyl peroxide [36-38] . A combination product, containing adapalene-benzoyl peroxide (Epiduo®) is available.

Patients should be directed to apply a thin layer of the topical retinoid to the affected areas; a pea-sized amount of medication is usually sufficient to cover the face. Due to the preventive effect of topical retinoids on acne, the medication should be applied to the entire affected area, not as spot treatment of individual lesions. Skin should be dry at the time of application.

Adverse effects — Topical retinoids cause irritation, dryness, and flaking of the skin, an effect most notable during the first month of therapy [16] . To minimize irritation, patients should avoid the concomitant use of over-the-counter irritating products, such as harsh soaps, toners, astringents, and alpha hydroxy acid or salicylic acid products [39] . A gentle non-soap cleanser should be recommended. (See 'Home skin care recommendations' below.)

If irritation is a problem, a decrease in the frequency of application to every other or every third night can be considered, and the frequency of application can be increased as tolerance improves. The fine skin flaking that is often seen can be gently exfoliated with a washcloth [40] . A non-comedogenic facial moisturizer can be applied on top of the retinoid if needed.

Some patients may notice a transient worsening of acne during the first few weeks of topical retinoid therapy [41] . These flares spontaneously resolve with continued treatment [42] .

Topical retinoids are not true photosensitizing drugs, but patients using topical retinoids have described symptoms of increased sun sensitivity. This is thought to be due to thinning of the stratum corneum leading to a decreased barrier against ultraviolet light exposure, as well as an enhanced sensitivity due to the presence of cutaneous irritation [40] . The use of sun-protective clothing and/or sunscreen is recommended, particularly when prolonged sun exposure is anticipated [40] .

A large randomized trial evaluating the use of long term topical tretinoin 0.1% cream for the prevention of basal cell and squamous cell carcinoma reported an increase in mortality in elderly men [43] . However, there is a possibility that these findings may have been due to chance in the population studied, and the applicability of these findings to the use of tretinoin in younger patients for the treatment of acne is uncertain. (See "Treatment of actinic keratosis", section on 'Overview of treatment'.)

The use of topical retinoids is not recommended in pregnancy. In particular, tazarotene is a pregnancy category X drug. (See 'Pregnancy and acne therapy' below.)

Tretinoin and isotretinoin — Topical tretinoin (all-trans retinoic acid) is available in multiple strengths and formulations. Irritation may be minimized by starting with the lowest strength preparation (0.025 percent cream) and then increasing the potency as tolerated (table 1). In one study in which different formulations of tretinoin were applied under occlusion to the backs of 28 healthy subjects, the irritation potential of tretinoin in ascending order was: 0.025% cream and 0.01% gel, followed by 0.025% gel, followed by 0.05% cream and 0.1% cream [44] . A newer 0.05% gel product is also available. Gels are more drying than creams, and patients may prefer one formulation over another.

A microencapsulated form of tretinoin gel (Retin-A Micro®) is less irritating, and is available as a 0.04% and 0.1% gel. Similarly, reduced irritation has been noted with a polyolprepolymer-2 base (Avita®) [45] .

Topical isotretinoin, the 13-cis isomer of retinoic acid, is not available in the United States, but is also effective for the treatment of acne vulgaris [46-48] . The drug is manufactured as a 0.05% gel and a 0.1% cream.

Adapalene — Adapalene is available as a 0.1% cream, 0.1% gel, 0.1% lotion, and a 0.3% gel. Adapalene 0.1% gel produces less irritation than tretinoin 0.025% gel and cream [49,50] . (See 'Comparative studies' below.)

Tazarotene — Tazarotene can be prescribed as a 0.05% or 0.1% cream or gel. Tazarotene is used for the treatment of psoriasis as well as acne. Only the 0.1% strength is approved by the US FDA for the treatment of acne. In general, tazarotene has been considered the most effective, but also most irritating topical retinoid, when compared with adapalene and tretinoin [40] . (See 'Comparative studies' below.)

A short-contact regimen with tazarotene is another treatment option, and can decrease irritation. Patients apply tazarotene for up to five minutes daily, then wash off the medication [51] .

Tazarotene is contraindicated in pregnancy (pregnancy category X (table 4)). (See 'Pregnancy and acne therapy' below.)

Comparative studies — Randomized trials and their meta-analyses have compared the efficacy and tolerability of topical retinoids. Interpretation of results needs to take into account the drug concentrations and formulations. The trials do not definitively support the use of one topical retinoid over another.

A meta-analysis of five randomized trials found that adapalene 0.1% gel and tretinoin 0.025% gel had similar efficacy, but adapalene was somewhat better tolerated and produced more rapid improvement [49] . Adapalene 0.1% gel also appeared to have equivalent efficacy and greater tolerability when compared to tretinoin microsphere 0.1% gel or tretinoin 0.05% cream [52,53] .

A multicenter randomized trial found that the reduction in noninflammatory lesions was greater with tazarotene 0.1% gel than tretinoin 0.025% gel (55 versus 42 percent reduction) [54] . The preparations were similarly effective in reducing inflammatory lesions; tazarotene caused more skin irritation.

Randomized trials found that tazarotene cream and gel were more efficacious than adapalene cream and gel at the same concentrations (0.1%); the creams had similar tolerability, but adapalene gel was better tolerated than tazarotene gel during the first few weeks of treatment [55,56] . In another trial, adapalene 0.3% gel was noninferior to tazarotene 0.1% gel and remained better tolerated [57] .

From these studies, it appears that adapalene is the best tolerated. Tazarotene may be more effective but is the most irritating.

TOPICAL ANTIMICROBIALS — Topical antimicrobials are used to decrease the number of P. acnes colonizing the skin, with the goal of reducing the inflammatory response that occurs in acne. The most commonly used topical antimicrobials include benzoyl peroxide, clindamycin, and erythromycin. Sulfacetamide and dapsone are additional treatment options. A list of topical antimicrobial preparations for the treatment of acne is provided (table 1).

Combination therapy with a topical antimicrobial plus a topical retinoid appears to be more effective than either agent alone, and is recommended for the treatment of patients with inflammatory acne [9,58] . (See 'Combination therapy' below.)

Benzoyl peroxide — In addition to its antibacterial properties, benzoyl peroxide is also comedolytic. The drug is available in the United States in both prescription and non-prescription products as 2.5 to 10% gels, lotions, creams, pads, masks, and cleansers, and is usually applied twice daily. Concentrations of benzoyl peroxide that are higher than 2.5% may not contribute to increased benefit. In one study, 2.5% benzoyl peroxide was as effective as 10% benzoyl peroxide in reducing the number of inflammatory acne lesions [59] . However, increased concentrations can lead to increased skin irritation.

Irritation caused by benzoyl peroxide may appear as erythema, scaling, xerosis, or stinging, tightening, or burning sensations [4] . Although irritation is common, true allergic contact dermatitis to benzoyl peroxide is rare. Only 0.25 to 2.5 percent of patients develop a true allergic contact sensitivity [60,61] . Patients should also be advised that benzoyl peroxide can cause bleaching of the hair and clothing.

READ MORE::  Acetaminophen for Low Back Pain

Antibiotics may promote the appearance of resistant strains of P. acnes when used alone. Resistance is diminished by combination use with benzoyl peroxide. (See 'Combination therapy' below.)

Tretinoin and benzoyl peroxide should not be applied simultaneously to the skin due to the oxidizing effect of benzoyl peroxide on tretinoin. If both agents are prescribed, benzoyl peroxide should be applied in the morning, and tretinoin in the evening. Adapalene and the microsphere formulation of tretinoin appear to be more stable in the presence of benzoyl peroxide. (See 'Instructions for application' above.)

Topical antibiotics — Topical antibiotics reduce the numbers of P. acnes in the sebaceous follicles and thereby suppress inflammation in patients with inflammatory acne. In addition to erythromycin and clindamycin, topical preparations of sulfacetamide and dapsone are available. All topical antibiotics may occasionally cause skin irritation.

Erythromycin and clindamycin — Topical erythromycin and clindamycin are the most common topical antibiotics used for the treatment of acne. Erythromycin is available in gel and solution formulations; clindamycin is available as a gel, solution, lotion, foam, or as pledgets (antibiotic impregnated wipes). Erythromycin and clindamycin are often used in 2 and 1% concentrations, respectively.

Topical erythromycin and clindamycin should not be used as monotherapy for acne, as evidence shows better treatment efficacy when these drugs are combined with retinoids or benzoyl peroxide [62] . In addition, the use of benzoyl peroxide with antibiotics decreases the occurrence of bacterial resistance. (See 'Combination therapy' below.)

Combination gels containing benzoyl peroxide or tretinoin combined with an antibiotic are available (table 3).

Sulfacetamide — Sulfacetamide is an antibacterial agent that inhibits P. acnes. It is often combined with 5% sulfur. (See "Light-based, adjunctive, and other therapies for acne vulgaris", section on 'Sulfur'.)

Sulfacetamide should not be used in patients with sulfa or sulfonamide allergies [4] . Data regarding the effectiveness of sulfacetamide in the treatment of acne are limited [63-65] , and other antimicrobials are preferred as first-line therapy.

Dapsone — Dapsone 5% gel is a newer effective treatment for acne vulgaris. Oral dapsone is known to have anti-inflammatory and antimicrobial properties, although the mechanism through which dapsone gel improves acne has not been confirmed. Both inflammatory and noninflammatory acne lesions improve with treatment, with the greatest improvement occurring in inflammatory lesions [66,67] . In two phase 3 randomized trials with a total of 3010 patients, the percent reduction of inflammatory lesions after 12 weeks of twice daily treatment was significantly greater in patients treated with topical dapsone than in those treated with vehicle (48 versus 42 percent) [66] . An open label long-term study of patients treated with the same regimen for up to 12 months (mean 253 days) found a reduction in inflammatory lesions of 58 percent [67] .

An increased risk of hemolytic anemia is seen in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency taking oral dapsone. However, patients with G6PD deficiency and acne have tolerated topical dapsone gel [66,68] . Testing for G6PD deficiency is not necessary for use of the topical preparation of dapsone. In addition, dapsone is a sulfone, not a sulfonamide, and topical dapsone is not contraindicated in sulfonamide (“sulfa”) allergic patients [69] .

Temporary yellow to orange discoloration of the skin and hair may occur when dapsone gel and topical benzoyl peroxide are applied concomitantly [70,71] . In one study, 7 out of 100 patients experienced this adverse effect when the two drugs were applied 10 minutes apart; discoloration resolved between 4 and 57 days after discontinuation of therapy [70] . If both drugs are prescribed for the treatment of acne, applying the drugs at separate times of the day and washing skin between applications may reduce the risk of this side effect.

COMBINATION THERAPY — For patients with inflammatory acne, combining a topical retinoid with antimicrobial agent(s) is recommended [9] . Combination therapy with a topical antibiotic plus a topical retinoid appears to be more effective than either agent alone. The use of benzoyl peroxide with topical or oral antibiotics is also recommended. Adding benzoyl peroxide reduces the development of antibiotic resistance.

Several combination products are available in the United States (table 3).

Topical retinoid and topical antimicrobial — Multiple studies comparing monotherapy versus combination therapy with topical retinoids and antimicrobials (erythromycin, clindamycin, or benzoyl peroxide) have demonstrated improved treatment efficacy with combination therapy [31,58,72-83] . Representative trials include:

  • A randomized controlled trial of 249 patients with mild to moderate acne vulgaris evaluated treatment with adapalene 0.1% gel plus clindamycin 1% lotion versus clindamycin plus vehicle [75] . Significantly greater reductions in total lesions were seen in patients who received combination therapy (46.7 versus 25.5 percent). Improvement was seen in both inflammatory and noninflammatory lesions.
  • Two 12-week randomized controlled trials involving a total of 2219 patients with acne vulgaris compared treatment with a combination hydrogel containing 1% clindamycin and 0.025% tretinoin to one of three treatments: each agent as monotherapy or vehicle [58] . The efficacy of the combination hydrogel was superior to monotherapy and vehicle in the reduction of inflammatory, noninflammatory, and total lesions. The reductions in total lesion counts for the combination hydrogel, clindamycin gel, tretinoin gel, or vehicle were 48.7, 38.3, 40.3, and 23.2 percent, respectively.
  • A 12-week randomized controlled trial with 517 subjects compared treatment of acne vulgaris with an adapalene 0.1% and benzoyl peroxide 2.5% combination gel to monotherapy with each drug and to vehicle [74] . Treatment with the combination gel was more effective, with a significantly greater reduction in total lesion counts noted as early as one week after starting therapy. At the end of treatment, the combination gel, adapalene, benzoyl peroxide, and vehicle groups exhibited 51, 35.4, 35.6, and 31 percent reductions in total lesion counts.

The use of multiple anti-acne active ingredients may cause skin irritation. In one small trial, adapalene 0.1% gel was less irritating than tazarotene 0.05% cream or tretinoin microsphere 0.04% gel when used in combination regimens [84] .

The topical retinoid and topical antimicrobial combination products available in the United States include:

  • Clindamycin 1.2% and tretinoin 0.025% gel (Ziana®, Veltin®)
  • Benzoyl peroxide 2.5% and adapalene 0.1% (Epiduo®)

Antibiotics and benzoyl peroxide — As a result of the widespread use of topical antibiotics, resistance to these agents has increased [85] . Unlike the topical antibiotics erythromycin and clindamycin, P. acnes resistance to benzoyl peroxide has not been identified. Combining antibiotic therapy with the use of benzoyl peroxide decreases the development of antibiotic resistance and improves treatment efficacy [62,85-89] .

One randomized trial found that a combination 3% erythromycin and 5% benzoyl peroxide gel was superior to either agent alone in terms of antibacterial activity [90] . The combination gel also led to clinical improvement in an open-label study of patients with pretreatment erythromycin-resistant P. acne strains [90] .

Combination therapy with clindamycin and benzoyl peroxide is also more potent than monotherapy with either agent. In an open-label study, the combination of benzoyl peroxide and clindamycin decreased the numbers of P. acnes found on healthy skin more effectively than clindamycin alone [91] . The clinical efficacy of combination benzoyl peroxide and clindamycin gel was assessed in a meta-analysis of randomized trials [92] . The meta-analysis found that gels containing benzoyl peroxide and clindamycin were modestly superior to benzoyl peroxide alone for the treatment of inflammatory acne lesions (mean percent reduction in lesions 56 (95% CI 54-58) versus 44 percent (95% CI 41-46) after treatment for 10 to 12 weeks). In addition, treatment with gels containing benzoyl peroxide and clindamycin resulted in more rapid improvement of both inflammatory and noninflammatory lesions than clindamycin alone (mean percentage reductions in lesions were 41 (95% CI 37-44) versus 21 percent (95% CI 17-26) and of 26 percent (95% CI 22-30) versus 10 percent (95% CI 5-15), respectively, after two to four weeks of treatment).

Three topical benzoyl peroxide and antibiotic combination products are available in the United States:

  • Benzoyl peroxide 5% and clindamycin 1% gel (Benzaclin®, Duac®)
  • Benzoyl peroxide 5% and erythromycin 3% gel (Benzamycin®)
  • Benzoyl peroxide 2.5% and clindamycin 1.2% gel (Acanya®)

When oral antibiotic therapy is indicated, concomitant use of topical benzoyl peroxide is also advised to decrease antibiotic resistance. For patients who may not tolerate continuous use of benzoyl peroxide, pulse therapy of benzoyl peroxide or use between antibiotic courses has been suggested [11] .

AZELAIC ACID — Azelaic acid is a naturally occurring dicarboxylic acid with antimicrobial, comedolytic, and mild anti-inflammatory properties. Azelaic acid also has an inhibitory effect on tyrosinase, and can improve acne-induced postinflammatory hyperpigmentation. The product is available in a 15% gel and 20% cream.

Azelaic acid 20% cream is effective for the treatment of both inflammatory and non-inflammatory acne, and has comparable efficacy to tretinoin 0.05% cream, benzoyl peroxide 5% gel, or topical 2% erythromycin for mild to moderate acne [93] .

The 15% gel is FDA approved only for the treatment of rosacea, although it is approved for the treatment of acne in many European countries. Two randomized controlled trials revealed that azelaic acid gel is well-tolerated and as effective as 5% benzoyl peroxide gel or 1% clindamycin gel in the treatment of mild to moderate acne vulgaris [94] .

ORAL ANTIBIOTICS — Multiple studies, including randomized trials, have shown oral antibiotics effective for the management of inflammatory acne [63,95-102] . Utilization of these drugs is primarily indicated for patients with moderate to severe inflammatory acne [103] . Oral antibiotics may also be used for patients who have milder truncal acne, for whom the application of topical antibiotics is difficult.

Oral antibiotics improve inflammatory acne by inhibiting the growth of P. acnes within the pilosebaceous unit. The tetracycline antibiotics also have direct anti-inflammatory properties [104] .

Systemic antibiotics produce more rapid clinical improvement than topical preparations, but may induce side effects such as vaginal candidiasis or gastrointestinal distress.

Oral antibiotics should be prescribed for a limited course to limit the emergence of antibiotic resistance. Optimally, they are prescribed for daily use for less than six months with subsequent discontinuation as acne improves [9,103] . In 2003, a panel of experts recommended limiting therapy to 12 to 18 weeks [9] . No consensus exists regarding whether oral antibiotics should be tapered or abruptly stopped [103] . Oral antibiotics used in the treatment of acne include tetracycline, doxycycline, minocycline, erythromycin, trimethoprim-sulfamethoxazole, clindamycin, and azithromycin (table 1).

Antibiotic resistance — Antibiotic resistance is increasing in patients with acne. One report suggests that the incidence of P. acnes antibiotic resistance increased from 20 percent in 1978 to 62 percent in 1996 [105] . Factors that contribute to this increasing incidence include the widespread use of oral antibiotics and the practice of rotating antibiotics. Resistance is most commonly reported with erythromycin; resistance to minocycline is rare, but may be emerging in the United States [106] .

The rise of P. acnes antibiotic resistance is a concern for acne management; there is some evidence that the presence of resistant organisms can reduce treatment efficacy [107] . There is also concern that long-term antibiotic therapy affects other host bacterial flora, although the clinical impact of this is unclear. In one cross-sectional study (n = 107), patients taking oral tetracyclines or topical antibiotics for at least three months had a three-fold increase in the prevalence of Streptococcus pyogenes in the oropharynx compared with those who were not on antibiotic therapy (33 versus 10 percent) [108] . However, the number of patients reporting upper respiratory tract illness or symptoms was not different in the two groups. In a separate retrospective study of 118,496 subjects, patients treated with topical or oral antibiotics for acne exhibited a two-fold greater risk of upper respiratory infections [109] .

The following practices may reduce the incidence of resistance:

  • Only prescribe antibiotics when necessary. The duration of treatment should be limited; an oral antibiotic should be discontinued when there is no additional clinical improvement or clinical improvement is absent [11] . One panel of experts suggested limiting treatment courses to a maximum of 12 to 18 weeks [9] .
  • In order to avoid changing oral antibiotics prematurely, six to eight weeks of therapy should be allowed prior to evaluating treatment efficacy [103,110] . After six to eight weeks, a change in the antibiotic can be considered if there is no response. In cases in which a partial response is seen, therapy should be continued and response reassessed after another six to eight weeks.
  • If oral antibiotics are stopped and need to be restarted, prescribe the same antibiotic the second time as long as it remains effective [11,103] .
  • An expert international panel, convened to develop optimal strategies for acne treatment, advises that patients should not be simultaneously treated with a topical antibiotic and an oral antibiotic that have different mechanisms of action [9] .
  • Prescribe benzoyl peroxide at the start of antibiotic therapy [103] . Concomitant use of benzoyl peroxide can decrease the incidence of antibiotic resistance. (See 'Topical antimicrobials' above.)
  • Prescribe a topical retinoid. A topical retinoid should be used at the start of treatment with an oral antibiotic [11,111] . Combination therapy with a retinoid and oral antibiotic improved treatment efficacy in several studies, including two randomized trials [112-116] .
  • Topical retinoids are effective as long-term maintenance therapy [31-34]  and can decrease dependence on the extended use of antibiotics [9] . (See 'Maintenance therapy' below.)

In select cases, antibiotics may be continued indefinitely at the lowest effective dose in patients with persistent acne, although this practice can lead to antibiotic resistance. Oral isotretinoin can be another option for patients who are unable to discontinue oral antibiotics despite adherence to a regimen for maintenance therapy [9] . (See 'Maintenance therapy' below.)

Macrolides — Erythromycin may be administered for acne in doses of 500 mg twice daily. However, it has less anti-inflammatory activity than the tetracyclines. In addition, P. acnes often develops resistance to this drug, resulting in treatment failure [117] . Many patients experience intolerable gastrointestinal side effects. The use of erythromycin is now recommended only for patients in whom tetracycline derivatives are contraindicated [63,95] . (See 'Tetracyclines' below.)

Azithromycin, another oral macrolide antibiotic, has shown efficacy for the treatment of acne [118-120] . The optimum dosing remains to be determined. Concern regarding the use of azithromycin for the routine treatment of acne is related to the rising incidence of antibiotic resistance to this drug. Azithromycin is often used as a first line agent for the treatment of respiratory infections and is also prescribed as an alternative drug for the treatment of other gram positive cocci infections in patients allergic to beta-lactam antibiotics. The risk of increasing the prevalence of antibiotic resistance makes azithromycin a less favorable choice for routine acne therapy. (See "Azithromycin, clarithromycin, and telithromycin", section on 'Resistance' and "Resistance of Streptococcus pneumoniae to the macrolides, azalides, lincosamines, and ketolides".)

Tetracyclines — In the past, tetracycline was the preferred oral antibiotic due to its low cost and studies showing high efficacy. However, newer generation tetracycline derivatives are now used more commonly.

Doxycycline and minocycline are newer generation tetracycline derivatives. These two drugs have replaced erythromycin and tetracycline as the most frequently used oral antibiotics for acne therapy by dermatologists in the United States, both due to better tolerability and the presence of higher rates of P. acnes resistance to erythromycin and tetracycline [85,121] . Unlike tetracycline, either drug can be taken with meals since absorption is not inhibited by food.

In clinical practice, minocycline is widely considered the most effective tetracycline derivative for the treatment of acne [85] . Biologic evidence suggests that minocycline may result in greater reductions in P. acnes than doxycycline or other antibiotics [122,123] , and that some tetracycline-resistant strains of P. acnes show cross-resistance to doxycycline, but not to minocycline [124] .

However, the evidence that supports the greater efficacy of minocycline in clinical response has methodological flaws, including lack of blinding in clinical studies [96] . A systematic review of minocycline for the treatment of acne did not find sufficient evidence to support the conclusion that minocycline is superior to other tetracyclines [96] .

Some studies have suggested that minocycline induces more rapid improvement in inflammatory acne than tetracycline [125-127] . However, the magnitude of clinical improvement with tetracycline or minocycline at the end of the treatment period was equivalent for all studies.

Minocycline is not used as first-line therapy due to its high cost and lack of clear benefit compared with tetracycline and doxycycline, as well as concerns about more severe toxicities than other tetracyclines [128,129] . Some patients who have failed therapy with doxycycline or tetracycline may respond to minocycline.

Tetracycline, doxycycline, and minocycline should not be administered to children under the age of nine or to pregnant women due to the potential for discoloration of developing permanent teeth and reduced bone growth. Antibiotics in the tetracycline class can cause gastrointestinal distress, and rarely esophagitis, esophageal ulceration, or idiopathic intracranial hypertension (pseudotumor cerebri). Photosensitivity may also occur, with doxycycline as the most photosensitizing drug. Patients taking doxycycline or tetracycline must be cautioned regarding this potential side effect, and should be encouraged to engage in sun-protective behavior.

Minocycline is the least photosensitizing of the three drugs, but can cause vertigo, skin discoloration (picture 3), serum sickness, and a lupus-like syndrome [130-133] .

Dosing for tetracyclines

Tetracyline is initiated at a dose of 500 mg twice daily, although 250 mg twice daily may also be effective. Absorption is inhibited by food, dairy products, antacids, and iron; it must be taken on an empty stomach. Patients should be instructed to take tetracycline at least one hour prior to a meal or two hours after eating. Because of these requirements, compliance to therapy may be difficult for some patients.

Unlike tetracycline, doxycycline and minocycline can be taken with food and drink; doing so may reduce the risk for gastrointestinal side effects. Typical doses of doxycyline are 50 to 100 mg twice daily or 150 mg once daily. Minocycline is usually prescribed as 50 to 100 mg twice daily. However, newer research has provided additional dosing options for these drugs.

Extended-release minocycline — Newer research has provided an additional dosing option for minocycline. A once daily, extended-release formulation of minocycline (Solodyn®) is prescribed as a weight-based dose. The lowest effective dose with the most favorable side effect profile was determined to be 1 mg/kg/day; higher doses did not offer additional benefit [134-136] . Extended-release minocycline is available as 45, 90, and 135 mg tablets.

Subantimicrobial dose doxycycline — Concern over the induction of antibiotic resistance with long-term antibiotic use for acne has led to the investigation of subantimicrobial doses of doxycycline for the treatment of acne vulgaris. Subantimicrobial doses of antibiotics are doses for which the antiinflammatory properties are maintained, but antibacterial action is absent. In this manner, the potential for inducing antibacterial resistance is diminished. The tetracyclines, particularly doxycycline, are often administered at subantimicrobial doses for treating acne. This lower dosage may block inflammation in acne through multiple mechanisms, including the inhibition of matrix metalloproteinases, regulation of inflammatory cytokines, inhibition of leukocyte chemotaxis and activation, and anti-oxidation [137] .

READ MORE::  Aloe

A multicenter, randomized trial revealed that doxycycline 20 mg twice daily was more effective than placebo for the treatment of moderate acne vulgaris [95] . However, there are minimal data comparing subantimicrobial doxycycline to higher doses of the drug. In one randomized trial (n = 100), patients with moderate acne treated with either 20 mg or 100 mg doxycycline twice daily exhibited numerically similar reductions in inflammatory lesions [138] . Additional studies are necessary prior to a recommendation that subantimicrobial dosing can replace traditional doses for the treatment of acne vulgaris.

Other antibiotics

Trimethoprim-sulfamethoxazole — Trimethoprim-sulfamethoxazole is effective in the treatment of severe acne. However, its use is limited by the potential for bone marrow suppression and for the development of severe immune-mediated drug eruptions such as toxic epidermal necrolysis. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Clinical manifestations; pathogenesis; and diagnosis".)

Clindamycin — The use of oral clindamycin is limited because of the potential to induce pseudomembranous colitis. Other antibiotics are generally preferred. (See "Epidemiology, microbiology, and pathophysiology of Clostridium difficile infection in adults", section on 'Pathophysiology'.)

Cephalexin — While some physicians use cephalexin to treat acne, the data to support its use are sparse. A retrospective study of 93 patients treated with cephalexin (primarily 500 mg twice daily) for a mean duration of nine months found that acne clearing or much improvement in acne occurred in 4 and 45 percent of patients, respectively [139] . Of note, most patients received concomitant therapy with other anti-acne agents.

Potential disadvantages of cephalosporin antibiotics include their hydrophilic nature, which prevents penetration into the pilosebaceous unit, the site of P. acnes colonization, and the potential for the promotion of methicillin resistant staphylococcus aureus. In general, we favor tetracyclines over cephalexin for the treatment of acne. (See "Epidemiology of methicillin-resistant Staphylococcus aureus infection in adults", section on 'Antibiotic use'.)

HORMONAL THERAPY — Further evaluation and hormonal therapies should be considered for patients with evidence for hyperandrogenism. Women without hyperandrogenism can also benefit from therapies that reduce androgen production or block androgen receptors. (See "Hormonal therapy for women with acne vulgaris" and "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris", section on 'Hyperandrogenism'.)

ORAL ISOTRETINOIN — Oral isotretinoin therapy is effective for the treatment of severe, recalcitrant nodular acne. In clinical practice, it is also used for milder acne that is resistant to other treatments or associated with significant scarring. The risk for adverse effects, including teratogenicity, precludes the use of this drug as routine acne therapy. (See "Oral isotretinoin therapy for acne vulgaris".)

NON-PRESCRIPTION TREATMENT — In addition to benzoyl peroxide, other non-prescription agents including salicylic acid, sulfur, alpha hydroxy acid, and tea tree oil have been used in the treatment of acne. (See "Light-based, adjunctive, and other therapies for acne vulgaris", section on 'Other topical medications'.)

PROCEDURAL THERAPY — Treatment of acne vulgaris with lasers, visible light, chemical peels, and other procedures is discussed separately. (See "Light-based, adjunctive, and other therapies for acne vulgaris", section on 'Light/laser therapies' and "Light-based, adjunctive, and other therapies for acne vulgaris", section on 'Adjunctive therapies'.)

MAINTENANCE THERAPY — In many patients, acne is a disorder in which symptoms typically recur over years. Consequently, identifying a sustainable treatment regimen is an important component of acne management. Concern regarding antibiotic resistance provides an incentive to limit the use of antibiotics, though effective, as long term therapy.

Topical retinoids are a compelling option for maintenance therapy for patients with acne vulgaris. In addition to their ability to combat active acne through comedolytic and anti-inflammatory properties, these drugs play a critical preventive role through the inhibition of the formation of the microcomedone, the precursor lesion in acne vulgaris.

Several randomized controlled trials support the use of retinoids as maintenance therapy following the cessation of antimicrobial agents [31-34,140] . Representative trials include:

  • A 12-week randomized controlled trial involving 241 patients with moderate to moderately severe acne evaluated the effect of maintenance therapy for patients who had at least moderate improvement after treatment with adapalene 0.1% gel and clindamycin 1% solution or clindamycin solution alone [31] . Patients who continued therapy with adapalene 0.1% gel had a 41.6 percent reduction in total lesion counts. Patients who stopped treatment exhibited a 92 percent increase in total lesion counts.
  • A 16-week randomized controlled trial evaluated 253 subjects with severe acne who achieved at least moderate improvement after treatment with adapalene 0.1% gel and doxycycline 100 mg or doxycycline 100 mg and a vehicle gel [33] . The percentage of patients sustaining 50 percent improvement in lesion counts was 75 percent in the adapalene group versus 54 percent in the vehicle group.

For some patients, monotherapy with a topical retinoid may not be sufficient to sustain clinical improvement. In these cases, an antimicrobial agent containing benzoyl peroxide can be added to the treatment regimen [11,141] .

Additional studies will be useful for determining the best maintenance regimens.

THERAPY FOR POSTINFLAMMATORY HYPERPIGMENTATION — Postinflammatory hyperpigmentation can be a significant problem for patients with darker skin complexions and acne. In many cases, patients are more distressed by the "dark spots" that take several months or more to resolve, than by active acne lesions which resolve more quickly (picture 4) [142] .

Both topical retinoids and azelaic acid accelerate the resolution of postinflammatory hyperpigmentation [143,144] . In one randomized trial, black patients who applied tretinoin 0.1% cream exhibited significantly greater lightening of facial postinflammatory hyperpigmentation than those treated with vehicle [143] . A regimen containing either of these agents will treat active acne and improve postinflammatory hyperpigmentation.

Topical hydroquinone is a depigmenting agent that inhibits melanin production, and is considered the "gold standard" for treatment of hyperpigmentation [142,144,145] . Hydroquinone is available as 2% over-the-counter formulations and in prescription products in a 3 or 4% concentration. Exogenous ochronosis, a condition in which grayish discoloration of the skin occurs in sites of application, is an uncommon consequence of topical hydroquinone usage [146] . Additional safety concerns were raised when oral hydroquinone was reported to be tumorigenic in rodents [147] . Carcinogenic effects have not been reported in humans [146] .

We suggest the use of a topical retinoid as a component of acne treatment regimens for patients with acne-induced postinflammatory hyperpigmentation [148] . Azelaic acid is an alternative to a topical retinoid in patients who cannot tolerate the latter. Topical hydroquinone can be applied twice daily to individual hyperpigmented lesions for greater improvement.

Additionally, patients may benefit from superficial chemical peels with glycolic acid or salicylic acid, although care must be taken to avoid chemical peel-induced postinflammatory hyperpigmentation.

HOME SKIN CARE RECOMMENDATIONS — Patients frequently ask questions about general skin care. The following are some suggestions that patients will find useful, based upon clinical experience and clinical trials:

  • Patients should apply a gentle synthetic detergent cleanser (ie, syndet) with their fingers, and rinse with warm (not hot) water twice daily [9] . Synthetic detergent cleansers possess a pH of 5.5 to 7, which is close to normal skin pH, while soap has a pH of 9 to 10. The lower pH of synthetic detergents, such as Cetaphil®, minimizes skin irritation and dryness [149,150] . In a small randomized trial, patients with moderate acne (treated with a benzoyl peroxide/erythromycin combination gel alone or combined with adapalene) were instructed to wash their faces with either a synthetic detergent bar (Dove® Sensitive Skin Bar) or soap [151] . After four weeks, the patients washing with the synthetic detergent bar exhibited less skin peeling, dryness, and irritation than those using soap.
  • Patients should not aggressively scrub the skin; gentle massage with the fingertips is sufficient for cleansing. Repetitive mechanical trauma can aggravate inflammatory acne and promote the development of new acne lesions [9] .
  • Several reports have suggested that antibacterial soaps such as triclosan, povidone-iodine, and chlorhexidine can improve acne vulgaris [152-154] . However, data supporting their use are limited, and these agents have not been proven superior to conventional therapy. We do not recommend these soaps for the management of acne vulgaris.
  • Water-based lotions, cosmetics, and hair products are less comedogenic than oil-based products. Patients should be encouraged to seek out noncomedogenic skin care and cosmetic products.
  • Patients should be advised not to pick their acne lesions, as this may exacerbate scarring.

PREGNANCY AND ACNE THERAPY — A number of treatments for acne are contraindicated in pregnancy. In particular, oral isotretinoin and topical tazarotene are classified as pregnancy category X drugs, and must never be given to pregnant women or women who are attempting pregnancy.

In deciding whether to treat acne during pregnancy, as well as choosing a specific therapy, careful consideration should be given to the grade of acne, the patient's risk tolerance, and the preferences of the patient's obstetrical provider. If acne therapy is desired, reasonable options include oral or topical erythromycin, topical clindamycin, and topical azelaic acid, which are pregnancy class B drugs [155,156] . Benzoyl peroxide is categorized as pregnancy class C.

A description of the pregnancy category labels (table 4) and a list of pregnancy categories of acne medications are provided (table 5).

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

  • Basics topics (see "Patient information: Acne (The Basics)")
  • Beyond the Basics topics (see "Patient information: Acne")

SUMMARY AND RECOMMENDATIONS

  • Determining the most effective course of treatment for acne involves a comprehensive assessment of the patient. Treatment of acne is aimed at counteracting follicular hyperproliferation, increased sebum production, Propionibacterium acnes (P. acnes) proliferation, and inflammation. (See 'Patient assessment' above and 'Overview of treatment' above.)
  • The choice of acne therapy should be individualized, depending on acne severity and type of lesions, as well as tolerance and other factors (figure 1). (See 'Patient assessment' above and 'Overview of treatment' above.)
  • Medications that are effective for comedonal acne include topical retinoids, benzoyl peroxide, azelaic acid, and salicylic acid. For patients with comedonal acne who desire treatment, we suggest topical retinoids as first line therapy (Grade 2A). (See 'Topical retinoids' above.)
  • For patients with mild to moderate inflammatory acne with or without prominent comedonal lesions, we suggest the use of a topical retinoid, topical antibiotic, and benzoyl peroxide (Grade 2A). When benzoyl peroxide is used with a topical antibiotic, treatment is more effective than either agent alone. To reduce the development of antibiotic resistance, we prescribe topical antibiotics with benzoyl peroxide. (See 'Topical antimicrobials' above and 'Combination therapy' above.)
  • For patients with moderate to severe inflammatory acne with or without prominent comedonal lesions, we suggest the use of a topical retinoid, topical benzoyl peroxide, and an oral antibiotic, rather than topical agents alone (Grade 2A). Oral antibiotics should be used for a limited course, ideally up to 12 to 18 weeks. Concomitant topical benzoyl peroxide should be prescribed to decrease the risk of antibiotic resistance. (See 'Oral antibiotics' above.)
  • Patients with severe, recalcitrant, nodular acne are generally treated with oral isotretinoin. Oral isotretinoin therapy is discussed separately. (See "Oral isotretinoin therapy for acne vulgaris".)
  • Women with signs of hyperandrogenism should be evaluated for underlying endocrine disorders. Hormonal therapy can be a useful addition to a therapeutic regimen for moderate to severe acne vulgaris in women with or without hyperandrogenism. (See 'Hormonal therapy' above and "Hormonal therapy for women with acne vulgaris".)
  • Acne may persist for years. In addition to their use in treatment, topical retinoids are also effective for the prevention of acne lesions, and can reduce the use of long term antibiotic therapy. In patients with acne that has improved with therapy, we suggest long-term treatment with a topical retinoid for maintenance, rather than discontinuing treatment (Grade 2A). For patients in whom improvement cannot be sustained with topical retinoids alone, an antimicrobial agent with benzoyl peroxide can be added. (See 'Maintenance therapy' above.)
  • Acne-induced postinflammatory hyperpigmentation is a particular concern for patients with dark skin pigmentation. For patients with acne-induced postinflammatory hyperpigmentation, we suggest the use of a topical retinoid as a component of acne therapy (Grade 2B). The use of hydroquinone, azelaic acid, or chemical peels can also be beneficial. (See 'Therapy for postinflammatory hyperpigmentation' above.)
  • Patients with acne should use gentle cleansers and should avoid irritating skin care products. Patients should select "non-comedogenic" skin care products and cosmetics. (See 'Home skin care recommendations' above.)
  • Pregnant women should not be treated with topical retinoids. If treatment during pregnancy is necessary, erythromycin, clindamycin, or azelaic acid may be considered after a review of the risks and benefits of therapy. (See 'Pregnancy and acne therapy' above.)

REFERENCES

  1. Klassen AF, Newton JN, Mallon E. Measuring quality of life in people referred for specialist care of acne: comparing generic and disease-specific measures. J Am Acad Dermatol 2000; 43:229.
  2. Dalgard F, Gieler U, Holm JØ, et al. Self-esteem and body satisfaction among late adolescents with acne: results from a population survey. J Am Acad Dermatol 2008; 59:746.
  3. Yazici K, Baz K, Yazici AE, et al. Disease-specific quality of life is associated with anxiety and depression in patients with acne. J Eur Acad Dermatol Venereol 2004; 18:435.
  4. Bowe WP, Shalita AR. Effective over-the-counter acne treatments. Semin Cutan Med Surg 2008; 27:170.
  5. Lehmann HP, Robinson KA, Andrews JS, et al. Acne therapy: a methodologic review. J Am Acad Dermatol 2002; 47:231.
  6. Haider A, Shaw JC. Treatment of acne vulgaris. JAMA 2004; 292:726.
  7. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet 2011.
  8. Thielitz A, Gollnick H. Topical retinoids in acne vulgaris: update on efficacy and safety. Am J Clin Dermatol 2008; 9:369.
  9. Gollnick H, Cunliffe W, Berson D, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol 2003; 49:S1.
  10. Leyden JJ, Shalita A, Thiboutot D, et al. Topical retinoids in inflammatory acne: a retrospective, investigator-blinded, vehicle-controlled, photographic assessment. Clin Ther 2005; 27:216.
  11. Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad Dermatol 2009; 60:S1.
  12. Liu A, Yang DJ, Gerhardstein PC, Hsu S. Relapse of acne following isotretinoin treatment: a retrospective study of 405 patients. J Drugs Dermatol 2008; 7:963.
  13. Brelsford M, Beute TC. Preventing and managing the side effects of isotretinoin. Semin Cutan Med Surg 2008; 27:197.
  14. Taglietti M, Hawkins CN, Rao J. Novel topical drug delivery systems and their potential use in acne vulgaris. Skin Therapy Lett 2008; 13:6.
  15. Date AA, Naik B, Nagarsenker MS. Novel drug delivery systems: potential in improving topical delivery of antiacne agents. Skin Pharmacol Physiol 2006; 19:2.
  16. Kang S, Voorhees JJ. Topical retinoids. In: Fitzpatrick's Dermatology in General Medicine, 7th ed, Wolff, K, Goldsmith, LA, Katz, SI, et al (Eds), McGraw Hill, 2008. p.2106.
  17. Fernandez [Graber] EM, Zaenglein A, Thiboutot D. Acne Treatment Methodologies. In: Cosmetic Formulation of Skin Care Products, Taylor and Francis Group, New York 2006. p.273.
  18. Benkoussa M, Brand C, Delmotte MH, et al. Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP1-responsive promoter. Mol Cell Biol 2002; 22:4522.
  19. Tenaud I, Khammari A, Dreno B. In vitro modulation of TLR-2, CD1d and IL-10 by adapalene on normal human skin and acne inflammatory lesions. Exp Dermatol 2007; 16:500.
  20. Liu PT, Krutzik SR, Kim J, Modlin RL. Cutting edge: all-trans retinoic acid down-regulates TLR2 expression and function. J Immunol 2005; 174:2467.
  21. Krishnan G. Comparison of two concentrations of tretinoin solution in the topical treatment of acne vulgaris. Practitioner 1976; 216:106.
  22. Webster GF. Safety and efficacy of Tretin-X compared with Retin-A in patients with mild-to-severe acne vulgaris. Skinmed 2006; 5:114.
  23. Webster G, Cargill DI, Quiring J, et al. A combined analysis of 2 randomized clinical studies of tretinoin gel 0.05% for the treatment of acne. Cutis 2009; 83:146.
  24. Berger R, Barba A, Fleischer A, et al. A double-blinded, randomized, vehicle-controlled, multicenter, parallel-group study to assess the safety and efficacy of tretinoin gel microsphere 0.04% in the treatment of acne vulgaris in adults. Cutis 2007; 80:152.
  25. Thiboutot D, Pariser DM, Egan N, et al. Adapalene gel 0.3% for the treatment of acne vulgaris: a multicenter, randomized, double-blind, controlled, phase III trial. J Am Acad Dermatol 2006; 54:242.
  26. Lucky A, Jorizzo JL, Rodriguez D, et al. Efficacy and tolerance of adapalene cream 0.1% compared with its cream vehicle for the treatment of acne vulgaris. Cutis 2001; 68:34.
  27. Pariser DM, Thiboutot DM, Clark SD, et al. The efficacy and safety of adapalene gel 0.3% in the treatment of acne vulgaris: A randomized, multicenter, investigator-blinded, controlled comparison study versus adapalene gel 0.1% and vehicle. Cutis 2005; 76:145.
  28. Shalita AR, Berson DS, Thiboutot DM, et al. Effects of tazarotene 0.1 % cream in the treatment of facial acne vulgaris: pooled results from two multicenter, double-blind, randomized, vehicle-controlled, parallel-group trials. Clin Ther 2004; 26:1865.
  29. Kawashima M, Harada S, Loesche C, Miyachi Y. Adapalene gel 0.1% is effective and safe for Japanese patients with acne vulgaris: a randomized, multicenter, investigator-blinded, controlled study. J Dermatol Sci 2008; 49:241.
  30. Eichenfield LF, Jarratt M, Schlessinger J, et al. Adapalene 0.1% lotion in the treatment of acne vulgaris: results from two placebo-controlled, multicenter, randomized double-blind, clinical studies. J Drugs Dermatol 2010; 9:639.
  31. Zhang JZ, Li LF, Tu YT, Zheng J. A successful maintenance approach in inflammatory acne with adapalene gel 0.1% after an initial treatment in combination with clindamycin topical solution 1% or after monotherapy with clindamycin topical solution 1%. J Dermatolog Treat 2004; 15:372.
  32. Leyden J, Thiboutot DM, Shalita AR, et al. Comparison of tazarotene and minocycline maintenance therapies in acne vulgaris: a multicenter, double-blind, randomized, parallel-group study. Arch Dermatol 2006; 142:605.
  33. Thiboutot DM, Shalita AR, Yamauchi PS, et al. Adapalene gel, 0.1%, as maintenance therapy for acne vulgaris: a randomized, controlled, investigator-blind follow-up of a recent combination study. Arch Dermatol 2006; 142:597.
  34. Alirezai M, George SA, Coutts I, et al. Daily treatment with adapalene gel 0.1% maintains initial improvement of acne vulgaris previously treated with oral lymecycline. Eur J Dermatol 2007; 17:45.
  35. Thielitz A, Abdel-Naser MB, Fluhr JW, et al. Topical retinoids in acne--an evidence-based overview. J Dtsch Dermatol Ges 2008; 6:1023.
  36. Nyirady J, Lucas C, Yusuf M, et al. The stability of tretinoin in tretinoin gel microsphere 0.1%. Cutis 2002; 70:295.
  37. Martin B, Meunier C, Montels D, Watts O. Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation. Br J Dermatol 1998; 139 Suppl 52:8.
  38. Nighland M, Yusuf M, Wisniewski S, et al. The effect of simulated solar UV irradiation on tretinoin in tretinoin gel microsphere 0.1% and tretinoin gel 0.025%. Cutis 2006; 77:313.
  39. Sami N, Harper JC. Topical retinoids. In: Comprehensive Dermatologic Drug Therapy, 2nd ed, Wolverton SE (Ed), Elsevier Inc, 2007. p.625.
  40. Zaenglein AL. Topical retinoids in the treatment of acne vulgaris. Semin Cutan Med Surg 2008; 27:177.
  41. Kligman AM, Fulton JE Jr, Plewig G. Topical vitamin A acid in acne vulgaris. Arch Dermatol 1969; 99:469.
  42. Zaenglein AK, Thiboutot DM. Acne Vulgaris. In: Dermatology, 2nd ed, Bolognia JL, Jorizzo JL, Rapini RP, et al (Eds), Elsevier, 2008. p.495.
  43. Weinstock MA, Bingham SF, Lew RA, et al. Topical tretinoin therapy and all-cause mortality. Arch Dermatol 2009; 145:18.
  44. Galvin SA, Gilbert R, Baker M, et al. Comparative tolerance of adapalene 0.1% gel and six different tretinoin formulations. Br J Dermatol 1998; 139 Suppl 52:34.
  45. Lucky AW, Cullen SI, Jarratt MT, Quigley JW. Comparative efficacy and safety of two 0.025% tretinoin gels: results from a multicenter double-blind, parallel study. J Am Acad Dermatol 1998; 38:S17.
  46. Chalker DK, Lesher JL Jr, Smith JG Jr, et al. Efficacy of topical isotretinoin 0.05% gel in acne vulgaris: results of a multicenter, double-blind investigation. J Am Acad Dermatol 1987; 17:251.
  47. Domínguez J, Hojyo MT, Celayo JL, et al. Topical isotretinoin vs. topical retinoic acid in the treatment of acne vulgaris. Int J Dermatol 1998; 37:54.
  48. Ioannides D, Rigopoulos D, Katsambas A. Topical adapalene gel 0.1% vs. isotretinoin gel 0.05% in the treatment of acne vulgaris: a randomized open-label clinical trial. Br J Dermatol 2002; 147:523.
  49. Cunliffe WJ, Poncet M, Loesche C, Verschoore M. A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials. Br J Dermatol 1998; 139 Suppl 52:48.
  50. Brand B, Gilbert R, Baker MD, et al. Cumulative irritancy comparison of adapalene gel 0.1% versus other retinoid products when applied in combination with topical antimicrobial agents. J Am Acad Dermatol 2003; 49:S227.
  51. Bershad S, Kranjac Singer G, Parente JE, et al. Successful treatment of acne vulgaris using a new method: results of a randomized vehicle-controlled trial of short-contact therapy with 0.1% tazarotene gel. Arch Dermatol 2002; 138:481.
  52. Thiboutot D, Gold MH, Jarratt MT, et al. Randomized controlled trial of the tolerability, safety, and efficacy of adapalene gel 0.1% and tretinoin microsphere gel 0.1% for the treatment of acne vulgaris. Cutis 2001; 68:10.
  53. Cunliffe WJ, Danby FW, Dunlap F, et al. Randomised, controlled trial of the efficacy and safety of adapalene gel 0.1% and tretinoin cream 0.05% in patients with acne vulgaris. Eur J Dermatol 2002; 12:350.
  54. Webster GF, Berson D, Stein LF, et al. Efficacy and tolerability of once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.025% gel in the treatment of facial acne vulgaris: a randomized trial. Cutis 2001; 67:4.
  55. Shalita A, Miller B, Menter A, et al. Tazarotene cream versus adapalene cream in the treatment of facial acne vulgaris: a multicenter, double-blind, randomized, parallel-group study. J Drugs Dermatol 2005; 4:153.
  56. Webster GF, Guenther L, Poulin YP, et al. A multicenter, double-blind, randomized comparison study of the efficacy and tolerability of once-daily tazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acne vulgaris. Cutis 2002; 69:4.
  57. Thiboutot D, Arsonnaud S, Soto P. Efficacy and tolerability of adapalene 0.3% gel compared to tazarotene 0.1% gel in the treatment of acne vulgaris. J Drugs Dermatol 2008; 7:s3.
  58. Leyden JJ, Krochmal L, Yaroshinsky A. Two randomized, double-blind, controlled trials of 2219 subjects to compare the combination clindamycin/tretinoin hydrogel with each agent alone and vehicle for the treatment of acne vulgaris. J Am Acad Dermatol 2006; 54:73.
  59. Mills OH Jr, Kligman AM, Pochi P, Comite H. Comparing 2.5%, 5%, and 10% benzoyl peroxide on inflammatory acne vulgaris. Int J Dermatol 1986; 25:664.
  60. Morelli R, Lanzarini M, Vincenzi C, Reggiani M. Contact dermatitis due to benzoyl peroxide. Contact Dermatitis 1989; 20:238.
  61. Gollnick H, Schramm M. Topical drug treatment in acne. Dermatology 1998; 196:119.
  62. Leyden JJ, Del Rosso JQ, Webster GF. Clinical considerations in the treatment of acne vulgaris and other inflammatory skin disorders: a status report. Dermatol Clin 2009; 27:1.
  63. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol 2007; 56:651.
  64. Tarimci N, Sener S, Kilinç T. Topical sodium sulfacetamide/sulfur lotion. J Clin Pharm Ther 1997; 22:301.
  65. Breneman DL, Ariano MC. Successful treatment of acne vulgaris in women with a new topical sodium sulfacetamide/sulfur lotion. Int J Dermatol 1993; 32:365.
  66. Draelos ZD, Carter E, Maloney JM, et al. Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris. J Am Acad Dermatol 2007; 56:439.e1.
  67. Lucky AW, Maloney JM, Roberts J, et al. Dapsone gel 5% for the treatment of acne vulgaris: safety and efficacy of long-term (1 year) treatment. J Drugs Dermatol 2007; 6:981.
  68. Piette WW, Taylor S, Pariser D, et al. Hematologic safety of dapsone gel, 5%, for topical treatment of acne vulgaris. Arch Dermatol 2008; 144:1564.
  69. Webster GF. Is topical dapsone safe in glucose-6-phosphate dehydrogenase-deficient and sulfonamide-allergic patients? J Drugs Dermatol 2010; 9:532.
  70. Fleischer, AB, Draelos, ZD, Abramovits, W, Pariser, DM. Dapsone gel 5% in combination with adapalene gel 0.1%, benzoyl peroxide gel 4%, or vehicle gel for the treatment of acne vulgaris: a randomized, double-blind study. J Am Acad Dermatol 2007; 56:AB16.
  71. Dubina MI, Fleischer AB Jr. Interaction of topical sulfacetamide and topical dapsone with benzoyl peroxide. Arch Dermatol 2009; 145:1027.
  72. Mills OH Jr, Kligman AM. Treatment of acne vulgaris with topically applied erythromycin and tretinoin. Acta Derm Venereol 1978; 58:555.
  73. Hurwitz S. Acne vulgaris: pathogenesis and management. Pediatr Rev 1994; 15:47.
  74. Thiboutot DM, Weiss J, Bucko A, et al. Adapalene-benzoyl peroxide, a fixed-dose combination for the treatment of acne vulgaris: results of a multicenter, randomized double-blind, controlled study. J Am Acad Dermatol 2007; 57:791.
  75. Wolf JE Jr, Kaplan D, Kraus SJ, et al. Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: a multicenter, randomized, investigator-blinded study. J Am Acad Dermatol 2003; 49:S211.
  76. Zouboulis CC, Derumeaux L, Decroix J, et al. A multicentre, single-blind, randomized comparison of a fixed clindamycin phosphate/tretinoin gel formulation (Velac) applied once daily and a clindamycin lotion formulation (Dalacin T) applied twice daily in the topical treatment of acne vulgaris. Br J Dermatol 2000; 143:498.
  77. Richter JR, Förström LR, Kiistala UO, Jung EG. Efficacy of the fixed 1.2% clindamycin phosphate, 0.025% tretinoin gel formulation (Velac) and a proprietary 0.025% tretinoin gel formulation (Aberela) in the topical control of facial acne. J Eur Acad Dermatol Venereol 1998; 11:227.
  78. Rietschel RL, Duncan SH. Clindamycin phosphate used in combination with tretinoin in the treatment of acne. Int J Dermatol 1983; 22:41.
  79. Shalita AR, Rafal ES, Anderson DN, et al. Compared efficacy and safety of tretinoin 0.1% microsphere gel alone and in combination with benzoyl peroxide 6% cleanser for the treatment of acne vulgaris. Cutis 2003; 72:167.
  80. Del Rosso JQ. Study results of benzoyl peroxide 5%/clindamycin 1% topical gel, adapalene 0.1% gel, and use in combination for acne vulgaris. J Drugs Dermatol 2007; 6:616.
  81. Draelos ZD, Tanghetti EA, Tazarotene Combination Leads to Efficacious Acne Results (CLEAR) Trial Study Group. Optimizing the use of tazarotene for the treatment of facial acne vulgaris through combination therapy. Cutis 2002; 69:20.
  82. Tanghetti E, Abramovits W, Solomon B, et al. Tazarotene versus tazarotene plus clindamycin/benzoyl peroxide in the treatment of acne vulgaris: a multicenter, double-blind, randomized parallel-group trial. J Drugs Dermatol 2006; 5:256.
  83. Amblard P, Bazex A, Beylot C, et al. [The association tretinoin-erythromycin base: a new topical treatment for acne. Results of a multicentric trial on 347 cases (authors transl)] . Sem Hop 1980; 56:911.
  84. Dosik JS, Gilbert RD, Arsonnaud S. Cumulative irritancy comparison of topical retinoid and antimicrobial combination therapies. Skinmed 2006; 5:219.
  85. Webster GF, Graber EM. Antibiotic treatment for acne vulgaris. Semin Cutan Med Surg 2008; 27:183.
  86. Cunliffe WJ, Holland KT, Bojar R, Levy SF. A randomized, double-blind comparison of a clindamycin phosphate/benzoyl peroxide gel formulation and a matching clindamycin gel with respect to microbiologic activity and clinical efficacy in the topical treatment of acne vulgaris. Clin Ther 2002; 24:1117.
  87. Eady EA, Farmery MR, Ross JI, et al. Effects of benzoyl peroxide and erythromycin alone and in combination against antibiotic-sensitive and -resistant skin bacteria from acne patients. Br J Dermatol 1994; 131:331.
  88. Thiboutot D, Zaenglein A, Weiss J, et al. An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% for the once-daily treatment of moderate to severe acne vulgaris: assessment of efficacy and safety in 2813 patients. J Am Acad Dermatol 2008; 59:792.
  89. Lookingbill DP, Chalker DK, Lindholm JS, et al. Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: combined results of two double-blind investigations. J Am Acad Dermatol 1997; 37:590.
  90. Eady EA, Bojar RA, Jones CE, et al. The effects of acne treatment with a combination of benzoyl peroxide and erythromycin on skin carriage of erythromycin-resistant propionibacteria. Br J Dermatol 1996; 134:107.
  91. Leyden J, Kaidbey K, Levy SF. The combination formulation of clindamycin 1% plus benzoyl peroxide 5% versus 3 different formulations of topical clindamycin alone in the reduction of Propionibacterium acnes. An in vivo comparative study. Am J Clin Dermatol 2001; 2:263.
  92. Seidler EM, Kimball AB. Meta-analysis comparing efficacy of benzoyl peroxide, clindamycin, benzoyl peroxide with salicylic acid, and combination benzoyl peroxide/clindamycin in acne. J Am Acad Dermatol 2010; 63:52.
  93. Graupe K, Cunliffe WJ, Gollnick HP, Zaumseil RP. Efficacy and safety of topical azelaic acid (20 percent cream): an overview of results from European clinical trials and experimental reports. Cutis 1996; 57:20.
  94. Gollnick HP, Graupe K, Zaumseil RP. [Azelaic acid 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies] . J Dtsch Dermatol Ges 2004; 2:841.
  95. Skidmore R, Kovach R, Walker C, et al. Effects of subantimicrobial-dose doxycycline in the treatment of moderate acne. Arch Dermatol 2003; 139:459.
  96. Garner SE, Eady EA, Popescu C, et al. Minocycline for acne vulgaris: efficacy and safety. Cochrane Database Syst Rev 2003; :CD002086.
  97. Smith JG Jr, Chalker DK, Wehr RF. The effectiveness of topical and oral tetracycline for acne. South Med J 1976; 69:695.
  98. Gratton D, Raymond GP, Guertin-Larochelle S, et al. Topical clindamycin versus systemic tetracycline in the treatment of acne. Results of a multiclinic trial. J Am Acad Dermatol 1982; 7:50.
  99. Blaney DJ, Cook CH. Topical use of tetracycline in the treatment of acne: a double-blind study comparing topical and oral tetracycline therapy and placebo. Arch Dermatol 1976; 112:971.
  100. Christian GL, Krueger GG. Clindamycin vs placebo as adjunctive therapy in moderately severe acne. Arch Dermatol 1975; 111:997.
  101. Bottomley WW, Cunliffe WJ. Oral trimethoprim as a third-line antibiotic in the management of acne vulgaris. Dermatology 1993; 187:193.
  102. Gammon WR, Meyer C, Lantis S, et al. Comparative efficacy of oral erythromycin versus oral tetracycline in the treatment of acne vulgaris. A double-blind study. J Am Acad Dermatol 1986; 14:183.
  103. Del Rosso JQ, Kim G. Optimizing use of oral antibiotics in acne vulgaris. Dermatol Clin 2009; 27:33.
  104. Webster GF, Toso SM, Hegemann L. Inhibition of a model of in vitro granuloma formation by tetracyclines and ciprofloxacin. Involvement of protein kinase C. Arch Dermatol 1994; 130:748.
  105. Cooper AJ. Systematic review of Propionibacterium acnes resistance to systemic antibiotics. Med J Aust 1998; 169:259.
  106. Ross JI, Snelling AM, Eady EA, et al. Phenotypic and genotypic characterization of antibiotic-resistant Propionibacterium acnes isolated from acne patients attending dermatology clinics in Europe, the U.S.A., Japan and Australia. Br J Dermatol 2001; 144:339.
  107. Eady AE, Cove JH, Layton AM. Is antibiotic resistance in cutaneous propionibacteria clinically relevant? : implications of resistance for acne patients and prescribers. Am J Clin Dermatol 2003; 4:813.
  108. Levy RM, Huang EY, Roling D, et al. Effect of antibiotics on the oropharyngeal flora in patients with acne. Arch Dermatol 2003; 139:467.
  109. Margolis DJ, Bowe WP, Hoffstad O, Berlin JA. Antibiotic treatment of acne may be associated with upper respiratory tract infections. Arch Dermatol 2005; 141:1132.
  110. Tan HH. Antibacterial therapy for acne: a guide to selection and use of systemic agents. Am J Clin Dermatol 2003; 4:307.
  111. Leyden JJ. A review of the use of combination therapies for the treatment of acne vulgaris. J Am Acad Dermatol 2003; 49:S200.
  112. Thiboutot DM, Shalita AR, Yamauchi PS, et al. Combination therapy with adapalene gel 0.1% and doxycycline for severe acne vulgaris: a multicenter, investigator-blind, randomized, controlled study. Skinmed 2005; 4:138.
  113. Mills OH Jr, Marples RR, Kligman AM. Acne vulgaris. Oral therapy with tetracycline and topical therapy with vitamin A. Arch Dermatol 1972; 106:200.
  114. Kligman AM, Mills OH, McGinley KJ, Leyden JJ. Acne therapy with tretinoin in combination with antibiotics. Acta Derm Venereol Suppl (Stockh) 1975; 74:111.
  115. Cunliffe WJ, Meynadier J, Alirezai M, et al. Is combined oral and topical therapy better than oral therapy alone in patients with moderate to moderately severe acne vulgaris? A comparison of the efficacy and safety of lymecycline plus adapalene gel 0.1%, versus lymecycline plus gel vehicle. J Am Acad Dermatol 2003; 49:S218.
  116. Campbell JL Jr, Weiss JS. The results of the MORE trial: overview. Cutis 2006; 78:5.
  117. Eady EA, Cove JH, Holland KT, Cunliffe WJ. Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure. Br J Dermatol 1989; 121:51.
  118. Rafiei R, Yaghoobi R. Azithromycin versus tetracycline in the treatment of acne vulgaris. J Dermatolog Treat 2006; 17:217.
  119. Kus S, Yucelten D, Aytug A. Comparison of efficacy of azithromycin vs. doxycycline in the treatment of acne vulgaris. Clin Exp Dermatol 2005; 30:215.
  120. Antonio JR, Pegas JR, Cestari TF, Do Nascimento LV. Azithromycin pulses in the treatment of inflammatory and pustular acne: efficacy, tolerability and safety. J Dermatolog Treat 2008; 19:210.
  121. Leyden JJ, Del Rosso JQ, Webster GF. Clinical considerations in the treatment of acne vulgaris and other inflammatory skin disorders: focus on antibiotic resistance. Cutis 2007; 79:9.
  122. Leyden JJ. The evolving role of Propionibacterium acnes in acne. Semin Cutan Med Surg 2001; 20:139.
  123. Eady EA, Cove JH, Holland KT, Cunliffe WJ. Superior antibacterial action and reduced incidence of bacterial resistance in minocycline compared to tetracycline-treated acne patients. Br J Dermatol 1990; 122:233.
  124. Eady EA, Jones CE, Gardner KJ, et al. Tetracycline-resistant propionibacteria from acne patients are cross-resistant to doxycycline, but sensitive to minocycline. Br J Dermatol 1993; 128:556.
  125. Khanna, N. Treatment of acne vulgaris with oral tetracyclines. Indian J Dermatol Venereol Leprol 1993; 59:74.
  126. Samuelson JS. An accurate photographic method for grading acne: initial use in a double-blind clinical comparison of minocycline and tetracycline. J Am Acad Dermatol 1985; 12:461.
  127. Hubbell CG, Hobbs ER, Rist T, White JW Jr. Efficacy of minocycline compared with tetracycline in treatment of acne vulgaris. Arch Dermatol 1982; 118:989.
  128. McManus P, Iheanacho I. Don't use minocycline as first line oral antibiotic in acne. BMJ 2007; 334:154.
  129. Purdy S, de Berker D. Acne. BMJ 2006; 333:949.
  130. Gough A, Chapman S, Wagstaff K, et al. Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome. BMJ 1996; 312:169.
  131. Elkayam O, Levartovsky D, Brautbar C, et al. Clinical and immunological study of 7 patients with minocycline-induced autoimmune phenomena. Am J Med 1998; 105:484.
  132. Sturkenboom MC, Meier CR, Jick H, Stricker BH. Minocycline and lupuslike syndrome in acne patients. Arch Intern Med 1999; 159:493.
  133. Elkayam O, Yaron M, Caspi D. Minocycline-induced autoimmune syndromes: an overview. Semin Arthritis Rheum 1999; 28:392.
  134. Extended-release minocycline (Solodyn) for acne. Med Lett Drugs Ther 2006; 48:95.
  135. Stewart DM, Torok HM, Weiss JS, et al. Dose-ranging efficacy of new once-daily extended-release minocycline for acne vulgaris. Cutis 2006; 78:11.
  136. Fleischer AB Jr, Dinehart S, Stough D, et al. Safety and efficacy of a new extended-release formulation of minocycline. Cutis 2006; 78:21.
  137. Monk E, Shalita A, Siegel DM. Clinical applications of non-antimicrobial tetracyclines in dermatology. Pharmacol Res 2011; 63:130.
  138. Toossi P, Farshchian M, Malekzad F, et al. Subantimicrobial-dose doxycycline in the treatment of moderate facial acne. J Drugs Dermatol 2008; 7:1149.
  139. Fenner JA, Wiss K, Levin NA. Oral cephalexin for acne vulgaris: clinical experience with 93 patients. Pediatr Dermatol 2008; 25:179.
  140. Thielitz A, Sidou F, Gollnick H. Control of microcomedone formation throughout a maintenance treatment with adapalene gel, 0.1%. J Eur Acad Dermatol Venereol 2007; 21:747.
  141. Poulin Y, Sanchez NP, Bucko A, et al. A 6-month maintenance therapy with adapalene-benzoyl peroxide gel prevents relapse and continuously improves efficacy among patients with severe acne vulgaris: results of a randomized controlled trial. Br J Dermatol 2011; 164:1376.
  142. Taylor SC, Cook-Bolden F, Rahman Z, Strachan D. Acne vulgaris in skin of color. J Am Acad Dermatol 2002; 46:S98.
  143. Bulengo-Ransby SM, Griffiths CE, Kimbrough-Green CK, et al. Topical tretinoin (retinoic acid) therapy for hyperpigmented lesions caused by inflammation of the skin in black patients. N Engl J Med 1993; 328:1438.
  144. Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther 2007; 20:308.
  145. Palumbo A, d'Ischia M, Misuraca G, Prota G. Mechanism of inhibition of melanogenesis by hydroquinone. Biochim Biophys Acta 1991; 1073:85.
  146. Levitt J. The safety of hydroquinone: a dermatologist's response to the 2006 Federal Register. J Am Acad Dermatol 2007; 57:854.
  147. Department of Health and Human Services. Food and Drug Administration. Skin Bleaching Drug Products For Over-the-Counter Human Use; Proposed Rule. 71 Federal Register 51146-5115521 (2006) (codified at 21 CFR Part 310).
  148. Callender VD. Considerations for treating acne in ethnic skin. Cutis 2005; 76:19.
  149. Draelos ZD. Cosmetics and cosmeceuticals. In: Dermatology, 2nd ed, Bolognia JL, Jorizzo JL, Rapini RP, et al (Eds), Elsevier, 2008. p.2301.
  150. Draelos ZD. Cosmetic therapy. In: Comprehensive Dermatologic Drug Therapy, 2nd ed, Wolverton SE (Ed), Elsevier Inc, 2007. p.761.
  151. Subramanyan, K, Johnson, AW. Role of mild cleansing in the management of sensitive skin. Poster presented at the American Academy of Dermatology 61st Annual Meeting, San Francisco, CA, March 21 to 26, 2004.
  152. Bettley FR, Dale TL. The local treatment of acne. Br J Clin Pract 1976; 30:67.
  153. Milikan LE. A double-blind study of Betadine skin cleanser in acne vulgaris. Cutis 1976; 17:394.
  154. Stoughton RB, Leyden JJ. Efficacy of 4 percent chlorhexidine gluconate skin cleanser in the treatment of acne vulgaris. Cutis 1987; 39:551.
  155. Worret WI, Fluhr JW. [Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid] . J Dtsch Dermatol Ges 2006; 4:293.
  156. Leachman SA, Reed BR. The use of dermatologic drugs in pregnancy and lactation. Dermatol Clin 2006; 24:167.
READ MORE::  Anaphylaxis treatment and prevention

About the author

ultimate

Add Comment

Click here to post a comment

Events Calender

<< Mar 2019 >>
MTWTFSS
25 26 27 28 1 2 3
4 5 6 7 8 9 10
11 12 13 14 15 16 17
18 19 20 21 22 23 24
25 26 27 28 29 30 31