The Global Alliance to Improve Outcomes in Acne (Global Alliance) was designed to develop consensus recommendations related primarily to treatment. A group of 20 recognized dermatologists with a strong interest in issues related to acne management, representing multiple countries, formally convened to discuss pathogenesis and to outline current guidelines regarding therapy. The results of this alliance were subsequently published, inclusive of a treatment algorithm correlating acne grade (severity) with treatment options.1
It should not be assumed that all recommendations received full and equal support from every dermatologist in the alliance. However, the recommendations served to reflect current management suggestions based on extensive clinical experience and vast literature review.
Previously, acne treatment guidelines had been developed between 1990 and 2001.1 The Global Alliance to Improve Outcomes in Acne guidelines represent the most recent thinking and offer the advantage of international participation. The following article provides highlights from the Global Alliance and commentary on specific related issues with emphasis on newer concepts.
Topical Retinoids in Initial and Maintenance Therapy for Acne
The Global Alliance recommendations have reinforced the pivotal role of topical retinoids (adapalene, tazarotene, tretinoin) in both the early and maintenance phases of acne management. Topical retinoids exhibit both direct anti-inflammatory and comedolytic activities, thus explaining the recommendation that they be used as a component of “first-line” therapy in patients with mild, moderate, and, in many cases, severe acne.1
Their role in long-term maintenance treatment is supported by their comedolytic activity and anti-inflammatory effects; the aim of therapy is to decrease the need for chronic systemic antibiotic therapy. Depending on clinical presentation, topical retinoids may be used in combination with other topical agents, including antibiotics and benzoyl peroxide, and in combination with oral antibiotics, with additive benefits observed.
Although topical retinoids do not reduce Propionibacterium acnes colony counts, the number of receptors available to interact with P. acnes exoproducts is reduced through downregulation of toll-like receptor-2 (TLR-2) expression by the retinoid.4 As a result, inflammation is mitigated. In addition, as topical retinoids downregulate the AP-1 transcription factor pathway, they lessen the activity of matrix metalloproteinase enzymes involved in collagenolysis. (See Figure 2.)4 The long-term impact of this latter mechanism may be decreased acne scarring and improved skin texture.
Important considerations emphasized by the Global Alliance related to topical retinoid use are listed as follows.1,4
• Topical retinoids may be used effectively as monotherapy for pure comedonal acne.
• Regardless of whether or not the acne presentation is predominantly comedonal or inflammatory, topical retinoid therapy is best initiated early in the course of therapy.
• Skin irritation associated with topical retinoid use (“retinoid dermatitis”), occurring most often within the first 2 to 4 weeks of therapy (period of retinization), may be mitigated by gentle skin cleansing and moisturization.
• The ability of topical retinoids to reduce microcomedo formation and produce direct anti-inflammatory activity supports their use as maintenance therapy to sustain control of acne.
• Topical retinoids may effectively reduce postinflammatory hyperpigmentation in dark-skinned individuals.
• Long-term use of topical retinoid therapy may diminish the need for chronic antibiotic use, especially with systemic agents. More recent data with use of topical adapalene over 12 months demonstrates continued reduction in comedonal, inflammatory and total acne lesions.
Combination Therapy: Concurrent Use of Topical Retinoid and Topical Antimicrobial Agents
With the exception of pure comedonal acne, combination therapy is fundamental to managing acne. Multiple agents are available that work at different points in the “acne lesion life cycle”, with rational combinations often exhibiting additive or synergistic benefit (Figure 3). The combined use of a topical retinoid with antimicrobial therapy expedites response to therapy and augments clinical benefit.1 It is also believed that reduced ductal keratinization and decreased hyperkeratosis related to topical retinoid use allow for greater follicular penetration of other topically applied medications.
Topical retinoids have been used concurrently with benzoyl peroxide, benzoyl peroxide-topical antibiotic combination products, topical antibiotics (eg., clindamycin, erythromycin) and oral antibiotics. Essentially, if inflammatory acne lesions are present, combination topical retinoid-antimicrobial therapy is indicated. The use of oral antibiotic therapy is based on severity of acne.
Benzoyl peroxide produces rapid suppression of P. acnes within days and is not associated with emergence of resistant bacterial strains.1,6 When used as monotherapy, topical antibiotics, such as clindamycin and erythromycin, decrease P. acnes organism counts over the course of weeks, and to a lesser degree than that which is achieved with benzoyl peroxide alone.1,6-9 Studies have confirmed that the combination of benzoyl peroxide and a topical antibiotic (eg. clindamycin, erythromycin) is more effective than either agent alone, with lesser skin irritation observed as compared to benzoyl peroxide monotherapy.1,8,9
Important observations regarding use of topical antimicrobial agents in the treatment of acne are:1,4,6-11
• Benzoyl peroxide, a topical antibiotic — or both — may be combined with topical retinoid therapy in order to maximize therapeutic benefit. These combinations exhibit greater lesion reduction than topical monotherapy.
• Benzoyl peroxide and topical antibiotics primarily reduce inflammatory acne lesions, although a modest to moderate reduction in comedonal lesions may be observed as well.
• Benzoyl peroxide may reduce the development of resistant P. acnes strains or the further emergence of resistant P. acnes strains that are already present.
• A benzoyl peroxide cleanser may serve as an important alternative to a “leave-on” formulation in several scenarios such as in patients demonstrating irritation with the latter; in those patients where compliance with application of multiple products is more of a challenge; and for truncal disease where bleaching of fabric is a major consideration.
• Topical antibiotic monotherapy is not recommended over a prolonged time period due to the high likelihood that antibiotic resistant bacterial strains, including P. acnes and other cutaneous flora, will develop.
• Topical tretinoin formulated in a conventional gel or cream vehicle is unstable in the presence of ultraviolet light or benzoyl peroxide. As a result, application of tretinoin should occur in the evening, with benzoyl peroxide applied in the morning. Greater stability of tretinoin is observed with use of the microsphere gel vehicle. Adapalene is stable in the presence of ultraviolet light and benzoyl peroxide. As a result, adapalene may be used during the day and may be applied immediately before or after a benzoyl peroxide-containing product is used. Tazarotene is rapidly converted to its active metabolite, tazarotenic acid, shortly after it is applied to the skin.
Oral Antibiotic Therapy in Acne Treatment
The use of an oral antibiotic, combined with a topical regimen (eg., retinoid, benzoyl peroxide, benzoyl peroxide-antibiotic combination) is generally selected when treating acne graded as moderate to severe.1 Oral teracyclines — minocycline, doxycycline, and tetracycline — are the most commonly prescribed agents; alternative options include trimethoprim-sulfamethoxazole and some macrolide agents.
Chronic administration of oral antibiotic therapy for acne may lead to antibiotic resistance among P. acnes and other bacteria such as staphylococci and streptococci.1,12 In the United States, P. acnes strains resistant to erythromycin and tetracycline are common.1,12 A new extended-release formulation of minocycline is available and approved by the FDA for treatment of acne vulgaris; dosing is based on weight (1 mg/kg/day) and recommended frequency of administration is once daily. This formulation has been shown to exhibit a reduced risk of vestibular side effects.
The Global Alliance recognized the need to limit oral antibiotic exposure to as short a time period as possible. However, the consensus group also recognized that “many patients may require periodic courses of antibiotic therapy to control acne flares.”1 A reasonable response to oral antibiotic therapy generally occurs over a period of 3 to 6 months.
Role of Oral Hormonal Therapy in Females with Acne
Hormonal therapy is primarily utilized in females, especially those with post-teenage or late-onset acne (acne tarda), SAHA syndrome (seborrhea, acne, hirsutism, alopecia) or hyperandogenism states.1 In the United States, the main oral hormonal therapy options for acne are oral contraceptives, spironolactone and glucocorticosteroids; the latter is used specifically in patients with endocrinopathies associated with adrenal androgen hyperproduction (Figure 4).
Estrogen-progestin combination oral contraceptives suppress ovarian androgen production and reduce circulating free testosterone.1
The most serious potential adverse event associated with oral contraceptive use is thromboembolism, associated more commonly with older formulations that contained higher doses of estrogen. Oral contraceptives are a logical approach in females desiring use for the purpose of contraception.
Oral spironolactone is a peripheral androgen receptor blocker and an inhibitor of 5-alpha reductase, which reduces sebum production. Benefit in acne has been established in female patients, especially the post-teen population and in those refractory to conventional therapy.1 When used as monotherapy, gynecomastia and menstrual irregularities may occur, especially at higher doses (>100 mg daily). Combined use with oral contraceptives obviates these side effects.
As spironolactone is a potassium-sparing mild diuretic, hyperkalemia is a potential risk. However, significant elevations of serum potassium levels are unlikely, except in patients using potassium supplementation, in those with renal disease, and in patients undergoing treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).
Round-up of Recommendations
• The Global Alliance to Improve Outcomes in Acne allowed for a thorough review of available data on acne management and shared perceptions based on clinical experience from an international perspective.
• Topical retinoids are a fundamental component of acne management, both early in the course of treatment and during long-term maintenance therapy.
• Topical combination therapy is also fundamental to acne management. Benzoyl peroxide, topical antibiotics, and benzoyl peroxide-antibiotic formulations may be used in combination with topical retinoid therapy to optimize therapeutic benefit.
• Oral antibiotic therapy, used in combination with a rational topical program, is usually recommended in cases of greater severity, graded as moderate to severe. Concerns regarding bacterial resistance secondary to chronic oral antibiotic administration have prompted some authorities to caution against prolonged use.
• Oral contraceptives and spironolactone are effective options primarily for adult female patients, especially those refractory to conventional therapy and in many forms of androgen excess.
The Global Alliance to Improve Outcomes in Acne (Global Alliance) was designed to develop consensus recommendations related primarily to treatment. A group of 20 recognized dermatologists with a strong interest in issues related to acne management, representing multiple countries, formally convened to discuss pathogenesis and to outline current guidelines regarding therapy. The results of this alliance were subsequently published, inclusive of a treatment algorithm correlating acne grade (severity) with treatment options.1
It should not be assumed that all recommendations received full and equal support from every dermatologist in the alliance. However, the recommendations served to reflect current management suggestions based on extensive clinical experience and vast literature review.
Previously, acne treatment guidelines had been developed between 1990 and 2001.1 The Global Alliance to Improve Outcomes in Acne guidelines represent the most recent thinking and offer the advantage of international participation. The following article provides highlights from the Global Alliance and commentary on specific related issues with emphasis on newer concepts.
Topical Retinoids in Initial and Maintenance Therapy for Acne
The Global Alliance recommendations have reinforced the pivotal role of topical retinoids (adapalene, tazarotene, tretinoin) in both the early and maintenance phases of acne management. Topical retinoids exhibit both direct anti-inflammatory and comedolytic activities, thus explaining the recommendation that they be used as a component of “first-line” therapy in patients with mild, moderate, and, in many cases, severe acne.1
Their role in long-term maintenance treatment is supported by their comedolytic activity and anti-inflammatory effects; the aim of therapy is to decrease the need for chronic systemic antibiotic therapy. Depending on clinical presentation, topical retinoids may be used in combination with other topical agents, including antibiotics and benzoyl peroxide, and in combination with oral antibiotics, with additive benefits observed.
Although topical retinoids do not reduce Propionibacterium acnes colony counts, the number of receptors available to interact with P. acnes exoproducts is reduced through downregulation of toll-like receptor-2 (TLR-2) expression by the retinoid.4 As a result, inflammation is mitigated. In addition, as topical retinoids downregulate the AP-1 transcription factor pathway, they lessen the activity of matrix metalloproteinase enzymes involved in collagenolysis. (See Figure 2.)4 The long-term impact of this latter mechanism may be decreased acne scarring and improved skin texture.
Important considerations emphasized by the Global Alliance related to topical retinoid use are listed as follows.1,4
• Topical retinoids may be used effectively as monotherapy for pure comedonal acne.
• Regardless of whether or not the acne presentation is predominantly comedonal or inflammatory, topical retinoid therapy is best initiated early in the course of therapy.
• Skin irritation associated with topical retinoid use (“retinoid dermatitis”), occurring most often within the first 2 to 4 weeks of therapy (period of retinization), may be mitigated by gentle skin cleansing and moisturization.
• The ability of topical retinoids to reduce microcomedo formation and produce direct anti-inflammatory activity supports their use as maintenance therapy to sustain control of acne.
• Topical retinoids may effectively reduce postinflammatory hyperpigmentation in dark-skinned individuals.
• Long-term use of topical retinoid therapy may diminish the need for chronic antibiotic use, especially with systemic agents. More recent data with use of topical adapalene over 12 months demonstrates continued reduction in comedonal, inflammatory and total acne lesions.
Combination Therapy: Concurrent Use of Topical Retinoid and Topical Antimicrobial Agents
With the exception of pure comedonal acne, combination therapy is fundamental to managing acne. Multiple agents are available that work at different points in the “acne lesion life cycle”, with rational combinations often exhibiting additive or synergistic benefit (Figure 3). The combined use of a topical retinoid with antimicrobial therapy expedites response to therapy and augments clinical benefit.1 It is also believed that reduced ductal keratinization and decreased hyperkeratosis related to topical retinoid use allow for greater follicular penetration of other topically applied medications.
Topical retinoids have been used concurrently with benzoyl peroxide, benzoyl peroxide-topical antibiotic combination products, topical antibiotics (eg., clindamycin, erythromycin) and oral antibiotics. Essentially, if inflammatory acne lesions are present, combination topical retinoid-antimicrobial therapy is indicated. The use of oral antibiotic therapy is based on severity of acne.
Benzoyl peroxide produces rapid suppression of P. acnes within days and is not associated with emergence of resistant bacterial strains.1,6 When used as monotherapy, topical antibiotics, such as clindamycin and erythromycin, decrease P. acnes organism counts over the course of weeks, and to a lesser degree than that which is achieved with benzoyl peroxide alone.1,6-9 Studies have confirmed that the combination of benzoyl peroxide and a topical antibiotic (eg. clindamycin, erythromycin) is more effective than either agent alone, with lesser skin irritation observed as compared to benzoyl peroxide monotherapy.1,8,9
Important observations regarding use of topical antimicrobial agents in the treatment of acne are:1,4,6-11
• Benzoyl peroxide, a topical antibiotic — or both — may be combined with topical retinoid therapy in order to maximize therapeutic benefit. These combinations exhibit greater lesion reduction than topical monotherapy.
• Benzoyl peroxide and topical antibiotics primarily reduce inflammatory acne lesions, although a modest to moderate reduction in comedonal lesions may be observed as well.
• Benzoyl peroxide may reduce the development of resistant P. acnes strains or the further emergence of resistant P. acnes strains that are already present.
• A benzoyl peroxide cleanser may serve as an important alternative to a “leave-on” formulation in several scenarios such as in patients demonstrating irritation with the latter; in those patients where compliance with application of multiple products is more of a challenge; and for truncal disease where bleaching of fabric is a major consideration.
• Topical antibiotic monotherapy is not recommended over a prolonged time period due to the high likelihood that antibiotic resistant bacterial strains, including P. acnes and other cutaneous flora, will develop.
• Topical tretinoin formulated in a conventional gel or cream vehicle is unstable in the presence of ultraviolet light or benzoyl peroxide. As a result, application of tretinoin should occur in the evening, with benzoyl peroxide applied in the morning. Greater stability of tretinoin is observed with use of the microsphere gel vehicle. Adapalene is stable in the presence of ultraviolet light and benzoyl peroxide. As a result, adapalene may be used during the day and may be applied immediately before or after a benzoyl peroxide-containing product is used. Tazarotene is rapidly converted to its active metabolite, tazarotenic acid, shortly after it is applied to the skin.
Oral Antibiotic Therapy in Acne Treatment
The use of an oral antibiotic, combined with a topical regimen (eg., retinoid, benzoyl peroxide, benzoyl peroxide-antibiotic combination) is generally selected when treating acne graded as moderate to severe.1 Oral teracyclines — minocycline, doxycycline, and tetracycline — are the most commonly prescribed agents; alternative options include trimethoprim-sulfamethoxazole and some macrolide agents.
Chronic administration of oral antibiotic therapy for acne may lead to antibiotic resistance among P. acnes and other bacteria such as staphylococci and streptococci.1,12 In the United States, P. acnes strains resistant to erythromycin and tetracycline are common.1,12 A new extended-release formulation of minocycline is available and approved by the FDA for treatment of acne vulgaris; dosing is based on weight (1 mg/kg/day) and recommended frequency of administration is once daily. This formulation has been shown to exhibit a reduced risk of vestibular side effects.
The Global Alliance recognized the need to limit oral antibiotic exposure to as short a time period as possible. However, the consensus group also recognized that “many patients may require periodic courses of antibiotic therapy to control acne flares.”1 A reasonable response to oral antibiotic therapy generally occurs over a period of 3 to 6 months.
Role of Oral Hormonal Therapy in Females with Acne
Hormonal therapy is primarily utilized in females, especially those with post-teenage or late-onset acne (acne tarda), SAHA syndrome (seborrhea, acne, hirsutism, alopecia) or hyperandogenism states.1 In the United States, the main oral hormonal therapy options for acne are oral contraceptives, spironolactone and glucocorticosteroids; the latter is used specifically in patients with endocrinopathies associated with adrenal androgen hyperproduction (Figure 4).
Estrogen-progestin combination oral contraceptives suppress ovarian androgen production and reduce circulating free testosterone.1
The most serious potential adverse event associated with oral contraceptive use is thromboembolism, associated more commonly with older formulations that contained higher doses of estrogen. Oral contraceptives are a logical approach in females desiring use for the purpose of contraception.
Oral spironolactone is a peripheral androgen receptor blocker and an inhibitor of 5-alpha reductase, which reduces sebum production. Benefit in acne has been established in female patients, especially the post-teen population and in those refractory to conventional therapy.1 When used as monotherapy, gynecomastia and menstrual irregularities may occur, especially at higher doses (>100 mg daily). Combined use with oral contraceptives obviates these side effects.
As spironolactone is a potassium-sparing mild diuretic, hyperkalemia is a potential risk. However, significant elevations of serum potassium levels are unlikely, except in patients using potassium supplementation, in those with renal disease, and in patients undergoing treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).
Round-up of Recommendations
• The Global Alliance to Improve Outcomes in Acne allowed for a thorough review of available data on acne management and shared perceptions based on clinical experience from an international perspective.
• Topical retinoids are a fundamental component of acne management, both early in the course of treatment and during long-term maintenance therapy.
• Topical combination therapy is also fundamental to acne management. Benzoyl peroxide, topical antibiotics, and benzoyl peroxide-antibiotic formulations may be used in combination with topical retinoid therapy to optimize therapeutic benefit.
• Oral antibiotic therapy, used in combination with a rational topical program, is usually recommended in cases of greater severity, graded as moderate to severe. Concerns regarding bacterial resistance secondary to chronic oral antibiotic administration have prompted some authorities to caution against prolonged use.
• Oral contraceptives and spironolactone are effective options primarily for adult female patients, especially those refractory to conventional therapy and in many forms of androgen excess.
The Global Alliance to Improve Outcomes in Acne (Global Alliance) was designed to develop consensus recommendations related primarily to treatment. A group of 20 recognized dermatologists with a strong interest in issues related to acne management, representing multiple countries, formally convened to discuss pathogenesis and to outline current guidelines regarding therapy. The results of this alliance were subsequently published, inclusive of a treatment algorithm correlating acne grade (severity) with treatment options.1
It should not be assumed that all recommendations received full and equal support from every dermatologist in the alliance. However, the recommendations served to reflect current management suggestions based on extensive clinical experience and vast literature review.
Previously, acne treatment guidelines had been developed between 1990 and 2001.1 The Global Alliance to Improve Outcomes in Acne guidelines represent the most recent thinking and offer the advantage of international participation. The following article provides highlights from the Global Alliance and commentary on specific related issues with emphasis on newer concepts.
Topical Retinoids in Initial and Maintenance Therapy for Acne
The Global Alliance recommendations have reinforced the pivotal role of topical retinoids (adapalene, tazarotene, tretinoin) in both the early and maintenance phases of acne management. Topical retinoids exhibit both direct anti-inflammatory and comedolytic activities, thus explaining the recommendation that they be used as a component of “first-line” therapy in patients with mild, moderate, and, in many cases, severe acne.1
Their role in long-term maintenance treatment is supported by their comedolytic activity and anti-inflammatory effects; the aim of therapy is to decrease the need for chronic systemic antibiotic therapy. Depending on clinical presentation, topical retinoids may be used in combination with other topical agents, including antibiotics and benzoyl peroxide, and in combination with oral antibiotics, with additive benefits observed.
Although topical retinoids do not reduce Propionibacterium acnes colony counts, the number of receptors available to interact with P. acnes exoproducts is reduced through downregulation of toll-like receptor-2 (TLR-2) expression by the retinoid.4 As a result, inflammation is mitigated. In addition, as topical retinoids downregulate the AP-1 transcription factor pathway, they lessen the activity of matrix metalloproteinase enzymes involved in collagenolysis. (See Figure 2.)4 The long-term impact of this latter mechanism may be decreased acne scarring and improved skin texture.
Important considerations emphasized by the Global Alliance related to topical retinoid use are listed as follows.1,4
• Topical retinoids may be used effectively as monotherapy for pure comedonal acne.
• Regardless of whether or not the acne presentation is predominantly comedonal or inflammatory, topical retinoid therapy is best initiated early in the course of therapy.
• Skin irritation associated with topical retinoid use (“retinoid dermatitis”), occurring most often within the first 2 to 4 weeks of therapy (period of retinization), may be mitigated by gentle skin cleansing and moisturization.
• The ability of topical retinoids to reduce microcomedo formation and produce direct anti-inflammatory activity supports their use as maintenance therapy to sustain control of acne.
• Topical retinoids may effectively reduce postinflammatory hyperpigmentation in dark-skinned individuals.
• Long-term use of topical retinoid therapy may diminish the need for chronic antibiotic use, especially with systemic agents. More recent data with use of topical adapalene over 12 months demonstrates continued reduction in comedonal, inflammatory and total acne lesions.
Combination Therapy: Concurrent Use of Topical Retinoid and Topical Antimicrobial Agents
With the exception of pure comedonal acne, combination therapy is fundamental to managing acne. Multiple agents are available that work at different points in the “acne lesion life cycle”, with rational combinations often exhibiting additive or synergistic benefit (Figure 3). The combined use of a topical retinoid with antimicrobial therapy expedites response to therapy and augments clinical benefit.1 It is also believed that reduced ductal keratinization and decreased hyperkeratosis related to topical retinoid use allow for greater follicular penetration of other topically applied medications.
Topical retinoids have been used concurrently with benzoyl peroxide, benzoyl peroxide-topical antibiotic combination products, topical antibiotics (eg., clindamycin, erythromycin) and oral antibiotics. Essentially, if inflammatory acne lesions are present, combination topical retinoid-antimicrobial therapy is indicated. The use of oral antibiotic therapy is based on severity of acne.
Benzoyl peroxide produces rapid suppression of P. acnes within days and is not associated with emergence of resistant bacterial strains.1,6 When used as monotherapy, topical antibiotics, such as clindamycin and erythromycin, decrease P. acnes organism counts over the course of weeks, and to a lesser degree than that which is achieved with benzoyl peroxide alone.1,6-9 Studies have confirmed that the combination of benzoyl peroxide and a topical antibiotic (eg. clindamycin, erythromycin) is more effective than either agent alone, with lesser skin irritation observed as compared to benzoyl peroxide monotherapy.1,8,9
Important observations regarding use of topical antimicrobial agents in the treatment of acne are:1,4,6-11
• Benzoyl peroxide, a topical antibiotic — or both — may be combined with topical retinoid therapy in order to maximize therapeutic benefit. These combinations exhibit greater lesion reduction than topical monotherapy.
• Benzoyl peroxide and topical antibiotics primarily reduce inflammatory acne lesions, although a modest to moderate reduction in comedonal lesions may be observed as well.
• Benzoyl peroxide may reduce the development of resistant P. acnes strains or the further emergence of resistant P. acnes strains that are already present.
• A benzoyl peroxide cleanser may serve as an important alternative to a “leave-on” formulation in several scenarios such as in patients demonstrating irritation with the latter; in those patients where compliance with application of multiple products is more of a challenge; and for truncal disease where bleaching of fabric is a major consideration.
• Topical antibiotic monotherapy is not recommended over a prolonged time period due to the high likelihood that antibiotic resistant bacterial strains, including P. acnes and other cutaneous flora, will develop.
• Topical tretinoin formulated in a conventional gel or cream vehicle is unstable in the presence of ultraviolet light or benzoyl peroxide. As a result, application of tretinoin should occur in the evening, with benzoyl peroxide applied in the morning. Greater stability of tretinoin is observed with use of the microsphere gel vehicle. Adapalene is stable in the presence of ultraviolet light and benzoyl peroxide. As a result, adapalene may be used during the day and may be applied immediately before or after a benzoyl peroxide-containing product is used. Tazarotene is rapidly converted to its active metabolite, tazarotenic acid, shortly after it is applied to the skin.
Oral Antibiotic Therapy in Acne Treatment
The use of an oral antibiotic, combined with a topical regimen (eg., retinoid, benzoyl peroxide, benzoyl peroxide-antibiotic combination) is generally selected when treating acne graded as moderate to severe.1 Oral teracyclines — minocycline, doxycycline, and tetracycline — are the most commonly prescribed agents; alternative options include trimethoprim-sulfamethoxazole and some macrolide agents.
Chronic administration of oral antibiotic therapy for acne may lead to antibiotic resistance among P. acnes and other bacteria such as staphylococci and streptococci.1,12 In the United States, P. acnes strains resistant to erythromycin and tetracycline are common.1,12 A new extended-release formulation of minocycline is available and approved by the FDA for treatment of acne vulgaris; dosing is based on weight (1 mg/kg/day) and recommended frequency of administration is once daily. This formulation has been shown to exhibit a reduced risk of vestibular side effects.
The Global Alliance recognized the need to limit oral antibiotic exposure to as short a time period as possible. However, the consensus group also recognized that “many patients may require periodic courses of antibiotic therapy to control acne flares.”1 A reasonable response to oral antibiotic therapy generally occurs over a period of 3 to 6 months.
Role of Oral Hormonal Therapy in Females with Acne
Hormonal therapy is primarily utilized in females, especially those with post-teenage or late-onset acne (acne tarda), SAHA syndrome (seborrhea, acne, hirsutism, alopecia) or hyperandogenism states.1 In the United States, the main oral hormonal therapy options for acne are oral contraceptives, spironolactone and glucocorticosteroids; the latter is used specifically in patients with endocrinopathies associated with adrenal androgen hyperproduction (Figure 4).
Estrogen-progestin combination oral contraceptives suppress ovarian androgen production and reduce circulating free testosterone.1
The most serious potential adverse event associated with oral contraceptive use is thromboembolism, associated more commonly with older formulations that contained higher doses of estrogen. Oral contraceptives are a logical approach in females desiring use for the purpose of contraception.
Oral spironolactone is a peripheral androgen receptor blocker and an inhibitor of 5-alpha reductase, which reduces sebum production. Benefit in acne has been established in female patients, especially the post-teen population and in those refractory to conventional therapy.1 When used as monotherapy, gynecomastia and menstrual irregularities may occur, especially at higher doses (>100 mg daily). Combined use with oral contraceptives obviates these side effects.
As spironolactone is a potassium-sparing mild diuretic, hyperkalemia is a potential risk. However, significant elevations of serum potassium levels are unlikely, except in patients using potassium supplementation, in those with renal disease, and in patients undergoing treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).
Round-up of Recommendations
• The Global Alliance to Improve Outcomes in Acne allowed for a thorough review of available data on acne management and shared perceptions based on clinical experience from an international perspective.
• Topical retinoids are a fundamental component of acne management, both early in the course of treatment and during long-term maintenance therapy.
• Topical combination therapy is also fundamental to acne management. Benzoyl peroxide, topical antibiotics, and benzoyl peroxide-antibiotic formulations may be used in combination with topical retinoid therapy to optimize therapeutic benefit.
• Oral antibiotic therapy, used in combination with a rational topical program, is usually recommended in cases of greater severity, graded as moderate to severe. Concerns regarding bacterial resistance secondary to chronic oral antibiotic administration have prompted some authorities to caution against prolonged use.
• Oral contraceptives and spironolactone are effective options primarily for adult female patients, especially those refractory to conventional therapy and in many forms of androgen excess.
