N early everyone suffers from acne at some point in life,1 and 20% of all patient visits to dermatologists are acne-related.2 Acne, a chronic disease, affects a majority of those 12 to 24 years of age and may continue to afflict some patients well into adulthood.2,3 The physiological, psychological, and quality-of-life impacts associated with acne are significant and well studied.4,5 The effective treatment of acne in sufferers of all ages and types is therefore critical. In this article, we’ll look at six patient composites to present an overview of the current approaches to treating and managing the most common types of acne patients. Also discussed are new or potential therapies for those suffering from acne. Pathogenesis and Life Cycle of Acne The pathogenesis of acne is multifactorial and involves the interaction of four processes.1 First, follicular keratinization is increased, which results in the follicles becoming plugged.4,6 There is an increase in sebum production, often related to increased hormone production, which contributes to the obstruction of the follicles.7 Propionibacterium acnes bacteria then proliferate in the obstructed follicles and cause the final process, the inflammatory and immune responses in the skin.8,9 Acne, typically, is first diagnosed in adolescence with onset of hormonal changes associated with puberty.10 Excessive sebum is produced by these patients, which results in oily skin and, when combined with follicular hyperkeratinization, comedonal acne. The inflammatory reaction to these initial lesions leads to the formation of the papules, pustules, and nodules seen in more severe forms of acne.6,10 The incidence of acne declines with age, but the disease may persist beyond adolescence. A recent study indicated the prevalence of adult acne at 3% in men and 12% in women.3,10 Hormonal fluctuations may influence the persistence or development of the disease in adult women.4 The type and severity of acne often differs by sex and age. Adult females are more likely than males to suffer from inflammatory acne that affects the lower face, whereas teenage males are more frequently affected by acne than teenage females.4,10 Thus, optimal treatment of acne vulgaris varies according to the age and sex of the patient, as well as the type and severity of disease. Overview of Acne Treatment The most effective acne treatments address the individual patient’s acne by targeting multiple pathogenic factors.1,4,11,12 For example, topical retinoids restore the normal follicular keratinization processes and reduce the formation of comedos;2 benzoyl peroxide (BPO) also is comedolytic.13 The production of sebum may be reduced by using the oral retinoid isotretinoin (Accutane, Amnesteem) or systemic hormonal agents (such as oral contraceptives)1 Antimicrobials, such as BPO and systemic antibiotic agents, reduce P. acnes counts and associated inflammation.11 The anti-inflammatory qualities of retinoids may also be used to control acne-related inflammation.1 Therapies should be initiated early to minimize or prevent the sequelae of acne, which include scarring and other psychological effects.14 Because acne treatments vary according to their mode of action and their effectiveness against the key causes of acne, specific agents are used to target specific types of acne. A brief review of the important classes of anti-acne agents and how they are used to treat mild, moderate and severe acne is presented below (See Figure 1). Topical retinoids. Topical retinoids, such as tretinoin (Avita, Renova, Retin-A, Solage, Tri Luma), adapalene (Differin) and tazarotene (Tazorac), are effective for the initial or early treatment of mild-to-moderate, non-inflammatory, comedonal acne when used alone.2,9,15 Retinoids can also be combined with antimicrobial treatments for inflammatory or more severe acne1,9,16 and used alone or in combination for long-term maintenance therapy.1,2 Oral antibiotics. Oral antibiotics are most effective for inflammatory acne lesions, moderate-to-severe acne,5,9 and in patients where topical treatments have failed. Commonly used agents, such as tetracycline and erythromycin, are generally not used as monotherapy because their use may contribute to P. acnes resistance.11 Oral antibiotics also may have rare, but in some cases severe, side effects that may influence their use as acne therapy.2,11 For all of these reasons, these agents should be prescribed at therapeutic doses for the minimal effective time period, discontinued, and then followed by long-term topical therapy.4,5 The use of oral antibiotics in combination with BPOs or retinoids is also effective in minimizing P acnes resistance and maximizing efficacy.11 Topical antibiotics. Topical antibiotics, such as clindamycin and erythromycin, are generally not recommended as monotherapy because they induce resistance in P. acnes, which results in decreased efficacy.4,5,18 These agents are, however, highly effective acne treatments when used in combination with other agents, such as OCs19 and BPO.11 Benzoyl peroxide. When used alone, this agent is an effective antimicrobial and has comedolytic activity.13,17,20 In combination with an antibiotic (e.g., 1% clindamycin/5% benzoyl peroxide), it is a well-studied, effective, well-tolerated treatment for inflammatory acne.20-22 Combination antibiotic/BPO therapies are effective when used with retinoids. Hormonal Therapies. These therapies are now recognized as effective acne therapies in women with inflammatory acne or certain hormonal conditions. These women may benefit from treatment with OC products, such as ethinyl estradiol/levonorgestrel (Alesse, Levlen, Levlite, Plan B, Seasonale, Tri-Levlen, Triphasil) and drospirenone/ethinyl estradiol (Yasmin).1,5,23 Antiandrogens, such as spironolactone, also have anti-acne benefits and may be used alone or in combination with oral antibiotics or topical therapies for certain women.19 Oral retinoids. Isotretinoin is a mainstay therapy for severe, scarring acne and acne that relapses or is resistant to oral and topical therapies.5,14 Isotretinoin addresses all four of the pathophysiologic factors of acne and is a highly effective therapy; however, it has side effects that include teratogenic effects in pregnant women and reports of potential psychological impacts.1,5,14,17 These side effects limit its use in certain patients, such as women of childbearing age.1,5,17 Adjunctive therapies. Novel adjunctive treatments for acne include photodynamic therapy, light and laser procedures that target specific causes of acne.1,5 Blue light treatments, for example, kill P. acnes, whereas red light treatments are anti-inflammatory.1 Chemical and microdermabrasive procedures, as well as procedures that involve comedo extraction, also may be useful components of acne treatment programs. Other Considerations An equally important factor in determining treatment for acne is consideration of the vehicle used to deliver the active ingredient of a particular therapy. The emollient, humectant, or occlusive properties of the treatment vehicle are a key factor in maximizing the overall health of skin: repairing skin barrier function and improving hydration, for example, are critical components of effective acne therapy.22,24,25 Additionally, environmental factors must be considered when evaluating certain acne treatments, because they may affect efficacy. (See The Building Blocks to Better Acne Treatment on page 74.) Case Study 1: Mild comedonal acne in a young teenager A 13-year-old, pubescent male presents with mild facial acne in the form of approximately 15 non-inflamed comedones in the T-zone of the face. The patient does not have acne in any other areas of the face, neck or back. He has no other inflammatory lesions and does not have any facial scarring. The patient reports that this is his first “breakout.” Treatment and Discussion Monotherapy with a topical retinoid, applied daily on all affected areas of the face, would be the preferred treatment for this patient’s comedonal lesions.5,9,26 The goal of treatment for this patient, as for other acne patients, would be to prevent the formation of new acne lesions. Another important consideration would be tolerability: certain topical retinoids may produce skin irritation.5,17 The topical retinoids currently available in the United States, namely tretinoin, tazarotene, and adapalene, have differences in terms of effectiveness, tolerability, and formulation/strength that must be considered for each potential patient.5,26 The use of a topical retinoid in combination with a benzoyl peroxide and antibiotic might also be considered for this patient. Application of one of the agents in morning followed by the other agent in evening might clear comedones faster than antibiotics alone and minimize potential flares.2,26 Case Study 2: Mild inflammatory acne in a teenager A 16-year-old male presents with approximately 10 comedones and 10 small inflammatory papules on his lower face, cheeks and neck. The patient reports that he has had several previous acne flares. He has used topical treatments previously that have been somewhat effective in reducing his acne, but have left his skin dry and irritated. There is no evidence of scarring in the areas that are currently affected by acne. Treatment and Discussion The patient can use a 1% clindamycin/5% benzoyl peroxide (Benzaclin, Duac) in conjunction with a topical retinoid to eliminate comedones and mild inflammation. After the lesions have cleared, a maintenance regimen of morning application of a topical retinoid plus an antimicrobial agent may be considered. The 1% clindamycin/5% benzoyl peroxide combination gel has comedolytic activity and proven efficacy in reducing non-inflammatory and inflammatory lesions and in clearing mild-to-moderate acne.21 This combination product also sigificantly reduces total and resistant P. acnes counts and prevents bacterial resistance that may be associated with other treatments, such as topical antibiotics.20,27 This combination effectively targets three of the four causes of acne. Additionally, 1% clindamycin/5% benzoyl peroxide has an excellent safety and tolerability profile; simple, once-daily dosing; and the option of a therapeutic vehicle formulation containing the skin-repairing and hydrating agents dimethicone and glycerin.26 Case Study 3: Moderate comedonal acne in a teenager A 15-year-old male presents with a mix of approximately 50 comedones and 30 papules/pustules around his mouth, on his cheeks and on his upper back. He reports that he has had mild-to-moderate acne since puberty, but has no acne scarring in the afflicted areas. Treatment and Discussion A combination of a retinoid, which normalizes keratinization, and an oral antibiotic (eg, tetracycline, minocycline, doxycycline), which reduces P acnes and associated inflammation, would be an effective therapy for this patient.2,5,28 The patient will need close monitoring, however, because of the potential safety issues and resistance associated with antibiotic agents.11,14 Monotherapies of a topical retinoid or benzoyl peroxide product also may be alternatives for this patient, as would topical or oral antibiotics; however, efficacy, tolerability and safety issues must be considered before empolying any of these agents.1,5,9 As discussed in the previous case study, a topical retinoid plus antiobiotic and benzoyl peroxide may be used for maintenance after successful initial treatment.1,2 Case Study 4: Moderate acne in an adult female A 25-year-old female presents with a moderate number of comedones (40) and several papules and nodules in a small area of her neck and lower face. She has minimal scarring present on her lower face and reports that her acne flares during her menstrual cycle. Treatment and Discussion Adult women typically require pregnancy testing as well as tests of hormonal function prior to initiating acne treatments. Assuming normal hormonal function, this patient’s acne would likely respond well to a regimen of 1% clindamycin/5% benzoyl peroxide plus an OC agent, which reduces sebum.26 An antibiotic/benzoyl peroxide product may be highly effective when used in combination with other agents, such as OCs.26 OCs or spirolactone are often used for women who do not respond to oral antibiotics and have primarily neck/chin breakouts; however, OCs and spironolactone have some safety issues that must be considered.5 OCs also are typically used for limited-area acne and are particularly appropriate if female patients also need contraception.5 Additionally, topical therapy on affected areas prior to menstrual cycle onset help this patient prevent breakouts. The patient also may benefit from lifestyle changes (changes in clothing types or certain activities) to minimize breakouts and associated discomfort. Case Study 5: Severe comedonal acne in an adult male A 23-year-old male presents with numerous comedones and a small number of papules/pustules spread across large areas of the forehead, lower face and upper back. The patient reports that he has had acne since his teenage years and has previously used a topical retinoid and antibiotic treatments, which have been ineffective. He has extensive scarring on his cheeks and upper back. Treatment and Discussion This patient is a likely candidate for isotretinoin therapy, which targets all four major causes of acne and is indicated for severe acne. It suppresses sebum and P. acnes, reduces inflammation and promotes normal keratin processes. It’s also effective in addressing acne scarring17,26 and may be effective because of his recalcitrant acne condition.5 The tolerability issues with isotretinoin must be considered; thus, patient education about associated health and possible psychological issues is critical for this patient.5,29 Alternative treatments for those with severe acne may include oral antibiotics, OCs and corticosteroids.5,26 Blue light and photo sensitizing agents, such as 20% 5-aminolevulinic acid (Levulan), are potential adjunctive therapies for severe acne and associated scarring, as are topical agents and surgery.1,26 Case Study 6: Severe acne in an adult female of childbearing age A 28-year-old female presents with multiple large, painful, inflammatory lesions and numerous smaller pustules and comedones on her face and neck. The patient explains that she has had acne since high school and exhibits scarring over affected areas of her face and neck. She is also concerned about the side effects of oral retinoid therapy. Treatment and Discussion As in the previous case study involving a female patient, endocrine function tests should precede acne therapy.5,26 Assuming normal health, a combination therapy of a 1% clindamycin/5% benzoyl peroxide product plus a retinoid would be effective in clearing this patient’s inflammatory lesions.16,21 A regimen that combines an antibiotic and an oral contraceptive might also be effective for this patient.26 Photodynamic therapy or isotretinoin could be considered if the patient does not respond; however, with the latter, pregnancy prevention must be addressed.5 Alternative therapies for this patient may be required if evaluations determine certain hormonal or health abnormalities.5 Selecting Therapy The following are critical considerations for selecting appropriate and effective therapies for patients with acne: • The most effective acne treatments attack multiple factors that cause disease. Products that address multiple causes and symptoms of acne, such as combination products, are often safer and more effective than monotherapies. • The severity and type of acne (mild, moderate, severe; comedonal vs. inflammatory), patient age and sex, and history/past therapy are factors that must be considered to successfully manage acne. Novel uses for more traditional treatments, as well as new therapies, are continually joining the anti-acne arsenal. • The vehicle of therapy is an important consideration when treating acne. Clinicians can maximize treatment efficacy by matching the therapy vehicle with the individual patient’s disease, skin type, and compliance or motivation level. An essential part of any acne management program is to maintain the health of the patient’s skin. • Patient education is a critical component of effective acne therapy. In order to safely and effectively use agents with side effects or those with special considerations for use, such as isotretinoin and OCs, patients must be well informed about the therapeutic agents in their acne treatment.
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Overcoming the Challenges of Difficult Acne Cases
N early everyone suffers from acne at some point in life,1 and 20% of all patient visits to dermatologists are acne-related.2 Acne, a chronic disease, affects a majority of those 12 to 24 years of age and may continue to afflict some patients well into adulthood.2,3 The physiological, psychological, and quality-of-life impacts associated with acne are significant and well studied.4,5 The effective treatment of acne in sufferers of all ages and types is therefore critical. In this article, we’ll look at six patient composites to present an overview of the current approaches to treating and managing the most common types of acne patients. Also discussed are new or potential therapies for those suffering from acne. Pathogenesis and Life Cycle of Acne The pathogenesis of acne is multifactorial and involves the interaction of four processes.1 First, follicular keratinization is increased, which results in the follicles becoming plugged.4,6 There is an increase in sebum production, often related to increased hormone production, which contributes to the obstruction of the follicles.7 Propionibacterium acnes bacteria then proliferate in the obstructed follicles and cause the final process, the inflammatory and immune responses in the skin.8,9 Acne, typically, is first diagnosed in adolescence with onset of hormonal changes associated with puberty.10 Excessive sebum is produced by these patients, which results in oily skin and, when combined with follicular hyperkeratinization, comedonal acne. The inflammatory reaction to these initial lesions leads to the formation of the papules, pustules, and nodules seen in more severe forms of acne.6,10 The incidence of acne declines with age, but the disease may persist beyond adolescence. A recent study indicated the prevalence of adult acne at 3% in men and 12% in women.3,10 Hormonal fluctuations may influence the persistence or development of the disease in adult women.4 The type and severity of acne often differs by sex and age. Adult females are more likely than males to suffer from inflammatory acne that affects the lower face, whereas teenage males are more frequently affected by acne than teenage females.4,10 Thus, optimal treatment of acne vulgaris varies according to the age and sex of the patient, as well as the type and severity of disease. Overview of Acne Treatment The most effective acne treatments address the individual patient’s acne by targeting multiple pathogenic factors.1,4,11,12 For example, topical retinoids restore the normal follicular keratinization processes and reduce the formation of comedos;2 benzoyl peroxide (BPO) also is comedolytic.13 The production of sebum may be reduced by using the oral retinoid isotretinoin (Accutane, Amnesteem) or systemic hormonal agents (such as oral contraceptives)1 Antimicrobials, such as BPO and systemic antibiotic agents, reduce P. acnes counts and associated inflammation.11 The anti-inflammatory qualities of retinoids may also be used to control acne-related inflammation.1 Therapies should be initiated early to minimize or prevent the sequelae of acne, which include scarring and other psychological effects.14 Because acne treatments vary according to their mode of action and their effectiveness against the key causes of acne, specific agents are used to target specific types of acne. A brief review of the important classes of anti-acne agents and how they are used to treat mild, moderate and severe acne is presented below (See Figure 1). Topical retinoids. Topical retinoids, such as tretinoin (Avita, Renova, Retin-A, Solage, Tri Luma), adapalene (Differin) and tazarotene (Tazorac), are effective for the initial or early treatment of mild-to-moderate, non-inflammatory, comedonal acne when used alone.2,9,15 Retinoids can also be combined with antimicrobial treatments for inflammatory or more severe acne1,9,16 and used alone or in combination for long-term maintenance therapy.1,2 Oral antibiotics. Oral antibiotics are most effective for inflammatory acne lesions, moderate-to-severe acne,5,9 and in patients where topical treatments have failed. Commonly used agents, such as tetracycline and erythromycin, are generally not used as monotherapy because their use may contribute to P. acnes resistance.11 Oral antibiotics also may have rare, but in some cases severe, side effects that may influence their use as acne therapy.2,11 For all of these reasons, these agents should be prescribed at therapeutic doses for the minimal effective time period, discontinued, and then followed by long-term topical therapy.4,5 The use of oral antibiotics in combination with BPOs or retinoids is also effective in minimizing P acnes resistance and maximizing efficacy.11 Topical antibiotics. Topical antibiotics, such as clindamycin and erythromycin, are generally not recommended as monotherapy because they induce resistance in P. acnes, which results in decreased efficacy.4,5,18 These agents are, however, highly effective acne treatments when used in combination with other agents, such as OCs19 and BPO.11 Benzoyl peroxide. When used alone, this agent is an effective antimicrobial and has comedolytic activity.13,17,20 In combination with an antibiotic (e.g., 1% clindamycin/5% benzoyl peroxide), it is a well-studied, effective, well-tolerated treatment for inflammatory acne.20-22 Combination antibiotic/BPO therapies are effective when used with retinoids. Hormonal Therapies. These therapies are now recognized as effective acne therapies in women with inflammatory acne or certain hormonal conditions. These women may benefit from treatment with OC products, such as ethinyl estradiol/levonorgestrel (Alesse, Levlen, Levlite, Plan B, Seasonale, Tri-Levlen, Triphasil) and drospirenone/ethinyl estradiol (Yasmin).1,5,23 Antiandrogens, such as spironolactone, also have anti-acne benefits and may be used alone or in combination with oral antibiotics or topical therapies for certain women.19 Oral retinoids. Isotretinoin is a mainstay therapy for severe, scarring acne and acne that relapses or is resistant to oral and topical therapies.5,14 Isotretinoin addresses all four of the pathophysiologic factors of acne and is a highly effective therapy; however, it has side effects that include teratogenic effects in pregnant women and reports of potential psychological impacts.1,5,14,17 These side effects limit its use in certain patients, such as women of childbearing age.1,5,17 Adjunctive therapies. Novel adjunctive treatments for acne include photodynamic therapy, light and laser procedures that target specific causes of acne.1,5 Blue light treatments, for example, kill P. acnes, whereas red light treatments are anti-inflammatory.1 Chemical and microdermabrasive procedures, as well as procedures that involve comedo extraction, also may be useful components of acne treatment programs. Other Considerations An equally important factor in determining treatment for acne is consideration of the vehicle used to deliver the active ingredient of a particular therapy. The emollient, humectant, or occlusive properties of the treatment vehicle are a key factor in maximizing the overall health of skin: repairing skin barrier function and improving hydration, for example, are critical components of effective acne therapy.22,24,25 Additionally, environmental factors must be considered when evaluating certain acne treatments, because they may affect efficacy. (See The Building Blocks to Better Acne Treatment on page 74.) Case Study 1: Mild comedonal acne in a young teenager A 13-year-old, pubescent male presents with mild facial acne in the form of approximately 15 non-inflamed comedones in the T-zone of the face. The patient does not have acne in any other areas of the face, neck or back. He has no other inflammatory lesions and does not have any facial scarring. The patient reports that this is his first “breakout.” Treatment and Discussion Monotherapy with a topical retinoid, applied daily on all affected areas of the face, would be the preferred treatment for this patient’s comedonal lesions.5,9,26 The goal of treatment for this patient, as for other acne patients, would be to prevent the formation of new acne lesions. Another important consideration would be tolerability: certain topical retinoids may produce skin irritation.5,17 The topical retinoids currently available in the United States, namely tretinoin, tazarotene, and adapalene, have differences in terms of effectiveness, tolerability, and formulation/strength that must be considered for each potential patient.5,26 The use of a topical retinoid in combination with a benzoyl peroxide and antibiotic might also be considered for this patient. Application of one of the agents in morning followed by the other agent in evening might clear comedones faster than antibiotics alone and minimize potential flares.2,26 Case Study 2: Mild inflammatory acne in a teenager A 16-year-old male presents with approximately 10 comedones and 10 small inflammatory papules on his lower face, cheeks and neck. The patient reports that he has had several previous acne flares. He has used topical treatments previously that have been somewhat effective in reducing his acne, but have left his skin dry and irritated. There is no evidence of scarring in the areas that are currently affected by acne. Treatment and Discussion The patient can use a 1% clindamycin/5% benzoyl peroxide (Benzaclin, Duac) in conjunction with a topical retinoid to eliminate comedones and mild inflammation. After the lesions have cleared, a maintenance regimen of morning application of a topical retinoid plus an antimicrobial agent may be considered. The 1% clindamycin/5% benzoyl peroxide combination gel has comedolytic activity and proven efficacy in reducing non-inflammatory and inflammatory lesions and in clearing mild-to-moderate acne.21 This combination product also sigificantly reduces total and resistant P. acnes counts and prevents bacterial resistance that may be associated with other treatments, such as topical antibiotics.20,27 This combination effectively targets three of the four causes of acne. Additionally, 1% clindamycin/5% benzoyl peroxide has an excellent safety and tolerability profile; simple, once-daily dosing; and the option of a therapeutic vehicle formulation containing the skin-repairing and hydrating agents dimethicone and glycerin.26 Case Study 3: Moderate comedonal acne in a teenager A 15-year-old male presents with a mix of approximately 50 comedones and 30 papules/pustules around his mouth, on his cheeks and on his upper back. He reports that he has had mild-to-moderate acne since puberty, but has no acne scarring in the afflicted areas. Treatment and Discussion A combination of a retinoid, which normalizes keratinization, and an oral antibiotic (eg, tetracycline, minocycline, doxycycline), which reduces P acnes and associated inflammation, would be an effective therapy for this patient.2,5,28 The patient will need close monitoring, however, because of the potential safety issues and resistance associated with antibiotic agents.11,14 Monotherapies of a topical retinoid or benzoyl peroxide product also may be alternatives for this patient, as would topical or oral antibiotics; however, efficacy, tolerability and safety issues must be considered before empolying any of these agents.1,5,9 As discussed in the previous case study, a topical retinoid plus antiobiotic and benzoyl peroxide may be used for maintenance after successful initial treatment.1,2 Case Study 4: Moderate acne in an adult female A 25-year-old female presents with a moderate number of comedones (40) and several papules and nodules in a small area of her neck and lower face. She has minimal scarring present on her lower face and reports that her acne flares during her menstrual cycle. Treatment and Discussion Adult women typically require pregnancy testing as well as tests of hormonal function prior to initiating acne treatments. Assuming normal hormonal function, this patient’s acne would likely respond well to a regimen of 1% clindamycin/5% benzoyl peroxide plus an OC agent, which reduces sebum.26 An antibiotic/benzoyl peroxide product may be highly effective when used in combination with other agents, such as OCs.26 OCs or spirolactone are often used for women who do not respond to oral antibiotics and have primarily neck/chin breakouts; however, OCs and spironolactone have some safety issues that must be considered.5 OCs also are typically used for limited-area acne and are particularly appropriate if female patients also need contraception.5 Additionally, topical therapy on affected areas prior to menstrual cycle onset help this patient prevent breakouts. The patient also may benefit from lifestyle changes (changes in clothing types or certain activities) to minimize breakouts and associated discomfort. Case Study 5: Severe comedonal acne in an adult male A 23-year-old male presents with numerous comedones and a small number of papules/pustules spread across large areas of the forehead, lower face and upper back. The patient reports that he has had acne since his teenage years and has previously used a topical retinoid and antibiotic treatments, which have been ineffective. He has extensive scarring on his cheeks and upper back. Treatment and Discussion This patient is a likely candidate for isotretinoin therapy, which targets all four major causes of acne and is indicated for severe acne. It suppresses sebum and P. acnes, reduces inflammation and promotes normal keratin processes. It’s also effective in addressing acne scarring17,26 and may be effective because of his recalcitrant acne condition.5 The tolerability issues with isotretinoin must be considered; thus, patient education about associated health and possible psychological issues is critical for this patient.5,29 Alternative treatments for those with severe acne may include oral antibiotics, OCs and corticosteroids.5,26 Blue light and photo sensitizing agents, such as 20% 5-aminolevulinic acid (Levulan), are potential adjunctive therapies for severe acne and associated scarring, as are topical agents and surgery.1,26 Case Study 6: Severe acne in an adult female of childbearing age A 28-year-old female presents with multiple large, painful, inflammatory lesions and numerous smaller pustules and comedones on her face and neck. The patient explains that she has had acne since high school and exhibits scarring over affected areas of her face and neck. She is also concerned about the side effects of oral retinoid therapy. Treatment and Discussion As in the previous case study involving a female patient, endocrine function tests should precede acne therapy.5,26 Assuming normal health, a combination therapy of a 1% clindamycin/5% benzoyl peroxide product plus a retinoid would be effective in clearing this patient’s inflammatory lesions.16,21 A regimen that combines an antibiotic and an oral contraceptive might also be effective for this patient.26 Photodynamic therapy or isotretinoin could be considered if the patient does not respond; however, with the latter, pregnancy prevention must be addressed.5 Alternative therapies for this patient may be required if evaluations determine certain hormonal or health abnormalities.5 Selecting Therapy The following are critical considerations for selecting appropriate and effective therapies for patients with acne: • The most effective acne treatments attack multiple factors that cause disease. Products that address multiple causes and symptoms of acne, such as combination products, are often safer and more effective than monotherapies. • The severity and type of acne (mild, moderate, severe; comedonal vs. inflammatory), patient age and sex, and history/past therapy are factors that must be considered to successfully manage acne. Novel uses for more traditional treatments, as well as new therapies, are continually joining the anti-acne arsenal. • The vehicle of therapy is an important consideration when treating acne. Clinicians can maximize treatment efficacy by matching the therapy vehicle with the individual patient’s disease, skin type, and compliance or motivation level. An essential part of any acne management program is to maintain the health of the patient’s skin. • Patient education is a critical component of effective acne therapy. In order to safely and effectively use agents with side effects or those with special considerations for use, such as isotretinoin and OCs, patients must be well informed about the therapeutic agents in their acne treatment.
N early everyone suffers from acne at some point in life,1 and 20% of all patient visits to dermatologists are acne-related.2 Acne, a chronic disease, affects a majority of those 12 to 24 years of age and may continue to afflict some patients well into adulthood.2,3 The physiological, psychological, and quality-of-life impacts associated with acne are significant and well studied.4,5 The effective treatment of acne in sufferers of all ages and types is therefore critical. In this article, we’ll look at six patient composites to present an overview of the current approaches to treating and managing the most common types of acne patients. Also discussed are new or potential therapies for those suffering from acne. Pathogenesis and Life Cycle of Acne The pathogenesis of acne is multifactorial and involves the interaction of four processes.1 First, follicular keratinization is increased, which results in the follicles becoming plugged.4,6 There is an increase in sebum production, often related to increased hormone production, which contributes to the obstruction of the follicles.7 Propionibacterium acnes bacteria then proliferate in the obstructed follicles and cause the final process, the inflammatory and immune responses in the skin.8,9 Acne, typically, is first diagnosed in adolescence with onset of hormonal changes associated with puberty.10 Excessive sebum is produced by these patients, which results in oily skin and, when combined with follicular hyperkeratinization, comedonal acne. The inflammatory reaction to these initial lesions leads to the formation of the papules, pustules, and nodules seen in more severe forms of acne.6,10 The incidence of acne declines with age, but the disease may persist beyond adolescence. A recent study indicated the prevalence of adult acne at 3% in men and 12% in women.3,10 Hormonal fluctuations may influence the persistence or development of the disease in adult women.4 The type and severity of acne often differs by sex and age. Adult females are more likely than males to suffer from inflammatory acne that affects the lower face, whereas teenage males are more frequently affected by acne than teenage females.4,10 Thus, optimal treatment of acne vulgaris varies according to the age and sex of the patient, as well as the type and severity of disease. Overview of Acne Treatment The most effective acne treatments address the individual patient’s acne by targeting multiple pathogenic factors.1,4,11,12 For example, topical retinoids restore the normal follicular keratinization processes and reduce the formation of comedos;2 benzoyl peroxide (BPO) also is comedolytic.13 The production of sebum may be reduced by using the oral retinoid isotretinoin (Accutane, Amnesteem) or systemic hormonal agents (such as oral contraceptives)1 Antimicrobials, such as BPO and systemic antibiotic agents, reduce P. acnes counts and associated inflammation.11 The anti-inflammatory qualities of retinoids may also be used to control acne-related inflammation.1 Therapies should be initiated early to minimize or prevent the sequelae of acne, which include scarring and other psychological effects.14 Because acne treatments vary according to their mode of action and their effectiveness against the key causes of acne, specific agents are used to target specific types of acne. A brief review of the important classes of anti-acne agents and how they are used to treat mild, moderate and severe acne is presented below (See Figure 1). Topical retinoids. Topical retinoids, such as tretinoin (Avita, Renova, Retin-A, Solage, Tri Luma), adapalene (Differin) and tazarotene (Tazorac), are effective for the initial or early treatment of mild-to-moderate, non-inflammatory, comedonal acne when used alone.2,9,15 Retinoids can also be combined with antimicrobial treatments for inflammatory or more severe acne1,9,16 and used alone or in combination for long-term maintenance therapy.1,2 Oral antibiotics. Oral antibiotics are most effective for inflammatory acne lesions, moderate-to-severe acne,5,9 and in patients where topical treatments have failed. Commonly used agents, such as tetracycline and erythromycin, are generally not used as monotherapy because their use may contribute to P. acnes resistance.11 Oral antibiotics also may have rare, but in some cases severe, side effects that may influence their use as acne therapy.2,11 For all of these reasons, these agents should be prescribed at therapeutic doses for the minimal effective time period, discontinued, and then followed by long-term topical therapy.4,5 The use of oral antibiotics in combination with BPOs or retinoids is also effective in minimizing P acnes resistance and maximizing efficacy.11 Topical antibiotics. Topical antibiotics, such as clindamycin and erythromycin, are generally not recommended as monotherapy because they induce resistance in P. acnes, which results in decreased efficacy.4,5,18 These agents are, however, highly effective acne treatments when used in combination with other agents, such as OCs19 and BPO.11 Benzoyl peroxide. When used alone, this agent is an effective antimicrobial and has comedolytic activity.13,17,20 In combination with an antibiotic (e.g., 1% clindamycin/5% benzoyl peroxide), it is a well-studied, effective, well-tolerated treatment for inflammatory acne.20-22 Combination antibiotic/BPO therapies are effective when used with retinoids. Hormonal Therapies. These therapies are now recognized as effective acne therapies in women with inflammatory acne or certain hormonal conditions. These women may benefit from treatment with OC products, such as ethinyl estradiol/levonorgestrel (Alesse, Levlen, Levlite, Plan B, Seasonale, Tri-Levlen, Triphasil) and drospirenone/ethinyl estradiol (Yasmin).1,5,23 Antiandrogens, such as spironolactone, also have anti-acne benefits and may be used alone or in combination with oral antibiotics or topical therapies for certain women.19 Oral retinoids. Isotretinoin is a mainstay therapy for severe, scarring acne and acne that relapses or is resistant to oral and topical therapies.5,14 Isotretinoin addresses all four of the pathophysiologic factors of acne and is a highly effective therapy; however, it has side effects that include teratogenic effects in pregnant women and reports of potential psychological impacts.1,5,14,17 These side effects limit its use in certain patients, such as women of childbearing age.1,5,17 Adjunctive therapies. Novel adjunctive treatments for acne include photodynamic therapy, light and laser procedures that target specific causes of acne.1,5 Blue light treatments, for example, kill P. acnes, whereas red light treatments are anti-inflammatory.1 Chemical and microdermabrasive procedures, as well as procedures that involve comedo extraction, also may be useful components of acne treatment programs. Other Considerations An equally important factor in determining treatment for acne is consideration of the vehicle used to deliver the active ingredient of a particular therapy. The emollient, humectant, or occlusive properties of the treatment vehicle are a key factor in maximizing the overall health of skin: repairing skin barrier function and improving hydration, for example, are critical components of effective acne therapy.22,24,25 Additionally, environmental factors must be considered when evaluating certain acne treatments, because they may affect efficacy. (See The Building Blocks to Better Acne Treatment on page 74.) Case Study 1: Mild comedonal acne in a young teenager A 13-year-old, pubescent male presents with mild facial acne in the form of approximately 15 non-inflamed comedones in the T-zone of the face. The patient does not have acne in any other areas of the face, neck or back. He has no other inflammatory lesions and does not have any facial scarring. The patient reports that this is his first “breakout.” Treatment and Discussion Monotherapy with a topical retinoid, applied daily on all affected areas of the face, would be the preferred treatment for this patient’s comedonal lesions.5,9,26 The goal of treatment for this patient, as for other acne patients, would be to prevent the formation of new acne lesions. Another important consideration would be tolerability: certain topical retinoids may produce skin irritation.5,17 The topical retinoids currently available in the United States, namely tretinoin, tazarotene, and adapalene, have differences in terms of effectiveness, tolerability, and formulation/strength that must be considered for each potential patient.5,26 The use of a topical retinoid in combination with a benzoyl peroxide and antibiotic might also be considered for this patient. Application of one of the agents in morning followed by the other agent in evening might clear comedones faster than antibiotics alone and minimize potential flares.2,26 Case Study 2: Mild inflammatory acne in a teenager A 16-year-old male presents with approximately 10 comedones and 10 small inflammatory papules on his lower face, cheeks and neck. The patient reports that he has had several previous acne flares. He has used topical treatments previously that have been somewhat effective in reducing his acne, but have left his skin dry and irritated. There is no evidence of scarring in the areas that are currently affected by acne. Treatment and Discussion The patient can use a 1% clindamycin/5% benzoyl peroxide (Benzaclin, Duac) in conjunction with a topical retinoid to eliminate comedones and mild inflammation. After the lesions have cleared, a maintenance regimen of morning application of a topical retinoid plus an antimicrobial agent may be considered. The 1% clindamycin/5% benzoyl peroxide combination gel has comedolytic activity and proven efficacy in reducing non-inflammatory and inflammatory lesions and in clearing mild-to-moderate acne.21 This combination product also sigificantly reduces total and resistant P. acnes counts and prevents bacterial resistance that may be associated with other treatments, such as topical antibiotics.20,27 This combination effectively targets three of the four causes of acne. Additionally, 1% clindamycin/5% benzoyl peroxide has an excellent safety and tolerability profile; simple, once-daily dosing; and the option of a therapeutic vehicle formulation containing the skin-repairing and hydrating agents dimethicone and glycerin.26 Case Study 3: Moderate comedonal acne in a teenager A 15-year-old male presents with a mix of approximately 50 comedones and 30 papules/pustules around his mouth, on his cheeks and on his upper back. He reports that he has had mild-to-moderate acne since puberty, but has no acne scarring in the afflicted areas. Treatment and Discussion A combination of a retinoid, which normalizes keratinization, and an oral antibiotic (eg, tetracycline, minocycline, doxycycline), which reduces P acnes and associated inflammation, would be an effective therapy for this patient.2,5,28 The patient will need close monitoring, however, because of the potential safety issues and resistance associated with antibiotic agents.11,14 Monotherapies of a topical retinoid or benzoyl peroxide product also may be alternatives for this patient, as would topical or oral antibiotics; however, efficacy, tolerability and safety issues must be considered before empolying any of these agents.1,5,9 As discussed in the previous case study, a topical retinoid plus antiobiotic and benzoyl peroxide may be used for maintenance after successful initial treatment.1,2 Case Study 4: Moderate acne in an adult female A 25-year-old female presents with a moderate number of comedones (40) and several papules and nodules in a small area of her neck and lower face. She has minimal scarring present on her lower face and reports that her acne flares during her menstrual cycle. Treatment and Discussion Adult women typically require pregnancy testing as well as tests of hormonal function prior to initiating acne treatments. Assuming normal hormonal function, this patient’s acne would likely respond well to a regimen of 1% clindamycin/5% benzoyl peroxide plus an OC agent, which reduces sebum.26 An antibiotic/benzoyl peroxide product may be highly effective when used in combination with other agents, such as OCs.26 OCs or spirolactone are often used for women who do not respond to oral antibiotics and have primarily neck/chin breakouts; however, OCs and spironolactone have some safety issues that must be considered.5 OCs also are typically used for limited-area acne and are particularly appropriate if female patients also need contraception.5 Additionally, topical therapy on affected areas prior to menstrual cycle onset help this patient prevent breakouts. The patient also may benefit from lifestyle changes (changes in clothing types or certain activities) to minimize breakouts and associated discomfort. Case Study 5: Severe comedonal acne in an adult male A 23-year-old male presents with numerous comedones and a small number of papules/pustules spread across large areas of the forehead, lower face and upper back. The patient reports that he has had acne since his teenage years and has previously used a topical retinoid and antibiotic treatments, which have been ineffective. He has extensive scarring on his cheeks and upper back. Treatment and Discussion This patient is a likely candidate for isotretinoin therapy, which targets all four major causes of acne and is indicated for severe acne. It suppresses sebum and P. acnes, reduces inflammation and promotes normal keratin processes. It’s also effective in addressing acne scarring17,26 and may be effective because of his recalcitrant acne condition.5 The tolerability issues with isotretinoin must be considered; thus, patient education about associated health and possible psychological issues is critical for this patient.5,29 Alternative treatments for those with severe acne may include oral antibiotics, OCs and corticosteroids.5,26 Blue light and photo sensitizing agents, such as 20% 5-aminolevulinic acid (Levulan), are potential adjunctive therapies for severe acne and associated scarring, as are topical agents and surgery.1,26 Case Study 6: Severe acne in an adult female of childbearing age A 28-year-old female presents with multiple large, painful, inflammatory lesions and numerous smaller pustules and comedones on her face and neck. The patient explains that she has had acne since high school and exhibits scarring over affected areas of her face and neck. She is also concerned about the side effects of oral retinoid therapy. Treatment and Discussion As in the previous case study involving a female patient, endocrine function tests should precede acne therapy.5,26 Assuming normal health, a combination therapy of a 1% clindamycin/5% benzoyl peroxide product plus a retinoid would be effective in clearing this patient’s inflammatory lesions.16,21 A regimen that combines an antibiotic and an oral contraceptive might also be effective for this patient.26 Photodynamic therapy or isotretinoin could be considered if the patient does not respond; however, with the latter, pregnancy prevention must be addressed.5 Alternative therapies for this patient may be required if evaluations determine certain hormonal or health abnormalities.5 Selecting Therapy The following are critical considerations for selecting appropriate and effective therapies for patients with acne: • The most effective acne treatments attack multiple factors that cause disease. Products that address multiple causes and symptoms of acne, such as combination products, are often safer and more effective than monotherapies. • The severity and type of acne (mild, moderate, severe; comedonal vs. inflammatory), patient age and sex, and history/past therapy are factors that must be considered to successfully manage acne. Novel uses for more traditional treatments, as well as new therapies, are continually joining the anti-acne arsenal. • The vehicle of therapy is an important consideration when treating acne. Clinicians can maximize treatment efficacy by matching the therapy vehicle with the individual patient’s disease, skin type, and compliance or motivation level. An essential part of any acne management program is to maintain the health of the patient’s skin. • Patient education is a critical component of effective acne therapy. In order to safely and effectively use agents with side effects or those with special considerations for use, such as isotretinoin and OCs, patients must be well informed about the therapeutic agents in their acne treatment.
