madman
Super Moderator
* Four main interrelated pathogenic factors, that act synergistically in a complex manner are involved in the development of acne lesions: 1. Increased sebum production due to androgen-driven sebaceous gland hyperplasia; 2. Hyperkeratinization of the follicular epithelium due to abnormal follicular growth and differentiation; 3.Colonization of Cutine bacterium acnes (C. acnes) within the pilosebaceous unit; and 4. Activation of innate and acquired immunity followed by the release of inflammatory mediators into the skin [1,2,4]. In addition, other elements such as neuroendocrine regulatory mechanisms, genetics, diet (namely a high glycemic index diet and dairy intake), the microbiome and environmental factors may contribute to this multifactorial process [5–7].
* There is a need for a blockbuster acne drug that simultaneously targets the four main pathogenic factors involved in the appearance of acne lesions while presenting with minimal side effects. Until such a drug exists, combination therapy will remain the standard of treatment for most acne patients.
1. Introduction
Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit [1,2] that affects approximately 9.4% of the global population, making it the eighth most prevalent disease worldwide and the most common skin conditions diagnosed and treated by dermatologists [3]. Although acne is present mainly in teenagers, affecting about 85% of them, it can persist into adulthood [3]. Four main interrelated pathogenic factors, that act synergistically in a complex manner are involved in the development of acne lesions: 1. Increased sebum production due to androgen-driven sebaceous gland hyperplasia; 2. Hyperkeratinization of the follicular epithelium due to abnormal follicular growth and differentiation; 3.Colonization of Cutine bacterium acnes (C. acnes) within the pilosebaceous unit; and 4. Activation of innate and acquired immunity followed by the release of inflammatory mediators into the skin [1,2,4]. In addition, other elements such as neuroendocrine regulatory mechanisms, genetics, diet (namely a high glycemic index diet and dairy intake), the microbiome and environmental factors may contribute to this multifactorial process [5–7].
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2. Topical therapies
Topical therapies (Table 1) are the foundation of acne treatment as they are used during the initial treatment as well as during maintenance therapy. These include topical retinoids, benzoyl peroxide (BP), azelaic acid, salicylic acid, topical antibiotics, and clascoterone. When managing acne with topical therapies, multimodal therapy combining multiple mechanisms of actions is recommended to optimize efficacy and to reduce the risk of antibiotic resistance [16].
2.1. Topical retinoids
2.2. Benzoyl peroxide
2.3. Azelaic acid
2.4. Salicylic acid
2.5. Topical antibiotics
2.6. Clascoterone
2.7. Combination treatments
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3. Systemic therapies
Systemic therapies (Table 2) are used in moderate-to-severe acne cases or in patients who did not respond to topical medication [2,4,9,10,15,16,18]. These include oral antibiotics,isotretinoin, combined oral contraceptives, and spironolactone[2,4,9,10,15,16,18]. Combined oral contraceptives and spironolactone will not be discussed in this article as they can only be prescribed to female subjects, due to their anti-androgenic side effects that lead to erectile dysfunction, gynecomastia,and feminization in males [88].
3.1. Oral antibiotics
3.2. Isotretinoin
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4. Maintenance therapy
Acne frequently follows a chronic remitting course [2,4,9,10,15,16,18]. Most patients experience a marked improvement with the initial treatment that is followed by severe relapses, sudden flares, or gradual re-occurrences [4] once the treatment is stopped [16]. Therefore, maintenance treatment should be prescribed once the patient is clear or almost clear of acne lesions, and clinical improvement has been achieved [2,4,9,10,15,16,18]. To avoid recurrences and relapses, maintenance treatment should target the formation of the microcomedo [2,4,16]. Therefore, topical retinoids are the gold-standard for maintenance [2,4,9,10,15,16,18]. Furthermore, topical retinoids also improve the development of secondary lesions, such as hyperpigmentation and scars [30–32], making them the preferred topical choice for treating these sequelae [31,32]. Azelaic acid [4,9,10,16,63] can also be used as an alternative to topical retinoids as it appears to have similar efficacy to adapalene during maintenance treatment [63]. Furthermore, azelaic acid also improves postinflammatory hyperpigmentation [64]. Benzoyl peroxide can also be added to treatment in patients recovering from inflammatory acne [9,10,16]; nevertheless, it should not be used as monotherapy for maintenance due to its lack of effect on microcomedos [16]. Topical or oral antibiotic monotherapy is not recommended for maintenance, not only because they increase antibiotic-resistant C. acnes but also because they do not prevent the development of microcomedos [75].
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5. Conclusions
Early diagnosis and treatment of acne vulgaris is imperative [15], because although acne tends to resolve naturally over the years [8] it can cause long-lasting side effects, such as permanent facial scarring, hyperpigmentation [1,2,4,9,10], and serious psychological afflictions [11,12], burdening those afflicted by the disease [12,13] and causing a negative impact on their quality of life [11,12]. Effective treatment involves the use of therapies that target most of the pathogenic factors attributed to the development of acne lesions as possible, and so, therapeutic strategies are centered on a systematic treatment escalation based on disease severity, extent, and treatment response; starting with topical treatment plans for mild to-moderate cases and progressing over to systemic therapies in more severe cases [1,2,4,9,10,15–18]. Correctly identifying the predominant type of lesion and the extent of the disease helps the clinicians decide on the type of treatment warranted [4,15].
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Topical retinoids should be the base of treatment in most acne patients [2,4,9,10,15,16,18] as they have comedolytic, anti-comedogenic [31–33], and anti-inflammatory properties [31,32]. Thus, monotherapy with a topical retinoid should be used as first-line treatment for acne that exclusively presents with comedos [2,4,9,10,15,16,18]. As acne becomes more inflammatory, with the presence of papules and pustules,adding an antimicrobial agent should be considered [2,4,9,10,15,16,18]. The choice of antimicrobial will largely depend on the severity of the papulopustular acne [2,4,9,10,15,16,18]. Topical antimicrobials such as BPO or topical antibiotics are preferred for mild-to-moderate papulopustular acne, while oral antibiotics are warranted in moderate-to severe cases [2,4,9,10,40,75]. Nodular and/or conglobate cases should preferably be treated with oral isotretinoin[2,4,9,10,15,16,18].
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After successful induction therapy, maintenance treatment should be initiated to avoid recurrences and relapses [2,4,9,10,15,16,18]. Topical retinoids are the treatment of choice for maintenance therapy [2,4,9,10,15,16,18]. Benzoyl peroxide can also be added to treatment in patients recovering from inflammatory acne [9,10]. In fact, BPO is currently the topical antimicrobial of choice for maintenance treatment as it has similar efficacy to topical antibiotics in treating acne [47] without inducing microbial resistance in the long run [47,50]. Alternately, azelaic acid can also be used in maintenance [10,63].
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Expert Opinion
There is a need for a blockbuster acne drug that simultaneously targets the four main pathogenic factors involved in the appearance of acne lesions while presenting with minimal side effects. Until such a drug exists, combination therapy will remain the standard of treatment for most acne patients.
* There is a need for a blockbuster acne drug that simultaneously targets the four main pathogenic factors involved in the appearance of acne lesions while presenting with minimal side effects. Until such a drug exists, combination therapy will remain the standard of treatment for most acne patients.
1. Introduction
Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit [1,2] that affects approximately 9.4% of the global population, making it the eighth most prevalent disease worldwide and the most common skin conditions diagnosed and treated by dermatologists [3]. Although acne is present mainly in teenagers, affecting about 85% of them, it can persist into adulthood [3]. Four main interrelated pathogenic factors, that act synergistically in a complex manner are involved in the development of acne lesions: 1. Increased sebum production due to androgen-driven sebaceous gland hyperplasia; 2. Hyperkeratinization of the follicular epithelium due to abnormal follicular growth and differentiation; 3.Colonization of Cutine bacterium acnes (C. acnes) within the pilosebaceous unit; and 4. Activation of innate and acquired immunity followed by the release of inflammatory mediators into the skin [1,2,4]. In addition, other elements such as neuroendocrine regulatory mechanisms, genetics, diet (namely a high glycemic index diet and dairy intake), the microbiome and environmental factors may contribute to this multifactorial process [5–7].
------------4
2. Topical therapies
Topical therapies (Table 1) are the foundation of acne treatment as they are used during the initial treatment as well as during maintenance therapy. These include topical retinoids, benzoyl peroxide (BP), azelaic acid, salicylic acid, topical antibiotics, and clascoterone. When managing acne with topical therapies, multimodal therapy combining multiple mechanisms of actions is recommended to optimize efficacy and to reduce the risk of antibiotic resistance [16].
2.1. Topical retinoids
2.2. Benzoyl peroxide
2.3. Azelaic acid
2.4. Salicylic acid
2.5. Topical antibiotics
2.6. Clascoterone
2.7. Combination treatments
-----------4
3. Systemic therapies
Systemic therapies (Table 2) are used in moderate-to-severe acne cases or in patients who did not respond to topical medication [2,4,9,10,15,16,18]. These include oral antibiotics,isotretinoin, combined oral contraceptives, and spironolactone[2,4,9,10,15,16,18]. Combined oral contraceptives and spironolactone will not be discussed in this article as they can only be prescribed to female subjects, due to their anti-androgenic side effects that lead to erectile dysfunction, gynecomastia,and feminization in males [88].
3.1. Oral antibiotics
3.2. Isotretinoin
------------4
4. Maintenance therapy
Acne frequently follows a chronic remitting course [2,4,9,10,15,16,18]. Most patients experience a marked improvement with the initial treatment that is followed by severe relapses, sudden flares, or gradual re-occurrences [4] once the treatment is stopped [16]. Therefore, maintenance treatment should be prescribed once the patient is clear or almost clear of acne lesions, and clinical improvement has been achieved [2,4,9,10,15,16,18]. To avoid recurrences and relapses, maintenance treatment should target the formation of the microcomedo [2,4,16]. Therefore, topical retinoids are the gold-standard for maintenance [2,4,9,10,15,16,18]. Furthermore, topical retinoids also improve the development of secondary lesions, such as hyperpigmentation and scars [30–32], making them the preferred topical choice for treating these sequelae [31,32]. Azelaic acid [4,9,10,16,63] can also be used as an alternative to topical retinoids as it appears to have similar efficacy to adapalene during maintenance treatment [63]. Furthermore, azelaic acid also improves postinflammatory hyperpigmentation [64]. Benzoyl peroxide can also be added to treatment in patients recovering from inflammatory acne [9,10,16]; nevertheless, it should not be used as monotherapy for maintenance due to its lack of effect on microcomedos [16]. Topical or oral antibiotic monotherapy is not recommended for maintenance, not only because they increase antibiotic-resistant C. acnes but also because they do not prevent the development of microcomedos [75].
------------4
5. Conclusions
Early diagnosis and treatment of acne vulgaris is imperative [15], because although acne tends to resolve naturally over the years [8] it can cause long-lasting side effects, such as permanent facial scarring, hyperpigmentation [1,2,4,9,10], and serious psychological afflictions [11,12], burdening those afflicted by the disease [12,13] and causing a negative impact on their quality of life [11,12]. Effective treatment involves the use of therapies that target most of the pathogenic factors attributed to the development of acne lesions as possible, and so, therapeutic strategies are centered on a systematic treatment escalation based on disease severity, extent, and treatment response; starting with topical treatment plans for mild to-moderate cases and progressing over to systemic therapies in more severe cases [1,2,4,9,10,15–18]. Correctly identifying the predominant type of lesion and the extent of the disease helps the clinicians decide on the type of treatment warranted [4,15].
----------
Topical retinoids should be the base of treatment in most acne patients [2,4,9,10,15,16,18] as they have comedolytic, anti-comedogenic [31–33], and anti-inflammatory properties [31,32]. Thus, monotherapy with a topical retinoid should be used as first-line treatment for acne that exclusively presents with comedos [2,4,9,10,15,16,18]. As acne becomes more inflammatory, with the presence of papules and pustules,adding an antimicrobial agent should be considered [2,4,9,10,15,16,18]. The choice of antimicrobial will largely depend on the severity of the papulopustular acne [2,4,9,10,15,16,18]. Topical antimicrobials such as BPO or topical antibiotics are preferred for mild-to-moderate papulopustular acne, while oral antibiotics are warranted in moderate-to severe cases [2,4,9,10,40,75]. Nodular and/or conglobate cases should preferably be treated with oral isotretinoin[2,4,9,10,15,16,18].
--------------
After successful induction therapy, maintenance treatment should be initiated to avoid recurrences and relapses [2,4,9,10,15,16,18]. Topical retinoids are the treatment of choice for maintenance therapy [2,4,9,10,15,16,18]. Benzoyl peroxide can also be added to treatment in patients recovering from inflammatory acne [9,10]. In fact, BPO is currently the topical antimicrobial of choice for maintenance treatment as it has similar efficacy to topical antibiotics in treating acne [47] without inducing microbial resistance in the long run [47,50]. Alternately, azelaic acid can also be used in maintenance [10,63].
---------4
Expert Opinion
There is a need for a blockbuster acne drug that simultaneously targets the four main pathogenic factors involved in the appearance of acne lesions while presenting with minimal side effects. Until such a drug exists, combination therapy will remain the standard of treatment for most acne patients.
