madman
Super Moderator
ABSTRACT
Background
Sebum physiology and its contributions to acne vulgaris (AV) pathophysiology have been long debated. Within the pilosebaceous unit, androgens drive sebocyte production of sebum, comprising mono-, di-, and triglycerides (the latter converted to fatty acids); squalene; cholesterol; cholesterol esters; and wax esters. Upon release to the skin surface, human sebum has important roles in epidermal water retention, antimicrobial defenses, and innate immune responses.
Aims
Alterations in sebum alone and with other pathogenic factors (inflammation, follicular hyperkeratinization, and Cutibacterium acnes [C. acnes] proliferation) contribute to AV pathophysiology. Androgen-driven sebum production, mandatory for AV development, propagates C. acnes proliferation and upregulates inflammatory and comedogenic cascades.
Results
Some sebum lipids have comedogenic effects in isolation, and sebum content alterations(including elevations in specific fatty acids) contribute to AV pathogenesis. Regional differences in facial sebum production, coupled with patient characteristics (including sex and age), help exemplify this link between sebum alterations and AV lesion formation.
Conclusions
To date, only combined oral contraceptives and oral spironolactone (both limited to female patients), oral isotretinoin, and topical clascoterone (cortexolone 17α-propionate) modulate serum production in patients with AV. A better understanding of mechanisms underlying sebaceous gland changes driving AV development is needed to expand the AV treatment armamentarium.
1. Introduction
Acne vulgaris (AV) is a chronic inflammatory and immune-mediated skin condition characterized by the presence of noninflammatory (open and closed comedones) and inflammatory (papules, pustules, and nodules) lesions, primarily on the face, chest, upper back, and shoulders (1,2). AV is the eighth most common disease among all diseases globally and can occur in individuals of any age, race, or sex/gender (1,3,4). The high prevalence of AV, coupled with the physical, social, psychological, and economic burdens experienced by patients, highlights the significant global disease burden (5).
AV is a multifactorial disease with 4 key interrelated processes driving pathophysiology: inflammation, increased sebaceous gland activity, and sebum production, follicular hyperkeratinization, and colonization of proinflammatory strains of Cutibacterium acnes (C.acnes) (1,6,7). Androgens are sex hormones that mediate excessive sebaceous gland activity and sebum production, representing the earliest step in AV lesion formation (8–12). A growing body of evidence also supports that alterations in sebum composition are important for AV development (13–16).
Commonly recommended therapies that are consistently mentioned in publications on AV management include retinoids, benzoyl peroxide, antibiotics, and hormonal therapies, all of which target 1 or more of these pathogenic factors (2,6,17). To date, only hormonal therapies and isotretinoin (a retinoid) are shown to address increased sebum production in AV (6). Systemic antiandrogenic therapies can induce feminization in male patients (e.g., gynecomastia), may elicit certain side effects in females, and are not recommended for use in pregnant patients (1,6,18–20). The risk of teratogenicity with isotretinoin contraindicates this treatment for patients who are pregnant and necessitates measures to completely avoid pregnancy in women undergoing oral isotretinoin therapy (21). Therefore, novel treatment options are needed that modulate sebaceous gland activity and have acceptable safety profiles in both males and females (6,22).
This review provides an overview of the role of sebum in the pathophysiology of AV from both compositional and quantitative perspectives, discusses factors that influence these changes in sebum and touches upon sebum-targeting therapeutic options for patients with AV.
2. Sebaceous immunobiology
3. Sebum in AV and other disorders
3.1. Sebum quantity
3.2. Sebum quality
4. Factors influencing sebum quality and quantity
5. Sebum-targeting therapies
5.1. Standard of care treatments
5.2. Emerging pharmacologic treatments and natural products
6. Conclusions
Although AV is highly prevalent across the globe, it is still not considered curable (52). An improved understanding of the mechanisms regulating sebum dysregulation in AV is needed to innovate therapeutic approaches for patients (30). Excess sebum production and changes in sebum composition are necessary early steps in AV pathophysiology (107). Alterations in sebum composition affect sebocyte proliferation, differentiation, and sebum production, as well as hyperkeratinization and inflammation within the sebaceous gland (22,25,47). Changes in sebum production vary by facial region as well as other factors, such as patient sex and age (84–87). There is an unmet need for agents that target excessive sebum production and alterations in sebum compositions that can be safely used in a variety of patients, including male patients and patients who are or may become pregnant (6,22). Topical antiandrogens devoid of systemic side effects, such as clascoterone, address many of these unmet needs for a more diverse group of patients, including males (6).
Background
Sebum physiology and its contributions to acne vulgaris (AV) pathophysiology have been long debated. Within the pilosebaceous unit, androgens drive sebocyte production of sebum, comprising mono-, di-, and triglycerides (the latter converted to fatty acids); squalene; cholesterol; cholesterol esters; and wax esters. Upon release to the skin surface, human sebum has important roles in epidermal water retention, antimicrobial defenses, and innate immune responses.
Aims
Alterations in sebum alone and with other pathogenic factors (inflammation, follicular hyperkeratinization, and Cutibacterium acnes [C. acnes] proliferation) contribute to AV pathophysiology. Androgen-driven sebum production, mandatory for AV development, propagates C. acnes proliferation and upregulates inflammatory and comedogenic cascades.
Results
Some sebum lipids have comedogenic effects in isolation, and sebum content alterations(including elevations in specific fatty acids) contribute to AV pathogenesis. Regional differences in facial sebum production, coupled with patient characteristics (including sex and age), help exemplify this link between sebum alterations and AV lesion formation.
Conclusions
To date, only combined oral contraceptives and oral spironolactone (both limited to female patients), oral isotretinoin, and topical clascoterone (cortexolone 17α-propionate) modulate serum production in patients with AV. A better understanding of mechanisms underlying sebaceous gland changes driving AV development is needed to expand the AV treatment armamentarium.
1. Introduction
Acne vulgaris (AV) is a chronic inflammatory and immune-mediated skin condition characterized by the presence of noninflammatory (open and closed comedones) and inflammatory (papules, pustules, and nodules) lesions, primarily on the face, chest, upper back, and shoulders (1,2). AV is the eighth most common disease among all diseases globally and can occur in individuals of any age, race, or sex/gender (1,3,4). The high prevalence of AV, coupled with the physical, social, psychological, and economic burdens experienced by patients, highlights the significant global disease burden (5).
AV is a multifactorial disease with 4 key interrelated processes driving pathophysiology: inflammation, increased sebaceous gland activity, and sebum production, follicular hyperkeratinization, and colonization of proinflammatory strains of Cutibacterium acnes (C.acnes) (1,6,7). Androgens are sex hormones that mediate excessive sebaceous gland activity and sebum production, representing the earliest step in AV lesion formation (8–12). A growing body of evidence also supports that alterations in sebum composition are important for AV development (13–16).
Commonly recommended therapies that are consistently mentioned in publications on AV management include retinoids, benzoyl peroxide, antibiotics, and hormonal therapies, all of which target 1 or more of these pathogenic factors (2,6,17). To date, only hormonal therapies and isotretinoin (a retinoid) are shown to address increased sebum production in AV (6). Systemic antiandrogenic therapies can induce feminization in male patients (e.g., gynecomastia), may elicit certain side effects in females, and are not recommended for use in pregnant patients (1,6,18–20). The risk of teratogenicity with isotretinoin contraindicates this treatment for patients who are pregnant and necessitates measures to completely avoid pregnancy in women undergoing oral isotretinoin therapy (21). Therefore, novel treatment options are needed that modulate sebaceous gland activity and have acceptable safety profiles in both males and females (6,22).
This review provides an overview of the role of sebum in the pathophysiology of AV from both compositional and quantitative perspectives, discusses factors that influence these changes in sebum and touches upon sebum-targeting therapeutic options for patients with AV.
2. Sebaceous immunobiology
3. Sebum in AV and other disorders
3.1. Sebum quantity
3.2. Sebum quality
4. Factors influencing sebum quality and quantity
5. Sebum-targeting therapies
5.1. Standard of care treatments
5.2. Emerging pharmacologic treatments and natural products
6. Conclusions
Although AV is highly prevalent across the globe, it is still not considered curable (52). An improved understanding of the mechanisms regulating sebum dysregulation in AV is needed to innovate therapeutic approaches for patients (30). Excess sebum production and changes in sebum composition are necessary early steps in AV pathophysiology (107). Alterations in sebum composition affect sebocyte proliferation, differentiation, and sebum production, as well as hyperkeratinization and inflammation within the sebaceous gland (22,25,47). Changes in sebum production vary by facial region as well as other factors, such as patient sex and age (84–87). There is an unmet need for agents that target excessive sebum production and alterations in sebum compositions that can be safely used in a variety of patients, including male patients and patients who are or may become pregnant (6,22). Topical antiandrogens devoid of systemic side effects, such as clascoterone, address many of these unmet needs for a more diverse group of patients, including males (6).
