Patients often perceive the cause of their acne to be related to a lack of proper cleansing, therefore many patients attempt to treat their acne either alone or with prescription therapy by frequent aggressive cleansing with harsh cleansing agents. Altered epidermal barrier function, inflammation, and Propionibacterium acnes are related to acne vulgaris (AV) pathophysiology; proper cleansing can favorably modulate the development of AV. The available clinical studies support gentle cleansing in AV by showing the ability to contribute to improving AV lesion counts and severity and minimizing the irritation seen with topical AV therapies such as retinoids and BP.
Key points
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Patients often perceive the cause of their acne to be related to poor hygiene and a lack of proper cleansing, therefore many patients with acne attempt to treat their acne either alone or with prescription therapy by frequent aggressive skin cleansing with harsh cleansing agents.
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Altered epidermal barrier function, inflammation, and Propionibacterium acnes are related components to acne vulgaris (AV) pathophysiology; proper cleansing can favorably modulate the development of AV.
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Benzoyl peroxide (BP) and topical retinoid therapy (ie, tretinoin) can adversely alter skin barrier function and cause cutaneous irritation, thus affecting patient tolerability and compliance with AV. Improvements in vehicle technology may mitigate the barrier impairment that may be associated with these therapeutic agents.
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Harsh cleansers, such as true soap and cleansers with high alkaline pH, adversely affect the skin by increasing skin pH, impairing the stratum corneum (SC) permeability barrier function, altering skin bacterial flora, desiccating the SC, increasing erythema, inducing symptoms of subjective irritation, and promoting follicular plugging.
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Combars with an added antibacterial agent do not decrease the amount of P acnes on skin and may promote gram-negative folliculitis if there is preferential reduction in commensal gram-positive bacteria. Therefore, true soap and combars are not ideal products to use in most skin diseases, including AV.
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Syndet bars and lipid-free cleansers have the potential to gently cleanse the skin without markedly diminishing epidermal barrier function. This process optimally prepares the SC for the application and absorption of topical therapies while minimizing skin irritation, reducing skin dehydration from prescription therapies, and maintaining the physiologic acid mantle pH of the skin.
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The limited clinical studies available support the benefit of gentle cleansing in AV by showing the ability to contribute to improving AV lesion counts and severity and minimizing the irritation seen with topical AV therapies such as retinoids and BP.
Introduction
Worldwide, acne vulgaris (AV) is one of the skin disorders for which patients most frequently consult a dermatologist. The economic and psychosocial burden of AV is high, and it constitutes the most common reason for dermatologist consultation. The direct cost of AV in the United States is estimated to exceed $1 billion per year, with $100 million spent on over-the-counter (OTC) AV products.
AV is a polymorphic skin disorder that produces a series of lesions: comedones, cysts, pustules, papules, or nodules. The primary goals of acne therapy are to achieve initial control, maintain therapy to prevent flares, and prevent persistent or permanent sequelae such as scarring. An important aspect of AV management that is often forgotten by physicians is to dispel any myths and misperceptions the patient may have about the cause of their AV, and to develop an appropriate management plan that includes adjunctive OTC products that serve to support their prescription regimen.
Many patients with AV mistakenly think that aggressively cleansing their skin with soap and water several times a day is therapeutic for AV. A survey of patient perceptions of AV showed that 29% of patients thought AV was caused by poor skin hygiene, and 18% thought it was caused by infection, with 61% of patients thinking dirt was an aggravating factor. Even among medical students, 25% thought poor facial hygiene was an exacerbating factor. For generations, even physicians thought that successful treatment of AV depended on the degreasing of the skin to an extent that produces desquamation with noticeable peeling. Because of these perceptions, patients tend to cleanse diligently and harshly with the belief that the more cleansing the better.
In the 1980s things started to change and the suggestion was made that inducing visible inflammation and desquamation of the skin was not necessary for acne control. Also, it was discovered that the lipid in the follicular reservoir that plays a role in AV pathogenesis cannot likely be reached by harsh soaps and detergents or by frenetic washing; aggressive cleansing with harsh soaps can aggravate AV and, under certain circumstances, cause a detergent-induced acneiform eruption. In addition, overzealous cleansing can lead to disruption of the epidermal barrier, increased transepidermal water loss (TEWL), roughened and irritated skin, increased bacterial colonization, increased comedonal formation, secondary irritant contact dermatitis, and burning and stinging. These negative effects caused by harsh soaps and aggressive cleansing make many prescription topical AV medications less tolerable. It is for these reasons that many dermatologists are now recommending gentle cleansers rather than the harsh soaps and cleansers used in the past with the hope of improved patient outcomes and increased compliance.
Although there is a plethora of data on the tolerability and benefits of mild cleansers in other skin disease, such as atopic dermatitis, data are more limited concerning their benefit in AV.
This article presents and summarizes the available scientific evidence concerning the use of gentle cleansers in AV.
Introduction
Worldwide, acne vulgaris (AV) is one of the skin disorders for which patients most frequently consult a dermatologist. The economic and psychosocial burden of AV is high, and it constitutes the most common reason for dermatologist consultation. The direct cost of AV in the United States is estimated to exceed $1 billion per year, with $100 million spent on over-the-counter (OTC) AV products.
AV is a polymorphic skin disorder that produces a series of lesions: comedones, cysts, pustules, papules, or nodules. The primary goals of acne therapy are to achieve initial control, maintain therapy to prevent flares, and prevent persistent or permanent sequelae such as scarring. An important aspect of AV management that is often forgotten by physicians is to dispel any myths and misperceptions the patient may have about the cause of their AV, and to develop an appropriate management plan that includes adjunctive OTC products that serve to support their prescription regimen.
Many patients with AV mistakenly think that aggressively cleansing their skin with soap and water several times a day is therapeutic for AV. A survey of patient perceptions of AV showed that 29% of patients thought AV was caused by poor skin hygiene, and 18% thought it was caused by infection, with 61% of patients thinking dirt was an aggravating factor. Even among medical students, 25% thought poor facial hygiene was an exacerbating factor. For generations, even physicians thought that successful treatment of AV depended on the degreasing of the skin to an extent that produces desquamation with noticeable peeling. Because of these perceptions, patients tend to cleanse diligently and harshly with the belief that the more cleansing the better.
In the 1980s things started to change and the suggestion was made that inducing visible inflammation and desquamation of the skin was not necessary for acne control. Also, it was discovered that the lipid in the follicular reservoir that plays a role in AV pathogenesis cannot likely be reached by harsh soaps and detergents or by frenetic washing; aggressive cleansing with harsh soaps can aggravate AV and, under certain circumstances, cause a detergent-induced acneiform eruption. In addition, overzealous cleansing can lead to disruption of the epidermal barrier, increased transepidermal water loss (TEWL), roughened and irritated skin, increased bacterial colonization, increased comedonal formation, secondary irritant contact dermatitis, and burning and stinging. These negative effects caused by harsh soaps and aggressive cleansing make many prescription topical AV medications less tolerable. It is for these reasons that many dermatologists are now recommending gentle cleansers rather than the harsh soaps and cleansers used in the past with the hope of improved patient outcomes and increased compliance.
Although there is a plethora of data on the tolerability and benefits of mild cleansers in other skin disease, such as atopic dermatitis, data are more limited concerning their benefit in AV.
This article presents and summarizes the available scientific evidence concerning the use of gentle cleansers in AV.
Acne pathogenesis
The pathogenesis of acne is multifactorial, involving follicular hyperkeratinization leading to (1) comedo formation; (2) hormonal (androgenic) stimulation of the sebaceous glands leading to increased sebaceous gland size and sebum secretion; (3) proliferation of Propionibacterium acnes ; and (4) induction of a variety of inflammatory cascades, some triggered in response to P acnes proliferation. These factors are summarized in Box 1 .
- 1.
Follicular hyperkeratinization
- 2.
Hormonal stimulation of the sebaceous glands
- 3.
Inflammation in response to P acnes
Follicular Wall Barrier Dysfunction
One of the primary events in the pathophysiology of acne is subclinical aberrant follicular wall hyperkeratinization, leading to a plugged follicular orifice (microcomedo). There several hypotheses regarding the pathophysiologic mechanism of follicular wall hyperkeratinization seen in acne; however, decreased stratum corneum (SC) barrier function (BF) has been suggested as a cause of reactive follicular wall hyperkeratinization, abnormal desquamation, and follicular plugging or comedo formation. Because pilosebaceous units have long canals through which sebum flows, hyperkeratinization of the follicular epithelium easily leads to sebum sequestration, which forms a microenvironment conducive to P acnes proliferation.
Two hypotheses suggest that the increased sebum secretion rate (SSR) in AV is associated with the decreased BF and follicular hyperkeratinization that leads to comedo formation. These hypotheses suggest that an increased sebum output dilutes the amount of certain epidermal lipids that are essential components of the SC barrier. One hypothesis in particular suggests that patients with AV have lower levels of the essential fatty acid (EFA) linoleic acid compared with healthy skin because of an increased SSR. The hypotheses further propose that relative linoleic/EFA deficiency in the cells of the follicular epithelium causes a resultant decrease in follicular epithelial BF, hyperkeratinization of the infundibulum, and comedo formation. This hypothesis is supported by a measureable inverse relationship between SSR and linoleic content at the skin surface in patients with AV and more specifically an inverse ratio between SSR and the proportion of linoleate in ceramide 1. A second hypothesis, by Melnik and colleagues, suggests that an imbalance of free sterol and cholesterol sulfate secondary to an increased SSR in acne causes follicular retention hyperkeratosis, impaired BF, and comedo formation.
In contrast, other investigators have found minimal to no increase in SSR in patients with AV with primarily comedonal lesions or mild AV. In addition, other investigators have found no evidence that SSR affects the composition of ceramide 1 in young adults, aged 15 to 25 years, and also showed no significant difference in the ratio of free sterols to cholesterol sulfate in the SC between patients with AV and control subjects. Although it is uncertain whether EFA deficiency and/or altered lipid ratios are caused by an increased SSR in AV, decreased epidermal BF as a pathologic mechanism for follicular plugging has been suggested by other investigators.
Yamamato and colleagues also suggest a comedogenic mechanism involving impaired epidermal BF. In order to prove their hypothesis, Yamamato and colleagues determined the SSR, lipid content, and barrier characteristics of the SC in patients with AV. Patients with mild AV had impaired SC permeability BF and decreased sphingolipids (ceramide and free sphingosine) compared with controls with healthy skin. In addition, a correlation was found between decreased sphingolipids and decreased BF in patients with AV. Despite a significant difference in BF between the patients with mild AV and the controls, both groups showed a similar SSR that was significantly lower than that of those patients with moderate AV. This finding suggests that follicular hyperkeratinization and microcomedo formation may still occur without a high SSR, and that an impaired BF is likely part of the pathophysiology leading to AV lesion formation in patients with mild acne. However, patients with moderate inflammatory AV showed a lower BF and a higher SSR than those with mild AV or a healthy control group. Therefore high SSR (and therefore androgens that stimulate a higher SSR) may play more of a pathogenic role in the inflammatory component of moderate to severe AV.
Similar to Yamamoto and colleagues, Knutson observed decreased lamellar granules in the infundibulum of comedo-affected follicles compared with the infundibulum of normal follicles. Decreased levels of lamellar granules in the epidermal granular layer lead to reduction in packaging of ceramides and their subsequent release into the SC. Ceramides are an essential component of the intercellular lipid bilayer of the SC, with impaired follicular BF associated with reactive epidermal hyperplasia or hyperkeratosis. Knutson and colleagues suggested that the decreased ceramide levels, and hence decreased follicular epithelial BF, are related to abnormal follicular hyperkeratinization and comedo formation. The theory of reactive SC hyperkeratinization secondary to impaired epidermal BF has also been suggested in diseases like atopic dermatitis. Thus, it is plausible that a similar reaction occurs in the pilosebaceous unit of patients secondary to disturbed follicular BF.
Calcium Gradient
Lee and colleagues investigated whether the disruption of the calcium gradient may play a key role in comedogenesis. Calcium is known to play a role in the restoration of BF after skin injury. After acute skin barrier impairment, the epidermal calcium gradient is disturbed secondary to loss from the upper epidermis. The loss of calcium from the upper epidermal layers stimulates the self-repair mechanism of lamellar body secretion of lipids into the SC, which promotes epidermal barrier recovery with restoration of the physiologic epidermal calcium gradient. To evaluate the SC intercellular lipids and calcium gradient in the presence of comedonal lesions, Choi and colleagues applied oleic acid on the inner surface of the ears of white rabbits to induce comedo formation, obtained representative specimens, and performed a calcium ion–capture cytochemical procedure with electron microscopy. Incomplete lipid bilayer structures, prominent dilatation of lacunar domains, and the loss of follicular epidermal calcium gradient were identified in the experimentally induced comedos. It was concluded that calcium gradient disruption may play a role in comedo formation in AV pathogenesis.
Subclinical Inflammation
More recent information on the pathophysiology of AV has shown that perifollicular subclinical inflammation is present either before or concurrently with microcomedo formation, suggesting that inflammation may play a role in the development of both comedonal and inflammatory AV lesions. The presence of postinflammatory hyperpigmentation after the resolution of comedonal lesions in darker skin types clinically supports the presence of subclinical perifollicular inflammation during the comedonal stage of AV. In addition, initiation of subclinical innate inflammation has been reported to be an initiating event, with increased infiltration of lymphocytes and macrophages with relative absence of neutrophils at the early phase of AV lesion formation. It has been suggested that stimulation of the innate immune system is a result of increased bacterial, environmental, and chemical insults that penetrate the impaired follicular barrier; however, confirmatory evidence warrants the support of well-designed studies.
In the hypotheses discussed earlier, the unifying concept is that impairment of the follicular barrier plays a contributory role in AV pathophysiology, including during early lesion formation. Whether it is from calcium gradient alteration, SC lipid impairment, or both, follicular barrier dysfunction seems to play a role in both comedonal and inflammatory lesion formation. Perhaps similar to AD, in which impaired epidermal BF is often multifactorial, epidermal barrier dysfunctions involving the pilosebaceous unit wall are significant. Further experimentation is needed.
Androgens
Androgenic hormones play a role in AV pathophysiology because androgens stimulate sebaceous gland proliferation and increased sebum secretion. The increased levels of sebum promote an excellent environment for P acnes to proliferate and colonize and, also as discussed earlier, may play a role in comedogensis. In addition, women with hormonal imbalance (ie, increased androgens) have been known to have significant acneiform eruptions, and therapies designed to decrease androgens are effective for some patients with AV. Presence of androgens is associated with emergence of AV; however, most adults with AV have no measurable hormonal imbalance and normal SSRs have been detected in mild acne.
Propionibacterium acnes
P acnes is a commensal bacterium present within in the pilosebaceous unit, with up to 10 7 viable organisms isolated from a single sebaceous unit. P acnes predominately exists in the sequestered, lipid-rich, anaerobic environment of the pilosebaceous unit; this bacterium metabolizes sebaceous triglycerides into fatty acids and glycerol and consumes the glycerol, leaving behind free fatty acids that may serve to promote perifollicular inflammation. The role of P acnes in comedogenesis remains controversial; however, some strains/subtypes of P acnes have been associated with induction of certain proinflammatory pathways. The observation that abnormal keratinization and comedogenesis can occur in the absence of P acnes does not exclude the possibility that this organism may contribute to microcomedo formation and AV lesion development.
Biofilms
Intrafollicular P acnes microorganisms are capable of encasing themselves in a capsule of extracellular polysaccharide, which they secrete after adherence to the follicular surface, forming what is called a biofilm. Biofilms are composed of populations or communities of bacteria that adhere to environmental surfaces, such as the pilosebaceous unit lining. The extracellular matrix usually comprises most of the biofilm mass and is composed of polysaccharides, water, extracellular DNA, and excreted cellular products. The matrix of the biofilm provides a protective barrier that impedes the penetration of antibiotics. The P acnes biofilm model may provide at least a partial explanation as to why antibiotics are often used over a duration of months in treating AV, whereas much shorter courses are used for standard bacterial infections. However, once antibiotic therapy is stopped, recolonization of P acnes occurs. In addition, it has been shown that there is no correlation between the severity of AV and the levels of P acnes .
The inherent immunologic response of the host and the strains/subtypes of P acnes may explain differences in the severity of inflammation in AV. P acnes instigates inflammatory acne via its interaction with humoral factors, cell mediated immunity, and complement, its secretion of neutrophil and monocyte chemotactic factors, and inducing lysosome enzyme release. However, other sources suggest that it is the activation of the innate immune system that initially promotes and influences many of the pathogenic factors in AV. Fig. 1 lists some of the known inflammatory factors that play a role in AV inflammation and pathogenesis.
Although the pathophysiology of AV is still unclear in many ways, the roles of impaired epidermal BF, stimulation of inflammatory cascades, and P acnes proliferation are clearer. Therefore it is important to have a cleansing and moisturizing formulation that first and foremost does not contribute to the impairment of BF, inflammation, and growth of P acnes .
Topical acne prescription therapies and the skin barrier
Topical retinoids and BP are two of the major recognized approaches in AV therapy. Despite their proven effectiveness in treating AV, cutaneous irritation associated with their use occurs in many cases, especially with certain formulations, or when adjunctive measures are not used to reduce the risk of local tolerability reactions. The magnitude of cutaneous irritation does vary among patients and with different chemical compounds and/or vehicles.
Topical Retinoids
Topical retinoids are associated with an irritant skin reaction, referred to as retinoid dermatitis, which correlates at least partially with their mechanism of action (MOA). In the skin, retinoids stimulate epidermal proliferation and differentiation, which leads to a thickened lower epidermis (or epidermal hyperplasia) with an upper epidermis (SC) that has greater dyscohesion. The thinning of the SC results clinically in a smoother skin surface, which is associated with altered BF and increased TEWL, especially during the initial few weeks of use. These retinoid-induced changes to the epidermis and the SC account for the scaling, peeling, erythema, dry appearance, and subjective symptoms of skin irritation that are frequently observed in the first few days and weeks of retinoid therapy. The occurrence of cutaneous side effects within the first few weeks of topical retinoid use is thought to be one of the main reasons for nonadherence and treatment failure by patients with AV.
Benzoyl Peroxide
BP is one of the most common topical antiacne agents present in many prescription and OTC products. Formulations containing BP include lotions, gels, creams, soaps, and washes, in varying concentrations from 2% to 10% (weight/volume). BP has been shown to have bactericidal properties for P acnes , with clinical studies showing that BP improves both inflammatory and comedonal AV lesions. The antimicrobial MOA of BP is secondary to direct oxidative effects on the bacterium; however, this same activity relates to many of the side effects associated with topical use of BP. BP induces peroxidation of SC lipids, which alters SC lipid composition. resulting in impairment of the epidermal barrier. Repeated applications of BP can result in SC lipid peroxidation and decreased BF with a significant increase in TEWL. The extent of measurable SC lipid peroxidation positively correlates with impairment of SC BF. Another reason for decreased BF with BP use may be damage to SC proteins. It has been shown that BP oxidizes SC proteins, such as keratins 1 and 10, in addition to oxidizing lipids of the SC. Most of these altered SC proteins play a role in the adverse effects on BF.
Given that patients with AV may have inherently impaired epidermal BF and/or barrier dysfunctions related to topically applied agents, properly selected adjunctive skin care mitigates barrier impairment and reduces inflammation. It is for this reason that adjunctive skin care has gained increased recognition as an integral component of AV management. Skin care products that have been properly designed and have been shown to support BF have the potential to ameliorate some of the cutaneous side effects of topical agents used to treat AV (ie, BP, topical retinoids). Reducing adverse side effects associated with AV therapy may foster better patient adherence and achieve better treatment outcomes.
Some of the different types of cleansers available in the marketplace, their potential benefits and detriments, and the clinical evidence that supports the use of well-designed gentle cleansers in AV are reviewed later.
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