It is difficult for rosacea patients to discern which products and ingredients will be beneficial to their skin and which products will lead to an exacerbation of the signs and symptoms of rosacea. In this paper, the authors provide a brief overview of rosacea, its pathogenesis, signs and symptoms, and the management of the two major rosacea subtypes—erythematotelangiectatic rosacea and papular pustular rosacea. Reviewed in greater detail are the common ingredients used in over-the-counter cleansers and moisturizers with discussion of how these ingredients potentially benefit or harm the skin of patients with rosacea. Clinical studies investigating the benefits of using certain over-the-counter cleansers and moisturizers in patients with erythematotelangiectatic rosacea and papular pustular rosacea with or without topical prescription therapy are also reviewed. The specific formulas used in the clinical studies include a sensitive skin synthetic detergent bar, a nonalkaline cleanser and moisturizer, polyhydroxy acid containing cleanser and moisturizer, and a ceramide-based cleanser and moisturizer formulated in a multivesicular emulsion. Based on review of available data, the authors conclude that the use of mild over-the-counter cleansers and moisturizers is beneficial for patients with erythematotelangiectatic rosacea and papular pustular rosacea. The properties of over-the-counter cleansers and moisturizers that contribute to their mildness include an acidic-neutral pH to minimize the flux in skin pH; surfactants or emulsifiers that will not strip the skin of its moisture or strip the lipids and proteins of the stratum corneum; moisturizing ingredients such as emollients, humectants, and occlusives; and formulas without potential irritants and allergens. The most consistent clinical benefits demonstrated in the reviewed studies were a subjectively perceived improvement in subjective symptoms of dryness and irritation as well as an objective improvement in dryness.
A common myth among the general public is that all over-the-counter (OTC) cleansers and moisturizers are created equal. This, however, is not the case. Many healthcare providers overlook the importance of OTC cleansers and moisturizers in the management of skin disease and may not consider their components to be actively involved in producing therapeutic benefit. Yet, use of OTC cleansers and moisturizers can potentially have multiple beneficial or deleterious effects on the skin and can induce changes in the superficial and deep layers of the epidermis.1 It is the specific ingredients in the formula and the properties of the formulation as a whole that determine whether the cleanser or moisturizer is truly a mild product and if the product will impact the skin, especially the integrity and function of the stratum corneum (SC), in a positive or negative manner.2
Importance of a mild OTC cleanser for rosacea patients. The ideal cleanser would function by removing dirt, oil, environmental pollutants, and harmful bacteria from skin without disrupting or removing the beneficial lipids, proteins, and normal flora that contribute to the integrity, function, and health of normal skin. However, this is often not the case. Strong OTC cleansers that are efficient at removing dirt, oil, and bacteria cannot distinguish between good and bad lipids, proteins, or bacteria. Therefore, strong cleansers that provide an efficient skin cleaning are also, in essence, damaging the SC by damaging or stripping some of its essential components, such as lipids, proteins, and natural moisturizing factor (NMF).14 Because ETR and PPR patients already have a compromised SC permeability barrier and sensitive skin, it is recommended that rosacea patients use mild OTC cleansers that do not exacerbate their skin disease. Recognition of the importance of mild cleansers in the management of rosacea and other sensitive skin diseases has spurred the development of mild therapeutic cleansers with the sole purpose of gently cleansing the skin without stripping the skin of its functional components.
OTC cleansers, their ingredients, and what they do to the stratum corneum. There are four general categories of skin cleansing agents including soaps, synthetic detergent (syndet) bars and liquid cleansers, combination bar (combar) antimicrobials, and lipid-free liquid cleansers.
True soap. True soap (soap) is created through a process called saponification, which is the chemical reaction that occurs when a fat, such as tallow (beef fat), and an alkali, such as lye, are combined to create long chain fatty acid alkali salts. The typical pH of a true soap is 9 to 10.15 Soaps are strong OTC cleansers that do an excellent job of removing skin sebum and debris. Yet, in the process, soaps can remove beneficial intercellular lipids and damage SC proteins. Removing these beneficial lipids and proteins impairs the SC as evidenced by an increase in TEWL, dehydration, altered desquamation, and increased penetration of topically applied substances, therefore increasing skin sensitivity and irritation in rosacea patients.15
Synthetic detergent (syndet) cleansers. Syndet bars are synthetic detergent-based cleansers that contain less than 10 percent of soap and typically have a more neutral/acidic pH (5.5–7) similar to the pH of normal skin.15,16 Syndet bars in general are designed to provide an effective skin cleaning with minimal stripping of essential SC lipids and proteins, ultimately making these types of cleansing bars less irritating and drying than the traditional soap bars. Syndet liquid cleansers are also available.
In an experiment done on ex-vivo arm skin, the ultrastructural skin changes were monitored after washing with a soap and mild syndet bar using a combination of measurements including TEWL, environmental scanning electron microscopy, and transmission electron microscopy.17,18 The results of this study clearly demonstrated changes to the skin's ultrastructure after multiple washes with the soap bar. Environmental electron microscopy revealed changes in the skin surface morphology including a significant uplifting of cells and increase in surface roughness after washing with the soap. In addition, transmission electron microscopy revealed significant damage to both lipid and protein regions after washing with the soap bar. In contrast, under the same conditions, the syndet-washed skin showed well-preserved surface morphology and well-preserved lipid and protein regions. The study also demonstrated a correlation between high TEWL and damage to SC ultrastructure after use of the soap bar, clearly illustrating the potential for soap to damage the SC and the mildness of the syndet bar in comparison.17,18
Combination bars (combars). Combars are antibacterial soap bars that contain a combination of true soap surfactants and syndet bar surfactants with an added antibacterial agent. Although the antibacterial agents in combars are beneficial for reducing harmful bacteria, they may also eradicate the normal flora of the skin and can cause an increase in skin dryness and irritation.19 Since patients with rosacea may already have an imbalance of skin flora and problems with skin dryness and sensitivity,8 in general, combars are not ideal for patients with rosacea.
Lipid-free liquid cleansers. Lipid-free liquid cleansers are very mild as they clean without soap formation and are designed to leave behind a thin moisturizing film on the skin.19 Evidence that supports the use of several lipid-free cleansers in rosacea patients will be presented in the next sections of this paper.
Given the sensitive nature of ETR and PPR skin, lipid-free cleansers and syndet cleansers are well suited for rosacea patients. However, within the lipid-free cleanser and syndet bar subtypes there are several other properties of these cleansers that determine their mildness. These properties include the type of surfactant used in the cleanser, the extent of surfactant interaction with skin proteins and lipids, the pH of the cleanser, and the extent of skin hydration or dehydration caused by cleansing.20–22
Surfactants. Surfactants are the principle ingredients in cleansers responsible for removing oil and debris from the skin surface. The extent to which a surfactant is able to “clean” the skin is relative to its critical micelle concentration (CMC). The CMC is a measure of a surfactant's efficacy in solubilizing dirt and oil on the skin and dispersing them into solution. The lower the CMC, the higher the efficacy of the surfactant and the lower the amount needed in the cleanser formula. However, a high cleansing efficacy (or a low CMC) usually correlates with an increased number of deleterious effects on the SC integrity and function.15
Surfactants are subdivided into the following four main groups based on their molecular charge or lack of molecular charge: anionic, cationic, amphoteric, and nonionic.21–24 According to Ananthapadmanabhan et al15 and Effendy et al,24 the order of surfactant potential for SC alteration and skin irritation is cationic=anionic>amphoteric>nonionic. However, it cannot be generalized that all cationic and anionic surfactants are the most irritating group of surfactants to the skin because the specific surfactant used, in addition to its molecular charge, has a major effect on irritant potential. For example, when comparing the irritation potential and penetration of two anionic surfactants, sodium lauryl sulfate and sodium cocoyl isethionate, sodium lauryl sulfate can cause significant skin irritation and penetration while sodium cocoyl isethionate has shown excellent skin compatibility.21,25 Despite the potential for some anionic surfactants to irritate the skin and diminish skin health, they are still the primary surfactants used today, even in mild cleanser formulations, due to their excellent foaming and lathering characteristics. Cationic surfactants, such as benzalkonium chloride, can have high irritant and cytotoxic effects on the skin.24 Therefore cationic surfactants are generally used in antimicrobial washes due to their excellent antimicrobial properties.24
To minimize the irritation potential of anionic and cationic surfactants in a cleansing formula, these surfactants can be used in small amounts and can be combined with other amphoteric and nonionic surfactants to minimize their irritation potential and negative effects on the stratum corneum.15,24,26 For example, sodium laureth sulfate, an anionic surfactant that is a close relative to sodium lauryl sulfate, is often used in combination with the amphoteric surfactant cocamidopropylbetaine. It is assumed that the use of the anionic and amphoteric surfactants results in a milder cleansing formula with a decreased anionic surfactant concentration, decreased skin irritation, and decreased interaction with skin proteins and lipids.15,24
Surfactants and skin proteins. Surfactants that interact with SC proteins are deleterious to overall skin health because of their ability to disrupt and damage the proteins of the SC. This insult to the SC proteins can result in changes in SC integrity leading to cutaneous irritation, inflammation, and dessication, all of which can ultimately lead to visible changes associated with dryness and irritation. It is thought that interaction of the charged (polar) heads of the surfactants with the charged proteins of the SC facilitates the penetration of surfactants as well as other cleanser ingredients into the deeper skin layers. The deeper penetration of these ingredients can cause chemical irritation or an inflammatory biochemical response in healthy skin, or in the case of rosacea patients, exacerbate inflammation and irritation that may already be present depending on the current magnitude of underlying rosacea at that time.27–29 However, for a surfactant with a given chain length, the larger the head group size, the lower the tendency to cause protein swelling and subsequent damage. This may be one of the reasons why sodium cocoyl isethionate, with its larger head group, is milder than sodium lauryl sulfate as discussed above.15,30 In addition, the interaction of the charged head of the surfactant with the skin proteins also reduces the ability of these proteins to bind and hold water, allowing increased evaporation and resultant SC dehydration.27–29,31
In a study by Ananthapadmanabhan,15 the interaction of skin proteins with a soap, syndet bar, and lipid-free cleanser were compared using infrared spectroscopy. In this study, the true soap caused the most interaction and change in the SC protein structure, therefore supporting the idea that soaps are capable of producing the greatest magnitude of SC damage. The clinical relevance that soaps can produce greater cutaneous desiccation, lessened innate ability for SC repair, and increased skin drying may all easily progress to augmented potential to produce signs and symptoms of cutaneous irritation. In patients with ETR and PPR, a group already affected inherently with impairment of the SC permeability barrier, these negative effects produced by soaps and poorly formulated skin cleansers are further magnified.
Surfactants and skin lipids. The interaction of surfactants with skin lipids have also been studied extensively31–34 However, the mechanism by which surfactants interact with lipids and cause SC permeability barrier disruption remains somewhat elusive. It has been suggested that surfactants either solubilize SC lipids into micelles and thereby cause subsequent SC delipidation, or that the incorporation of surfactants, especially charged surfactants, into SC lipid bilayer results in bilayer destabilization and increased SC permeability33,35–37 Although it has been hypothesized that charged anionic surfactants have a greater effect on the lipid bilayer than nonionic surfactants, a greater skin defatting effect may actually occur with the use of nonionic surfactants compared to anionic surfactants. This consideration stems from the fact that nonionic surfactants have a greater tendency to dissolve stearic acid than do anionic surfactants.15 Also, transmission electron microscopic studies have shown that nonionic-surfactant-based cleansers alter the lipid region to a greater extent than do mild cleansing bars with sodium cocoyl isethionate (an anionic surfactant).17,18
Mendelsohn and Moore used infrared spectroscopy to compare the perturbation of the lipid layers in the SC after the use of a true soap, syndet bar, or water alone (as the control).38,39 The results showed significant disruption of the lipid layer after the use of a soap as compared to the syndet bar and water alone. In comparing the effects of the syndet bar versus the control (water alone), analysis showed no discernable difference in lipid chain fluidity or rotational freedom. However, further analysis of the syndet bar did show a significant decrease in the cooperativity of the lipid bilayer after syndet bar use indicating a significant alteration in lipid organization and a resultant decrease in SC cohesion. Such changes can be a result of alterations in SC lipid composition either through the removal of endogenous lipid fractions or subfractions or the incorporation of surfactant molecules into the SC lipid layer. Overall, these results further support the common belief that true soaps impart the greatest magnitude of deleterious effects on SC integrity, followed by syndet bars and water, respectively.
Stratum corneum pH. Maintaining SC pH in an acid range of 4 to 6 is important for the overall health, integrity, and function of the SC, as discussed in a previous paper by Levin et al.40 Due to their inherent alkaline pH, soaps have the potential to change the pH of skin and therefore are not ideal for support of the permeability barrier of the SC. It is important to emphasize that a single or occasional use of an alkaline soap is not likely to significantly affect skin pH given the innate buffering capacity of skin.40 However, Fluhr et al41 have demonstrated that small and sustained pH increases, such as those caused by the daily use of soaps, induces changes in skin pH and adversely influences the SC barrier repair mechanism.41 Syndet bars and lipid-free cleansers are generally formulated to have a neutral or slightly acidic pH to ensure skin compatibility, decrease the alkaline flux of skin pH, and decrease the compromise of SC barrier function caused by alkaline pH alterations.
Deposition characteristics of some cleanser formulations. An additional benefit of some syndet bars, syndet liquid cleansers, and lipid-free cleansers is that they can be designed to deposit beneficial ingredients onto the skin even with short contact during cleansing and after rinsing. However, compared to bar technology, advances in liquid cleansing technology allow more efficient cutaneous deposition of beneficial agents, such as lipids.15 These cleansers, in essence, are using the same technology that is used in shampoos to deposit conditioning agents onto the hair. Some of the liquid cleansers currently available contain vegetable oils such as sunflower or soybean oil, occlusives such as petrolatum, humectants such as glycerol, and other ingredients such as ceramides and cholesterol that have beneficial effects on the skin. Cleanser formulations that allow for true deposition of specific major ingredients produce greater benefit and are less likely to damage the SC. Deposition technology with proper cleanser formulation, including with liquid cleansers, has the potential to minimize surfactant-mediated depletion of skin lipids, reduce the visible signs of dryness after cleansing, and assist in mitigating increases in TEWL. Today, in the OTC cleanser market, we now see some specific wash-off systems offering novel combinations of ingredients that can be deposited on the skin by cleansers, leading to a range of skin care claims that are supported by cogent scientific evidence.15
Putting it all together, it becomes clear that certain cleansers can disrupt the health of the SC more than others. Using a cleanser that may truly be more effective at removing surface oils and debris, such as a true soap or a cleanser with low CMC surfactants, on the sensitive skin of a patient with ETR or PPR, will likely cause exacerbation of their underlying SC impairment and can trigger signs and symptoms. Patients with ETR or PPR who use well-formulated, mild cleansing agents such as syndet cleansers and lipid-free cleansers with a neutral to slightly acidic pH may not only avoid exacerbation of their skin disorder, but also may note adjunctive benefit in combination with therapies being used to treat their rosacea.