Effect of soaps and detergents on epidermal barrier function

Clinics in Dermatology (2012) 30, 297–300 Effect of soaps and detergents on epidermal barrier function☆ Ronni Wolf, MD a,⁎, Lawrence Charles Parish, MD, MD (Hon)b a The Dermatology Unit, Kaplan Medical Center, Rehovot 76100, Israel (affiliated to the Hebrew University–Hadassah Medical School, Jerusalem, Israel) b Department of Dermatology and Cutaneous Biology and Jefferson Center for International Dermatology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19101, USA Abstract The past decade has witnessed an explosion of new impartial information about the complex interaction of the skin with topically applied substances, including soaps and detergents. Despite of all these new data, our knowledge on the exact pathomechanism and molecular events leading to detergentinduced barrier dysfunction remains incomplete and the answers continue to elude us. The longtime prevailing opinion which contends that the damaging effect of soaps and detergents is related to their property to extract and remove useful intercellular lipids has mostly been abandoned. Although this effect might be involved in the damaging effect, it is definitely not the sole mechanism, nor, indeed, is it even the main one. Skin proteins damage, the interaction with keratins and their denaturation, swelling of cell membranes and collagen fibers, cytotoxicity expressed with cellular lysis are other important mechanisms. One proposed mechanism is that an initial stratum corneum hyper-hydration results from a continuous disruption of the secondary and tertiary structures of keratin protein by surfactants, exposing new waterbinding sites, thereby increasing the hydration of the membrane. Following evaporation of excess water, the denatured keratin possesses a decreased water-binding capacity and decreased ability to function as a barrier. Recent studies have also emphasized the effects of detergents on lipid synthesis, on lipid-metabolizing enzymes and on keratinocyte differentiation. © 2012 Elsevier Inc. All rights reserved. The attitude toward soap and washing throughout time The Phoenicians invented soap some 2300 years ago, and views toward its actions, benefits, and hazards have changed greatly over time. Physicians realized the medicinal value of soap during the 19th century. Perhaps, the best-known protagonist of soap ☆ Portions of this contribution were adapted with permission from the following: Wolf R, Orion E, Parish LC. A scientific soap opera and winter itch. Skinmed 2004;3:9-10. Wolf R, Orion E, Davidovici B. Skin care products and subtle data manipulation. Clin Dermatol 2007;25:222-4. ⁎ Corresponding author. Fax: +972 9 9560978. E-mail address: [email protected] (R. Wolf). 0738-081X/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.clindermatol.2011.08.021 was Ignaz Philipp Semmelweis who, in 1847, discovered the infectious etiology of puerperal fever and required all of his medical students to wash their hands before examining patients. His immortal words were, “I am not asking anything world shaking. I am asking you only to wash … For God's sake, wash your hands,” and, to the parturients, “Unless everything that touches you is washed with soap and water and then chlorine solution, you will die and your child with you!” 1 The 19th century German chemist Baron Justus von Liebig argued that the wealth of a nation and its degree of civilization could be measured by the quantity of soap it consumed. The expression “soap opera” came from the afternoon radio serials of the 1930s and 1940s (eg, “Ma Perkins,” 298 “Stella Dallas,” “Helen Trent”), sponsored by the purveyors of soap and detergents (99 and 44/100% pure, Duz does everything….). Indeed, they convinced our grandmothers and mothers that they bore the grim responsibility of bringing the quality of the family's skin as close as possible to the look and feel of Ivory soap and to the pure whiteness and softness of Dove. The enthusiastic support of soap was then followed by a reactionary swing around the time of World War II. Some reputable dermatologists considered the product bad for the skin, even to the point of being hazardous. With the increasing use of household detergents, it became fashionable to blame every case of hand dermatitis on these cleansers. The uproar eventually calmed down, when leading dermatologists realized that the damaging and harmful effects of soaps and detergents had been highly exaggerated. A profusion of tests for the evaluation of the effect of soaps on skin and its barrier The present era—the erstwhile modern age—has witnessed yet another abrupt change in the attitude toward soap, in terms of its usefulness and harmfulness. The specific turning point was the publication of a paper by Frosch and Kligman in 1979, in which they described a new method for “objectively,” assessing the irritation potential of various soaps, called the “soap chamber test.” 2 Dozens of other tests for evaluating changes in skin barrier function in reaction to soaps followed, often using sophisticated instrumentation and methodologies. What was the evolutionary sequence here? Did the development of new instrumental techniques for noninvasive investigation of skin physiology result in increasing interest in the harming effect of soaps on the skin barrier, or did the fear of a toxic effect of soap result in the search and development of effective tests to evaluate these characteristics? There is a third and more insidious possibility: that the plethora of tests were created primarily in response to the influence of soap manufacturers, whose interests were to create conditions in which their product would rank highest in mildness and lowest in damaging effects to the skin and its barrier function. In any case, whatever the motives for creating these tests, the fortuitous result is that we have gathered a wealth of knowledge on the effects of soaps on the skin barrier. In an issue of Clinics in Dermatology published in 1996 on soaps and detergents, 3 3 sections were devoted to tests involving tens of different methods (such as transepidermal water loss, replica technique, electrical properties [capacitance, impedance], laser Doppler flowmetry, skin color measurements, contact thermography, and skin thickness measurements with ultrasound) for assessing the irritancy potential of soaps and their influence on various parameters of the skin barrier. R. Wolf, L.C. Parish There was only one chapter devoted to tests for evaluating their efficacy. All testing methods showed that frequent exposure to surfactants induces barrier damage and skin dryness followed by inflammation. Both the quality and the severity of the skin reaction depend on the surfactant chemistry and concentration, exposure time, number of and interval between exposures, and individually related variables, such as skin hydration, skin type, atopy, age, and anatomic site. Is there any objectivity out there? As mentioned previously, the past 2 decades have witnessed enormous progress in biophysical techniques and the emergence of numerous devices for quantitative measurement of various properties of the skin and skin care products. We have good reason to believe that our decisions are based on what at least appears to be objective scientific facts and professionally conducted research rather than on suspiciously subjective, inaccurate, and inconsistent findings. The multimillion-dollar question is whether the results of new, sophisticated bioengineering techniques that are published in scientific, peer-reviewed journals are really as clear-cut as they claim to be and to what extent they are relevant to our patients. In other words, how far can we trust the data in scientific publications? One look at the advertisements in dermatologic journals and those available on the Internet is enough to reveal that each company presents its preferred method of analysis in which, to no one's surprise, its product ranks highest in efficacy and lowest in toxicity and damaging effects. A simple search in PubMed reveals that there are many contributions devoted to methods of evaluation of a variety of skin care products, including surfactants, soaps, and detergents. Many of them aim to present a new test method or a new and more effective and “real” protocol. Some of them will also “reveal” data on specific products, as if it were a by-product (the main issue being the test method). A closer appraisal of many of these contributions, however, will expose the authors of the presentation as being affiliated with the company whose product ranks first in that survey or that the described research is sponsored by the respective company. How does this clever hat trick work? How can supposedly objective methods, performed by reliable manufacturers and testing organizations and according to standards of valid scientific investigation, lead to different results and conclusions? The answer is simple. Although the methods and measuring devices are generally objective, their results can be and often are manipulated to support the claims of superiority of given products. Specifically, the study design, protocols, techniques, and end points can legitimately be adapted to the special characteristics of the Soap, detergents, and epidermal barrier function specific product, emphasizing its advantages. The following is an example of how they pull the proverbial wool over our eyes. Let us make it clear at the outset, there is no consensus on which methodology best reflects the real-life performance, the benefit, and the damage of a given product — there is no single ideal lab test that can supply the answers we seek. Consequently, an investigator can legitimately shop around and select the test and all experimental conditions/designs/settings/devices/protocols that have what it takes to arrive at the predetermined desired outcome. If, for example, a soap has a high affinity to proteins, a characteristic that causes more damage when it is allowed to come in contact with proteins, the study designers will be sure to choose a test method that prevents or at least hinders the contact of their soap with protein structures of the skin. For such a soap, particularly if it has a large molecule (or more correctly, if it builds large micelles when in contact with water) that might not easily penetrate the stratum corneum, the preferred test is one that emphasizes the penetration potential of soaps. The choice could be, for example, the “thick” skin of the back as the preferred test area. In vitro tests combining that soap with proteins, allowing it to enter the eyes of experimental animals, or testing it on the delicate thin skin of the forearm would yield less desirable results. Obtaining the desired “scientific” results has been a matter of choosing the test method and the protocol that yields them. The manufacturers, whose imagination and resources would appear to be unlimited, have known only too well how to harness our scientific knowledge to suit their interest. Pathomechanisms involved in soap-induced skin barrier damage/impairment We wish to emphasize that our critique on the motives behind the analysis and study of the effect of soaps on skin barrier does not apply to most of the studies. The past decade has witnessed an explosion of new impartial information about the complex interaction of the skin with topically applied substances, including soaps and detergents, accompanied by the emergence of the field of bioengineering and its many devices for measuring quantitative data on various properties of the skin. Despite of all these new data, our knowledge on the exact pathomechanism and molecular events leading to detergent-induced barrier dysfunction remains incomplete, and the answers continue to elude us. The longtime prevailing opinion, which contends that the damaging effect of soaps and detergents is related to their property to extract and remove useful intercellular lipids, has mostly been abandoned. The generally accepted view had been that because the dirt and grime to be removed is embedded in the outer fat layer, the cleansing process will 299 always remove useful skin lipids. This was thought to be the main mechanism for the negative and harmful effect of detergents on the skin and its barrier. This belief led to the assumption that there must be a close correlation between a soap's capacity to clean and its ability to dissolve oils, removing them from the skin. The effect of delipidation or degreasing (ie, the ability of detergents to solubilize and remove stratum corneum lipids) might be involved in the damaging effect, but it is definitely not the sole mechanism, nor, indeed, is it even the main one. Skin proteins are damaged by the interaction with keratins and their denaturation; the swelling of cell membranes and collagen fibers, as well as the cytotoxicity expressed with cellular lysis, are other important mechanisms. 4 A direct interaction between surfactants and keratin proteins appears to be responsible for the early events in the damage caused to the skin barrier by the washing process. This surfactant–stratum corneum interaction probably involves a denaturation of α-helical keratin by unfolding the coiled polypeptide protein chain, as suggested by several in vivo experiments. 5,6 This, initially, reversible conformational change of keratin proteins is most likely also responsible for the surfactant-induced swelling of various membranes, eg, isolated stratum corneum, gelatin, and collagen film. The swelling of these membranes, after contact with surfactants resulting from increased water absorption, appeared to be related to the in vivo irritation potential and damaging effects of detergents. These early subclinical in vivo effects of surfactants on the stratum corneum had been investigated in several experiments. In an early experiment, 5 the exposure of skin to surfactant solutions significantly increased hydration of the stratum corneum compared with controls. It increased with the length of application time and was concentration dependent, saturable with increasing concentration, and rapidly reversible. Induction of hydration was closely correlated with the irritation potential of the investigated compounds. It initially increased with increasing carbon chain length. The maximum response was obtained for the C12 analogue (sodium lauryl sulfate). It has been suggested that the initial stratum corneum hyper-hydration results from a continuous disruption of the secondary and tertiary structures of keratin protein, exposing new water-binding sites, thereby increasing the hydration of the membrane. Following evaporation of excess water, the denatured keratin possesses a decreased water-binding capacity and decreased ability to function as a barrier. Recent studies have also emphasized the effects of detergents on lipid synthesis, on lipid-metabolizing enzymes, and on keratinocyte differentiation. 7,8 Conclusions Results of studies that were performed over the past 2 decades challenge earlier assumptions that a surfactant's 300 degreasing of the stratum corneum is the main mechanism involved in its negative and damaging effect on the skin barrier. References 1. Elek SD. Semmelweis commemoration. Semmelweis and the oath of Hippocrates. Proc R Soc Med 1966;59:346-52. 2. Frosch PJ, Kligman AM. The soap chamber test. A new method for assessing the irritancy of soaps. J Am Acad Dermatol 1979;1:35-41. 3. Wolf R. Soaps, shampoos, and detergents: a scientific soap opera. Clin Dermatol 1996;14:1-132. R. Wolf, L.C. Parish 4. Corazza M, Lauriola MM, Zappaterra M, et al. Surfactants, skin cleansing protagonists. J Eur Acad Dermatol Venereol 2010;24:1-6. 5. Wilhelm KP, Cua AB, Wolff HH, et al. Surfactant-induced stratum corneum hydration in vivo: prediction of the irritation potential of anionic surfactants. J Invest Dermatol 1993;101:310-5. 6. Wilhelm KP. Effects of surfactants on skin hydration. Curr Probl Dermatol 1995;22:72-9. 7. Wei T, Geijer S, Lindberg M, et al. Detergents with different chemical properties induce variable degree of cytotoxicity and mRNA expression of lipid-metabolizing enzymes and differentiation markers in cultured keratinocytes. Toxicol In Vitro 2006;20:1387-94. 8. Torma H, Berne B. Sodium lauryl sulphate alters the mRNA expression of lipid-metabolizing enzymes and PPAR signalling in normal human skin in vivo. Exp Dermatol 2009;18:1010-5.