Skinlab.ru

This article was downloaded by: [Gouic, sabine le][Content Ed Net]On: 3 September 2009Access details: Access Details: [subscription number 908611115]Publisher Informa HealthcareInforma Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,37-41 Mortimer Street, London W1T 3JH, UK Journal of Dermatological TreatmentPublication details, including instructions for authors and subscription information: Lowering lesional surface pH in acne: A new treatment modality for Herpifix®Nanna Y. Schürer a; Meike Bock a a Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Germany Online Publication Date: 01 February 2009 To cite this Article Schürer, Nanna Y. and Bock, Meike(2009)'Lowering lesional surface pH in acne: A new treatment modality forHerpifix®',Journal of Dermatological Treatment,20:1,27 — 31 To link to this Article: DOI: 10.1080/09546630802178240 This article may be used for research, teaching and private study purposes. Any substantial orsystematic reproduction, re-distribution, re-selling, loan or sub-licensing, systematic supply ordistribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the contentswill be complete or accurate or up to date. The accuracy of any instructions, formulae and drug dosesshould be independently verified with primary sources. The publisher shall not be liable for any loss,actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directlyor indirectly in connection with or arising out of the use of this material.
Journal of Dermatological Treatment. 2009; 20:1; 27–31 Lowering lesional surface pH in acne: A new treatment modality
for Herpifi x ®
Department of Dermatology , Environmental Medicine and Health Theory, University of Osnabrück , Germany Abstract
The acid skin surface pH has antimicrobial activities. Increased growth of
Propionibacterium acnes contributes to the pathogenesis of acne. Therefore, the pH of infl ammatory acne lesions was determined prior to and after lesional acidifi cation employing Herpifi x (Courage ϩ Khazaka, Cologne, Germany), a microphoretic system. The pH was correlated with the number of acne lesions. A total of 30 volunteers with acne vulgaris participated in this crossover study applying either Herpifi x or a dummy to infl ammatory lesions. Prior to treatment, the pH of acne lesions was 5.7 Ϯ 0.2 (mean Ϯ SD) and 22 lesions (mean Ϯ 10) were counted in an 8 ϫ 8 cm 2 facial surface area. Fifteen volunteers (group A) used Herpifi x fi rst for 3 weeks and then the dummy, while the other group of 15 volunteers (group B) used the dummy fi rst and then Herpifi x. In group A, the lesional surface pH and number of lesions decreased ( p Ͻ 0.01) initially. When the dummy was used over a second 3-week treatment period, the skin surface pH and number of acne lesions increased. Findings for group B were vice versa. When both groups were compared at the end of the study, a signifi cant difference in pH values ( p Ͻ 0.001) and the number of acne lesions ( p Ͻ 0.05) was obtained. Herpifi x may be considered as a new therapeutic option for infl ammatory acne. Key words: Acne treatment , acne vulgaris , lesional acidifi cation , skin surface pH
Introduction
sphingo myelinase, acylcoenzyme A transferase) are activated at a pH of 5 ( According to Braun-Falco and Korting ( 1 ), normal pH gradient within the epidermis, with a neutral skin surface is known to have an acid pH ( 2 ). The pH in the basal layer and an acid pH in the stratum relationship between this acid mantel and the corneum, is crucial in terms of the activation and Downloaded By: [Gouic, sabine le][Content Ed Net] At: 08:42 3 September 2009 resident fl ora has been studied intensively ( 3 ). inhibition of these mentioned enzymes ( 11 ). Furthermore, some of the biological activities of Increased sebaceous gland activity, excessive the stratum corneum are infl uenced by pH variations growth of residential micro-organisms, as well as ( 4–6 ). A functional stratum corneum requires the hyperkeratosis of the infundibulum are major combined action of many enzymes. All of these pathophysiological components of acne vulgaris. derive from the stratum granulosum and most Downing and co-workers hypothesized an essential of them are located in the intercorneal space ( 7 , 8 ). fatty acid defi ciency within the follicular epithelium, Two main groups of enzymes are differentiated: which may reason the follicular hyperkeratosis ( 12 ). lipid modifi ers and proteases. Both types of enzymes At the time of their hypothesis, the importance are important for barrier homeostasis and corneo- of an acid pH for the activation of epidermal cyte desquamation. Stratum corneum chymotryptic lipid synthesizing enzymes was not known. enzyme, phospholipase A2, and steroid sulfatase Barrier disturbances, infl ammation and altered are neutral enzymes and are activated at a desquamation are infl uenced by pH variations ( 4–6 ). pH of 7, whereas acidic enzymes (β-glucocerebrosidase, A lesional increase of skin surface pH may not Correspondence: Nanna Y. Schürer, Sedanstrasse 115 , 49090 Osnabrück , Germany . Fax: 49 541 969 2445 . E-mail: [email protected] (Received 5 February 2008; accepted 16 March 2008) ISSN 0954-6634 print/ISSN 1471-1753 online 2009 Informa UK Ltd.
DOI: 10.1080/09546630802178240 only infl uence the growth of infundibular micro- This blinded crossover design of the study included organisms, but also the fi ne-tuning of local, lesional the home use of the Herpifi x and a specially designed stratum corneum enzymatic activities ( 3 , 13 ). There- dummy thereof. After study inclusion, acne lesions fore, lesional pH may contribute to the pathogenesis on both cheeks were counted within a given 8 ϫ 8 cm surface area, the pH values of acne lesions were It is well known that superfi cial chemical peels taken and participants were instructed in the use (pH of 2–3), accompanied by the use of skin care and handling of Herpifi x or the dummy thereof. products with a pH of 4, clear papulopustular acne Volunteers were told to use the Herpifi x at least without much irritation. Focus has been given so far three times daily on given acne lesions. There was to the keratolytic effect of either salicylic acid or not much concern about participants’ compliance alpha hydroxyacids, but not so much to their pka as all of them were university students and were (acid dissociation constant) ( 14–16 ). interested in the improvement of their skin disease. In the following study, papular or pustular acne Volunteers were instructed not to use any other lesions were subjected to acidifi cation employing specifi c acne treatment during the course of the Herpifi x ® ; the pH of the lesions was taken and study. Initially, 15 participants were supplied with acne lesions were counted prior to and after a Herpifi x (group A) and 15 participants with the 3-week treatment course. A total of 30 volunteers, dummy (group B). After the fi rst 3-week treatment aged between 20 and 26 years, with acne vulgaris course, lesions were counted in the given 8 ϫ 8 cm participated in this crossover study employing surface area, the pH was taken as described above and according to the crossover design of the study, group A was supplied with the dummy and group B was supplied with the Herpifi x. At the end of the Materials and methods
treatment course (i.e. after another 3-week period) the acne lesions were counted again and the pH of The study was carried out at the University of Osnabrück, Germany, between October 2005 and Data were calculated with SPSS Base for March 2006. A total of 30 healthy volunteers Windows (version 16.0). The median and 25/75 (15 females and 15 males), mean age 25 years percentiles were chosen as the standard for the (Ϯ 3.9), enrolled with randomized assignment after descriptive statistics. Differences between groups were tested for their statistical signifi cance A fl at glass electrode (Mettler-Toledo, Giessen, Germany) attached to a precision pH meter normally distributed non-paired data. The Wilcoxon (PH 900; Courage & Khazaka, Cologne, Germany) signed rank test was used to compare results in was used to measure skin lesional pH. The readings the course of each group. The chosen level of were taken in an air-conditioned room with the temperature set at 25ЊC. The lesional pH was measured by applying the fl at glass electrode of Downloaded By: [Gouic, sabine le][Content Ed Net] At: 08:42 3 September 2009 the pH meter directly to the surface of the lesion and was allowed to equilibrate for 7 seconds ( 17 ). The skin pH was monitored between 11 am and 2 pm to avoid diurnal fl uctuations ( 18 ). acne lesions ranged from 5.3 to 6.1. Group A Papules and pustules were counted on both cheeks ( n ϭ 15) revealed a mean lesional pH of 5.66 Ϯ 0.24 in a fi xed surface area employing an 8 ϫ 8 cm (Figure 1 ) and a total of n ϭ 22.5 (mean Ϯ 10.1) template. Participants were white Caucasians papules and pustules in surface areas of 8 ϫ 8 cm (Fitzpatrick skin types I–II) to avoid racial differences in pH values ( 19 ). The female:male ratio was 1:1, n ϭ 15) revealed a mean lesional with 15 males and 15 females participating in pH of 5.72 Ϯ 0.25 (Figure 1 ) and a total of n ϭ 21.6 (mean Ϯ 8.0) papules and pustules in both surface Herpifi x is a battery-operated, micro-iontophoretic areas of 8 ϫ 8 cm (Figure 2 ). There was no statistical system with a central pin and a surrounding ring, difference in the number of lesions and the pH value using an electrical fi eld with a very low current. between the two groups at the start of the study. The acidity of the treated area can be changed to After the initial 3-week treatment course, the below pH 2. Herpifi x was originally designed to number of lesions had declined in group A to a treat herpes labialis in its early development. mean value of 14.5 Ϯ 5.7 ( p Ͻ 0.01) while that of Lowering lesional surface pH in acne After the initial 3-week treatment course, the crossover point was reached: group A then received the dummy and group B received the Herpifi x. Another 3-week treatment course followed before fi nal measurements were taken. After the total study duration of 6 weeks, fi nal measurements revealed a mean lesional pH in group A of 5.48 Ϯ 0.19 accompanied by a mean After the total study duration of 6 weeks, a signifi cant reduction in the number of lesions was noted in group B (from 20.5 Ϯ 8.0 to 13.6 Ϯ 6.0, p Ͻ 0.01) (Figure 2 ), accompanied by a decrease in mean lesional skin pH (from 5.63 Ϯ 0.19 to 4.96 Ϯ 0.39, p Ͻ 0.001) (Figure 1 ). The Mann–Whitney U -test revealed a signifi cant Figure 1. The pH values of group A: prior to a 3-week period use of Herpifi x ® (startA) and thereafter (W3A), and after crossover at 3 weeks followed by a 3-week period using a of acne lesions ( p Ͻ 0.05) when both groups were dummy (endA). The pH values of group B: prior to an initial 3-week period use of a dummy (startB) and thereafter (W3B), and after crossover at 3 weeks followed by a 3-week period using Herpifi x (endB). Discussion
According to the results of this crossover study, Herpifi x is another treatment modality of infl amma-tory acne lesions. The number of acne lesions decrease with the daily repeated use of Herpifi x, accompanied by a decrease of lesional pH. The success of the treatment depends on its continuous usage (i.e. as soon as the treatment is stopped, infl ammatory acne lesions revive). Hence, the treat- ment with Herpifi x is accompanied by a slight sting, which the dummy does not have; most of the group A participants thought that the treatment pin they received at the time of the crossover was ‘not functioning properly’. Because group B was used to the dummy at the start of the study, a Downloaded By: [Gouic, sabine le][Content Ed Net] At: 08:42 3 September 2009 comparison to the slightly stinging Herpifi x could As only young adults of skin types I–II participated Total number of papules and pustules in a defi ned in the study, neither age nor sex will have 8 ϫ 8 cm facial area. Group A: prior to a 3-week period use of uenced the data obtained. Endogenous and Herpifi x ® (startA) and thereafter (W3A), and after crossover at 3 weeks followed by a 3-week period using a dummy (endA). exogenous factors infl uence the pH of the skin Group B: prior to an initial 3-week period use of a dummy (startB) surface ( 17 , 20 , 21 ). Further, skin pH is infl uenced on and thereafter (W3B), and after crossover at 3 weeks followed by a the anatomical site by numerous external factors; of which, the most important is skin cleansing. In order to avoid external factors which could affect the measured pH of skin lesions, participants were group B remained unchanged (from n ϭ 21.6 Ϯ 8.0 told not to use any topicals except for an acidic to 20.5 Ϯ 8.0, NS) (Figure 2 ). The decrease in skin skin cleanser, which was to be used once daily, lesions in Group A was accompanied by a decrease if desired. However, home treatments cannot be in lesional surface pH (from 5.66 Ϯ 0.24 to a mean pH of 4.84 Ϯ 0.33, p Ͻ 0.01), while that of The anatomical study site was the cheek, a group B remained unchanged (from 5.72 Ϯ 0.25 to body area rich in sebaceous glands. Sebum secretion may indeed affect the skin surface pH. A signifi cant increase in skin pH was shown in If a neutral to alkaline preparation is applied, an increase of skin surface pH is accompanied skin dryness accompanied by an increased skin pH may infl uence the bacterial skin fl ora. While the antibacterial effect of the ingredient. Further- Staphylococcus aureus strains show an optimum more, the prevalence and antibiotic susceptibility an optimal growth peak at pH 6.0–6.5. Prior to acne patients. Patients treated with antibiotics the start of the study, the pH of the acne lesions (tetra cycline, erythromycin, clindamycin, trimethoprim- was 5.7 Ϯ 0.2, which may have enhanced the sulfamethoxazole) revealed signifi cantly more P acnes . Upon the Herpifi x treatment, P. acnes strains than the non-antibiotic the lesional surface pH decreased to 4.84 Ϯ 0.33, control group. Therefore, according to these authors, while 14.5 Ϯ 5.7 lesions were counted. This positive long-term antibiotic therapy in acne patients should explain the clinical effect obtained with Herpifi x Further studies are required to link lesional on acne lesions. However, since an increase of bacterial growth and lesional pH to the extent of skin surface pH disturbs the barrier and is lowering the pH in acne lesions may have more impact on the pathogenesis of acne than just on Declaration of interest: The authors report no con-
fl icts of interest. The authors alone are responsible Management of acne vulgaris includes non- for the content and writing of the paper. ablative chemical peels ( 23 ). The accumulative effects of more than two superfi cial peel treatments of facial acne do not affect the sebum secretion ( 24 ). References
been linked suffi ciently to the change of lesional 1. Braun-Falco O , Korting HC. [Normal pH value of human pH, which is the subject of an ongoing study. skin.] Hautarzt. 1986 ; 37 : 126 – 9 . Keeping the effect of an acid pH on bacterial Infl uence of repeated washings with soap and synthetic growth as well as barrier homeostasis in mind, forehead and forearm. Results of a cross-over trial in health probationers. Acta Derm Venereol. 1987 ; 67 : 41 – 7 . The standard regimen for infl ammatory acne P. acnes is topical erythromycin, growth of Staphylococcus epidermidis , which has an alkaline pH. Therefore, topical erythro- Propionibacterium acnes in continuous culture. mycin preparations from a pharmacological point Zentralbl Hyg Umweltmed. 1992 ; 193 : 78 – 90 . of view have a pH of above 7. Korting et al. ( have infl uenced the use of topical erythromycin Elias PM. Generation of free fatty acids from phospholipids regulates stratum corneum acidifi Downloaded By: [Gouic, sabine le][Content Ed Net] At: 08:42 3 September 2009 preparations for acne vulgaris on skin surface pH. J Invest Dermatol. 2001 ; 117 : 44 – 51 . Keeping in mind that the pH can only be measured 5. Hachem JP , Crumrine D , Fluhr J , Brown BE , Feingold KR , in extractable water-soluble components, acne- Elias PM. pH directly regulates epidermal permeability related abnormalities in skin surface pH may be barrier homeostasis, and stratum corneum integrity/cohesion. considered in future drug pharmacokinetics for J Invest Dermatol. 2003 ; 121 : 345 – 53 . topical acne treatment. The pH is defi ned as the Man MQ , Kriehuber E , et al. Barrier recovery is impeded negative logarithm (base 10) of the concentration at neutral pH, independent of ionic effects: Implications of free hydrogen ions in aqueous solution. The neutral point equals 7, ranging from 0 (most acidic) 7. Elias PM , Feingold KR. Coordinate regulation of epidermal differentiation and barrier homeostasis. Skin Pharmacol Appl Knowing the dramatic effect of age on the Skin Physiol. 2001 ; 14 : (suppl 1) 28 – 34 . lipid solubility of many amphophilic drugs, the 8. Madison KC. Barrier function of the skin: ‘La raison d’etre’ transcutaneous penetration of such compounds of the epidermis. J Invest Dermatol. 2003 ; 121 : 231 – 41 . could be affected by the pH of the stratum corneum, 9. Elias PM. Stratum corneum defensive functions: An the initial barrier. Charged substances will permeate integrated view. J Invest Dermatol. 2005 ; 125 : 183 – 200 . Choi EH. Interactions among stratum corneum intercellular lipids more than uncharged ones. defensive functions. Exp Dermatol. 2005 ; 14 : 719 – 26 . Charged compounds may be more effi ciently retained et al. NHE1 regulates the stratum corneum Lowering lesional surface pH in acne permeability barrier homeostasis. Microenvironment acidi- loss, stratum corneum hydration, skin surface pH, and skin temperature. J Invest Dermatol. 1998 ; 110 : 20 – 3 . J Biol Chem. 2002 ; 277 : 47 399 – 406 . in stratum corneum pH gradient when comparing white Caucasian and black African-American skin. Br J Dermatol. skin surface and its impact on the barrier function. Skin Pharmacol Physiol. 2006 ; 19 : 296 – 302 . 14. Briden ME. Alpha-hydroxyacid chemical peeling agents: Case studies and rationale for safe and effective use. 21. Schmid MH , Korting HC. The concept of the acid mantle Cutis. 2004 ; 73 (2 suppl) : 18 – 24 . of the skin: Its relevance for the choice of skin cleansers. 15. Cotellessa C , Manunta T , Ghersetich I , Brazzini B , Peris K. The use of pyruvic acid in the treatment of acne. Acad Dermatol Venereol. 2004 ; 18 : 275 – 8 . Kim IH. Salicylic acid peels for the treatment stratum corneum hydration, trans-epidermal water loss and skin roughness related to atopic eczema and skin dryness in a population of primary school children. Acta Derm Venereol. 2000 ; 80 : 188 – 91 . 24. Lee SH , Huh CH , Park KC , Youn SW. Effects of repetitive Maibach HI. Time-dependent variations of superfi cial chemical peels on facial sebum secretion in acne the skin barrier function in humans: Transepidermal water patients. J Eur Acad Dermatol Venereol. 2006 ; 20 : 964 – 8 . Downloaded By: [Gouic, sabine le][Content Ed Net] At: 08:42 3 September 2009

Source: http://www.skinlab.ru/download/publications/1310%20-%20Lowering%20lesional%20surface%20pH%20in%20acne.pdf