Dermatológica 158: 55-59 (1979)
Effect of Benzoyl Peroxide on Skin Surface Lipids D. Fanta and M. M. Muller Ilnd Department of Dermatology (Head: Prof. G. N iebauer), and the Institute for Medical Chemistry (Head: Prof. E. K aiser), University of Vienna, Vienna
Key Words. Benzoyl peroxide • Skin surface lipids • Sebostatic effect • Acne Abstract. Investigations have been performed on the effect of benzoyl peroxide on skin surface lipids by direct lipid extraction with petrol ether and quantitative determination. Though there was no change after 1 week treatment, after 4 weeks a significant reduction of the casual level as well as the replacement sum could be observed.
Introduction
The beneficial effect of local treatment with benzoyl peroxide (BP) on acne vulgaris has so far mainly been attributed to the bacteriostatic qualities of this material [5,6, 8]. A sebostatic effect has also been demonstrated; after a short period of treatment, clinical examination shows a marked diminution in the oily sheen of affected skin. Autoradiographic studies have shown that this is not merely the result of desquamation, caused by the release of benzoic acid in contact with organic tissues, with consequent loosening of the stratum corneum: after 3 weeks’ application of a 5% BP preparation, there was a significant reduction in the labelling index of the germinative cells of the sebaceous glands suggesting decreased sebum production [4]. In the present study we investigated the effect of BP on the quantity of skin surface lipids, using direct extraction with petroleum ether.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:02:30 PM
Investigations A commercially obtainable 5% BP preparation (PanOxyl 5, Stiefel Laboratories, Offenbach/Main) was used, its base being made up of colloidal magnesium aluminium silicate, hydroxypropyl methylcellulose, polyoxy ethylene lauryl ether, citric acid, absolute alcohol and distilled water.
Fanta/Müller
56
M aterials and Methods 10 treated subjects and 4 controls were studied, the controls being treated with the base alone. Before treatment, after 1 and after 4 weeks of treatment with the 5% BP pre paration, quantitative measurements of ‘casual levels’ [7] of skin fat were carried out using the modified method of Schirren and H onsig [10]. For at least a week before the test, no other treatment was applied to the skin. Patients were instructed to cleanse their facial skin thoroughly with an alcohol-containing tonic on the evening before the lipid extraction, and again on the morning of the test; they were also told to use no skin ointments or make-up. To minimize variations due to methodology, investigations were carried out during a cool time of year, at constant room temperature (23 °C), at the same time of day (noon); in female subjects, the first and last measurements were always carried out in the middle of the menstrual cycle. Direct extraction of skin surface lipids was carried out by applying four test tubes of standard diameter, each containing 2 ml of petroleum ether, to the side of the cheek; a total skin surface of 7 cm2 was extracted. The same method was used to measure lipid regeneration, i.e. the film of lipid appearing on the skin surface after thorough defatting (the ‘replacement sum’) [7]; after the first lipid extraction, the skin was thoroughly washed with petroleum ether, till fine scales became visible on the surface, indicating that defatting was adequate. 2 h later the lipid extraction was repeated. Chemical analysis. Lipid extracts from the four test tubes were pooled, filtered and dried in nitrogen at 40 'C. The lipids were then dissolved in an as small as possible volume of petroleum ether. The quantity of lipids was measured photometrically using the phosphorus/vanillic acid reactions [11]. Statistical evaluation. The difference between pretreatment values and values after the end of treatment were estimated, and assessed using the Student’s t test.
Results
After 1 week’s treatment with 5% BP, there was no significant change in lipid values; after 4 weeks’ treatment, however, there was a significant re duction in skin surface lipids both in the ‘casual level’ (p 0.0001). Controls treated with the base alone showed no reduction in total skin surface lipids (table I).
Seborrhea (increased sebum production) is an essential mechanism in the pathogenesis of acne. The greater the degree of seborrhoea, the worse the acne [1].
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:02:30 PM
Discussion
Table I. Skin surface lipids in treatment with benzoyl peroxide 5% Casual level I* 1 2 3 4 5 6 7 8 9 10 Sum Average
Replacement sum
II
n
s2 Range
1+
II
III+
1.9 1.1 1.59 1.85 1.14 1.15 1.32 0.98 1.7 2.1
1.43 1.32 0.87 0.62 0.97 1.22 1.28 0.50 1.46 1.9
0.4 1.1 0.2 0.38 0.85 0.29 0.37 0.95 1.08 1.5
0.8 1.29 1.58 1.76 1.06 1.76 0.68 1.68 1.33 1.24
1.08 1.28 1.57 0.54 1.42 1.67 0.72 1.30 1.88 1.32
0.36 0.85 0.48 0.57 0.43 0.91 0.46 0.56 0.3 1.1
14.83 1.48
11.57 1.15
7.12 0.71
13.18 1.32
12.78 1.28
6.02 0.60
after
+before
after
1.32 13.18 10 0.38 0.68-1.76
0.60
•before X
III*
Control No. Casual level
1.48 14.83 10 0.39 0.98-2.1
0.71 7.12 10 0.44 0.44-1.5 p0.0001
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:02:30 PM
Skin surface lipids in mg/7 cm*. I = Before treatment; II = after 1 week’s treatment; III = after 2 week’s treatment.
Fanta/Muller
58
Knowledge about the hormonal regulation of sebaceous secretion stimulation by androgens and inhibition by estrogens - has lead to attempts to control seborrhea by hormonal methods. These have sometimes been successful. Local or systemic treatment with estrogens can bring about a satisfactory reduction in sebum secretion [9]. The doses required, however, may lead to menstrual disturbances in females and to gynecomastia in males. A more powerful effect can be obtained with the use of antiandrogens synthetic hormones based on progesterone - but this form of treatment is only suitable for systemic use in female patients, in combination with ethinyl estradiol to inhibit ovulation [1, 2], When treating acne vulgaris with BP, we made the clinical observation that sebum production was inhibited [3]. After no more than a few days of local treatment, there is a noticeable diminution in the oily aspect of affected skin. The observation was confirmed by autoradiographic studies, which showed a decrease in the labelling index of the germinative cells of the sebaceous glands. Previous studies of skin surface lipids during acne treatment with BP have been concerned only with its effect on the percentage content of free fatty acids, which serve as an indication of the presence of Propionibacterium acnes [5, 6]; it was shown that after several days of treatment, the content of free fatty acids were also reduced during treatment with the base alone. In the present study we extended our observations to the quantity of skin surface lipids during treatment with BP. After 1 weeks’ treatment, there was no significant change in total skin surface lipids (though clinically at this time there was a marked degree of desquamation and some defatting). The unchanged values for the total skin surface lipids may be explained by a greater efficiency of extraction of epi dermal lipids due to marked loosening of the epidermis. After 4 weeks, by which time scaling was considerably less, there was a marked reduction in skin surface lipids in every case, and this was statistically significant by the Student’s t test. Controls treated with base alone showed no significant change after 1 or 4 weeks’ treatment. These findings provide further evidence of the important sebostatic effect of BP.
We thank Ing. L egenstein for the chemical analysis and Ing. J arischko for the statistical evaluation.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:02:30 PM
Acknowledgement
Effect of Benzoyl Peroxide on Skin Surface Lipids
59
References 1 B urton, J.L. and S huster, S.: The relationship between seborrhoea and acne vulgaris. Br. J. Derm. 84: 600 (1971). 2 F anta, D.; Schneider, W.H.; Spona , J. und N eufeld, T .: Die Anwendung von Antiandrogenen in der Behandlung der Akne. Wien. klin. Wschr. 89: 622 (1977). 3 F anta, D.; Bardach , H. und J urecka, W.: Klinische Erfahrungen mit Benzoyl peroxyd in der Behandlung der Akne vulgaris. Wien. klin. Wschr. 22: 748 (1977). 4 F anta, D. and J urecka , W .: Autoradiographic investigations in benzoyl peroxide treated skin. Acta derm.-vener., Stockh. (in press). 5 F ulton , J.E .; F arzad -B akshandeh, A., and B radley, S .: The mechanism of benzoylperoxide in acne and the use with topical vitamin A acid. J. cutan. Path. 1: 191 (1974). 6 G loor, M.; H ummel, A. und F riederich, H.C.: Experimentelle Untersuchungen zur Benzoylperoxydtherapie der Acne vulgaris. Z. Haut-GeschlKrankh. 50: 657 (1975). 7 H errmann, F .; P rose, P.H., and S ulzberger, M.B.: Studies on the ether-soluble substances on the human skin. J. invest. Derm. 21: 397 (1953). 8 W eigel, W.N. und P rückner , H .: Therapie der Akne vulgaris mit PanOxyl. Z. HautGeschlkrankh. 52: 725 (1977). 9 P ochi, P.E. and Strauss, J.S.: Sebaceous gland supression with ethinyl estradiol and diethylstilbestrol. Archs Derm. 108: 210 (1973). 10 Schirren , C.G. und H onsig, C.: Über die Lipidregenerationszeit im Bereich talg drüsenfreier Haut. Hautarzt 19: 53 (1969). 11 Z öllner, N. und K irsch, K .: Über die quantitative Bestimmung von Lipoiden. Z. ges. exp. Med. 135: 545 (1962).
OA Dr. D oris F anta, Ilnd Department of Dermatology, University of Vienna, Alser Strasse 4, A-1090 Vienna (Austria)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:02:30 PM
Received: December 29, 1977; accepted: January 16, 1978.
Effect of Benzoyl Peroxide on Skin Surface Lipids D. Fanta and M. M. Muller Ilnd Department of Dermatology (Head: Prof. G. N iebauer), and the Institute for Medical Chemistry (Head: Prof. E. K aiser), University of Vienna, Vienna
Key Words. Benzoyl peroxide • Skin surface lipids • Sebostatic effect • Acne Abstract. Investigations have been performed on the effect of benzoyl peroxide on skin surface lipids by direct lipid extraction with petrol ether and quantitative determination. Though there was no change after 1 week treatment, after 4 weeks a significant reduction of the casual level as well as the replacement sum could be observed.
Introduction
The beneficial effect of local treatment with benzoyl peroxide (BP) on acne vulgaris has so far mainly been attributed to the bacteriostatic qualities of this material [5,6, 8]. A sebostatic effect has also been demonstrated; after a short period of treatment, clinical examination shows a marked diminution in the oily sheen of affected skin. Autoradiographic studies have shown that this is not merely the result of desquamation, caused by the release of benzoic acid in contact with organic tissues, with consequent loosening of the stratum corneum: after 3 weeks’ application of a 5% BP preparation, there was a significant reduction in the labelling index of the germinative cells of the sebaceous glands suggesting decreased sebum production [4]. In the present study we investigated the effect of BP on the quantity of skin surface lipids, using direct extraction with petroleum ether.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:02:30 PM
Investigations A commercially obtainable 5% BP preparation (PanOxyl 5, Stiefel Laboratories, Offenbach/Main) was used, its base being made up of colloidal magnesium aluminium silicate, hydroxypropyl methylcellulose, polyoxy ethylene lauryl ether, citric acid, absolute alcohol and distilled water.
Fanta/Müller
56
M aterials and Methods 10 treated subjects and 4 controls were studied, the controls being treated with the base alone. Before treatment, after 1 and after 4 weeks of treatment with the 5% BP pre paration, quantitative measurements of ‘casual levels’ [7] of skin fat were carried out using the modified method of Schirren and H onsig [10]. For at least a week before the test, no other treatment was applied to the skin. Patients were instructed to cleanse their facial skin thoroughly with an alcohol-containing tonic on the evening before the lipid extraction, and again on the morning of the test; they were also told to use no skin ointments or make-up. To minimize variations due to methodology, investigations were carried out during a cool time of year, at constant room temperature (23 °C), at the same time of day (noon); in female subjects, the first and last measurements were always carried out in the middle of the menstrual cycle. Direct extraction of skin surface lipids was carried out by applying four test tubes of standard diameter, each containing 2 ml of petroleum ether, to the side of the cheek; a total skin surface of 7 cm2 was extracted. The same method was used to measure lipid regeneration, i.e. the film of lipid appearing on the skin surface after thorough defatting (the ‘replacement sum’) [7]; after the first lipid extraction, the skin was thoroughly washed with petroleum ether, till fine scales became visible on the surface, indicating that defatting was adequate. 2 h later the lipid extraction was repeated. Chemical analysis. Lipid extracts from the four test tubes were pooled, filtered and dried in nitrogen at 40 'C. The lipids were then dissolved in an as small as possible volume of petroleum ether. The quantity of lipids was measured photometrically using the phosphorus/vanillic acid reactions [11]. Statistical evaluation. The difference between pretreatment values and values after the end of treatment were estimated, and assessed using the Student’s t test.
Results
After 1 week’s treatment with 5% BP, there was no significant change in lipid values; after 4 weeks’ treatment, however, there was a significant re duction in skin surface lipids both in the ‘casual level’ (p 0.0001). Controls treated with the base alone showed no reduction in total skin surface lipids (table I).
Seborrhea (increased sebum production) is an essential mechanism in the pathogenesis of acne. The greater the degree of seborrhoea, the worse the acne [1].
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:02:30 PM
Discussion
Table I. Skin surface lipids in treatment with benzoyl peroxide 5% Casual level I* 1 2 3 4 5 6 7 8 9 10 Sum Average
Replacement sum
II
n
s2 Range
1+
II
III+
1.9 1.1 1.59 1.85 1.14 1.15 1.32 0.98 1.7 2.1
1.43 1.32 0.87 0.62 0.97 1.22 1.28 0.50 1.46 1.9
0.4 1.1 0.2 0.38 0.85 0.29 0.37 0.95 1.08 1.5
0.8 1.29 1.58 1.76 1.06 1.76 0.68 1.68 1.33 1.24
1.08 1.28 1.57 0.54 1.42 1.67 0.72 1.30 1.88 1.32
0.36 0.85 0.48 0.57 0.43 0.91 0.46 0.56 0.3 1.1
14.83 1.48
11.57 1.15
7.12 0.71
13.18 1.32
12.78 1.28
6.02 0.60
after
+before
after
1.32 13.18 10 0.38 0.68-1.76
0.60
•before X
III*
Control No. Casual level
1.48 14.83 10 0.39 0.98-2.1
0.71 7.12 10 0.44 0.44-1.5 p0.0001
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:02:30 PM
Skin surface lipids in mg/7 cm*. I = Before treatment; II = after 1 week’s treatment; III = after 2 week’s treatment.
Fanta/Muller
58
Knowledge about the hormonal regulation of sebaceous secretion stimulation by androgens and inhibition by estrogens - has lead to attempts to control seborrhea by hormonal methods. These have sometimes been successful. Local or systemic treatment with estrogens can bring about a satisfactory reduction in sebum secretion [9]. The doses required, however, may lead to menstrual disturbances in females and to gynecomastia in males. A more powerful effect can be obtained with the use of antiandrogens synthetic hormones based on progesterone - but this form of treatment is only suitable for systemic use in female patients, in combination with ethinyl estradiol to inhibit ovulation [1, 2], When treating acne vulgaris with BP, we made the clinical observation that sebum production was inhibited [3]. After no more than a few days of local treatment, there is a noticeable diminution in the oily aspect of affected skin. The observation was confirmed by autoradiographic studies, which showed a decrease in the labelling index of the germinative cells of the sebaceous glands. Previous studies of skin surface lipids during acne treatment with BP have been concerned only with its effect on the percentage content of free fatty acids, which serve as an indication of the presence of Propionibacterium acnes [5, 6]; it was shown that after several days of treatment, the content of free fatty acids were also reduced during treatment with the base alone. In the present study we extended our observations to the quantity of skin surface lipids during treatment with BP. After 1 weeks’ treatment, there was no significant change in total skin surface lipids (though clinically at this time there was a marked degree of desquamation and some defatting). The unchanged values for the total skin surface lipids may be explained by a greater efficiency of extraction of epi dermal lipids due to marked loosening of the epidermis. After 4 weeks, by which time scaling was considerably less, there was a marked reduction in skin surface lipids in every case, and this was statistically significant by the Student’s t test. Controls treated with base alone showed no significant change after 1 or 4 weeks’ treatment. These findings provide further evidence of the important sebostatic effect of BP.
We thank Ing. L egenstein for the chemical analysis and Ing. J arischko for the statistical evaluation.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:02:30 PM
Acknowledgement
Effect of Benzoyl Peroxide on Skin Surface Lipids
59
References 1 B urton, J.L. and S huster, S.: The relationship between seborrhoea and acne vulgaris. Br. J. Derm. 84: 600 (1971). 2 F anta, D.; Schneider, W.H.; Spona , J. und N eufeld, T .: Die Anwendung von Antiandrogenen in der Behandlung der Akne. Wien. klin. Wschr. 89: 622 (1977). 3 F anta, D.; Bardach , H. und J urecka, W.: Klinische Erfahrungen mit Benzoyl peroxyd in der Behandlung der Akne vulgaris. Wien. klin. Wschr. 22: 748 (1977). 4 F anta, D. and J urecka , W .: Autoradiographic investigations in benzoyl peroxide treated skin. Acta derm.-vener., Stockh. (in press). 5 F ulton , J.E .; F arzad -B akshandeh, A., and B radley, S .: The mechanism of benzoylperoxide in acne and the use with topical vitamin A acid. J. cutan. Path. 1: 191 (1974). 6 G loor, M.; H ummel, A. und F riederich, H.C.: Experimentelle Untersuchungen zur Benzoylperoxydtherapie der Acne vulgaris. Z. Haut-GeschlKrankh. 50: 657 (1975). 7 H errmann, F .; P rose, P.H., and S ulzberger, M.B.: Studies on the ether-soluble substances on the human skin. J. invest. Derm. 21: 397 (1953). 8 W eigel, W.N. und P rückner , H .: Therapie der Akne vulgaris mit PanOxyl. Z. HautGeschlkrankh. 52: 725 (1977). 9 P ochi, P.E. and Strauss, J.S.: Sebaceous gland supression with ethinyl estradiol and diethylstilbestrol. Archs Derm. 108: 210 (1973). 10 Schirren , C.G. und H onsig, C.: Über die Lipidregenerationszeit im Bereich talg drüsenfreier Haut. Hautarzt 19: 53 (1969). 11 Z öllner, N. und K irsch, K .: Über die quantitative Bestimmung von Lipoiden. Z. ges. exp. Med. 135: 545 (1962).
OA Dr. D oris F anta, Ilnd Department of Dermatology, University of Vienna, Alser Strasse 4, A-1090 Vienna (Austria)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:02:30 PM
Received: December 29, 1977; accepted: January 16, 1978.
