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Sodium lauryl suifate-induced irritant contact dermatitis in vulvar and forearm skin of premenopausal and postmenopausal women
Sodium lauryl sulfate-induced irritant contact dermatitis in vulvar and forearm skin of premenopausal and postmenopausal women Peter Elsner, MD,a,b Dorothea Wilhelm, MD,a and Howard 1. Maibach, MDa
San Francisco, California, and Wurzburg, West Germany Reactivity of the skin of the forearm and labia majora to three concentrations (2%,3%,5%) of sodium lauryl sulfate was studied in 20 healthy women, 10 premenopausaland 10 postmenopausal. Patches with theirritant wereapplied on day 0 for 24 hours.Skin changeswere monitored by visual scoring and by the measurement of transepidermal water loss and capacitance as indicators ofstratum corneum hydration on days 2, 3, 7, and 10.Inforearm skin, irritant dermatitis developedin the majority of subjects as indicated by visualscoringand increase of transepidermal water loss. These changes were not significantly dependenton the concentration of sodium lauryl sulfate. In labia majora skin, irritant dermatitisdeveloped in 50% of the women as determined by visual scoring; however, because of the pigmentation, visual scoring readings were less reliable in labia majora skin.Transepidermalwater lossdid not increase, but a significantand immediate decrease in capacitance wasnotedin labia majora skin. In forearm skin, postmenopausal women reacted less frequently and more slowly to sodium lauryl sulfate than premenopausal womenwhereasno age-relateddifferences were observed in reaction of the vulvar skin. It is concluded that labia majora skinis not more reactive to sodium lauryl sulfate than forearm skinand that capacitanceis moresensitive than transepidermal water loss in monitoring vulvar irritant dermatitis. Age-related differences in irritant reaction are apparent in the forearm, but not the vulva. (J AM ACAD DERMATOL 1990;23:648-52.)
The study of irritant dermatitis in genital skin has been largely neglected. Only recently has it been recognized that irritant dermatitis may be one ofthe causes of "vulvodynia."! Because no experimental data exist for surfactant-induced. vulvar irritant dermatitis, we studied the effect of three concentrations of the anionic surfactant sodium lauryl sulfate (SLS), 2%, 3%, and 5%,on vulvar and forearm skin of premenopausal and postmenopausal women. MATERIAL AND METHODS Study population. Twenty healthy female volunteers, 10 premenopausal and 10 postmenopausal, entered the study after informed consent was obtained. The study had been approved by the University of California San FranFrom the Departments of Dermatology, School ofMedicine, University of California San Francisco' and University of Wurzburg," Supported in part by a grant of Tambrands Inc., Palmer, Mass. Dr. Elsner received a grant from the German Research Foundation. Accepted for publication Jan. 27,1990. Reprint requests: H. I. Maibach, MD, Professor of Dermatology, Department of Dermatology, University of California School of Medicine, Box 0989, Surge 110, San Francisco, CA 94143-0989.
16/1/19831
648
ciscoCommittee for Human Research. The ages of premenopausal womenwerebetween 22 and 40 years (mean 32.3years,standard error ofthe mean [SEM] 2.0 years), and those ofthe postmenopausal womenwerebetween47 and 78 years (mean 62.6 years, SEM 2.9 years). Applicatiom. The following aqueous solutions of SLS (Sigma ChemicalCo.,S1. Louis,Mo.) were used: 2%,3%, 5% (wt/vol). Fifteen microliters of the solutions was applied to filter paper disks in small Finn Chambers (inner diameter 0.8em, EpitestLtd., Hyrla, Finland).The Finn Chambers were applied to the skin on a sheet of paper impregnantedwith 1%dansylchloride in petrolatum (as a fluorescent marker) andfixed with adhesive transparent dressing (1625/Tegaderm, 3M Co, St. Paul, Minn.). Application siteswerethevolaraspectofoneforearm and onelabium majus according to a randomizationprotocol. After 24 hours the Finn Chamberswere removed and the application sites identified under ultraviolet light. Measurements. All measurements wereperformed after the subjectshad beenphysically inactivefor at least 15 minutes.Beforemeasurements were made on vulvarskin for the first time, hairs wereclippedoff both labia majora. Visualscoringand transepidermalwater loss(TEWL) and capacitance measurements of treatment and symmetric controlsiteswere performedbeforeapplicationof
Volume 23 Number 4, Part I October 1990
the patches (day 0), 1 and 2 days after removal of the patches (days 2 and 3), and on days 7 and 10. Visual scoring. Each site was examined and graded according to a visualscoring system? by the same investigator: 1= slightredness,spottyor diffuse; 2 = moderate, uniformredness; 3 = intenseredness;4 = fieryerythema and edema. TEWL TEWL was measured with an evaporimeter (Servo Med Ep 1, Servo Med, Stockholm, Sweden) under neutral environmental circumstances (room temperature 19° to 23°C, relative humidity 48% to 57%.3 The hand-held probe was fitted with a 1 em extension to reduce air turbulencearound the hydrosensors and the metallic shield (suppliedby Servo Med) minimized the possibility of sensor contamination. Skin temperature was monitored by placing a thermistor (Tele-Thermometer, Yellow Springs Instruments, Yellow Springs, Ohio) on the skin surface.TEWL valueswere converted to values at a standard referencetemperature of30°C as previously described," Capacitance. Electricalcapacitance of the skinsurface as an indicator of stratum corneum moisture was measured with a capacitometer (Corneometer CM 820 PC, Courage & Khazaka, Cologne, West Germany) according to the manufacturer's guidelines as described by Blichmann and Serup' The capacitance is expressed digitally in arbitrary units (a.u.). Statisticalmethods. Statistical computationswere performed with a statistical package (SPSS-PC +, SPSS, Chicago, 111.) on an IBM XT-compatible computer. For TEWL and capacitance, valuesfor each treatment were computed in percentage of control sites (subsequently named relative TEWL and relative capacitance). Independence ofvariablesin a cross-tabulationwastestedwith the chi-square statistic (procedure CROSSTABS). Because the distribution of TEWL and capacitance values in our study population does not differ significantly from a normal distribution (P. Elsner and H. I. Maibach, unpublished data), differences between meansof treatment and control values were checked for significance with Student's t test for paired data (procedureT-TEST). The influence of independent factors on a dependentvariable wasevaluated withanalysisofvariance(procedureANOVA). Differences in frequencydistributionweretestedfor significance with the chi-square test (procedure CROSSTABS). RESULTS
The absolute values of TEWL and capacitance at day 0 (before SLS application) are given in Table 1. TEWL was significantly higher in labia majora than in forearm skin both in premenopausal and postmenopausal women, whereas the difference for capacitance did not reach significance. No significant age-related variations were observed.
Vulvar irritant contact dermatitis 649 Table I. Transepidermal water loss (TEWL) and capacitance of forearm and vulvar skin in premenopausal and postmenopausal women at day 0 Vulva
Forearm
I
p Value
Premenopausal women (n = 10) 17.3 ± 2.6 3.8 ± 0.4 <0.01 TEWL (gmjm2 j hr) 99.6 ± 4.8 81.0 ± 8,4 N.S. Capacitance (a.u.)
Postmenopausal women (n = 10) TEWL 15.2 ± 3.2 4.8 ± 2.3 <0.05 (gmjm 2 j hr) Capacitance 94.6 ± 6.5 92.1 ± 3.5 N.S. (a.u.) Vulvar TEWL was significantly higher than forearm TEWL both in premenopausal and in postmenopausal women. Vulvar capacitance was higher than forearm capacitance in both age groups, but the differences did not reach significance, No significant differences were found between the corresponding values in premenopausal and postmenopausal women. a.u., Absolute units; N,S., no significance.
The visual scores of sites treated with 2%, 3%,and 5% SLS did not differ significantly. Eight of 10 premenopausal women and 6 of 10 postmenopausal women reacted to the 5% SLS irritation with some degree of erythema in the forearm. In the vulva, however, visible erythema was observed only in 5 of 10 premenopausal and postmenopausal women. This difference in frequency between forearm and vulva was not significant in the chi-square test (p> 0.05). Significant TEWL increases were found in the forearm for all SLS concentrations tested. In vulvar skin, however, the TEWL increase was minimal and reached significance only in 3% SLS-treated site on day 2. In 5% SLS-treated vulvar skin, a significant TEWL decrease was observed on days 7 and 10. A clear pattern of concentration-dependent TEWL changes could be recognized neither in forearm nor in vulvar skin. This was confirmed by ANOVA, which showed SLS concentration in the tested range not to be a variable that influenced the value of relative TEWL significantly. Whereas hardly any capacitance changes occurred in forearm skin, significant capacitance decreases were observed in vulvar skin for all concentrations tested. These changes were not dose related, as was confirmed by variance analysis. In Fig. I, the TEWL changes in the 5% SLStreated sites are shown for premenopausal and post-
Journal of the American Academy of Dermatology
650 Elsner et al. 400 . , . . . . - - - - - - - - - - - - - - - - - - - - - .
-
1=:=
300
!.
...~ ~
..
Forearm Vutva
** 200
*
> ;;
•
ii
~------io.....- --2
II:
100
*
0
A
2
0
10
8 4 8 Days atter applicatIon
12
400
...
z
-0-
Forearm
~
Vulva
300
..J
~
W IIJ
200
..
>
;;
ii II:
100
* 0
B
0
2
4 6 8 Dlya after application
10
12
Fig. 1. Relative transepidermal water loss (rEWL) after 5%SL$-induced irritation in (A) premenopausal and (D) postmenopausal women (mean ± SEM [bars]). *, p < 0.05.
menopausal women separately. In both age groups, TEWL increased significantly in the forearm, but not in the vulva, where a significant decrease was found on day 7 (premenopausal women) and day 10 (postmenopausal women). The variation of values, as expressed by SEM, was much higher in the older age group. The relative capacitance curves indicate agerelated differences (Fig. 2). In the forearms of premenopausal women, there was a significant capacitance increase on day 2, followed by a decrease, which was significant on days 7 and 10. In the forearms of postmenopausal women, a delayed capacitance increase, which was significant on day 7, was
observed.In both age groups, capacitance decreased early and significantly in SLS-treated vulvar sites. DISCUSSION
TEWL in vulvar skin was significantly higher than in forearm skin, which is in accordance with previous reports.P" Even allowing for occlusion, TEWL is higher in the vulva than in the forearm. This indicates that vulvar skin is a less complete functional barrier than forearm skin. Skin capacitance as a measurement of stratum corneum hydration was higher in vulvar than in forearm skin, but the difference did not reach significance as in previous studies.i-" By visual scoring, 5% SLS caused
Volume 23 Number 4, Part 1 October 1990
Vulvar irritant contact dermatitis 651
1210
I~
110
......
~ II
.•. u
100
'ii a.
90
e
• •
Forearm Vulva
*
CJ II
> ;:
..•
80
II:
70
80
A
0
2
4
a
6
10
12
Daya after application 120
g II
.•.
110
c
100
'ii a.
to
U
• •
CJ II
>
.• ;:
80
*
*
II:
-0-- Forearm 70
B
~
Vulva
8O+----.-......-......--,..-...---'T--r-......,r--....,..-...----.--1 o 2 4 6 8 12 10 Day. after appllcetlon
Fig. 2. Relative capacitance after1%SLS-induced irritation in (A) premenopausal and (B) postmenopausal women (mean ± SEM [bars]). -, p < 0.05.
acute irritant contact dermatitis in the forearms of 8 of 10 premenopausal and 6 of 10 postmenopausal women. Willis et al.? induced irritant dermatitis in the forearms of 77% of their subjects with the same dosage (t5j.LI in the 8 mm Finn Chamber) and the same experimental protocol. Bruynzeel et al. I6 who alsoused a 5%SLS concentration,but a higher dose per area, induced irritant dermatitis in the forearms of 100% of their subjects. In labia majora skin, however, we observed erythema onlyin 50% of our subjects. Becauseof the higher pigmentation of vulvar skin, we experienced considerable difficulty in judging vulvar erythema and may have missedsome reactions. Evenallowing for this methodologic problem, vulvar skincertainly
doesnot seemto bemore susceptibleto SLS-induced irritation than forearm skin. In a previous study, we were unable to induce irritant dermatitis in vulvar skin with low concentrations of SLS (0.1 % to 1%), which did cause irritation on the forearm," These findings are in contrast to a study on the effect of two different irritants, benzalkonium chloride (17%) and maleic acid (20%), on forearm and vulvar skin.II In the latter study, the subjects reacted more frequently and more intensively in vulvar than in forearm skin. It should be stressed that the findings on labia majora skin may not apply to the labia minora, where symptoms of vulvoclynia may be localized and effectsof hormonal changes are considered to be most significant.
Journal of the American Academy of Dermatology
652 Elsner et al.
We conclude that labia majora irritant reactivity does not seem to be higher than that of the forearm for all irritants and that data from irritation tests on the ann should not be simply extrapolated to vulvar skin. The irritant potential of substances to be used on vulvar skin should be tested on vulvar skin. If extrapolation of forearm test results to vulvar skin was to be attempted, however, forearm tests should be performed in younger women because irritant reactions will be more intense in this age group. TEWL measurement is regarded as a sensitive method for the assessment of epidermal damage caused by irritants. 12 Our TEWL measurements at the SLS-treated forearm sites confirm this judgment: we saw a significant TEWL increase that slowly returned to normal. In vulvar skin, however; TEWL changes do not clearly parallel irritant dermatitis. The significant vulvar TEWL decreased on days 7 and lOin the 5% SLS treated sites are difficult to interprete; they might reflect a higher functional barrier against water loss, but also (and more probably so) a decreased water-holding capacity resulting in lower postocclusion water loss. Skin capacitance as an indicator of epidermal hydration has been rarely used for assessment of irritant dermatitis. In a recent study, an increase of capacitance was found after a 24-hour patch test with 2.5% SLS.13 We found a significant increase on day 2 in the forearm capacitance of premenopausal women, which was followed by a significant decrease on days 7 and 10, which indicated "dry eczema." In vulvar skin, however, a significant decrease occurred already on day 2 and lasted until day 7. This reduction of the epidermal water content could explain the mentioned vulvar TEWL decrease. It seems noteworthy that TEWL and capacitance dynamics in labia majora skin were similar for premenopausal and postmenopausal women. Differences were observed in the forearm, where postmenopausal women showed a delayed irritant reaction to SLS. When the two methods, TEWL and capacitance measurement, are compared, capacitance measurement seems to be more useful for the objective evaluation of vulvar irritant dermatitis, whereas TEWL measurement is superior in the forearm. Regarding the influence of age on irritant reactivity, some differences in the irritant responses between premenopausal and postmenopausal women were observed in the forearm. Eight of 10 premenopausal, but only 6 of 10 postmenopausal, women had
abnormal visual scores. TEWL and capacitance showed a delayed irritant reaction in postmenopausal women with maximal increases on day 7 compared with days 2 and 3 in the premenopausal group. This is in accordance with findings that elderly subjects react more slowlyand with a lower intensity to cutaneous irritants than younger adults. 14 In vulvar skin, however, these differences were not apparent. In contrast to forearm skin, vulvar skin is not subject to photoaging. On the other hand, hormonal influences on vulvar skin change with menopause. Furthermore, external factors modulating irritant response like anatomically and garment-related occlusionmay remain constant with age. Considering the complexity of these factors, the lack of age-related differences in vulvar irritant reactivity cannot be easily explained.
REFERENCES I. McKay M. Vulvodynia. A multifactorial clinical problem. Arch Dennatol 1989;125:256-62. 2. Frosch PJ, Kligman AM. The soap chamber test. J AM ACAD DERMATOL 1979;1:35-41. 3. Nilsson GE. Measurement of water exchange through skin. Med Bioi Eng Comput 1960;72:67-76. 4. Mathias CGT, Wilson DM, Maibach HI. Transepidermal water loss as a function of skin surface temperature. J Invest DermatoI1981;77:219-20. 5. Blichmann CW, Serup J. Assessment of skin moisure. Measurement of electrical conductance, capacitance and transepidennal water loss. Acta Derm Venereol (Stockh) 1988;68:284-90. 6. Britz MB, Maibach HI. Human labia majora skin: Transepidermal water loss in vivo. Acta Derm Venereal Suppl (Stockh) 1979;59:23-5. 7. Elsner P, Wilhelm D, Maibach HI. The effect of low-concentration sodium lauryl sulfate on human forarrn and vulvar skin: age-related differences. J Reprod Moo (In press.) 8. Elsner P, Wilhelm D, Maibach HI. Frictional properties of human forearm and vulvar skin: influence of age and correlation with transepidermal water loss and capacitance. Dermatologica (In press.) 9. Willis CM, Stephens eJM, Wilkinson JD. Experimentally-induced irritant contact dermatitis. Determination of optimum irritant concentrations. Contact Dermatitis 1988;18:20-4. 10. Bruynzeel DP, Van Ketel WG, Scheper RJ, et al. Delayed time course of irritation by sodium lauryl sulphate: observations on threshold reactions. Contact Dermatitis 1982; 8:236-9. 11. Britz M, Maibach HI. Human cutaneous vulvar reactivity to irritants. Contact Dermatitis 1979;5:375-7. 12. Berardesca E, Maibach HI. Bioengineering and patch test. Contact Dermatitis 1988;18:3-9. 13. Agner T, Serup J. Comparison oftwo electrical methods for measurement of skin hydration. An experimental study on irritant patch test reactions. Bioeng Skin 1988;4:263-9. 14. Lejman E, Stoudemayer T, Grove G, et al. Age differences in poison ivy dermatitis. Contact Dermatitis 1984;11: 163-7.
San Francisco, California, and Wurzburg, West Germany Reactivity of the skin of the forearm and labia majora to three concentrations (2%,3%,5%) of sodium lauryl sulfate was studied in 20 healthy women, 10 premenopausaland 10 postmenopausal. Patches with theirritant wereapplied on day 0 for 24 hours.Skin changeswere monitored by visual scoring and by the measurement of transepidermal water loss and capacitance as indicators ofstratum corneum hydration on days 2, 3, 7, and 10.Inforearm skin, irritant dermatitis developedin the majority of subjects as indicated by visualscoringand increase of transepidermal water loss. These changes were not significantly dependenton the concentration of sodium lauryl sulfate. In labia majora skin, irritant dermatitisdeveloped in 50% of the women as determined by visual scoring; however, because of the pigmentation, visual scoring readings were less reliable in labia majora skin.Transepidermalwater lossdid not increase, but a significantand immediate decrease in capacitance wasnotedin labia majora skin. In forearm skin, postmenopausal women reacted less frequently and more slowly to sodium lauryl sulfate than premenopausal womenwhereasno age-relateddifferences were observed in reaction of the vulvar skin. It is concluded that labia majora skinis not more reactive to sodium lauryl sulfate than forearm skinand that capacitanceis moresensitive than transepidermal water loss in monitoring vulvar irritant dermatitis. Age-related differences in irritant reaction are apparent in the forearm, but not the vulva. (J AM ACAD DERMATOL 1990;23:648-52.)
The study of irritant dermatitis in genital skin has been largely neglected. Only recently has it been recognized that irritant dermatitis may be one ofthe causes of "vulvodynia."! Because no experimental data exist for surfactant-induced. vulvar irritant dermatitis, we studied the effect of three concentrations of the anionic surfactant sodium lauryl sulfate (SLS), 2%, 3%, and 5%,on vulvar and forearm skin of premenopausal and postmenopausal women. MATERIAL AND METHODS Study population. Twenty healthy female volunteers, 10 premenopausal and 10 postmenopausal, entered the study after informed consent was obtained. The study had been approved by the University of California San FranFrom the Departments of Dermatology, School ofMedicine, University of California San Francisco' and University of Wurzburg," Supported in part by a grant of Tambrands Inc., Palmer, Mass. Dr. Elsner received a grant from the German Research Foundation. Accepted for publication Jan. 27,1990. Reprint requests: H. I. Maibach, MD, Professor of Dermatology, Department of Dermatology, University of California School of Medicine, Box 0989, Surge 110, San Francisco, CA 94143-0989.
16/1/19831
648
ciscoCommittee for Human Research. The ages of premenopausal womenwerebetween 22 and 40 years (mean 32.3years,standard error ofthe mean [SEM] 2.0 years), and those ofthe postmenopausal womenwerebetween47 and 78 years (mean 62.6 years, SEM 2.9 years). Applicatiom. The following aqueous solutions of SLS (Sigma ChemicalCo.,S1. Louis,Mo.) were used: 2%,3%, 5% (wt/vol). Fifteen microliters of the solutions was applied to filter paper disks in small Finn Chambers (inner diameter 0.8em, EpitestLtd., Hyrla, Finland).The Finn Chambers were applied to the skin on a sheet of paper impregnantedwith 1%dansylchloride in petrolatum (as a fluorescent marker) andfixed with adhesive transparent dressing (1625/Tegaderm, 3M Co, St. Paul, Minn.). Application siteswerethevolaraspectofoneforearm and onelabium majus according to a randomizationprotocol. After 24 hours the Finn Chamberswere removed and the application sites identified under ultraviolet light. Measurements. All measurements wereperformed after the subjectshad beenphysically inactivefor at least 15 minutes.Beforemeasurements were made on vulvarskin for the first time, hairs wereclippedoff both labia majora. Visualscoringand transepidermalwater loss(TEWL) and capacitance measurements of treatment and symmetric controlsiteswere performedbeforeapplicationof
Volume 23 Number 4, Part I October 1990
the patches (day 0), 1 and 2 days after removal of the patches (days 2 and 3), and on days 7 and 10. Visual scoring. Each site was examined and graded according to a visualscoring system? by the same investigator: 1= slightredness,spottyor diffuse; 2 = moderate, uniformredness; 3 = intenseredness;4 = fieryerythema and edema. TEWL TEWL was measured with an evaporimeter (Servo Med Ep 1, Servo Med, Stockholm, Sweden) under neutral environmental circumstances (room temperature 19° to 23°C, relative humidity 48% to 57%.3 The hand-held probe was fitted with a 1 em extension to reduce air turbulencearound the hydrosensors and the metallic shield (suppliedby Servo Med) minimized the possibility of sensor contamination. Skin temperature was monitored by placing a thermistor (Tele-Thermometer, Yellow Springs Instruments, Yellow Springs, Ohio) on the skin surface.TEWL valueswere converted to values at a standard referencetemperature of30°C as previously described," Capacitance. Electricalcapacitance of the skinsurface as an indicator of stratum corneum moisture was measured with a capacitometer (Corneometer CM 820 PC, Courage & Khazaka, Cologne, West Germany) according to the manufacturer's guidelines as described by Blichmann and Serup' The capacitance is expressed digitally in arbitrary units (a.u.). Statisticalmethods. Statistical computationswere performed with a statistical package (SPSS-PC +, SPSS, Chicago, 111.) on an IBM XT-compatible computer. For TEWL and capacitance, valuesfor each treatment were computed in percentage of control sites (subsequently named relative TEWL and relative capacitance). Independence ofvariablesin a cross-tabulationwastestedwith the chi-square statistic (procedure CROSSTABS). Because the distribution of TEWL and capacitance values in our study population does not differ significantly from a normal distribution (P. Elsner and H. I. Maibach, unpublished data), differences between meansof treatment and control values were checked for significance with Student's t test for paired data (procedureT-TEST). The influence of independent factors on a dependentvariable wasevaluated withanalysisofvariance(procedureANOVA). Differences in frequencydistributionweretestedfor significance with the chi-square test (procedure CROSSTABS). RESULTS
The absolute values of TEWL and capacitance at day 0 (before SLS application) are given in Table 1. TEWL was significantly higher in labia majora than in forearm skin both in premenopausal and postmenopausal women, whereas the difference for capacitance did not reach significance. No significant age-related variations were observed.
Vulvar irritant contact dermatitis 649 Table I. Transepidermal water loss (TEWL) and capacitance of forearm and vulvar skin in premenopausal and postmenopausal women at day 0 Vulva
Forearm
I
p Value
Premenopausal women (n = 10) 17.3 ± 2.6 3.8 ± 0.4 <0.01 TEWL (gmjm2 j hr) 99.6 ± 4.8 81.0 ± 8,4 N.S. Capacitance (a.u.)
Postmenopausal women (n = 10) TEWL 15.2 ± 3.2 4.8 ± 2.3 <0.05 (gmjm 2 j hr) Capacitance 94.6 ± 6.5 92.1 ± 3.5 N.S. (a.u.) Vulvar TEWL was significantly higher than forearm TEWL both in premenopausal and in postmenopausal women. Vulvar capacitance was higher than forearm capacitance in both age groups, but the differences did not reach significance, No significant differences were found between the corresponding values in premenopausal and postmenopausal women. a.u., Absolute units; N,S., no significance.
The visual scores of sites treated with 2%, 3%,and 5% SLS did not differ significantly. Eight of 10 premenopausal women and 6 of 10 postmenopausal women reacted to the 5% SLS irritation with some degree of erythema in the forearm. In the vulva, however, visible erythema was observed only in 5 of 10 premenopausal and postmenopausal women. This difference in frequency between forearm and vulva was not significant in the chi-square test (p> 0.05). Significant TEWL increases were found in the forearm for all SLS concentrations tested. In vulvar skin, however, the TEWL increase was minimal and reached significance only in 3% SLS-treated site on day 2. In 5% SLS-treated vulvar skin, a significant TEWL decrease was observed on days 7 and 10. A clear pattern of concentration-dependent TEWL changes could be recognized neither in forearm nor in vulvar skin. This was confirmed by ANOVA, which showed SLS concentration in the tested range not to be a variable that influenced the value of relative TEWL significantly. Whereas hardly any capacitance changes occurred in forearm skin, significant capacitance decreases were observed in vulvar skin for all concentrations tested. These changes were not dose related, as was confirmed by variance analysis. In Fig. I, the TEWL changes in the 5% SLStreated sites are shown for premenopausal and post-
Journal of the American Academy of Dermatology
650 Elsner et al. 400 . , . . . . - - - - - - - - - - - - - - - - - - - - - .
-
1=:=
300
!.
...~ ~
..
Forearm Vutva
** 200
*
> ;;
•
ii
~------io.....- --2
II:
100
*
0
A
2
0
10
8 4 8 Days atter applicatIon
12
400
...
z
-0-
Forearm
~
Vulva
300
..J
~
W IIJ
200
..
>
;;
ii II:
100
* 0
B
0
2
4 6 8 Dlya after application
10
12
Fig. 1. Relative transepidermal water loss (rEWL) after 5%SL$-induced irritation in (A) premenopausal and (D) postmenopausal women (mean ± SEM [bars]). *, p < 0.05.
menopausal women separately. In both age groups, TEWL increased significantly in the forearm, but not in the vulva, where a significant decrease was found on day 7 (premenopausal women) and day 10 (postmenopausal women). The variation of values, as expressed by SEM, was much higher in the older age group. The relative capacitance curves indicate agerelated differences (Fig. 2). In the forearms of premenopausal women, there was a significant capacitance increase on day 2, followed by a decrease, which was significant on days 7 and 10. In the forearms of postmenopausal women, a delayed capacitance increase, which was significant on day 7, was
observed.In both age groups, capacitance decreased early and significantly in SLS-treated vulvar sites. DISCUSSION
TEWL in vulvar skin was significantly higher than in forearm skin, which is in accordance with previous reports.P" Even allowing for occlusion, TEWL is higher in the vulva than in the forearm. This indicates that vulvar skin is a less complete functional barrier than forearm skin. Skin capacitance as a measurement of stratum corneum hydration was higher in vulvar than in forearm skin, but the difference did not reach significance as in previous studies.i-" By visual scoring, 5% SLS caused
Volume 23 Number 4, Part 1 October 1990
Vulvar irritant contact dermatitis 651
1210
I~
110
......
~ II
.•. u
100
'ii a.
90
e
• •
Forearm Vulva
*
CJ II
> ;:
..•
80
II:
70
80
A
0
2
4
a
6
10
12
Daya after application 120
g II
.•.
110
c
100
'ii a.
to
U
• •
CJ II
>
.• ;:
80
*
*
II:
-0-- Forearm 70
B
~
Vulva
8O+----.-......-......--,..-...---'T--r-......,r--....,..-...----.--1 o 2 4 6 8 12 10 Day. after appllcetlon
Fig. 2. Relative capacitance after1%SLS-induced irritation in (A) premenopausal and (B) postmenopausal women (mean ± SEM [bars]). -, p < 0.05.
acute irritant contact dermatitis in the forearms of 8 of 10 premenopausal and 6 of 10 postmenopausal women. Willis et al.? induced irritant dermatitis in the forearms of 77% of their subjects with the same dosage (t5j.LI in the 8 mm Finn Chamber) and the same experimental protocol. Bruynzeel et al. I6 who alsoused a 5%SLS concentration,but a higher dose per area, induced irritant dermatitis in the forearms of 100% of their subjects. In labia majora skin, however, we observed erythema onlyin 50% of our subjects. Becauseof the higher pigmentation of vulvar skin, we experienced considerable difficulty in judging vulvar erythema and may have missedsome reactions. Evenallowing for this methodologic problem, vulvar skincertainly
doesnot seemto bemore susceptibleto SLS-induced irritation than forearm skin. In a previous study, we were unable to induce irritant dermatitis in vulvar skin with low concentrations of SLS (0.1 % to 1%), which did cause irritation on the forearm," These findings are in contrast to a study on the effect of two different irritants, benzalkonium chloride (17%) and maleic acid (20%), on forearm and vulvar skin.II In the latter study, the subjects reacted more frequently and more intensively in vulvar than in forearm skin. It should be stressed that the findings on labia majora skin may not apply to the labia minora, where symptoms of vulvoclynia may be localized and effectsof hormonal changes are considered to be most significant.
Journal of the American Academy of Dermatology
652 Elsner et al.
We conclude that labia majora irritant reactivity does not seem to be higher than that of the forearm for all irritants and that data from irritation tests on the ann should not be simply extrapolated to vulvar skin. The irritant potential of substances to be used on vulvar skin should be tested on vulvar skin. If extrapolation of forearm test results to vulvar skin was to be attempted, however, forearm tests should be performed in younger women because irritant reactions will be more intense in this age group. TEWL measurement is regarded as a sensitive method for the assessment of epidermal damage caused by irritants. 12 Our TEWL measurements at the SLS-treated forearm sites confirm this judgment: we saw a significant TEWL increase that slowly returned to normal. In vulvar skin, however; TEWL changes do not clearly parallel irritant dermatitis. The significant vulvar TEWL decreased on days 7 and lOin the 5% SLS treated sites are difficult to interprete; they might reflect a higher functional barrier against water loss, but also (and more probably so) a decreased water-holding capacity resulting in lower postocclusion water loss. Skin capacitance as an indicator of epidermal hydration has been rarely used for assessment of irritant dermatitis. In a recent study, an increase of capacitance was found after a 24-hour patch test with 2.5% SLS.13 We found a significant increase on day 2 in the forearm capacitance of premenopausal women, which was followed by a significant decrease on days 7 and 10, which indicated "dry eczema." In vulvar skin, however, a significant decrease occurred already on day 2 and lasted until day 7. This reduction of the epidermal water content could explain the mentioned vulvar TEWL decrease. It seems noteworthy that TEWL and capacitance dynamics in labia majora skin were similar for premenopausal and postmenopausal women. Differences were observed in the forearm, where postmenopausal women showed a delayed irritant reaction to SLS. When the two methods, TEWL and capacitance measurement, are compared, capacitance measurement seems to be more useful for the objective evaluation of vulvar irritant dermatitis, whereas TEWL measurement is superior in the forearm. Regarding the influence of age on irritant reactivity, some differences in the irritant responses between premenopausal and postmenopausal women were observed in the forearm. Eight of 10 premenopausal, but only 6 of 10 postmenopausal, women had
abnormal visual scores. TEWL and capacitance showed a delayed irritant reaction in postmenopausal women with maximal increases on day 7 compared with days 2 and 3 in the premenopausal group. This is in accordance with findings that elderly subjects react more slowlyand with a lower intensity to cutaneous irritants than younger adults. 14 In vulvar skin, however, these differences were not apparent. In contrast to forearm skin, vulvar skin is not subject to photoaging. On the other hand, hormonal influences on vulvar skin change with menopause. Furthermore, external factors modulating irritant response like anatomically and garment-related occlusionmay remain constant with age. Considering the complexity of these factors, the lack of age-related differences in vulvar irritant reactivity cannot be easily explained.
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