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Sodium lauryl sulfate irritant patch tests. III. Evaporation of aqueous vehicle influences inflammatory response
Volume 11 Number 3 September, 1984
Sodium lauryl sulfate irritant patch tests. II
3. Bruynzeel DP, van Ketel WG, Scheper RJ, et al: Delayed time course of irritation by sodium lauryl sulfate: Observations on threshold reactions. Contact Dermatitis 8:236-239, 1982. 4. Kaidhey KH, Kligman AM: AssaY of topical corticosteroid. Arch Dermatol 112:808-810, 1976. 5. Skog 13, Forsbeck M: Comparison between 24-48 hour exposure time in patch testing. Contact Dermatitis 4:362-364, 1978. 6. Mathias CGT, Maibach HI: Dermatotoxicology. Monograph I. Cutaneous irritation: Factors influencing the response to irritants. Clin Toxieol 13:333-346, 1978.
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7. Czerwinska-Dihm I, Rudzki E: Skin reactions to primary irritants. Contact Dermatitis 7:315-319, 1981. 8. Bjornberg A: Skin reactions to primary irritants in patients with hand eczema. G6teberg, I968, Oscar Isacsons Trycked AB. 9. Bruynzeel DP, van Ketel WG, yon Blomberg-van der Flier M, Scheper P,J: Angry back or the excited skin syndrome: A prospective study. J AM ACADDERI~IATOL 8:392-397, 1983. 10. Frosh PJ, Kligman AM: The Duhring chamber: An improved technique for epicutaneous testing of irritant and allergic reactions. Contact Dermatitis 5:73-81, 1979.
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Sodium lauryl sulfate irritant patch tests. III. Evaporation of aqueous vehicle influences inflammatory response M a r k V. Dahl, M . D . , and Mary Jane Roering, B.S.N~
Minneapolis, MN Patch tests with aqueous solutions of the irritating detergent sodium lauryl sulfate (SLS) elicit varying degrees of inflammation from subject to subject and from site to site, For an investigation of the causes of this variability, two patch tests with 10% aqueous solutions of SLS were applied to adjacent areas o f ventral forearm skin of eighteen volunteers. In one test the water vehicle was allowed to evaporate from the patch test unit before the patches were applied. After 22 hours the patch tests were removed, and 2 hours later the degree of inflammation was graded. Less inflammation was present at the site of the dry patch test in fifteen of eighteen subjects, and the score of inflammation between each pair was significantly less at the dry patch test site (p < 0.001). These studies show that evaportion of water from aqueous solutions can influence the irritating potential of SLS on human skin. (J AM A c a o DERMATOL 11:477-479, 1984.)
A t v a r i o u s times and for various reasons, inv e s t i g a t o r s h a v e applied irritating chemicals to the s k i n o f h u m a n subjects and produced inflammat i o n . T h e d e g r e e o f inflammation elicited from
such tests is highly variable. This variability occurs not only from subject to subject but also from patch test to patch test in individual patients.1-'~'*'t S o m e causes o f this variability h a v e
From the Department of Dermatology, Universityof MinnesotaMedical School. Accepted for publication March 7, 1984. Reprint requests to: Dr. Mark V. Dahl, Box 98 Mayo, Universityof Minnesota Medical School. Minneapolis, MN 55455.
*RietschelRL: Advancesand pitfalls in irritant and allergen testing. ] Soc Cosmet Chem 33:309-313, 1982. 'l'BrownVKH: A comparisonof predictive irritation tests with suffactants on human and animal skin. J Soe Cosmet Chern 22:411-420, 1971. 477
478
Journal of the American Academy of Dermatology
Dahl and Roering
been identified and include regional variation, age, sex, race, environmental temperature, season, sweating, and prior exposure to irritants. G While routinely applying 10% aqueous sodium lauryl sulfate (SLS) patch tests to patients with suspected allergic contact dermatitis who were undergoing routine patch tests for allergy, we observed that the degree of inflammation was less intense when the water vehicle of the patch test evaporated before the patch test was applied. The object Of this study is tO prospectively study the diminished reaction to SLS elicited by dry patch tests in comparison with the reaction to wet ones. M'ETI-IODS The subjects consisted of 18 young adult volunteers. Eleven subjects were men and seven were women. After informed consent was obtained, two patch tests With 25/~1 10% aqueous SLS were applied to the upper inner arm with the use of Al-test patches and B]enderm tape. In one pa!ch test the water in the 10% aqueous SLS solution was allowed to evaporate at room temperature. When the patch was dry, an identical quantity of 10% aqueous SLS was applied to the adjacent patch and the pair of patch tests attached to the subject. In other words, the only difference between the two patches wasthat one of them was dry and the other was wet. Subjects were instructed to keep the patch tests dry. For practical reasons the test sites were evaluated approximately 2 hours after removal--about 24 hours after application. The degree of inflammation was recorded with the use of an eight-point grading scale, as follows: 0 = No visible reaction + = Barely perceptible erythema 1 = Mild erythema 2 = Moderateerythema 3 = Intense erythema 4 = Intense erythema with edema 5 = Intense erythema with edema and vesiculation 6 = Intense erythema with edema and vesicular erosion In practice this resulted in an eight-point grading scale with fairly uniform dermarcations in degree of inflammation observed clinically. The degree of inflammation was determined by one of us (M. V. D.), who had no knowledge of which site was which. The degree of inflammation at the two sites was analyzed by the paired comparison test,
RESULTS The degree of inflammation observed after the application of wet SLS patch tests was greater t h a n that observed with ,dry patch tests. This difference in pairs was significant (p < 0.001). In fifteen o f eighteen subjects the reaction at the wet site w a s greater than the reaction at the dry site. tn the other three, the reaction appeared equal. T h e dominance of reaction at the site of the wet t e s t was present not only 2 hours after patch test removal but also at the time of removal and for at least 24 hours in the subset of subjects who w e r e observed at these times. Only six of the eighteen subjects showed a n y inflammation at the dry patch test site, whereas fifteen of eighteen subjects showed at least s o m e inflammation at the wet test site. The m e a n inflammation score at the dry site was 0.42, a n d the mean score at the wet site was 1.64. DISCUSSION The degree of inflammation observed at sites o f irritant patch tests is highly variable. We recently compared the variability of the degree o f inflammation among replicate patch tests w i t h aqueous SLS in given individual subjects. ~ W e found that great variability existed, especially in comparison to the variability elicited b y similar testing for allergy to Toxicodendron antigen. Others have also found marked variability in t h e degree of inflammation resulting f r o m irritant patch tests.2-~'*'? Some of the reasons for this variability are known , and this subject has recently been reviewed. ~ W e identified one possible cause of variability in the degree of inflammation elicited by patch tests using aqueous solutions of SLS. That variable is evaporation of water from the patch test between the time the test material is applied to the patch test unit and the time the patch test is applied to the skin of the subject. Although one m i g h t *RietschelRL: Advancesand pitfallsin irritantand allergentesting. J Soc CosmetChem33:309-313. 1982. CBrownVKH:A comparisonof predictiveirritationtests withsurfactants on humanand animalskin. J Soc CosmetChem22:411-420, 1971.
Volume I 1 Number 3 September, 1984
Sodium lauryl sulfate irritant patch tests. III
predict that evaporation would increase the relative concentration of SLS and thereby elicit a more intense inflammatory response, this did not occur w h e n the test was completely dry. Instead, c o m p l e t e evaporation s o m e h o w inhibited the inf l a m m a t o r y response in comparison to the response at the wet patch test sites. Presumably e v a p o r a t i o n renders the irritant insoluble or less able to intimately contact the skin, although it is possible that hydration o f the stratum corneum by the wet patch test s o m e h o w changes the barrier function. 6'7 A direct effect on the inflammatory r e s p o n s e seems unlikely. I f irritant patch tests are used to create inflammation or assess inflammatory activity, the conditions m u s t be carefully controlled. If SLS is the irritant and if water in the aqueous vehicle is all o w e d to completely evaporate, then the intensity o f inflammation is likely t o be less than it would h a v e b e e n if evaporation had not occurred. The r e l e v a n c e of these findings to testing with other vehicles and irritants is uncertain. T h e s e findings might also have some clinical significance. Patients with dermatitis often worry that they are not adequately removing soap from
479
their skin or clothing. If irritation f r o m unoccluded soap is similar to irritation f r o m SLS, then irritation f r o m soapy solutions could be more likely than irritation from residual soap on the skin or clothing, given the same amount and duration of contact. REFERENCES i. Dahl MV, Pass F, Trancik RJ: Sodium lauryl sulfate irritant patch tests. II. Variations of test responses among subjects and comparison to variations of allergic responses elicited by Toxicodendron extract, J AM AcAt) DERMATOL 11:474-477, 1984. 2. Bjomberg A: Skin reactions to primary irritants in patients with hand eczema. G6teberg, 1968, Oscar Isacsons Trycheri AB. 3. Frosch PF, KIigman AM: The soap chamber test: A new method for assaying the irritaney of soaps. J A~a ACAD DERMATOL1:35-41, 1979. 4. Frosch PF, Duncan S, Kligman AM: Cutaneous biometrics. I. The response of human skin to dimethyl sulfoxide. Br J Dermatol 102:263-274, 1980. 5. Kligman AM, Wooding WM: A method for the measurement and evaluation of irritants on human skin. J Invest Dermatol 49:78-94, 1967. 6. Mathias CGT, Maibaeh HI: Dermatotoxicology monographs. L Cutaneous irritation: Factors influencing the response to irritants. Clin Toxicol 13:333-346, 1978, 7. Behley FR, Grice KA: The effect of sweating on patch test reactions to soap. Br J Dermatol 78:636, 1966,
ABSTRACTS Detection, isolation, and continuous production of cytopathi c retroviruses (HTLV.III) from patients with AIDS and pre-AIDS Popovic M, Sarngadharan MG, Read E, Gallo RC: Science 224:497-500, 1984 The isolation of the putative etiologic agent of AIDS, human T-lymphotropic retrovirus III, is reported.
J.G.S.
Reduced Langerhans' cell la antigen and ATPase activity in patients with the acquired immun0deficiency syndrome Belsita DV, Sanchez MR, Baer RL, et al: N Engl J Med 310:1279-!282, 1984 In a controlled study, Langerhans ceils were studied in acquired immunodeficiency syndrome (AIDS), pre-AIDS, and controls. A significant reduction of la antigen and ATPase, markers for Langerhans cells, was found in twenty-
four patients with AIDS as compared with thirty-eight controls. Six patients with AIDS-related complex had significant reduction of la antigen but not ATPase activity. The authors postulate that AIDS may represent a generalized loss of antigen-processing ability in dendritic ceils as a mechanism for the immunologic abnormalities in AIDS.
J.G.S.
Live attenuated varicella virus vaccine: :Efficacy trial in healthy children Weibel RE, Neff BJ, Kuter B J, et al: N Engl J Med 3i0:1409-1415, 1984 A doubie-b!ind placebo-controlled efficacy trial of the live attenuated Oka/Merck varicella vaccine was carried out in 956 children aged 1 to 14 years, There were thirty-nine clinically diagnosed cases of varieeUa, thirty-eight were confirmed by laboratory tests, and all occurred in placebo recipients.
J.G.S.
Sodium lauryl sulfate irritant patch tests. II
3. Bruynzeel DP, van Ketel WG, Scheper RJ, et al: Delayed time course of irritation by sodium lauryl sulfate: Observations on threshold reactions. Contact Dermatitis 8:236-239, 1982. 4. Kaidhey KH, Kligman AM: AssaY of topical corticosteroid. Arch Dermatol 112:808-810, 1976. 5. Skog 13, Forsbeck M: Comparison between 24-48 hour exposure time in patch testing. Contact Dermatitis 4:362-364, 1978. 6. Mathias CGT, Maibach HI: Dermatotoxicology. Monograph I. Cutaneous irritation: Factors influencing the response to irritants. Clin Toxieol 13:333-346, 1978.
i
i
i
7. Czerwinska-Dihm I, Rudzki E: Skin reactions to primary irritants. Contact Dermatitis 7:315-319, 1981. 8. Bjornberg A: Skin reactions to primary irritants in patients with hand eczema. G6teberg, I968, Oscar Isacsons Trycked AB. 9. Bruynzeel DP, van Ketel WG, yon Blomberg-van der Flier M, Scheper P,J: Angry back or the excited skin syndrome: A prospective study. J AM ACADDERI~IATOL 8:392-397, 1983. 10. Frosh PJ, Kligman AM: The Duhring chamber: An improved technique for epicutaneous testing of irritant and allergic reactions. Contact Dermatitis 5:73-81, 1979.
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i
i
Sodium lauryl sulfate irritant patch tests. III. Evaporation of aqueous vehicle influences inflammatory response M a r k V. Dahl, M . D . , and Mary Jane Roering, B.S.N~
Minneapolis, MN Patch tests with aqueous solutions of the irritating detergent sodium lauryl sulfate (SLS) elicit varying degrees of inflammation from subject to subject and from site to site, For an investigation of the causes of this variability, two patch tests with 10% aqueous solutions of SLS were applied to adjacent areas o f ventral forearm skin of eighteen volunteers. In one test the water vehicle was allowed to evaporate from the patch test unit before the patches were applied. After 22 hours the patch tests were removed, and 2 hours later the degree of inflammation was graded. Less inflammation was present at the site of the dry patch test in fifteen of eighteen subjects, and the score of inflammation between each pair was significantly less at the dry patch test site (p < 0.001). These studies show that evaportion of water from aqueous solutions can influence the irritating potential of SLS on human skin. (J AM A c a o DERMATOL 11:477-479, 1984.)
A t v a r i o u s times and for various reasons, inv e s t i g a t o r s h a v e applied irritating chemicals to the s k i n o f h u m a n subjects and produced inflammat i o n . T h e d e g r e e o f inflammation elicited from
such tests is highly variable. This variability occurs not only from subject to subject but also from patch test to patch test in individual patients.1-'~'*'t S o m e causes o f this variability h a v e
From the Department of Dermatology, Universityof MinnesotaMedical School. Accepted for publication March 7, 1984. Reprint requests to: Dr. Mark V. Dahl, Box 98 Mayo, Universityof Minnesota Medical School. Minneapolis, MN 55455.
*RietschelRL: Advancesand pitfalls in irritant and allergen testing. ] Soc Cosmet Chem 33:309-313, 1982. 'l'BrownVKH: A comparisonof predictive irritation tests with suffactants on human and animal skin. J Soe Cosmet Chern 22:411-420, 1971. 477
478
Journal of the American Academy of Dermatology
Dahl and Roering
been identified and include regional variation, age, sex, race, environmental temperature, season, sweating, and prior exposure to irritants. G While routinely applying 10% aqueous sodium lauryl sulfate (SLS) patch tests to patients with suspected allergic contact dermatitis who were undergoing routine patch tests for allergy, we observed that the degree of inflammation was less intense when the water vehicle of the patch test evaporated before the patch test was applied. The object Of this study is tO prospectively study the diminished reaction to SLS elicited by dry patch tests in comparison with the reaction to wet ones. M'ETI-IODS The subjects consisted of 18 young adult volunteers. Eleven subjects were men and seven were women. After informed consent was obtained, two patch tests With 25/~1 10% aqueous SLS were applied to the upper inner arm with the use of Al-test patches and B]enderm tape. In one pa!ch test the water in the 10% aqueous SLS solution was allowed to evaporate at room temperature. When the patch was dry, an identical quantity of 10% aqueous SLS was applied to the adjacent patch and the pair of patch tests attached to the subject. In other words, the only difference between the two patches wasthat one of them was dry and the other was wet. Subjects were instructed to keep the patch tests dry. For practical reasons the test sites were evaluated approximately 2 hours after removal--about 24 hours after application. The degree of inflammation was recorded with the use of an eight-point grading scale, as follows: 0 = No visible reaction + = Barely perceptible erythema 1 = Mild erythema 2 = Moderateerythema 3 = Intense erythema 4 = Intense erythema with edema 5 = Intense erythema with edema and vesiculation 6 = Intense erythema with edema and vesicular erosion In practice this resulted in an eight-point grading scale with fairly uniform dermarcations in degree of inflammation observed clinically. The degree of inflammation was determined by one of us (M. V. D.), who had no knowledge of which site was which. The degree of inflammation at the two sites was analyzed by the paired comparison test,
RESULTS The degree of inflammation observed after the application of wet SLS patch tests was greater t h a n that observed with ,dry patch tests. This difference in pairs was significant (p < 0.001). In fifteen o f eighteen subjects the reaction at the wet site w a s greater than the reaction at the dry site. tn the other three, the reaction appeared equal. T h e dominance of reaction at the site of the wet t e s t was present not only 2 hours after patch test removal but also at the time of removal and for at least 24 hours in the subset of subjects who w e r e observed at these times. Only six of the eighteen subjects showed a n y inflammation at the dry patch test site, whereas fifteen of eighteen subjects showed at least s o m e inflammation at the wet test site. The m e a n inflammation score at the dry site was 0.42, a n d the mean score at the wet site was 1.64. DISCUSSION The degree of inflammation observed at sites o f irritant patch tests is highly variable. We recently compared the variability of the degree o f inflammation among replicate patch tests w i t h aqueous SLS in given individual subjects. ~ W e found that great variability existed, especially in comparison to the variability elicited b y similar testing for allergy to Toxicodendron antigen. Others have also found marked variability in t h e degree of inflammation resulting f r o m irritant patch tests.2-~'*'? Some of the reasons for this variability are known , and this subject has recently been reviewed. ~ W e identified one possible cause of variability in the degree of inflammation elicited by patch tests using aqueous solutions of SLS. That variable is evaporation of water from the patch test between the time the test material is applied to the patch test unit and the time the patch test is applied to the skin of the subject. Although one m i g h t *RietschelRL: Advancesand pitfallsin irritantand allergentesting. J Soc CosmetChem33:309-313. 1982. CBrownVKH:A comparisonof predictiveirritationtests withsurfactants on humanand animalskin. J Soc CosmetChem22:411-420, 1971.
Volume I 1 Number 3 September, 1984
Sodium lauryl sulfate irritant patch tests. III
predict that evaporation would increase the relative concentration of SLS and thereby elicit a more intense inflammatory response, this did not occur w h e n the test was completely dry. Instead, c o m p l e t e evaporation s o m e h o w inhibited the inf l a m m a t o r y response in comparison to the response at the wet patch test sites. Presumably e v a p o r a t i o n renders the irritant insoluble or less able to intimately contact the skin, although it is possible that hydration o f the stratum corneum by the wet patch test s o m e h o w changes the barrier function. 6'7 A direct effect on the inflammatory r e s p o n s e seems unlikely. I f irritant patch tests are used to create inflammation or assess inflammatory activity, the conditions m u s t be carefully controlled. If SLS is the irritant and if water in the aqueous vehicle is all o w e d to completely evaporate, then the intensity o f inflammation is likely t o be less than it would h a v e b e e n if evaporation had not occurred. The r e l e v a n c e of these findings to testing with other vehicles and irritants is uncertain. T h e s e findings might also have some clinical significance. Patients with dermatitis often worry that they are not adequately removing soap from
479
their skin or clothing. If irritation f r o m unoccluded soap is similar to irritation f r o m SLS, then irritation f r o m soapy solutions could be more likely than irritation from residual soap on the skin or clothing, given the same amount and duration of contact. REFERENCES i. Dahl MV, Pass F, Trancik RJ: Sodium lauryl sulfate irritant patch tests. II. Variations of test responses among subjects and comparison to variations of allergic responses elicited by Toxicodendron extract, J AM AcAt) DERMATOL 11:474-477, 1984. 2. Bjomberg A: Skin reactions to primary irritants in patients with hand eczema. G6teberg, 1968, Oscar Isacsons Trycheri AB. 3. Frosch PF, KIigman AM: The soap chamber test: A new method for assaying the irritaney of soaps. J A~a ACAD DERMATOL1:35-41, 1979. 4. Frosch PF, Duncan S, Kligman AM: Cutaneous biometrics. I. The response of human skin to dimethyl sulfoxide. Br J Dermatol 102:263-274, 1980. 5. Kligman AM, Wooding WM: A method for the measurement and evaluation of irritants on human skin. J Invest Dermatol 49:78-94, 1967. 6. Mathias CGT, Maibaeh HI: Dermatotoxicology monographs. L Cutaneous irritation: Factors influencing the response to irritants. Clin Toxicol 13:333-346, 1978, 7. Behley FR, Grice KA: The effect of sweating on patch test reactions to soap. Br J Dermatol 78:636, 1966,
ABSTRACTS Detection, isolation, and continuous production of cytopathi c retroviruses (HTLV.III) from patients with AIDS and pre-AIDS Popovic M, Sarngadharan MG, Read E, Gallo RC: Science 224:497-500, 1984 The isolation of the putative etiologic agent of AIDS, human T-lymphotropic retrovirus III, is reported.
J.G.S.
Reduced Langerhans' cell la antigen and ATPase activity in patients with the acquired immun0deficiency syndrome Belsita DV, Sanchez MR, Baer RL, et al: N Engl J Med 310:1279-!282, 1984 In a controlled study, Langerhans ceils were studied in acquired immunodeficiency syndrome (AIDS), pre-AIDS, and controls. A significant reduction of la antigen and ATPase, markers for Langerhans cells, was found in twenty-
four patients with AIDS as compared with thirty-eight controls. Six patients with AIDS-related complex had significant reduction of la antigen but not ATPase activity. The authors postulate that AIDS may represent a generalized loss of antigen-processing ability in dendritic ceils as a mechanism for the immunologic abnormalities in AIDS.
J.G.S.
Live attenuated varicella virus vaccine: :Efficacy trial in healthy children Weibel RE, Neff BJ, Kuter B J, et al: N Engl J Med 3i0:1409-1415, 1984 A doubie-b!ind placebo-controlled efficacy trial of the live attenuated Oka/Merck varicella vaccine was carried out in 956 children aged 1 to 14 years, There were thirty-nine clinically diagnosed cases of varieeUa, thirty-eight were confirmed by laboratory tests, and all occurred in placebo recipients.
J.G.S.