Epidermal barrier in atopic dermatitis

Atopic Dermatitis

Volumn , Issue , 2002, Pages 123-143

  Proksch, Ehrhardt ^a   Elias, Peter M ^b  

^a UNIVERSITY OF KIEL   (Germany)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 14544282318     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (116)

1. Aalto-Korte K. Improvement of skin barrier function during treatment of atopic dermatitis. J Am Acad Dermatol 33:969-972, 1995.
2. Adinoff AD, Tellez P, Clark RA. Atopic dermatitis and aeroallergen contact sensitivity. J Allergy Clin Immunol 81:736-742, 1988.
3. Agner T. Noninvasive measuring methods for the investigation of irritant patch test reactions. A study of patients with hand eczema, atopic dermatitis and controls. Acta Derm Venereol Suppl (Stockh) 173:1-26, 1992.
4. Arlian LG, Neal JS, Morgan MS, Vyszenski-Moher DL, Rapp CM, Alexander AK. Reducing relative humidity is a practical way to control dust mites and their allergens in homes in temperate climates. J Allergy Clin Immunol 107:99-104, 2001.
5. Barba A, Schena D, Andreaus MC, Faccini G, Pasini F, Brocco G, Cavallini G, Scuro LA, Chieregato GC. Intestinal permeability in patients with atopic eczema. Br J Dermatol 120:71-75, 1989.
6. Barth J, Gatti S, Jatzke M. Skin surface lipids in atopic eczema and ichthyosis. Chron Derm 10:609-612, 1989.
7. Behne M, Uchida Y, Seki T, de Montellano PO, Elias PM, Holleran WM. Omega-hydroxyceramides are required for corneocyte lipid envelope (CLE) formation and normal epidermal permeability barrier function. J Invest Dermatol 114:185-192, 2000.
8. Berth-Jones J, Graham-Brown RA. Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis. Lancet 342:564, 1993.
9. Bleck O, Abeck D, Ring J, Hoppe U, Vietzke JP, Wolber R, Brandt O, Schreiner V. Two ceramide subfractions detectable in Cer(AS) position by HPTLC in skin surface lipids of non-lesional skin of atopic eczema. J Invest Dermatol 113:894-900, 1999.
10. Bouwstra JA, Gooris GS, Dubbelaar FE, Weerheim AM, Ijzerman AP, Ponec M. Role of ceramide 1 in the molecular organization of the stratum corneum lipids. J Lipid Res 39:186-196, 1998.
11. Bos JD, Kapsenberg ML, Smitt JH. Pathogenesis of atopic eczema. Lancet 343: 1338-1341, 1994.
12. Burton JL. Dietary fatty acids and inflammatory skin disease. Lancet 1(8628):27-31, 1989.
13. Chamlin SL, Frieden IJ, Fowler A, Williams M, Kao J. Ceramide-dominant barrier repair moisturizer in childhood dermatitis. Submitted.
14. Conti A, Di Nardo A, Seidenari S. No alteration of biophysical parameters in the skin of subjects with respiratory atopy. Dermatology 192:317-320, 1996.
15. Conti A, Seidenari S. No increased skin reactivity in subjects with allergic rhinitis during the active phase of the disease. Acta Derm Venereol 80:192-195, 2000.
16. Cui CY, Kusuda S, Seguchi T, Takahashi M, Aisu K, Tezuka T. Decreased level of prosaposin in atopic skin. J Invest Dermatol 109:319-323, 1997.
17. Denda M, Sato J, Masuda Y, Tsuchiya T, Koyama J, Kuramoto M, Elias PM, Feingold KR. Exposure to a dry environment enhances epidermal permeability barrier function. J Invest Dermatol 111:858-863, 1998.
18. Denda M, Wood LC, Emami S, Calhoun C, Brown BE, Elias PM, Feingold KR. The epidermal hyperplasia associated with repeated barrier disruption by acetone treatment or tape stripping cannot be attributed to increased water loss. Arch Dermatol Res 288:230-238, 1996.
19. Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol 78:27-30, 1998.
20. Doering T, Holleran WM, Potratz A, Vielhaber G, Elias PM, Suzuki K, Sandhoff. Sphingolipid activator proteins are required for epidermal permeability barrier formation. J Biol Chem 274:11038-11045, 1999.
21. Ekanayake-Mudiyanselage S, Aschauer H, Schmook FP, Jensen JM, Meingassner JG, Proksch E. Expression of epidermal keratins and the cornified envelope protein involucrin is influenced by permeability barrier disruption. J Invest Dermatol 111: 517-523, 1998.
22. Elias PM, Brown BE. The mammalian cutaneous permeability barrier: defective barrier function is essential fatty acid deficiency correlates with abnormal intercellular lipid deposition. Lab Invest 39:574-583, 1978.
23. Elias PM, Menon GK. Structural and lipid biochemical correlates of the epidermal permeability barrier. Adv Lipid Res 24:1-26, 1991.
24. Elias PM. Stratum corneum architecture, metabolic activity, and interactivity with subjacent cell layers. Exp Dermatol 5:191-201, 1996.
25. Elias PM, Ansel JC, Woods LC, Feingold KR. Signalling networks in barrier homeostasis: the mystery widens. Arch Dermatol 132:1505-1506, 1996.
26. Elias PM, Wood LC, Feingold KR. Relationship of the epidermal permeability barrier to irritant contact dermatitis. In: Beltrani V, ed. Immunology and Allergy Clinics of North America. Vol. 17. Contact Dermatitis: Irritant and Allergic. Philadelphia: Saunders, 1997, pp 417-430.
27. Elias PM, Wood LC, Feingold KR. Epidermal pathogenesis of inflammatory dermatoses. Am J Contact Derm 10:119-126, 1999.
28. Elias PM, Brown BEJ. The mammalian cutaneous permeability barrier: defective barrier function in essential fatty acid deficiency correlates with abnormal intercellular lipid deposition. Lab Invest 39:574-583, 1978.
29. Fartasch M, Diepgen TL. The barrier function in atopic dry skin. Disturbance of membrane-coating granule exocytosis and formation of epidermal lipids? Acta Derm Venereol Suppl (Stockh) 176:26-31, 1992.
30. Feingold KR. The regulation and role of epidermal lipid synthesis. Adv Lipid Res24:57-82, 1991.
31. Feliciani C, Gupta AK, Sauder DN. Keratinocytes and cytokine/growth factors. Crit Rev Oral Biol Med 7:300-318, 1996.
32. Grubauer G, Feingold KR, Elias PM. The relationship of epidermal lipogenesis to cutaneous barrier function. J Lipid Res 28:746-752, 1987.
33. Grubauer G, Elias PM, Feingold KR. Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res 30:323-334, 1989.
34. Garg A, Chren M-M, Sands LP, Matsui MS, Marenus KD, Feingold KR, Elias PM. Psychological stress perturbs epidermal permeability barrier homeostasis: implications for the pathogenesis and treatment of stress-associated skin disorders. Arch Dermatol 137:53-59, 2001.
35. Gfesser M, Abeck D, Riigemer J, Schreiner V, Stab F, Disch R, Ring J. The early phase of epidermal barrier regeneration is faster in patients with atopic eczema. Dermatology 195:332-336, 1997.
36. Gfesser M, Rakoski J, Ring J. The disturbance of epidermal barrier function in atopy patch test reactions in atopic eczema. Br J Dermatol 135:560-565, 1996.
37. Ghadially R, Halkier-Sorensen L, Elias PM. Effects of petrolatum on stratum cor-neum structure and function. J Am Acad Dermatol 26:387-396, 1992.
38. Hara J, Higuchi K, Okamoto R, Kawashima M, Imokawa G. High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatitis. J Invest Dermatol 115:406-413, 2000.
39. Henz BM, Jablonska S, van de Kerkhof PC, Stingl G, Blaszczyk M, Vandervalk PG, Veenhuizen R, Muggli R, Raederstorff D. Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema. Br J Dermatol 140(4): 685-688, 1999.
40. Higuchi K, Hara J, Okamoto R, Kawashima M, Imokawa G. The skin of atopic dermatitis patients contains a novel enzyme, glucosylceramide sphingomyelin de-acylase, which cleaves the N-acyl linkage of sphingomyelin and glucosylceramide. Biochem J 350:747-756, 2000.
41. Holleran WM, Man MQ, Gao WN, Menon GK, Elias PM, Feingold KR. Sphingo-lipids are required for mammalian epidermal barrier function. Inhibition of sphingo-lipid synthesis delays barrier recovery after acute perturbation. J Clin Invest 88: 1338-1345, 1991.
42. Holleran WM, Takagi Y, Menon GK, Legler G, Feingold KR, Elias PM. Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function. J Clin Invest 91:1656-1664, 1993.
43. Holleran WM, Takagi Y, Menon GK, Jackson SM, Lee JM, Feingold KR, Elias PM. Permeability barrier requirements regulate epidermal beta-glucocerebrosidase. J Lipid Res 35:905-912, 1994.
44. Holleran WM, Gao WN, Feingold KR, Elias PM. Localization of epidermal sphin-golipid synthesis and serine palmitoyl transferase activity: alterations imposed by permeability barrier requirements. Arch Dermatol Res 287:254-258, 1995.
45. Horrobin DF. Essential fatty acid metabolism and its modification in atopic eczema. Am J Clin Nutr 71:367S-372S, 2000.
46. Imokawa G, Abe A, Jin Y, Higaki Y, Kawashima M, Hidano A. Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J Invest Dermatol 96:523-526, 1991.
47. Jakobza D, Reichmann G, Langnick W, Langnick A, Schulze P. [Surface skin lipids in atopic dermatitis (author’s transl)] [article in German]. Dermatol Monatsschr 167:26-29, 1981.
48. Jensen JM, Schutze S, Forl M, Kronke M, Proksch E. Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier. J Clin Invest 104:1761-1770, 1999.
49. Jin K, Higaki Y, Takagi Y, Higuchi K, Yada Y, Kawashima M, Imokawa G. Analysis of beta-glucocerebrosidase and ceramidase activities in atopic and aged dry skin. Acta Derm Venereol 74:337-340, 1994.
50. Komuves LG, Hanley K, Man MQ, Elias PM, Williams ML, Feingold KR. Keratino-cyte differentiation in hyperproliferative epidermis: topical application of PPARal-pha activators restores tissue homeostasis. J Invest Dermatol 115:361-367, 2000.
51. Komuves LG, Hanley K, Lefebvre AM, Man MQ, Ng DC, Bikle DD, Williams ML, Elias PM, Auwerx J, Feingold KR. Stimulation of PPARalpha promotes epidermal keratinocyte differentiation in vivo. J Invest Dermatol 115:353-360, 2000.
52. Kreder D, Krut O, Adam-Klages S, Wiegmann K, Scherer G, Plitz T, Jensen JM, Proksch E, Steinmann J, Pfeffer K, Kronke M. Impaired neutral sphingomyelinase activation and cutaneous barrier repair in FAN-deficient mice. EMBO J 18:2472-2479, 1999.
53. Kusuda S, Cui CY, Takahashi M, Tezuka T. Localization of sphingomyelinase in lesional skin of atopic dermatitis patients. J Invest Dermatol 111:733-738, 1998.
54. Lee SH, Elias PM, Proksch E, Menon GK, Mao-Qiang M, Feingold KR. Calcium and potassium are important regulators of barrier homeostasis in murine epidermis. J Clin Invest 89:530-538, 1992.
55. Loden M, Andersson AC, Lindberg M Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Cano-derm). Br J Dermatol 140:264-267, 1999.
56. Mao-Qiang M, Brown BE, Wu-Pong S, Feingold KR, Elias PM. Exogenous nonphysiologic vs. physiologic lipids. Divergent mechanisms for correction of permeability barrier dysfunction. Arch Dermatol 131:809-816, 1995.
57. Mar A, Tarn M, Jolley D, Marks R. The cumulative incidence of atopic dermatitis in the first 12 months among Chinese, Vietnamese, and Caucasian infants born in Melbourne, Australia. J Am Acad Dermatol 40:597-602, 1999.
58. Marekov LN, Steinert PM. Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope. J Biol Chem 273:17763-17770, 1998.
59. Matsumoto M, Sugiura H, Uehara M. Skin barrier function in patients with completely healed atopic dermatitis. J Dermatol Sci 23:178-182, 2000.
60. Matsumoto Y, Hamashima H, Masuda K, Shiojima K, Sasatsu M, Arai T. The antibacterial activity of plaunotol against Staphylococcus aureus isolated from the skin of patients with atopic dermatitis. Microbios 96:149-155, 1998.
61. Mauro T, Bench G, Sidderas-Haddad E, Feingold K, Elias P, Cullander C. Acute barrier perturbation abolishes the Ca2+ and K+ gradients in murine epidermis: quantitative measurement using PIXE. J Invest Dermatol 111:1198-1201, 1998.
62. Mauro T, Holleran WM, Grayson S, Gao WN, Mao-Qiang M, Kriehuber E, Behne, Feingold KR, Elias PM. Barrier recovery is impeded at neutral pH, independent of ionic effects: implications for extracellular lipid processing. Arch Dermatol Res290:215-222, 1998.
63. McNally NJ, Williams HC, Phillips DR, Smallman-Rayanor M, Lems S, Venn A, Britton J. Atopic eczema and domestic water hardness. Lancet 352:527-531, 1998.
64. Meguro S, Arai Y, Masukawa Y, Uie K, Tokimitsu I. Relationship between covalently bound ceramides and transepidermal water loss (TEWL). Arch Dermatol Res292:463-468, 2000.
65. Melnik B, Hollmann J, Plewig G. Decreased stratum corneum ceramides in atopic individuals—a pathobiochemical factor in xerosis? Br J Dermatol 119:547-549, 1988.
66. Melnik BC, Hollmann J, Erler E, Verhoeven B, Plewig G. Microanalytical screening of all major stratum corneum lipids by sequential high-performance thin-layer chromatography. J Invest Dermatol 92:231-234, 1989.
67. Melnik BC, Plewig G. Is the origin of atopy linked to deficient conversion of omega-6-fatty acids to prostaglandin E1? J Am Acad Dermatol 21:557-563, 1989.
68. Menon GK, Grayson S, Elias PM. Cytochemical and biochemical localization of lipase and sphingomyelinase activity in mammalian epidermis. J Invest Dermatol86:591-597, 1986.
69. Menon GK, Feingold KR, Elias PM. Lamellar body secretory response to barrier disruption. J Invest Dermatol 98:279-289, 1992.
70. Melton JL, Wertz PW, Swartzendruber DC, Downing DT. Effects of essential fatty acid deficiency on epidermal O-acylsphingolipids and transepidermal water loss in young pigs. Biochim Biophys Acta 921:191-197, 1987.
71. Mitchell EB, Crow J, Chapman MD, Jouhal SS, Pope FM, Platts-Mills T. Basophils in allergen-induced patch test sites in atopic dermatitis. Lancet. 16:127-130, 1982.
72. Morse PF, Horrobin DF, Manku MS, Stewart JC, Allen R, Littlewood S, Wright S, Burton J, Gould DJ, Holt PJ, et al. Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and clinical response. Br J Dermatol 121:7590, 1989.
73. Motta S, Monti M, Sesana S, Caputo R, Carelli S, Ghidoni R. Ceramide composition of the psoriatic scale. Biochim Biophys Acta 1182:147-151, 1993.
74. Murata Y, Ogata J, Higaki Y, Kawashima M, Yada Y, Higuchi K, Tsuchiya T, Kawainami S, Imokawa G. Abnormal expression of sphingomyelin acylase in atopic dermatitis: an etiologic factor for ceramide deficiency? J Invest Dermatol106:1242-1249, 1996.
75. Murphy JE, Robert C, Kupper TS. Interleukin-1 and cutaneous inflammation: a crucial link between innate and acquired immunity. J Invest Dermatol 114:602-608, 2000.
76. Mustakallio KK, Kiistala U, Piha HJ, Nieminen E. Epidermal lipids in Besnier’s prurigo (atopic eczema). Ann Med Exp Biol Fenn 45:323-325, 1967.
77. Nassif A, Chan SC, Storrs FJ, Hanifin JM. Abnormal skin irritancy in atopic dermatitis and in atopy without dermatitis. Arch Dermatol 130:1402-1407, 1994.
78. Nemes Z, Marekov LN, Steinert PM. Involucrin cross-linking by transglutaminase 1. Binding to membranes directs residue specificity. J Biol Chem 274:11013-11021, 1999.
79. Nishijima T, Tokura Y, Imokawa G, Seo N, Furukawa F, Takigawa M. Altered permeability and disordered cutaneous immunoregulatory function in mice with acute barrier disruption. J Invest Dermatol 109:175-182, 1997.
80. Ochs HD. The Wiskott-Aldrich syndrome. ClinRev Allergy Immunol 20:61-86,2001.
81. Ogawa H, Yoshiike TJ. A speculative view of atopic dermatitis: barrier dysfunction in pathogenesis. Dermatol Sci 5:197-204, 1993.
82. Ohnishi Y, Okino N, Ito M, Imayama S. Ceramidase activity in bacterial skin flora as a possible cause of ceramide deficiency in atopic dermatitis. Clin Diagn Lab Immunol 6:101-104, 1999.
83. Pagnelli R, Atherton DJ, Levinski RI: Differences between normal and milk allergic subjects in their immune response after milk ingestion. Arch Dis Child 58:201-206, 1983.
84. Pike MG, Heddle RJ, Boulton P, Turner MW, Atherton DJ: Increased intestinal permeability in atopic eczema. J Invest Dermatol 86:101-104, 1986.
85. Proksch E, Feingold KR, Mao-Quiang M, Elias PM. Barrier function regulates epidermal DNA-synthesis. J Clin Invest 87:1668-1673, 1991.
86. Proksch E, Brasch J, Sterry W. Integrity of the permeability barrier regulates epidermal Langerhans cell density. Br J Dermatol 134:630-638, 1996.
87. Proksch E, Brasch J. Influence of epidermal permeability barrier disruption and Langerhans’ cell density on allergic contact dermatitis. Acta Derm Venereol 77: 102-104, 1997.
88. Proksch E, Feingold KR, Elias PM. Epidermal HMG CoA reductase activity in essential fatty acid deficiency: barrier requirements rather than eicosanoid generation regulate cholesterol synthesis. J Invest Dermatol 99:216-220, 1992.
89. Redoules D, Tarroux R, Assalit MF, Peri JJ. Characterisation and assay of five enzymatic activities in the stratum corneum using tape-strippings. Skin Pharmacol Appl Skin Physiol 12:182-192, 1999.
90. Robson KJ, Stewart ME, Michelsen S, Lazo ND, Downing DT. 6-Hydroxy-4-sphingenine in human epidermal ceramides. J Lipid Res 35:2060-2068, 1994.
91. Schafer L, Kragballe K. Abnormalities in epidermal lipid metabolism in 11 patients with atopic dermatitis. J Invest Dermatol 96:10-15, 1991.
92. Schmuth M, Man MQ, Weber F, Gao W, Feingold KR, Fritsch P, Elias PM, Hol-leran WM. Permeability barrier disorder in Niemann-Pick disease: sphingomyelin-ceramide processing required for normal barrier homeostasis. J Invest Dermatol115:459-466, 2000.
93. Schurer NY, Plewig G, Elias PM. Seratum corneum lipid function. Dermatologica 183:77-94, 1991.
94. Scott IR, Harding CR. Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol 115:84-92, 1986.
95. Seguchi T, Cui CY, Kusuda S, Takahashi M, Aisu K, Tezuka T. Decreased expression of filaggrin in atopic skin. Arch Dermatol Res 288:442-446, 1996.
96. Seidenari S, Giusti G. Objective assessment of the skin of children affected by atopic dermatitis: a study of pH, capacitance and TEWL in eczematous and clinically uninvolved skin. Acta Derm Venereol 75:429-433, 1995.
97. Shahidullah M, Raffle EJ, Rimmer AR, Frain-Bell W. Transepidermal water loss in patients with dermatitis. Br J Dermatol 81:722-730, 1969.
98. Spitz JL. Genodermatosis. Baltimore: Williams and Wilkins, 1996, pp 214-215.
99. Swartzendruber DC, Wertz PW, Madison KC, Downing DT. Evidence that the corneocyte has a chemically bound lipid envelope. J Invest Dermatol 88:709-713, 1987.
100. Tabata N, O’Goshi K, Zhen YX, Kligman AM, Tagami H. Biophysical assessment of persistent effects of moisturizers after their daily applications: evaluation of cor-neotherapy. Dermatology 200:308-313, 2000.
101. Taieb A. Hypothesis: from barrier dysfunction to atopic disorders. Contact Dermatitis 41:177-180, 1999.
102. Tupker RA, Pinnagoda J, Coenraads PJ, Nater JP. Susceptibility to irritants: role of barrier function, skin dryness and history of atopic dermatitis. Br J Dermatol123:199-205, 1990.
103. Uchida Y, Hara M, Nishio H, Sidransky E, Inoue S, Otsuka F, Suzuki A, Elias PM, Holleran WM, Hamanaka S. Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. J Lipid Res 41:2071-2082, 2000.
104. Ukabam SO, Mann RJ, Cooper BT. Small intestinal permeability to sugars in patients with atopic eczema. Br J Dermatol 110:649-652, 1984.
105. Vanselow NA, Yamate M, Adams MS, Callies Q. The increased prevalence of allergic disease in anhidrotic congenital ectodermal dysplasia. J Allergy 45:302-309, 1970.
106. Werner Y, Lindberg M. Transepidermal water loss in dry and clinically normal skin in patients with atopic dermatitis. Acta Derm Venereol 65:102-105, 1985.
107. Wertz PW, Cho ES, Downing DT. Effect of essential fatty acid deficiency on the epidermal sphingolipids of the rat. Biochim Biophys Acta 753:350-355, 1983.
108. Wertz PW, Downing DT. Covalent attachment of omega-hydroxyacid derivatives to epidermal macromolecules: a preliminary characterization. Biochem Biophys Res Commun 137:992-997, 1986.
109. Wertz PW, Swartzendruber DC, Abraham W, Madison KC, Downing DT. Essential fatty acids and epidermal integrity. Arch Dermatol 123:1381-1384, 1987.
110. Wertz PW, Swartzendruber DC, Kitko DJ, Madison KC, Downing DT. The role of the corneocyte lipid envelopes in cohesion of the stratum corneum. J Invest Dermatol 93:169-172, 1989.
111. Williams HC, Forsdyke H, Boodoo G, Hay RJ, Burney PG. A protocol for recording the sign of flexural dermatitis in children. Br J Dermatol 133:941-949, 1995.
112. Williams HC. Atopic eczema. Br Med J 311:1241-1242, 1995.
113. Wood LC, Jackson SM, Elias PM, Grunfeld C, Feingold KR. Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. J Clin Invest90:482-487, 1992.
114. Wood LC, Elias PM, Calhoun C, Tsai J-C, Grunfeld C, Feingold KR. Barrier disruption stimulates interleukin-1 alpha expression and release from a preformed pool in murine epidermis. J Invest Dermatol 106:397-403, 1996.
115. Yamamoto A, Serizawa S, Ito M, Sato Y. Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res 283:219-223, 1991.
116. Yoshiike T, Aikawa Y, Sindhvananda J, Suto H, Nishimura K, Kawamoto T, Ogawa H. Skin barrier defect in atopic dermatitis: increased permeability of the stratum corneum using dimethyl sulfoxide and theophylline. J Dermatol Sci 5:9296, 1993.