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Etretinate increases carcinoembryonic antigen in palmar scrapings
Journal of the American Academy of Dermatology
Dutrbe-Meulenberg et al. 21. Kaaber S, Thulin H, Nielsen E. Skin sensitivity to denture base materials in the burning mouth syndrome. Contact Dermatitis 1979;5:90-6. 22. Tosti A, Bardazzi F, Piancastelli E. Contact stomatitis due to N,N-dimethyl-para-toluidine. Contact Dermatitis 1990; 22:113. 23. Van Loon LAJ, van Elsas PW, van Joost Th, et al. Test battery for metal allergy in dentistry. Contact Dermatitis 1986;14:158-61. 24. Van den Akker ThW, Roesyanto-Mahadi ID, van Toorenenbergen AW, et al. Contact allergy to spices. Contact Dermatitis 1990;22:267-72. 25. Vittek J, Hernandez MR, Wenk E J, et al. Specific estrogen receptors in human gingiva. J Clin Endocrinol Metab 1982;54:608-12. 26. Dani~ls TE, Talal N. Diagnosis and differential diagnosis of Sjrgren's syndrome. In: Talal N, Moutsopoulos HM, Kassan SS, eds. Sjrgren's syndrome. Berlin: Springer Vetlag, 1987:193-9. 27. Dani~ls TE. Labial salivary gland biopsy in Sjrgren's syn-
28. 29.
30. 31. 32, 33.
drome. Assessment as a diagnostic criterion in 362 suspected cases. Arthritis Rheum 1984;27:147-56. Van Loon LAJ, Van Elzas PW, van Joost Th, et al. Contact stomatitis and dermatitis to nickel and palladiuml Contact Dermatitis 1984;11:294-7. Huggett R, Brooks SC, Bates JF. The effect of different curing cycles on levels of residual monomer in acrylic resin denture base materials. Quintessence Dent Technol 1984;8:356-71. Verschuren GLA, Bruijnzeel DP. Allergy to N,N-dimethyl-p-toluidine in dental materials. Contact Dermatitis 1991;24:149. Lamey PJ, Lewis MAO. Oral medicine in practice: orofacial allergic reactions. Br Dent J 1990;168:59-63. Todd P, Garioch J, Lamey P J, et al. Patch testing in liehenoid reactions of the lnouth and oral lichen planus. Contact Dermatitis 1990;23:300-1. Dooms-Goossens A, Dubelloy R, Degreef H. Contact and systemic contact-type dermatitis to spices. Dermatol Clin 1990;8:89-93.
Etretinate increases carcinoembryonic antigen in palmar scrapings Neal S. Penneys, MD, PhD, Richard Taylor, MD, and D. Hernandez MiamL Florida
Background: Retinoids can affect epithelial structure and function. Patients who take etretinate can develop stickiness o f their palms and soles. Objective: W e measured carcinoembryonic antigen, a representative glycoprotein in palmar scrapings, to see whether levels were increased in patients taking etretinate when compared
with a variety of controls. Methods: Carcinoembryonic antigen was measured by a standard immunoassayin scrapings taken from the palm.
Results: Carcinoembryonic antigen is increased in palmar scrapings in patients taking etretinate. Conclusion: Etretinate usage may affect sweat gland function or possibly adherence of carcinoembryonic antigen to surface keratinocytes. The presence of increased amounts of glycoprotein on the surface of the skin may explain the stickinessoften noted by patients taking etretinate. (J AM ACAD DERMATOL 1992;26:'940-2.)
We recently described a m a n with a curious complaint while taking etretinate to manage severe psoriasis.t He noted an annoying stickiness of the palms and soles and observed that materials adhered to From the Department of Dermatology and Dermatologie Surgery, University of Miami School of Medicine. Accepted for publication Dec. 26, 1991. Reprint requests: Neal S. Penneys,MD, PhD, Divisionof Dermatology, St. Louis University School of Medicine, 1402S. Grand, St. Louis, MO 63104.
1~i/1/358~8 940
these surfaces (Fig. t). We hypothesized that the stickiness could be related to the adherence of sweat glycoproteins to surface stratum corneum. In this patient, we documented increased levels of carcinoembryonic antigen (CEA) in palmar scrapings. By immunohistochemical means, CEA was found in palmar skin only in eccrine gland, duct, and acrosyringium, suggesting that its presence in palmar scrapings is secondary to secretion from the eccrine gland. Furthermore, as the dosage of etretinate was reduced in this patient, the levels of CEA in palmar
Volmne 26
Number 6 June 1992
Etretinate increases CEA in palm serapings
941
scrapings approached those of untreated control subjects, which suggests a dose-response phenomenon. We extend our observations by studying a series of patients taking etretinat e tO manage psoriasis and comparing them to normal control subjects, untreated psoriatic control subjects, and methotrexatetreated psoriatic Control subjects to determine whether CEA levels in palmar scrapings are altered in the etretinate-treated group. MATERIAL AND METHODS Palmar scrapings were obtained from the thenar eminence and placed in 0.5 ml of distilled water. We attempted to obtain similar amounts of stratum corneum in each sample. Scrapings were obtained from 11 normal control subjects, 9 untreated psoriasis control subjects, 7 psoriasis patients receiving etretinate, and 4 psoriasis patients receiving methotrexate. The palms were unaffected in all patients. Oral methotrexate dosages varied between 2.5 and 10 mg per week; etretinate schedules varied between 25 and 50 mg daily. CEA levels were determined with the IMX method (Abbott Laboratories, Abbott Park, Ill.) with standard techniques.2 Data were analyzed with the Minitab statistics program and a test for analysis of variance. RESULTS
The results are summarized in Table I. There were no significant differences between the levels of C E A measured in palmar scrapings of normal controls, untreated psoriasis controls, and psoriasis patients treated with methotrexate. C E A levels in the palmar scrapings of subjects receiving etretinate were significantly increased when compared with those in all other groups. DISCUSSION Several glycoproteins have been identified in eccrine sweat by gel filtration and electrophoretic methods. 36 Although the contents of eccrine sweat are not completely defined, serum albumin, al-antitrypsin, CEA, zinc-o~2-glycoprotein, lysozyme, orosomucoid, transferrin, IgG, and IgA have been identified. W e hypothesized that the stickiness noted occasionally by patients ingesting etretinate represents an alteration in eccrine gland function with the secretion of increased amounts of proteinaceous material. We measured one of these, CEA, 3 eluted from palmar stratum corneum scrapings. CEA was selected because of a well-standardized immunoassay
Fig. 1. A sheet of paper adheres to sole of patient who is taking 75 mg of etretinate daily and who complains that materials adhere to his palms and soles.
available for its measurement. 2 Because a reproducible method for collection of samples could not be devised, we designated one person to collect aU specimens, in this way minimizing variations in cop lection size from person to person. Our results confirm an earlier observation that etretinate alters surface levels of CEA. Because palmar skin does not contain sebaceous gland or hair follicles, the effects of etretinate on these adnexae can be excluded. Our results do not preclude the possibilities that etretinate can alter the concentration of other materials in sweat not measured or that etretinate can directly affect ker atinocytes (although CEA could not be demonstrated in keratinoeytes by immunohistochemical methods).
942
Journal of the American Academy of Dermatology
Penneys etal.
Table I. Statistical evaluation of treatment groups Treatmentgroup Normal control Psoriasis Psoriasis and methotrexate Psoriasis and etretinate
I
Mean CEA
Standard deviation
0.882 1.100 1.120 10.500
0.721 1.230 0.383 6.650
I .... t Value,
I.
3.81 3.69 3.72 --
p Value* 0.0088 0.0100 0.0098
*Two-sided t test compared with psoriasis and etretinate group.
We conclude that increased quantities of CEA, and possibly other glycoproteins, may be present in the stratum corneum of the palms and soles of patients taking etretinate. We believe that our finding explains in part the curious symptom of sticky palms and soles. REFERENCES 1. Penneys NS, Hernandez D. Etretinate and sticky palms [Letter]. N Engl J Med 1991;325:521. 2. IMX System. Abbott Laboratories, Diagnostics Division, Abbott Park, Ill, 1990.
3. Rubin RW, Penneys NS. Subpicogram analysis of sweat proteins using two-dimensional polyacrylamide gel electrophoresis. Anal Biochem 1983;131:520-4. 4. Nakayashild N. Sweat protein components tested by SDSpolyaerylamidegel electrophoresis followed by immunoblotring, Tohoku J Exp Med 1990;161:25-31. 5. Penneys NS, Nadji M, McKinney EC. Carcinoembryonic antigen present in human eccrine sweat. J AM ACAD DERMATOL 1981;4:401-3. 6. Yanagawa S, Yokozeki H, Sate K. Origin of periodic acidSehiff-reactive glycoprotein in human eccrine sweat. J Appl Physiol 1986;60:1615-22.
BOUND VOLUMES AVAILABLETO SUBSCRIBERS
Bound volumesof the JOURNALOFTHEAMERICANACADEMYOF DERMATOLOGYare availableto subscribers (only) for the 1992 issues from the Publisherat a cost of $66.00 for domestic,$88.62 for Canadian, and $84.00 for international for volume 26 (January-June) and volume 27 (July-December).Shipping chargesare included.Each bound volume contains a subject and author index and all advertising is removed. Copiesare shipped within 60 days after publicationof the last issue in the volume.The binding is durable buckram with the journal name, volumenumber, and year stamped in gold on the spine. Payment mu.rt accompany all orders. Contact Mosby-Year Book, Inc., SubseriptibnServices, 11830 Westline Industrial Dr., St. Louis, MO 63146-3318. USA: phone (800) 325-4177, ext. 4351; (314) 453-4351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular journal ¢ubscription.
Dutrbe-Meulenberg et al. 21. Kaaber S, Thulin H, Nielsen E. Skin sensitivity to denture base materials in the burning mouth syndrome. Contact Dermatitis 1979;5:90-6. 22. Tosti A, Bardazzi F, Piancastelli E. Contact stomatitis due to N,N-dimethyl-para-toluidine. Contact Dermatitis 1990; 22:113. 23. Van Loon LAJ, van Elsas PW, van Joost Th, et al. Test battery for metal allergy in dentistry. Contact Dermatitis 1986;14:158-61. 24. Van den Akker ThW, Roesyanto-Mahadi ID, van Toorenenbergen AW, et al. Contact allergy to spices. Contact Dermatitis 1990;22:267-72. 25. Vittek J, Hernandez MR, Wenk E J, et al. Specific estrogen receptors in human gingiva. J Clin Endocrinol Metab 1982;54:608-12. 26. Dani~ls TE, Talal N. Diagnosis and differential diagnosis of Sjrgren's syndrome. In: Talal N, Moutsopoulos HM, Kassan SS, eds. Sjrgren's syndrome. Berlin: Springer Vetlag, 1987:193-9. 27. Dani~ls TE. Labial salivary gland biopsy in Sjrgren's syn-
28. 29.
30. 31. 32, 33.
drome. Assessment as a diagnostic criterion in 362 suspected cases. Arthritis Rheum 1984;27:147-56. Van Loon LAJ, Van Elzas PW, van Joost Th, et al. Contact stomatitis and dermatitis to nickel and palladiuml Contact Dermatitis 1984;11:294-7. Huggett R, Brooks SC, Bates JF. The effect of different curing cycles on levels of residual monomer in acrylic resin denture base materials. Quintessence Dent Technol 1984;8:356-71. Verschuren GLA, Bruijnzeel DP. Allergy to N,N-dimethyl-p-toluidine in dental materials. Contact Dermatitis 1991;24:149. Lamey PJ, Lewis MAO. Oral medicine in practice: orofacial allergic reactions. Br Dent J 1990;168:59-63. Todd P, Garioch J, Lamey P J, et al. Patch testing in liehenoid reactions of the lnouth and oral lichen planus. Contact Dermatitis 1990;23:300-1. Dooms-Goossens A, Dubelloy R, Degreef H. Contact and systemic contact-type dermatitis to spices. Dermatol Clin 1990;8:89-93.
Etretinate increases carcinoembryonic antigen in palmar scrapings Neal S. Penneys, MD, PhD, Richard Taylor, MD, and D. Hernandez MiamL Florida
Background: Retinoids can affect epithelial structure and function. Patients who take etretinate can develop stickiness o f their palms and soles. Objective: W e measured carcinoembryonic antigen, a representative glycoprotein in palmar scrapings, to see whether levels were increased in patients taking etretinate when compared
with a variety of controls. Methods: Carcinoembryonic antigen was measured by a standard immunoassayin scrapings taken from the palm.
Results: Carcinoembryonic antigen is increased in palmar scrapings in patients taking etretinate. Conclusion: Etretinate usage may affect sweat gland function or possibly adherence of carcinoembryonic antigen to surface keratinocytes. The presence of increased amounts of glycoprotein on the surface of the skin may explain the stickinessoften noted by patients taking etretinate. (J AM ACAD DERMATOL 1992;26:'940-2.)
We recently described a m a n with a curious complaint while taking etretinate to manage severe psoriasis.t He noted an annoying stickiness of the palms and soles and observed that materials adhered to From the Department of Dermatology and Dermatologie Surgery, University of Miami School of Medicine. Accepted for publication Dec. 26, 1991. Reprint requests: Neal S. Penneys,MD, PhD, Divisionof Dermatology, St. Louis University School of Medicine, 1402S. Grand, St. Louis, MO 63104.
1~i/1/358~8 940
these surfaces (Fig. t). We hypothesized that the stickiness could be related to the adherence of sweat glycoproteins to surface stratum corneum. In this patient, we documented increased levels of carcinoembryonic antigen (CEA) in palmar scrapings. By immunohistochemical means, CEA was found in palmar skin only in eccrine gland, duct, and acrosyringium, suggesting that its presence in palmar scrapings is secondary to secretion from the eccrine gland. Furthermore, as the dosage of etretinate was reduced in this patient, the levels of CEA in palmar
Volmne 26
Number 6 June 1992
Etretinate increases CEA in palm serapings
941
scrapings approached those of untreated control subjects, which suggests a dose-response phenomenon. We extend our observations by studying a series of patients taking etretinat e tO manage psoriasis and comparing them to normal control subjects, untreated psoriatic control subjects, and methotrexatetreated psoriatic Control subjects to determine whether CEA levels in palmar scrapings are altered in the etretinate-treated group. MATERIAL AND METHODS Palmar scrapings were obtained from the thenar eminence and placed in 0.5 ml of distilled water. We attempted to obtain similar amounts of stratum corneum in each sample. Scrapings were obtained from 11 normal control subjects, 9 untreated psoriasis control subjects, 7 psoriasis patients receiving etretinate, and 4 psoriasis patients receiving methotrexate. The palms were unaffected in all patients. Oral methotrexate dosages varied between 2.5 and 10 mg per week; etretinate schedules varied between 25 and 50 mg daily. CEA levels were determined with the IMX method (Abbott Laboratories, Abbott Park, Ill.) with standard techniques.2 Data were analyzed with the Minitab statistics program and a test for analysis of variance. RESULTS
The results are summarized in Table I. There were no significant differences between the levels of C E A measured in palmar scrapings of normal controls, untreated psoriasis controls, and psoriasis patients treated with methotrexate. C E A levels in the palmar scrapings of subjects receiving etretinate were significantly increased when compared with those in all other groups. DISCUSSION Several glycoproteins have been identified in eccrine sweat by gel filtration and electrophoretic methods. 36 Although the contents of eccrine sweat are not completely defined, serum albumin, al-antitrypsin, CEA, zinc-o~2-glycoprotein, lysozyme, orosomucoid, transferrin, IgG, and IgA have been identified. W e hypothesized that the stickiness noted occasionally by patients ingesting etretinate represents an alteration in eccrine gland function with the secretion of increased amounts of proteinaceous material. We measured one of these, CEA, 3 eluted from palmar stratum corneum scrapings. CEA was selected because of a well-standardized immunoassay
Fig. 1. A sheet of paper adheres to sole of patient who is taking 75 mg of etretinate daily and who complains that materials adhere to his palms and soles.
available for its measurement. 2 Because a reproducible method for collection of samples could not be devised, we designated one person to collect aU specimens, in this way minimizing variations in cop lection size from person to person. Our results confirm an earlier observation that etretinate alters surface levels of CEA. Because palmar skin does not contain sebaceous gland or hair follicles, the effects of etretinate on these adnexae can be excluded. Our results do not preclude the possibilities that etretinate can alter the concentration of other materials in sweat not measured or that etretinate can directly affect ker atinocytes (although CEA could not be demonstrated in keratinoeytes by immunohistochemical methods).
942
Journal of the American Academy of Dermatology
Penneys etal.
Table I. Statistical evaluation of treatment groups Treatmentgroup Normal control Psoriasis Psoriasis and methotrexate Psoriasis and etretinate
I
Mean CEA
Standard deviation
0.882 1.100 1.120 10.500
0.721 1.230 0.383 6.650
I .... t Value,
I.
3.81 3.69 3.72 --
p Value* 0.0088 0.0100 0.0098
*Two-sided t test compared with psoriasis and etretinate group.
We conclude that increased quantities of CEA, and possibly other glycoproteins, may be present in the stratum corneum of the palms and soles of patients taking etretinate. We believe that our finding explains in part the curious symptom of sticky palms and soles. REFERENCES 1. Penneys NS, Hernandez D. Etretinate and sticky palms [Letter]. N Engl J Med 1991;325:521. 2. IMX System. Abbott Laboratories, Diagnostics Division, Abbott Park, Ill, 1990.
3. Rubin RW, Penneys NS. Subpicogram analysis of sweat proteins using two-dimensional polyacrylamide gel electrophoresis. Anal Biochem 1983;131:520-4. 4. Nakayashild N. Sweat protein components tested by SDSpolyaerylamidegel electrophoresis followed by immunoblotring, Tohoku J Exp Med 1990;161:25-31. 5. Penneys NS, Nadji M, McKinney EC. Carcinoembryonic antigen present in human eccrine sweat. J AM ACAD DERMATOL 1981;4:401-3. 6. Yanagawa S, Yokozeki H, Sate K. Origin of periodic acidSehiff-reactive glycoprotein in human eccrine sweat. J Appl Physiol 1986;60:1615-22.
BOUND VOLUMES AVAILABLETO SUBSCRIBERS
Bound volumesof the JOURNALOFTHEAMERICANACADEMYOF DERMATOLOGYare availableto subscribers (only) for the 1992 issues from the Publisherat a cost of $66.00 for domestic,$88.62 for Canadian, and $84.00 for international for volume 26 (January-June) and volume 27 (July-December).Shipping chargesare included.Each bound volume contains a subject and author index and all advertising is removed. Copiesare shipped within 60 days after publicationof the last issue in the volume.The binding is durable buckram with the journal name, volumenumber, and year stamped in gold on the spine. Payment mu.rt accompany all orders. Contact Mosby-Year Book, Inc., SubseriptibnServices, 11830 Westline Industrial Dr., St. Louis, MO 63146-3318. USA: phone (800) 325-4177, ext. 4351; (314) 453-4351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular journal ¢ubscription.