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Podophyllin Therapy in Acanthosis Nigricans
PRELIMINARY AND SHORT REPORTS PODOPHYLLIN THERAPY IN ACANTHOSIS NIGRICANS ERVIN EPSTEIN, M.D.
Obviously, removing the cutaneous lesions of the adult form of acanthosis nigricans is not
of import alice. This entity is fatal because of an underlying malignancy. While the cutaneous manifestations may be disfiguring and uncomfortable, their presence is of diagnostic rather than prognostic significance. However, this case is being presented with the hope that this therapeutic approach will be utilized in cases of juvenile acanthosis nigricans. The removal of the verrucous growths in such cases may be of psychologic henefit. This attempt was stimulated by the successful use of podophyllin in condylomata acuminata as first re-
ported by Kaplan'. REPORT OP CASE
Mrs. L. B., 72 year old white housewife, developed a severe inflammatory eruption of her submammary areas and groins in April of 1948. The lesions were erythematoua and edematous with some tendency toward weeping. By May 7th, pigmentation and warty growths had started in these areas. Three weeks later, rapidly growing masses of discreto. tiny warts were noted on the fingers. These failed to respond to treatment with light electrodesiccation and trichloroacetic acid. By the middle of June, the process had spread to her mouth,
ears, cubital fossae, back and feet. The clinical and histologic diagnosis was acanthosis nigricans. The patient was presented before the San Francisco DermatoloEic Society on September 17th and all members present agreed with this diagnosis. In 1944, a tumor had been removed from her pelvis and a diagnosis of adenocarcinoma of the ovary made. However, there were no symptoms referrable to a malianancy until October 1948, when weakness and loss of weight developed. In September 1948, an exploratory laparotomy was performed and the operating surgeon stated that the peritoneum and all of the
intra-abdominal viscera were studded with metastases. A biopsy of the metastases at this time showed changes of adenocarcinoma. The patient died on December 27, 1948. 20% podophyllin in alcohol was painted on some of the lesions on the hands on September 27, 1948. A rather severe reaction developed, but three days later, the treated areas were
completely smooth. Because the patient complained bitterly of the local reaction and because there did not seem to he much point to the treatment, it was not repeated. The warty lesions slowly regrew in the treated areas. COMMENT
As stated previously, treatment of the skin lesions in this form of acanthosis nigricans is not necessary. Furthermore, the results obtained in one patient are without real significance. On the other hand, this report does suggest that if the juvenile and adult forms of acanthosis nigricans are identical, the disfiguring lesions of the former type may respond also to local podophyllin therapy. SUMMARY
The cutaneous manifestations in a woman with the adult form of acanthosis nigricans responded dramatically but temporarily to the local application of 20% podophyllin in alcohol. It is suggested that this treatment may be of value in the benign form of this disease.
REFERENCE 1. KAPLAN, I. W.: Condylomata acuminata. New Orleans M. & S. J. 94: 338, 1942.
Received for publication March 19, 1951.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
94
linolenic acid extract. Arch. This pdf is a scanned copy UV of irradiated a printed document.
24. Wynn, C. H. and Iqbal, M.: Isolation of rat
skin lysosomes and a comparison with liver Path., 80: 91, 1965. and spleen lysosomes. Biochem. J., 98: lOP, 37. Nicolaides, N.: Lipids, membranes, and the 1966.
human epidermis, p. 511, The Epidermis
Eds., Montagna, W. and Lobitz, W. C. Acascopic localization of acid phosphatase in demic Press, New York. human epidermis. J. Invest. Derm., 46: 431, 38. Wills, E. D. and Wilkinson, A. E.: Release of 1966. enzymes from lysosomes by irradiation and 26. Rowden, C.: Ultrastructural studies of kerathe relation of lipid peroxide formation to tinized epithelia of the mouse. I. Combined enzyme release. Biochem. J., 99: 657, 1966. electron microscope and cytochemical study 39. Lane, N. I. and Novikoff, A. B.: Effects of of lysosomes in mouse epidermis and esoarginine deprivation, ultraviolet radiation and X-radiation on cultured KB cells. J. phageal epithelium. J. Invest. Derm., 49: 181, 25. Olson, R. L. and Nordquist, R. E.: Ultramicro-
No warranty is given about the accuracy of the copy.
Users should refer to the original published dermal cells. Nature, 216: 1031, 1967. version of1965. the material. vest. Derm., 45: 448, 28. Hall, J. H., Smith, J. G., Jr. and Burnett, S. 41. Daniels, F., Jr. and Johnson, B. E.: In prepa1967.
Cell Biol., 27: 603, 1965.
27. Prose, P. H., Sedlis, E. and Bigelow, M.: The 40. Fukuyama, K., Epstein, W. L. and Epstein, demonstration of lysosomes in the diseased J. H.: Effect of ultraviolet light on RNA skin of infants with infantile eczema. J. Inand protein synthesis in differentiated epi-
C.: The lysosome in contact dermatitis: A ration. histochemical study. J. Invest. Derm., 49: 42. Ito, M.: Histochemical investigations of Unna's oxygen and reduction areas by means of 590, 1967. 29. Pearse, A. C. E.: p. 882, Histochemistry Theoultraviolet irradiation, Studies on Melanin, retical and Applied, 2nd ed., Churchill, London, 1960.
30. Pearse, A. C. E.: p. 910, Histacheini.stry Thearetscal and Applied, 2nd ed., Churchill, London, 1960.
31. Daniels, F., Jr., Brophy, D. and Lobitz, W. C.: Histochemical responses of human skin fol-
lowing ultraviolet irradiation. J. Invest. Derm.,37: 351, 1961.
32. Bitensky, L.: The demonstration of lysosomes by the controlled temperature freezing section method. Quart. J. Micr. Sci., 103: 205, 1952.
33. Diengdoh, J. V.: The demonstration of lysosomes in mouse skin. Quart. J. Micr. Sci., 105: 73, 1964.
34. Jarret, A., Spearman, R. I. C. and Hardy, J. A.:
Tohoku, J. Exp. Med., 65: Supplement V, 10, 1957.
43. Bitcnsky, L.: Lysosomes in normal and pathological cells, pp. 362—375, Lysasames Eds., de Reuck, A. V. S. and Cameron, M. Churchill, London, 1953.
44. Janoff, A. and Zweifach, B. W.: Production of inflammatory changes in the microcirculation by cationic proteins extracted from lysosomes. J. Exp. Med., 120: 747, 1964.
45. Herion, J. C., Spitznagel, J. K., Walker, R. I. and Zeya, H. I.: Pyrogenicity of granulocyte lysosomes. Amer. J. Physiol., 211: 693, 1966.
46. Baden, H. P. and Pearlman, C.: The effect of ultraviolet light on protein and nucleic acid synthesis in the epidermis. J. Invest. Derm.,
Histochemistry of keratinization. Brit. J. 43: 71, 1964. Derm., 71: 277, 1959. 35. De Duve, C. and Wattiaux, R.: Functions of 47. Bullough, W. S. and Laurence, E. B.: Mitotic control by internal secretion: the role of lysosomes. Ann. Rev. Physiol., 28: 435, 1966. the chalone-adrenalin complex. Exp. Cell. 36. Waravdekar, V. S., Saclaw, L. D., Jones, W. A. and Kuhns, J. C.: Skin changes induced by
Res., 33: 176, 1964.
Obviously, removing the cutaneous lesions of the adult form of acanthosis nigricans is not
of import alice. This entity is fatal because of an underlying malignancy. While the cutaneous manifestations may be disfiguring and uncomfortable, their presence is of diagnostic rather than prognostic significance. However, this case is being presented with the hope that this therapeutic approach will be utilized in cases of juvenile acanthosis nigricans. The removal of the verrucous growths in such cases may be of psychologic henefit. This attempt was stimulated by the successful use of podophyllin in condylomata acuminata as first re-
ported by Kaplan'. REPORT OP CASE
Mrs. L. B., 72 year old white housewife, developed a severe inflammatory eruption of her submammary areas and groins in April of 1948. The lesions were erythematoua and edematous with some tendency toward weeping. By May 7th, pigmentation and warty growths had started in these areas. Three weeks later, rapidly growing masses of discreto. tiny warts were noted on the fingers. These failed to respond to treatment with light electrodesiccation and trichloroacetic acid. By the middle of June, the process had spread to her mouth,
ears, cubital fossae, back and feet. The clinical and histologic diagnosis was acanthosis nigricans. The patient was presented before the San Francisco DermatoloEic Society on September 17th and all members present agreed with this diagnosis. In 1944, a tumor had been removed from her pelvis and a diagnosis of adenocarcinoma of the ovary made. However, there were no symptoms referrable to a malianancy until October 1948, when weakness and loss of weight developed. In September 1948, an exploratory laparotomy was performed and the operating surgeon stated that the peritoneum and all of the
intra-abdominal viscera were studded with metastases. A biopsy of the metastases at this time showed changes of adenocarcinoma. The patient died on December 27, 1948. 20% podophyllin in alcohol was painted on some of the lesions on the hands on September 27, 1948. A rather severe reaction developed, but three days later, the treated areas were
completely smooth. Because the patient complained bitterly of the local reaction and because there did not seem to he much point to the treatment, it was not repeated. The warty lesions slowly regrew in the treated areas. COMMENT
As stated previously, treatment of the skin lesions in this form of acanthosis nigricans is not necessary. Furthermore, the results obtained in one patient are without real significance. On the other hand, this report does suggest that if the juvenile and adult forms of acanthosis nigricans are identical, the disfiguring lesions of the former type may respond also to local podophyllin therapy. SUMMARY
The cutaneous manifestations in a woman with the adult form of acanthosis nigricans responded dramatically but temporarily to the local application of 20% podophyllin in alcohol. It is suggested that this treatment may be of value in the benign form of this disease.
REFERENCE 1. KAPLAN, I. W.: Condylomata acuminata. New Orleans M. & S. J. 94: 338, 1942.
Received for publication March 19, 1951.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
94
linolenic acid extract. Arch. This pdf is a scanned copy UV of irradiated a printed document.
24. Wynn, C. H. and Iqbal, M.: Isolation of rat
skin lysosomes and a comparison with liver Path., 80: 91, 1965. and spleen lysosomes. Biochem. J., 98: lOP, 37. Nicolaides, N.: Lipids, membranes, and the 1966.
human epidermis, p. 511, The Epidermis
Eds., Montagna, W. and Lobitz, W. C. Acascopic localization of acid phosphatase in demic Press, New York. human epidermis. J. Invest. Derm., 46: 431, 38. Wills, E. D. and Wilkinson, A. E.: Release of 1966. enzymes from lysosomes by irradiation and 26. Rowden, C.: Ultrastructural studies of kerathe relation of lipid peroxide formation to tinized epithelia of the mouse. I. Combined enzyme release. Biochem. J., 99: 657, 1966. electron microscope and cytochemical study 39. Lane, N. I. and Novikoff, A. B.: Effects of of lysosomes in mouse epidermis and esoarginine deprivation, ultraviolet radiation and X-radiation on cultured KB cells. J. phageal epithelium. J. Invest. Derm., 49: 181, 25. Olson, R. L. and Nordquist, R. E.: Ultramicro-
No warranty is given about the accuracy of the copy.
Users should refer to the original published dermal cells. Nature, 216: 1031, 1967. version of1965. the material. vest. Derm., 45: 448, 28. Hall, J. H., Smith, J. G., Jr. and Burnett, S. 41. Daniels, F., Jr. and Johnson, B. E.: In prepa1967.
Cell Biol., 27: 603, 1965.
27. Prose, P. H., Sedlis, E. and Bigelow, M.: The 40. Fukuyama, K., Epstein, W. L. and Epstein, demonstration of lysosomes in the diseased J. H.: Effect of ultraviolet light on RNA skin of infants with infantile eczema. J. Inand protein synthesis in differentiated epi-
C.: The lysosome in contact dermatitis: A ration. histochemical study. J. Invest. Derm., 49: 42. Ito, M.: Histochemical investigations of Unna's oxygen and reduction areas by means of 590, 1967. 29. Pearse, A. C. E.: p. 882, Histochemistry Theoultraviolet irradiation, Studies on Melanin, retical and Applied, 2nd ed., Churchill, London, 1960.
30. Pearse, A. C. E.: p. 910, Histacheini.stry Thearetscal and Applied, 2nd ed., Churchill, London, 1960.
31. Daniels, F., Jr., Brophy, D. and Lobitz, W. C.: Histochemical responses of human skin fol-
lowing ultraviolet irradiation. J. Invest. Derm.,37: 351, 1961.
32. Bitensky, L.: The demonstration of lysosomes by the controlled temperature freezing section method. Quart. J. Micr. Sci., 103: 205, 1952.
33. Diengdoh, J. V.: The demonstration of lysosomes in mouse skin. Quart. J. Micr. Sci., 105: 73, 1964.
34. Jarret, A., Spearman, R. I. C. and Hardy, J. A.:
Tohoku, J. Exp. Med., 65: Supplement V, 10, 1957.
43. Bitcnsky, L.: Lysosomes in normal and pathological cells, pp. 362—375, Lysasames Eds., de Reuck, A. V. S. and Cameron, M. Churchill, London, 1953.
44. Janoff, A. and Zweifach, B. W.: Production of inflammatory changes in the microcirculation by cationic proteins extracted from lysosomes. J. Exp. Med., 120: 747, 1964.
45. Herion, J. C., Spitznagel, J. K., Walker, R. I. and Zeya, H. I.: Pyrogenicity of granulocyte lysosomes. Amer. J. Physiol., 211: 693, 1966.
46. Baden, H. P. and Pearlman, C.: The effect of ultraviolet light on protein and nucleic acid synthesis in the epidermis. J. Invest. Derm.,
Histochemistry of keratinization. Brit. J. 43: 71, 1964. Derm., 71: 277, 1959. 35. De Duve, C. and Wattiaux, R.: Functions of 47. Bullough, W. S. and Laurence, E. B.: Mitotic control by internal secretion: the role of lysosomes. Ann. Rev. Physiol., 28: 435, 1966. the chalone-adrenalin complex. Exp. Cell. 36. Waravdekar, V. S., Saclaw, L. D., Jones, W. A. and Kuhns, J. C.: Skin changes induced by
Res., 33: 176, 1964.