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Treatment of Alopecia Areata Totalis and Universalis with Cortisone Acetate
SHORT PRELIMINARY REPORT TREATMENT OF ALOPECIA AREATA TOTALIS AND UNIVERSALIS WITH CORTISONE ACETATE* CALVIN J. DILLAHA, M.D. AND STEPHEN ROTRMAN, M.D.
Walker and Rothman (1) in a recent study emphasized clinical observations which suggest that hormonal factors may play an accessory role in modifying the course of alopecia areata, or may serve as a trigger mechanism in its onset. These observations were: 1. Patients with long standing alopecia areata totalis may recover completely during one or more pregnancies only to relapse with the reestablishment of menses. Several observations
of this kind have been reported in the literature (2, 3, 4) and Walker and Rothman (1) added three more cases. 2. The onset of alopecia areata in a certain number of cases coincides with the onset of thyrotoxicosis. 3. The course of alopecia areata is more severe if it begins before puberty. These observations were made before the advent of corticotrophin and cortisone. When the question arose as to what the reason could be for the precipitation of some eases of alopecia areata during thyrotoxicosis, and the improvement of others during pregnancy, it was suggested that retention of water and sodium chloride in the body during pregnancy might be the beneficial, and loss of these substances during thyrotoxicosis, the harmful factor. On this basis a therapeutic trial was made with desoxycorticosterone. However, there was no effect on hair growth. The observation of Hench and co-workers (5) that the symptoms of rheumatoid arthritis may be ameliorated by pregnancy and that a similar effect could be produced by the administration of cortisone, prompted us to evaluate the effect of cortisone on patients suffering from alopecia areata. CA5E aEP0RT5
Case 1. Alopecia areata fere totalis. W. L., a 27 year old barber first noted large circular patches of hair loss on his legs at the age of 20. This was gradually progressive over his entire body and at the age of 23 alopecia appeared on the scalp in circular slowly enlarging patches. The axillary and pubic hair remained normal. There had been no significant regrowth until the initiation of therapy with cortisone. At that time body hair was entirely absent. The beard, eyelashes and eyebrows were sparse. The scalp was bald except for three or four locks of long hair on the vertex of the scalp. At the outset the patient received 150 mg. daily of oral cortisone and over a period of four weeks a total of 2.7 grams was administered. At this time a growth of fine hair was noted for the first time on most of the scalp previously bald, and new hairs were present in eyelashes and eyebrows and the beard; body hair had begun to grow. The cortisone dosage was gradually reduced over the next six weeks to 25 mg. daily. This dosage has been continued to date. After seventeen weeks of therapy the scalp hair is pigmented, of normal texture, one and one-half inches long and firmly rooted. The eyelashes, eyebrows and beard are normal. Case 2. Alopecia areata totalis. F. L., a 21 year old laborer, first began losing his scalp hair at age of eight. At the onset the loss was patchy and circular and within one year the * From the Section of Dermatology, School of Medicine, University of Chicago, Chicago, Illinois. This work was supported in part by an Institutional Research Grant from the American
Cancer Society and in part by a grant from the United States Public Health Service. Received for publication November 14, 1951. 5
6
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
entire scalp became bald. There had never been any significant regrowth. There had been no loss of the eyelashes or eyebrows but body hair was very sparse. At the age of twelve the
pubic and axillary hair and the beard began to develop normally. Initially the patient received 200 mg. daily of oral cortisone and over the next fourteen weeks the patient received a total of 11.5 grams of cortisone. There was no significant change
in the alopecia.
Case 3. Alopecia areata universalis. G. R., a 34 year old machinist, began losing hair from his eyebrows and beard at the age of 24 years and in six months this had evolved into alopecia universalis. There had been no significant regrowth in the past 10 years.
After four weeks of oral cortisone therapy (150 mg. daily) new hair was noted over the entire body excepting the axillary and pubic regions. After seven weeks the hair has continued to grow and the scalp hair now is one-half inch in length, pigmented, firmly rooted, and of normal texture. At this time the cortisone dosage was lowered to 100 mg. daily. Case 4. Alopecia areata universalis. S. 0., a 35 year old Mexican laborer, developed alopecia universalis within eight months after a patchy baldness developed in the scalp at the age of 26. Only significant regrowth had been a few terminal hairs scattered over the scalp. After four weeks of oral cortisone therapy (150 mg. daily) there was new hair in all areas excepting axillary and pubic regions. The hair is well pigmented and firmly rooted. COMMENT
Three out of four patients suffering from long-standing alopecia areata have responded to oral treatment with cortisone acetate. It is interesting to note that in the one patient who didn't respond, the onset of the disease was pre-pubertal as contrasted with the postpubertal onset in the three other patients. The appearance of new hair in three patients occurred uniformily after a period of four weeks therapy. This uniformity as well as the fact that the disease in all three cases was present for five or more years without any tendency to spontaneous remission, we believe makes it unlikely that the regrowth reported here was spontaneous and coincident with therapy. At the time of this writing all three patients are still under treatment, and normal hair growth is progressing. We wish to emphasize that these are short-term and preliminary observations. SU11MARY
Three of four patients with alopecia areata, varying from almost total to universal, experienced a regrowth of hair detectable after one month of therapy with oral cortisone acetate. REFERENCES 1. WALKER, S. A. AND ROTEMAN, S.: Alopecia Areata. A statistical study and consideration
of endocrine influences. J. Invest. Dermat., 14: 403, 1950. 2. WAISMAN, M. AND KEPLER, E. J.: Alopecia areata, an appraisal of endocrine factors in its causation. J. A. M. A., 116: 2004, 1941. 3. MEACHEN, G. N. AND Paows, F. L.: Case presentation before Royal Society of Medi-
cine. Brjt. J. Dermat. & Syph., 24: 272, 1912. 4. STRANDEERO, J.: Haut und innere Sekretion, in Jadassohn, J.: Handbuch der Haut-und Geschlechtskrankheiten, Berlin, Julius Springer, 1929, vol. 3, p. 211. 5 HENCE, P. S., KENDALL, E. C., SLOCtrMB, S. H. AND POLLEY, H. F.: The effect of a hor-
mone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone: Compound E) and of pituitary adrenocorticotrophic hormone of rheumatic arthritis. Proc. Staff Meet. Mayo Clinic, 24: 181 (April 13) 1949.
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.
Walker and Rothman (1) in a recent study emphasized clinical observations which suggest that hormonal factors may play an accessory role in modifying the course of alopecia areata, or may serve as a trigger mechanism in its onset. These observations were: 1. Patients with long standing alopecia areata totalis may recover completely during one or more pregnancies only to relapse with the reestablishment of menses. Several observations
of this kind have been reported in the literature (2, 3, 4) and Walker and Rothman (1) added three more cases. 2. The onset of alopecia areata in a certain number of cases coincides with the onset of thyrotoxicosis. 3. The course of alopecia areata is more severe if it begins before puberty. These observations were made before the advent of corticotrophin and cortisone. When the question arose as to what the reason could be for the precipitation of some eases of alopecia areata during thyrotoxicosis, and the improvement of others during pregnancy, it was suggested that retention of water and sodium chloride in the body during pregnancy might be the beneficial, and loss of these substances during thyrotoxicosis, the harmful factor. On this basis a therapeutic trial was made with desoxycorticosterone. However, there was no effect on hair growth. The observation of Hench and co-workers (5) that the symptoms of rheumatoid arthritis may be ameliorated by pregnancy and that a similar effect could be produced by the administration of cortisone, prompted us to evaluate the effect of cortisone on patients suffering from alopecia areata. CA5E aEP0RT5
Case 1. Alopecia areata fere totalis. W. L., a 27 year old barber first noted large circular patches of hair loss on his legs at the age of 20. This was gradually progressive over his entire body and at the age of 23 alopecia appeared on the scalp in circular slowly enlarging patches. The axillary and pubic hair remained normal. There had been no significant regrowth until the initiation of therapy with cortisone. At that time body hair was entirely absent. The beard, eyelashes and eyebrows were sparse. The scalp was bald except for three or four locks of long hair on the vertex of the scalp. At the outset the patient received 150 mg. daily of oral cortisone and over a period of four weeks a total of 2.7 grams was administered. At this time a growth of fine hair was noted for the first time on most of the scalp previously bald, and new hairs were present in eyelashes and eyebrows and the beard; body hair had begun to grow. The cortisone dosage was gradually reduced over the next six weeks to 25 mg. daily. This dosage has been continued to date. After seventeen weeks of therapy the scalp hair is pigmented, of normal texture, one and one-half inches long and firmly rooted. The eyelashes, eyebrows and beard are normal. Case 2. Alopecia areata totalis. F. L., a 21 year old laborer, first began losing his scalp hair at age of eight. At the onset the loss was patchy and circular and within one year the * From the Section of Dermatology, School of Medicine, University of Chicago, Chicago, Illinois. This work was supported in part by an Institutional Research Grant from the American
Cancer Society and in part by a grant from the United States Public Health Service. Received for publication November 14, 1951. 5
6
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
entire scalp became bald. There had never been any significant regrowth. There had been no loss of the eyelashes or eyebrows but body hair was very sparse. At the age of twelve the
pubic and axillary hair and the beard began to develop normally. Initially the patient received 200 mg. daily of oral cortisone and over the next fourteen weeks the patient received a total of 11.5 grams of cortisone. There was no significant change
in the alopecia.
Case 3. Alopecia areata universalis. G. R., a 34 year old machinist, began losing hair from his eyebrows and beard at the age of 24 years and in six months this had evolved into alopecia universalis. There had been no significant regrowth in the past 10 years.
After four weeks of oral cortisone therapy (150 mg. daily) new hair was noted over the entire body excepting the axillary and pubic regions. After seven weeks the hair has continued to grow and the scalp hair now is one-half inch in length, pigmented, firmly rooted, and of normal texture. At this time the cortisone dosage was lowered to 100 mg. daily. Case 4. Alopecia areata universalis. S. 0., a 35 year old Mexican laborer, developed alopecia universalis within eight months after a patchy baldness developed in the scalp at the age of 26. Only significant regrowth had been a few terminal hairs scattered over the scalp. After four weeks of oral cortisone therapy (150 mg. daily) there was new hair in all areas excepting axillary and pubic regions. The hair is well pigmented and firmly rooted. COMMENT
Three out of four patients suffering from long-standing alopecia areata have responded to oral treatment with cortisone acetate. It is interesting to note that in the one patient who didn't respond, the onset of the disease was pre-pubertal as contrasted with the postpubertal onset in the three other patients. The appearance of new hair in three patients occurred uniformily after a period of four weeks therapy. This uniformity as well as the fact that the disease in all three cases was present for five or more years without any tendency to spontaneous remission, we believe makes it unlikely that the regrowth reported here was spontaneous and coincident with therapy. At the time of this writing all three patients are still under treatment, and normal hair growth is progressing. We wish to emphasize that these are short-term and preliminary observations. SU11MARY
Three of four patients with alopecia areata, varying from almost total to universal, experienced a regrowth of hair detectable after one month of therapy with oral cortisone acetate. REFERENCES 1. WALKER, S. A. AND ROTEMAN, S.: Alopecia Areata. A statistical study and consideration
of endocrine influences. J. Invest. Dermat., 14: 403, 1950. 2. WAISMAN, M. AND KEPLER, E. J.: Alopecia areata, an appraisal of endocrine factors in its causation. J. A. M. A., 116: 2004, 1941. 3. MEACHEN, G. N. AND Paows, F. L.: Case presentation before Royal Society of Medi-
cine. Brjt. J. Dermat. & Syph., 24: 272, 1912. 4. STRANDEERO, J.: Haut und innere Sekretion, in Jadassohn, J.: Handbuch der Haut-und Geschlechtskrankheiten, Berlin, Julius Springer, 1929, vol. 3, p. 211. 5 HENCE, P. S., KENDALL, E. C., SLOCtrMB, S. H. AND POLLEY, H. F.: The effect of a hor-
mone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone: Compound E) and of pituitary adrenocorticotrophic hormone of rheumatic arthritis. Proc. Staff Meet. Mayo Clinic, 24: 181 (April 13) 1949.
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.