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The Effect of Gamma Globulin in Pustular Acne1
PRELIMINARY AND SHORT REPORT THE EFFECT OF GAMMA GLOBULIN IN PUSTULAR ACNE* LOREN W. SHAFFER, M.D., BENJAMIN SdHWIMMER, M.D. AND RENATO J. STANICCO, M.D.
One of us (LWS) bad occasion to treat a young white man with gamma globulin for prophylaxis
after exposure to infectious hepatitis. He was given two injections, 10 cc. each, of human Polio-
Clinical Response: Patient 1: New lesions ceased
appearing immediately after the first injection. By the third week most of the cystic and pustular lesions had dried up, and no new ones had ap-
myelitis Immune Globulin, one week apart. It peared. Comedones were not decreased in number. was observed that shortly after the second injec-
tion, his severe pustular and indurated acne improved considerably. This observation led to the present study, of which this is a preliminary report. This study of the therapeutic effect of gamma globulin in pustular acne is coupled with a study of the serum protein and C-reactive protein levels before and after treatment. Method: Four patients in their late teens, otherwise healthy, but with severe pustular and cystic
The patient maintained his improvement through the fifth week when the cystic and pustular lesions began to recur.
Patient 2: New lesions continued to develop throughout the period of treatment and the one month follow up.
Patient 3: There was no observable effect of treatment. Patient 4: The first improvement was seen in the second week and by the third, all cystic and
pustular lesions were dry. The improvement acne that had been resistant to conventional lasted for two weeks after which the lesions began to return. Discussion: The expected rise in gamma glosuccessive weeks 10 cc. of Poliomyelitis Immune bulin that accompanies chronic infections was Globulin containing 165 15 mg per cc of the not seen in any of the four cases. (The normal globulin fraction of pooled normal human plasma, values for gamma globulin by the Ammonium were injected intramuscularly. At the time of the Sulfate precipitation method employed are 1 to first injection and one week after the second, 1.4 Gm%). One patient ( 3) showed a moderate fasting blood specimens were drawn for C-reactive deficiency. The C-reactive protein was positive or methods of treatment were selected for the study.
All therapy for acne was discontinued. On two
protein, serum albumin, serum globulin, and showed a trace in three of the four patients. gamma globulin determinations. The patients Further investigation will be necessary to deterwere observed at two week intervals for observa- mine whether a significant number of patients tion of the clinical response. with severe pustular acne show a systemic response as indicated by elevation of the serum Results:
Polio Gm % Immune Serum Globulin AlbuInjected mm
Patient 1
Patient 2
1 2 3
10 cc
1 2
Gm
,,
olin
ulin
5.3 2.5
1.4
—
— 4.9
— 2.2
10 cc
4.7
10cc 10cc
Gm%
Serum Serum Gamma Glob- Glob-
—
2.4
1.23
Negative
Trace
—
—
5.1
2.2
1.23
10 cc
5.2
1.8
.81
2
10cc
—
— 1.8
—
5.2
— .81
sedimentation rate, and leukocyte count, are nor-
mal in
patients with pustular acne. The mechanism of the clinical improvement in the two patients that improved is unknown. It is unlikely that passive transfer of antistaphy-
Negative — Trace
3 Patient 3 1
3
Serum
C-reartive Protein
1.41
— —
gamma globulin and appearance of the C-reactive protein. Previous experience indicates that other indications of systemic response, temperature,
lococcol immune antibodies is a factor because of
the well known failure to develop circulating antibody titer or clinical immunity to this or-
—
ganism. Further work will be done to determine dosage schedules to obtain and maintain improve-
Faint Trace
ment, and to determine whether the gamma
—
globulin directly and/or indirectly aids in local skin resistance.
Faint Trace
Patient 4
1
2 3
10cc 10cc
—
4.9 2.8
1.53
—
-—
—
5.1
2.6
1.35
Conclusions: No valid conclusions can be drawn
2+
—
State University and Detroit Receiving Hospital and the Social Hygiene Clinic, Detroit Department of Health, 660 Clinton Street, Detroit 26,
Negative
Michigan. Received for publication December 3, 1957.
* From the Department of Dermatology, Wayne 97
98
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
from the small number of patients studied. However, the results were interesting enough to warrant further study. We wish to acknowledge the helpful suggestions of Samuel Albert, M.D., Ph.D. of the Detroit Institute of Cancer Research. The gamma globuun used in this study was supplied by the Michigan Department of Health Laboratories. REFERENCES 1. MULARGIA, A. AND VANNINI, P.: Gamma globu-
un eleetrophoretic patterns in patients with
tuberculosis. Riv. ist. Sieroterap. ital., 30: 287—296, 1954.
2. BJAGINI, H. AND P0LL&ccl, M.: Serum elec-
trophoretic aspects in some children's dis-
eases. Atti acad. fisiocrit. Siena, Sea. med.—
fis.
(13), 2; 19—22, 1955. 3. SHETLAR, M. H., BULLOCK, JANE A., SHETLAR, CLARA L. AND PAYNE, RIcHARD W.: Compari-
son of Serum C-reactive Protein, Glycopro-
tein and Seromucoid in Cancer, Arthritis,
Tuberculosis and Pregnancy. Proceedings of
the Society for Experimental Biology and Medicine, 88: 107—109, 1955.
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.
One of us (LWS) bad occasion to treat a young white man with gamma globulin for prophylaxis
after exposure to infectious hepatitis. He was given two injections, 10 cc. each, of human Polio-
Clinical Response: Patient 1: New lesions ceased
appearing immediately after the first injection. By the third week most of the cystic and pustular lesions had dried up, and no new ones had ap-
myelitis Immune Globulin, one week apart. It peared. Comedones were not decreased in number. was observed that shortly after the second injec-
tion, his severe pustular and indurated acne improved considerably. This observation led to the present study, of which this is a preliminary report. This study of the therapeutic effect of gamma globulin in pustular acne is coupled with a study of the serum protein and C-reactive protein levels before and after treatment. Method: Four patients in their late teens, otherwise healthy, but with severe pustular and cystic
The patient maintained his improvement through the fifth week when the cystic and pustular lesions began to recur.
Patient 2: New lesions continued to develop throughout the period of treatment and the one month follow up.
Patient 3: There was no observable effect of treatment. Patient 4: The first improvement was seen in the second week and by the third, all cystic and
pustular lesions were dry. The improvement acne that had been resistant to conventional lasted for two weeks after which the lesions began to return. Discussion: The expected rise in gamma glosuccessive weeks 10 cc. of Poliomyelitis Immune bulin that accompanies chronic infections was Globulin containing 165 15 mg per cc of the not seen in any of the four cases. (The normal globulin fraction of pooled normal human plasma, values for gamma globulin by the Ammonium were injected intramuscularly. At the time of the Sulfate precipitation method employed are 1 to first injection and one week after the second, 1.4 Gm%). One patient ( 3) showed a moderate fasting blood specimens were drawn for C-reactive deficiency. The C-reactive protein was positive or methods of treatment were selected for the study.
All therapy for acne was discontinued. On two
protein, serum albumin, serum globulin, and showed a trace in three of the four patients. gamma globulin determinations. The patients Further investigation will be necessary to deterwere observed at two week intervals for observa- mine whether a significant number of patients tion of the clinical response. with severe pustular acne show a systemic response as indicated by elevation of the serum Results:
Polio Gm % Immune Serum Globulin AlbuInjected mm
Patient 1
Patient 2
1 2 3
10 cc
1 2
Gm
,,
olin
ulin
5.3 2.5
1.4
—
— 4.9
— 2.2
10 cc
4.7
10cc 10cc
Gm%
Serum Serum Gamma Glob- Glob-
—
2.4
1.23
Negative
Trace
—
—
5.1
2.2
1.23
10 cc
5.2
1.8
.81
2
10cc
—
— 1.8
—
5.2
— .81
sedimentation rate, and leukocyte count, are nor-
mal in
patients with pustular acne. The mechanism of the clinical improvement in the two patients that improved is unknown. It is unlikely that passive transfer of antistaphy-
Negative — Trace
3 Patient 3 1
3
Serum
C-reartive Protein
1.41
— —
gamma globulin and appearance of the C-reactive protein. Previous experience indicates that other indications of systemic response, temperature,
lococcol immune antibodies is a factor because of
the well known failure to develop circulating antibody titer or clinical immunity to this or-
—
ganism. Further work will be done to determine dosage schedules to obtain and maintain improve-
Faint Trace
ment, and to determine whether the gamma
—
globulin directly and/or indirectly aids in local skin resistance.
Faint Trace
Patient 4
1
2 3
10cc 10cc
—
4.9 2.8
1.53
—
-—
—
5.1
2.6
1.35
Conclusions: No valid conclusions can be drawn
2+
—
State University and Detroit Receiving Hospital and the Social Hygiene Clinic, Detroit Department of Health, 660 Clinton Street, Detroit 26,
Negative
Michigan. Received for publication December 3, 1957.
* From the Department of Dermatology, Wayne 97
98
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
from the small number of patients studied. However, the results were interesting enough to warrant further study. We wish to acknowledge the helpful suggestions of Samuel Albert, M.D., Ph.D. of the Detroit Institute of Cancer Research. The gamma globuun used in this study was supplied by the Michigan Department of Health Laboratories. REFERENCES 1. MULARGIA, A. AND VANNINI, P.: Gamma globu-
un eleetrophoretic patterns in patients with
tuberculosis. Riv. ist. Sieroterap. ital., 30: 287—296, 1954.
2. BJAGINI, H. AND P0LL&ccl, M.: Serum elec-
trophoretic aspects in some children's dis-
eases. Atti acad. fisiocrit. Siena, Sea. med.—
fis.
(13), 2; 19—22, 1955. 3. SHETLAR, M. H., BULLOCK, JANE A., SHETLAR, CLARA L. AND PAYNE, RIcHARD W.: Compari-
son of Serum C-reactive Protein, Glycopro-
tein and Seromucoid in Cancer, Arthritis,
Tuberculosis and Pregnancy. Proceedings of
the Society for Experimental Biology and Medicine, 88: 107—109, 1955.
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.