Short Communication • Kurze Mitteilung Brève communication Dermatológica 155: 315-318 (1977)
Immunological Properties in Staphylococcal Toxic Epidermal Necrolysis Yasunaga Sarai, H ideomi N akahara, T omoaki Ishikawa , Isamu K ondo , Siiohei F utaki , Y utaka Ichizawa , and K aoru H irayama Departments of Pediatrics, Microbiology and Dermatology, Jikei University School of Medicine, Tokyo
Key Words. Staphylococcal toxic epidermal necrolysis • Cell-mediated immunity • Tuberculin reaction Abstract. The analysis of host defenses in 4 patients with staphylococcal toxic epidermal necrolysis revealed normal serum immunoglobulin levels, but a deficiency in cell-mediated immunity as detected by the tuberculin reactions. We suspected that the transient deficiency of cell-mediated immunity may have contributed to the development of this disease.
Introduction
Received: March 11, 1977; accepted: April 16, 1977.
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Impetigo and staphylococcal toxic epidermal necrolysis (s-TEN) are clinically distinct entities, however, it is well known that both diseases are caused by an infection with Staphylococcus aureus. Recently, the etiological agent for both of these diseases has been isolated and variously named exfoliatin [2, 3], epidermolytic toxin [1] or exfoliative toxin [6]. Physico chemical and serological properties of this exotoxin have been examined [4], A difficulty arises in that there is no difference in the quantity and the type of exfoliatin which is produced by isolates from impetigo and s-TEN [4, 10], In addition, it is not yet clearly known why a single strain can be associated with s-TEN in one member of a household yet with impetigo in another [5], These findings indicate that host factors may be a major cause involving these
316
Sarai /N akahara/I shikawa/K ondo/ F utaki /I chizawa /H irayama
diseases. The purpose of this paper is to report about the properties of the cell-mediated immunity, tested by the skin reaction using tuberculoprotein, in patients with s-TEN and with impetigo.
Patients and Methods Four patients with s-TEN, aged 2-8 years, were studied. The diagnosis in all was established by the same criteria which was previously reported [10]. 15 patients with impetigo, aged 1-9 years, were also tested as controls. A purified protein derivative (PPD; 0.001 mg) was used to determine the reaction of each individual to tuberculin. The antigen was injected intracutaneously in 0.1-ml doses, and the reactions were read after 48 h. During the severe erythematous phase, patients were not given this test. Therefore, PPD was injected on the 3rd or 4th day after the onset of s-TEN and at about I month after admission. We also studied the serum immunoglobulin levels of IgG, IgA and IgM in the patients with s-TEN, using the single radial immunodiffusion method.
Results The results of the tuberculin tests are shown in Table 1. Upon admission, all cases showed either a negative or doubtful positive, but about 1 month later, the patients reverted to a positive or doubtful positive. There was no change in the skin reaction to PPD in the controls. The serum immunoglobulin levels in the four patients with s-TEN were found to be within the normal range.
Table I. Tuberculin test in patients with s-TEN Case No.
Age
1 2
2 years 4 years
3 4
8 years 2 years
Sex
Reaction Age at 1st positive reaction upon admission
after 1 month
F
NT1
-
+
M M M
1 year
-
6 years NT
-
± +
±
+
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 12:51:42 AM
' NT = Not tested prior to admission.
Immunological Properties in Staphylococcal TEN
317
Discussion Sarai [9] and W iley el al. [11] reported about the distribution of anti-
exfoliatin antibodies in humans and suggested that the humoral antibody may not play an important role in the prevention of s-TEN. We suspected that the deficiency of cell-mediated immunity may have contributed to the development of this disease. Although the immunological properties of patients in childhood have not been studied until now, R eid et al. [8] have reported a case of s-TEN which developed in an adult patient while he was receiving long-term therapy with corticosteroid which caused a deficiency of cell-mediated immunity. Simi larly, the analysis of host defenses in our present patients revealed normal serum immunoglobulin levels, but a deficiency in cell-mediated immunity as detected by the tuberculin reactions. In general, cell-mediated immunity is more important than humoral immunity in defense against S. aureus infection [7]. Therefore, the transient deficiency of cell-mediated immunity in childhood may have allowed the unrestrained multiplication of exfoliatin-elaborating organisms and may have contributed to the development of this disease. Further studies are currently in progress to test this hypothesis using other methods for detecting cellmediated immunity. References
2
3
4
5 6
7
lysis produced by an extracellular product of Staphylococcus aureus. Br. J. Dermat. 85: 145-149(1971). K apral, F.A. and M iller, M .M .: Product of Staphylococcus aureus responsible for the scalded-skin syndrome. Infec. Immunity 4: 541-545 (1971). Kondo , I.; Sakurai, S., and Sarai, Y .: Purification of exfoliatin produced by Sta phylococcus aureus of bacteriophage group 2 and its physiochemical properties Infec Immunity 8: 156-164(1973). K ondo, I.; Sakurai, S., and Sarai, Y .: New type of exfoliatin obtained from Staphylo coccal strains, belonging to phage groups other than 2, isolated from patients with impetigo and Ritter’s disease. Infec. Immunity 10: 851-861 (1974). L yell, A.; D ick , H.M., and A lexander, J. O’D.: Outbreak of toxic epidermal necrolysis associated with staphylococci. L a n c e t 787-790 (1969). M elish, M .E.; G lasgow, L.A., and T urner, M .D.: Staphylococcal scalded skin syndrome. Isolation and partial characterization of the exfoliative toxin. J. infect. Dis. 125: 129-140 (1972). M udd , S .: Resistance against Staphylococcus aureus. J. Am. med. Ass. 218: 1671-1673 (1971).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 12:51:42 AM
1 A rbuthnott, J.P.; K ent, J.; L yell, A., and G emmell, C .G .: Toxic epidermal necro
318
S arai / N akahara /I shikawa / K ondo / F utaki /I c h iz a w a / H irayama
8 R eid, L .; W eston, W., and H umbert, J.: Staphylococcal scalded skin syndrome.
Y asunaga S arai, MD, Department of Pediatrics, National Medical Center Hospital of Japan, I Toyamacho, Shinjuku-ku, Tokyo 162 (Japan)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 12:51:42 AM
Archs Derm. 109: 239-241 (1974). 9 Sarai, Y.: Distribution of anti-exfoliatin hemagglutination titers in normal human population. Jikei. med. J. 22: 227-235 (1975). 10 Sarai, Y.; N akahara, H.; Ishikawa , T.; Kondo , I.; F utaki, S., and H irayama, K.: A bacteriological study on children with staphylococcal toxic epidermal necrolysis in Japan. Dermatológica 154: 161-167 (1977). 11 W iley, B.; G lasgow, L., and R ogolsky, M.: Staphylococcal scalded-skin syndrome. Development of a primary binding assay for human antibody to the exfoliative toxin. Infec. Immunity 13: 513-520 (1976).
Immunological Properties in Staphylococcal Toxic Epidermal Necrolysis Yasunaga Sarai, H ideomi N akahara, T omoaki Ishikawa , Isamu K ondo , Siiohei F utaki , Y utaka Ichizawa , and K aoru H irayama Departments of Pediatrics, Microbiology and Dermatology, Jikei University School of Medicine, Tokyo
Key Words. Staphylococcal toxic epidermal necrolysis • Cell-mediated immunity • Tuberculin reaction Abstract. The analysis of host defenses in 4 patients with staphylococcal toxic epidermal necrolysis revealed normal serum immunoglobulin levels, but a deficiency in cell-mediated immunity as detected by the tuberculin reactions. We suspected that the transient deficiency of cell-mediated immunity may have contributed to the development of this disease.
Introduction
Received: March 11, 1977; accepted: April 16, 1977.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 12:51:42 AM
Impetigo and staphylococcal toxic epidermal necrolysis (s-TEN) are clinically distinct entities, however, it is well known that both diseases are caused by an infection with Staphylococcus aureus. Recently, the etiological agent for both of these diseases has been isolated and variously named exfoliatin [2, 3], epidermolytic toxin [1] or exfoliative toxin [6]. Physico chemical and serological properties of this exotoxin have been examined [4], A difficulty arises in that there is no difference in the quantity and the type of exfoliatin which is produced by isolates from impetigo and s-TEN [4, 10], In addition, it is not yet clearly known why a single strain can be associated with s-TEN in one member of a household yet with impetigo in another [5], These findings indicate that host factors may be a major cause involving these
316
Sarai /N akahara/I shikawa/K ondo/ F utaki /I chizawa /H irayama
diseases. The purpose of this paper is to report about the properties of the cell-mediated immunity, tested by the skin reaction using tuberculoprotein, in patients with s-TEN and with impetigo.
Patients and Methods Four patients with s-TEN, aged 2-8 years, were studied. The diagnosis in all was established by the same criteria which was previously reported [10]. 15 patients with impetigo, aged 1-9 years, were also tested as controls. A purified protein derivative (PPD; 0.001 mg) was used to determine the reaction of each individual to tuberculin. The antigen was injected intracutaneously in 0.1-ml doses, and the reactions were read after 48 h. During the severe erythematous phase, patients were not given this test. Therefore, PPD was injected on the 3rd or 4th day after the onset of s-TEN and at about I month after admission. We also studied the serum immunoglobulin levels of IgG, IgA and IgM in the patients with s-TEN, using the single radial immunodiffusion method.
Results The results of the tuberculin tests are shown in Table 1. Upon admission, all cases showed either a negative or doubtful positive, but about 1 month later, the patients reverted to a positive or doubtful positive. There was no change in the skin reaction to PPD in the controls. The serum immunoglobulin levels in the four patients with s-TEN were found to be within the normal range.
Table I. Tuberculin test in patients with s-TEN Case No.
Age
1 2
2 years 4 years
3 4
8 years 2 years
Sex
Reaction Age at 1st positive reaction upon admission
after 1 month
F
NT1
-
+
M M M
1 year
-
6 years NT
-
± +
±
+
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 12:51:42 AM
' NT = Not tested prior to admission.
Immunological Properties in Staphylococcal TEN
317
Discussion Sarai [9] and W iley el al. [11] reported about the distribution of anti-
exfoliatin antibodies in humans and suggested that the humoral antibody may not play an important role in the prevention of s-TEN. We suspected that the deficiency of cell-mediated immunity may have contributed to the development of this disease. Although the immunological properties of patients in childhood have not been studied until now, R eid et al. [8] have reported a case of s-TEN which developed in an adult patient while he was receiving long-term therapy with corticosteroid which caused a deficiency of cell-mediated immunity. Simi larly, the analysis of host defenses in our present patients revealed normal serum immunoglobulin levels, but a deficiency in cell-mediated immunity as detected by the tuberculin reactions. In general, cell-mediated immunity is more important than humoral immunity in defense against S. aureus infection [7]. Therefore, the transient deficiency of cell-mediated immunity in childhood may have allowed the unrestrained multiplication of exfoliatin-elaborating organisms and may have contributed to the development of this disease. Further studies are currently in progress to test this hypothesis using other methods for detecting cellmediated immunity. References
2
3
4
5 6
7
lysis produced by an extracellular product of Staphylococcus aureus. Br. J. Dermat. 85: 145-149(1971). K apral, F.A. and M iller, M .M .: Product of Staphylococcus aureus responsible for the scalded-skin syndrome. Infec. Immunity 4: 541-545 (1971). Kondo , I.; Sakurai, S., and Sarai, Y .: Purification of exfoliatin produced by Sta phylococcus aureus of bacteriophage group 2 and its physiochemical properties Infec Immunity 8: 156-164(1973). K ondo, I.; Sakurai, S., and Sarai, Y .: New type of exfoliatin obtained from Staphylo coccal strains, belonging to phage groups other than 2, isolated from patients with impetigo and Ritter’s disease. Infec. Immunity 10: 851-861 (1974). L yell, A.; D ick , H.M., and A lexander, J. O’D.: Outbreak of toxic epidermal necrolysis associated with staphylococci. L a n c e t 787-790 (1969). M elish, M .E.; G lasgow, L.A., and T urner, M .D.: Staphylococcal scalded skin syndrome. Isolation and partial characterization of the exfoliative toxin. J. infect. Dis. 125: 129-140 (1972). M udd , S .: Resistance against Staphylococcus aureus. J. Am. med. Ass. 218: 1671-1673 (1971).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 12:51:42 AM
1 A rbuthnott, J.P.; K ent, J.; L yell, A., and G emmell, C .G .: Toxic epidermal necro
318
S arai / N akahara /I shikawa / K ondo / F utaki /I c h iz a w a / H irayama
8 R eid, L .; W eston, W., and H umbert, J.: Staphylococcal scalded skin syndrome.
Y asunaga S arai, MD, Department of Pediatrics, National Medical Center Hospital of Japan, I Toyamacho, Shinjuku-ku, Tokyo 162 (Japan)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 12:51:42 AM
Archs Derm. 109: 239-241 (1974). 9 Sarai, Y.: Distribution of anti-exfoliatin hemagglutination titers in normal human population. Jikei. med. J. 22: 227-235 (1975). 10 Sarai, Y.; N akahara, H.; Ishikawa , T.; Kondo , I.; F utaki, S., and H irayama, K.: A bacteriological study on children with staphylococcal toxic epidermal necrolysis in Japan. Dermatológica 154: 161-167 (1977). 11 W iley, B.; G lasgow, L., and R ogolsky, M.: Staphylococcal scalded-skin syndrome. Development of a primary binding assay for human antibody to the exfoliative toxin. Infec. Immunity 13: 513-520 (1976).
