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INTRAVENOUS GAMMAGLOBULIN AND REDUCTION OF CORONARY ARTERY ABNORMALITIES IN CHILDREN WITH KAWASAKI DISEASE
973
Subsequent follow-up samples were collected every 15 days until negative results were obtained. Examination of blood smears, both by Giemsa and acridine orange fluorescent stains was judged
FREQUENCY AND GRADE OF CORONARY ABNORMALITIES IN BABIES WITH KAWASAKI DISEASE TREATED WITH INTRAVENOUS
two
GAMMAGLOBULIN
appropriate since only 0-12% of subjects demonstrated parasites, compared with detection of antigen by monoclonal
not
antibody in 9-4% subjects. Of 25 previously antigen-positive subjects (both donors and recipients) 23 did not demonstrate antigen in blood samples taken on the 15th and 30th day after treatment. 2 children who had not completed the treatment were antigen-positive on their subsequent visit. However, after completion of treatment, they also became negative for malarial antigen on the 15th day. Thus our subjects were free of antigen on the 15th day, as well as the 30th day, after a full course of treatment. We can therefore conclude that it is safe to donate blood 3 months after full treatment for malaria infection. Since the possibility of reinfection cannot be ruled out, we advise screening of such donors for antigen detection by monoclonal antibody.
NABAJYOTI CHOUDHURY Departments of Transfusion and Immunohaematology, Parasitology and Experimental Medicine, Postgraduate Institute of Medical Examination and Research,
Chandigarh, India
J. G. JOLLY R. C. MAHAJAN M. L. DUBEY A. KALRA N. K. GANGULY
1.
Bowley CC, Goldsmith KLG, Maycock WD, eds. Blood transfusion, a guide to the formation and operation of a transfusion service. Geneva: World Health Organisation, 1971. 2. Technical Manual. 9th ed. Arlington, Virginia: American Association of Blood Banks, 1985. 3. Wells L, Ala FA. Malana and blood transfusion. Lancet 1985; i: 1317-19. 4. Hassig A. International forum; which are the appropriate modifications of existing regulation designed to prevent the transfusion of malaria by blood transfusion, in view of the increasing frequency of travel to endemic areas? Vox Sang 1987; 52: 138-48.
INTRAVENOUS GAMMAGLOBULIN AND REDUCTION OF CORONARY ARTERY ABNORMALITIES IN CHILDREN WITH KAWASAKI DISEASE
SIR,-Kawasaki disease is an acute febrile mucocutaneous lymph node syndrome first described in Japan that has been diagnosed in North America, Europe, and Asia among children of all races. 20-42% of patients have coronary artery abnormalities and this complication carries an unfavourable prognosis.1,2 Furusho et aF reported that a high dose of intravenous gammaglobulin added to conventional therapy prevented coronary artery aneurysms in children with Kawasaki disease. This observation has been confirmed.3,4 The dose-response of gammaglobulin has received less attention. We report a multicentre randomised trial of gammaglobulin given intravenously in different doses. 160 Japanese patients with Kawasaki disease were treated in 13 paediatric clinics in the Kumamoto district of Japan from July, 1984, to March, 1988. All children had full clinical expression of Kawasaki disease and were under 4 years of age. Gammaglobulin was started within 7 days after the onset and no treatment had been given before the study. 18 patients were excluded from the study retrospectively because the clinical features and dose or duration of gammaglobulin did not meet the criteria. All patients received oral aspirin, 30 mg/kg per day, and gammaglobulin was given intravenously for 5 days as follows: group A received 50-100 mg/kg, B 200 mg/kg, and C 400 mg/kg. The preparation was Ssulphonated human gammaglobulin or polyethylene-glycol-treated human gammaglobulin. Patients who had been treated with oral aspirin only in the same clinics in 1984 served as controls. Two-dimensional echocardiograms were done once a week for at least 3 weeks, including views of the right coronary artery and of the left main, anterior descending, and circumflex branches of the left coronary artery. The views were interpreted blindly and independently and were categorised into three depending on the largest diameter of the coronary artery at the third week of examination: score 0 (normal) and score 2 (severe) were given for cases of a diameter less than 3 mm and larger than 5-5 mm,
*p <
0-05 and
t2p <
0-025
CX’ test with Yates’ correction).
respectively. The remaining patients scored 1 (mild). Only the group C patients showed a significant reduction in the coronary artery abnormality (scores 1 plus 2) compared with controls (table). Furusho et alNewburger et al,3 and Matsushima et al4 found that gammaglobulin 400 mg/kg intravenously for 4-5 days was safe and effective in the prevention of coronary artery aneurysms. Gammaglobulin given intravenously in a dose of less than 400 mg/kg was reported to have a negative effect (200 mg/kg for 3 days )6,7 or a positive effect (100 mg/kg for 5 days)8 in the prevention of abnormalities. Our study shows that gammaglobulin at less than 400 mg/kg did not reduce the frequency of coronary artery abnormalities (treated babies 39-2% controls 43-8%), but did prevent aggravation of arterial changes. This was shown by the ratio of patients with score 2 to those with scores 1 and 2, which was significantly decreased in groups A and B combined compared with controls and in all the gammaglobulin treated patients combined compared with controls. Laboratory data and the duration of febrile stage were similar in the groups during the treatment. In patients with Kawasaki disease, not only the presence or absence of coronary artery abnormalities but also the severity will affect prognosis.9 At present it is generally accepted that gammaglobulin (400 mg/kg daily for 4 days) should be administered to any baby under 12 months of age with Kawasaki disease. Controversy remains as to whether patients over 12 months of age should receive a high dose of gammaglobulin.1O Proper doses for the various ages and conditions need to be investigated because gammaglobulin is expensive, side-effects may occur, and the clinical features are not homologous. This study was in collaboration with Dr M. Migita, Dr Y. Nobukuni, Y. Arizono, Dr A. Tanoue, Dr T. Namikawa, Dr S. Tomoeda, H. Mitsubuchi, Dr K. Yatsunami, Dr S. Matsumoto, Dr A. Taniyama, Dr K. Takashima, Dr Y. Itai, Dr T. Uchino, and Dr H. Motomura.
We thank M. Ohara for her
comments.
Departments of Pediatrics, Kumamoto Red Cross Hospital; Kumamoto City Hospital; and Kumamoto University Hospital, Kumamoto 860, Japan
S. NISHIHARA K. ISHIBASHI K. IRIBE I. MATSUDA
H, Ichinose E, Yoshioka F, et al. Fate of coronary aneurysms in Kawasaki disease: serial coronary angiography and long-term follow-up study. Am J Cardiol 1982; 49: 1758-66. 2. Furusho K, Kamiya T, Nakano H, et al. High-dose intravenous gammaglobulin for Kawasaki disease. Lancet 1984; ii: 1055-59. 3. Newburger JW, Takahashi M, Burns JC, et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med 1986; 315: 341-47. 4. Matsushima, Nagashima M, Matsuoka H. High-dose immunoglobulin therapy for Kawasaki disease. Prog Med 1986; 6: 129-36 (Jap). 5. Satomi G, Nakamura K, Narai S, et al. Systemic visualization of coronary arteries by two-dimensional echocardiography in children and infants: evaluation in Kawasaki’s disease and coronary arteriovenous fistulas. Am Heart J 1984; 107: 479-505. 6. Ogino K, Ogawa M, Harima R, et al. Clinical evaluation of gamma globulin infusion in Kawasaki disease. J Jap Pediat Soc 1985; 89: 1069 (Jap). 7. Furusho K. Intravenous gamma globulin for Kawasaki disease: dose response. Prog Med 1987; 7: 77-81 (Jap). 8. Okuni M, Harada K, Yamaguchi. Intravenous gamma globulin therapy in Kawasaki disease. Prog Med 1987; 7: 83-87 (Jap). 9 Tatara K, Kusakawa S. Long-term prognosis of giant coronary aneurysms in Kawasaki disease: an angiographic study. J Pediatr 1987; 111: 705-10. 10. Bierman FZ, Gersony WM. Kawasaki disease: clinical perspective. J Pediatr 1987; 111: 789-93. 1. Kato
Subsequent follow-up samples were collected every 15 days until negative results were obtained. Examination of blood smears, both by Giemsa and acridine orange fluorescent stains was judged
FREQUENCY AND GRADE OF CORONARY ABNORMALITIES IN BABIES WITH KAWASAKI DISEASE TREATED WITH INTRAVENOUS
two
GAMMAGLOBULIN
appropriate since only 0-12% of subjects demonstrated parasites, compared with detection of antigen by monoclonal
not
antibody in 9-4% subjects. Of 25 previously antigen-positive subjects (both donors and recipients) 23 did not demonstrate antigen in blood samples taken on the 15th and 30th day after treatment. 2 children who had not completed the treatment were antigen-positive on their subsequent visit. However, after completion of treatment, they also became negative for malarial antigen on the 15th day. Thus our subjects were free of antigen on the 15th day, as well as the 30th day, after a full course of treatment. We can therefore conclude that it is safe to donate blood 3 months after full treatment for malaria infection. Since the possibility of reinfection cannot be ruled out, we advise screening of such donors for antigen detection by monoclonal antibody.
NABAJYOTI CHOUDHURY Departments of Transfusion and Immunohaematology, Parasitology and Experimental Medicine, Postgraduate Institute of Medical Examination and Research,
Chandigarh, India
J. G. JOLLY R. C. MAHAJAN M. L. DUBEY A. KALRA N. K. GANGULY
1.
Bowley CC, Goldsmith KLG, Maycock WD, eds. Blood transfusion, a guide to the formation and operation of a transfusion service. Geneva: World Health Organisation, 1971. 2. Technical Manual. 9th ed. Arlington, Virginia: American Association of Blood Banks, 1985. 3. Wells L, Ala FA. Malana and blood transfusion. Lancet 1985; i: 1317-19. 4. Hassig A. International forum; which are the appropriate modifications of existing regulation designed to prevent the transfusion of malaria by blood transfusion, in view of the increasing frequency of travel to endemic areas? Vox Sang 1987; 52: 138-48.
INTRAVENOUS GAMMAGLOBULIN AND REDUCTION OF CORONARY ARTERY ABNORMALITIES IN CHILDREN WITH KAWASAKI DISEASE
SIR,-Kawasaki disease is an acute febrile mucocutaneous lymph node syndrome first described in Japan that has been diagnosed in North America, Europe, and Asia among children of all races. 20-42% of patients have coronary artery abnormalities and this complication carries an unfavourable prognosis.1,2 Furusho et aF reported that a high dose of intravenous gammaglobulin added to conventional therapy prevented coronary artery aneurysms in children with Kawasaki disease. This observation has been confirmed.3,4 The dose-response of gammaglobulin has received less attention. We report a multicentre randomised trial of gammaglobulin given intravenously in different doses. 160 Japanese patients with Kawasaki disease were treated in 13 paediatric clinics in the Kumamoto district of Japan from July, 1984, to March, 1988. All children had full clinical expression of Kawasaki disease and were under 4 years of age. Gammaglobulin was started within 7 days after the onset and no treatment had been given before the study. 18 patients were excluded from the study retrospectively because the clinical features and dose or duration of gammaglobulin did not meet the criteria. All patients received oral aspirin, 30 mg/kg per day, and gammaglobulin was given intravenously for 5 days as follows: group A received 50-100 mg/kg, B 200 mg/kg, and C 400 mg/kg. The preparation was Ssulphonated human gammaglobulin or polyethylene-glycol-treated human gammaglobulin. Patients who had been treated with oral aspirin only in the same clinics in 1984 served as controls. Two-dimensional echocardiograms were done once a week for at least 3 weeks, including views of the right coronary artery and of the left main, anterior descending, and circumflex branches of the left coronary artery. The views were interpreted blindly and independently and were categorised into three depending on the largest diameter of the coronary artery at the third week of examination: score 0 (normal) and score 2 (severe) were given for cases of a diameter less than 3 mm and larger than 5-5 mm,
*p <
0-05 and
t2p <
0-025
CX’ test with Yates’ correction).
respectively. The remaining patients scored 1 (mild). Only the group C patients showed a significant reduction in the coronary artery abnormality (scores 1 plus 2) compared with controls (table). Furusho et alNewburger et al,3 and Matsushima et al4 found that gammaglobulin 400 mg/kg intravenously for 4-5 days was safe and effective in the prevention of coronary artery aneurysms. Gammaglobulin given intravenously in a dose of less than 400 mg/kg was reported to have a negative effect (200 mg/kg for 3 days )6,7 or a positive effect (100 mg/kg for 5 days)8 in the prevention of abnormalities. Our study shows that gammaglobulin at less than 400 mg/kg did not reduce the frequency of coronary artery abnormalities (treated babies 39-2% controls 43-8%), but did prevent aggravation of arterial changes. This was shown by the ratio of patients with score 2 to those with scores 1 and 2, which was significantly decreased in groups A and B combined compared with controls and in all the gammaglobulin treated patients combined compared with controls. Laboratory data and the duration of febrile stage were similar in the groups during the treatment. In patients with Kawasaki disease, not only the presence or absence of coronary artery abnormalities but also the severity will affect prognosis.9 At present it is generally accepted that gammaglobulin (400 mg/kg daily for 4 days) should be administered to any baby under 12 months of age with Kawasaki disease. Controversy remains as to whether patients over 12 months of age should receive a high dose of gammaglobulin.1O Proper doses for the various ages and conditions need to be investigated because gammaglobulin is expensive, side-effects may occur, and the clinical features are not homologous. This study was in collaboration with Dr M. Migita, Dr Y. Nobukuni, Y. Arizono, Dr A. Tanoue, Dr T. Namikawa, Dr S. Tomoeda, H. Mitsubuchi, Dr K. Yatsunami, Dr S. Matsumoto, Dr A. Taniyama, Dr K. Takashima, Dr Y. Itai, Dr T. Uchino, and Dr H. Motomura.
We thank M. Ohara for her
comments.
Departments of Pediatrics, Kumamoto Red Cross Hospital; Kumamoto City Hospital; and Kumamoto University Hospital, Kumamoto 860, Japan
S. NISHIHARA K. ISHIBASHI K. IRIBE I. MATSUDA
H, Ichinose E, Yoshioka F, et al. Fate of coronary aneurysms in Kawasaki disease: serial coronary angiography and long-term follow-up study. Am J Cardiol 1982; 49: 1758-66. 2. Furusho K, Kamiya T, Nakano H, et al. High-dose intravenous gammaglobulin for Kawasaki disease. Lancet 1984; ii: 1055-59. 3. Newburger JW, Takahashi M, Burns JC, et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med 1986; 315: 341-47. 4. Matsushima, Nagashima M, Matsuoka H. High-dose immunoglobulin therapy for Kawasaki disease. Prog Med 1986; 6: 129-36 (Jap). 5. Satomi G, Nakamura K, Narai S, et al. Systemic visualization of coronary arteries by two-dimensional echocardiography in children and infants: evaluation in Kawasaki’s disease and coronary arteriovenous fistulas. Am Heart J 1984; 107: 479-505. 6. Ogino K, Ogawa M, Harima R, et al. Clinical evaluation of gamma globulin infusion in Kawasaki disease. J Jap Pediat Soc 1985; 89: 1069 (Jap). 7. Furusho K. Intravenous gamma globulin for Kawasaki disease: dose response. Prog Med 1987; 7: 77-81 (Jap). 8. Okuni M, Harada K, Yamaguchi. Intravenous gamma globulin therapy in Kawasaki disease. Prog Med 1987; 7: 83-87 (Jap). 9 Tatara K, Kusakawa S. Long-term prognosis of giant coronary aneurysms in Kawasaki disease: an angiographic study. J Pediatr 1987; 111: 705-10. 10. Bierman FZ, Gersony WM. Kawasaki disease: clinical perspective. J Pediatr 1987; 111: 789-93. 1. Kato