THE JOURNAL qF I~FECTIO.US DISEASES • VOL. 134, NO.3 © 1976 by the Dniversity of Chicago. All rights reserved.
•
SEPTEMBER 19 6 7
EDITORIAL ~nd
Mucocutaneous Lymph Node Syndrome (I(avvasald Ilisease)
11 deaths (1.7 % ). Epidemiological surveys Japan showed that the incidence in males was higher than that in females (1.5: 1), that the incidence was highest in one-year-old children with four-fifths of the patients younger than four years, that the incidence was highest from May to July, and that the incidence had increased sharply since 1970 [2, 3]. Kawasaki [1] noted some resemblance of MCLS to Stevens-Johnson syndrome and to scarlet fever, but he was confident that MCLS was different from and could be differentiated from these disorders. Examination of biopsy specimens of cervical lymph nodes from three cases in Kawasaki's original series [1] revealed swelling of endothelial cells of postcapillary venules and hyperplasia of reticulum cells. Biopsy specimens of skin taken from seven of Kawasaki's patients showed edema of dermis, dilatation of capillaries, and mild perivascular infiltration of lymphocytes and monocytes. None of these changes was specific. Although appropriate studies were carefully pursued in Kawasaki's series, no evidence for a bacterial or viral etiology could be identified. The possibility that MCLS is a "collagen disease" was considered but not proven [1, 3, 4]. Thus, it appeared highly likely that many cases of a new or previously unrecognized disease of unknown etiology had been described [5]. Outside of Japan the disease has so far been reported from South Korea (eight cases) , Greece (eight), the United States (five to 12), and Canada (13). The first reported instances of the disorder in the United States were in nine children of multiple races in Hawaii; these cases were described in 1974 by Melish et al. [5]. The first case was seen in 1971, and emphasis was placed on MCLS as a distinctive disease. Goldsmith et al. [6] reported a case in a two-year-old boy (August 1974)l residing in the New York City area. A second case with strikingly similar clinical features was subsequently seen in the same area. In III
[3].
With these diagnostic guidelines, the Japanese study group sent surveys to the pediatric units of the larger hospitals. These surveys identified 6,537 cases (5,524 definite and 1,013 probable) Received for publication July 13, 1976. Please address requests for reprints to Dr. Harris D. Riley, Jr., Department of Pediatrics, The University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, Oklahoma 73190.
. 1 Dates in parentheses indicate dates on which patients were first observed to have manifestations compatible with MCLS.
302
Downloaded from http://jid.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 23, 2015
In 1967, Kawasaki [1] described 50 cases in infants and young children of a seemingly selflimited disease syndrome of unknown etiology; the disease was designated as mucocutaneous lymph node syndrome (MCLS). The patients ranged in age from two months to nine years, with the great majority younger than five years of age. The cases had come to Kawasaki's attention during the six-year period from 1961 through 1966 [1, 2]. In 1970 the Japanese Ministry of Health and Welfare established a special MCLS study group [3]. This body defined the principal findings as fever (101 F-I04 F) lasting for longer than five days and not responding to antibiotics; changes of peripheral extremities (reddening and indurative edema of palms and soles and membranous desquamation from fingertips in the convalescent stage); polymorphous exanthema of the trunk without vesicles or crusts; bilateral conjunctival congestion; changes in lips and oral cavity (redness and fissuring of lips, strawberry tongue, and diffuse reddening of oropharyngeal mucosa); and acute, nonpurulent swelling of cervical lymph nodes. Other important signs were tachycardia, gallop rhythm, distant heart sounds, heart murmurs, and electrocardiographic changes; diarrhea; proteinuria and increased leukocytes in urine sediment; leukocytosis with shift to the left, slight anemia, elevated platelet count, increased erythrocyte sedimentation rate, positive C-reactive protein, increased serum u2-globulin, and no increase in titer of antistreptolysin 0; and, rarely, arthralgia, arthritis, aseptic meningitis, and mild jaundice or slight increase of serum transaminase
Editorial
75 %, swelling of cervical lymph nodes [l, 2]. The incidence of these manifestations is similar in patients reported from this country. Other findings compatible with an infection include myocarditis and pericarditis, arthritis, leukocytosis with shift to the left, increased sedimentation rate, abnormal acute-phase reactants, and occasionally aseptic meningitis and jaundice. In his early report, Kawasaki [1, 2] referred to "abnormal host response ... to infection" in patients with MCLS. Goldsmith et al. [6] speculated about the possible occurrence of "a rare but ubiquitous infectious disease which has reached epidemic proportions in Japan and which in time may become common experience elsewhere" and suggested alternatively that MCLS may represent a distinctive exanthematous disease of childhood. Kawasaki and his colleagues [2] mentioned early the clinical resemblance of MCLS to scarlet fever, particularly because of the rash and strawberry tongue. However, hemolytic streptococci have seldom been isolated, and the titer of antistreptolysin 0 is not increased in MCLS. No virus has been found, and there is no strong serological evidence of a viral origin. Hamashima et al. [14] caused excitement when they reported the presence of rickettsia-like bodies identified by electron microscopy of biopsy specimens of skin and cervical lymph nodes from 12 of 23 patients with MCLS. The bodies were located in the cytoplasm of macrophages and endothelial cells of arterioles and clustered inside the vascular lumen. These workers [15] claimed to have isolated Rickettsia from patients' whole blood by inoculation into yolk sacs after successive inoculation in guinea pigs and mice. Shishido and Adachi [16], however, failed to confirm these results. Furthermore, the epidemiological features and the unresponsiveness of the disease to antibiotics are evidence against a rickettsial etiology. Environmental pollutants, unidentified toxic agents, specific patterns of drug therapy, and an allergic reaction to chemical detergents have been considered as possible causes for explanation of the concentration of the syndrome to an as yet limited geographic area [2, 3, 6]. The similarities to another disease caused by an exogenous toxin, acrodynia, are not only clinical; acrodynia, like MCLS, appeared suddenly (at the beginning of this century) and affects persons in much the
Downloaded from http://jid.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 23, 2015
January 1976, Brown et al. [7] reported three cases that occurred in Memphis, Tenn. (November 1974, May 1975, and June 1975). Robinson and Adler [8] reported two cases recently observed in California, a 21-month-old Caucasian boy and a 3.5-year-old MexicanAmerican male. In addition to the usual clinical findings, the older child exhibited a striking polyarticular arthritis. Lauer et at [9] described four children, from eight months to 10 years old, seen in Denver during 1974-1976. None were of Oriental extraction, but one had previously resided in Hawaii. John et al. [10] reported in June 1976 four cases seen in Arizona (November 1972, December 1974, April 1975, and September 1975). Melish et al. [11] have recently described seven additional cases seen in Hawaii between 1971 and t 975. Eight of the 16 patients were Japanese, and all but one had some Oriental ethnic admixture; however, this racial background is representative of the population at the hospital where these patients were seen. In the 12 months before May 28, 1976, 14 suspect cases that have met the diagnostic criteria for the syndrome have been reported to the Center for Disease Control (Atlanta, Ga. ) from Arizona, California, Florida, Hawaii, Iowa, New York, Tennessee, and Washington, D.C. [12]. In addition, a case has been reported recently from Toronto (February 1974) [13]. As mentioned previously, the early reports of the disorder indicated that the disease was seemingly self-limited and that all patients had recovered. However, as the number of cases of MCLS increased, a new but not entirely unexpected feature was added. Fatalities were reported in 1% -2 % of cases. The deaths were more common in young infants and occurred suddenly a short time after apparent recovery from MCLS. At autopsy the cause of death appeared to be cardiovascular in origin. The etiology of MCLS is unknown at present. There are many features that suggest an infectious etiology. In the Japanese patients these features include the following: 95% of the patients have fever; 92%, polymorphous exanthema; 90%, diffuse reddening of oral mucosa; 88 % -94 %, reddening of the palms and soles with subsequent desquamation; 88%, conjunctival congestion; and
303
304
months [22]. This finding is compatible with the view that allergic arteritis plays a major role in the syndrome. If a microbial agent is identified as etiologic in MCLS, the role of IgE will not be diminished; MCLS may be an infection in which IgE plays an important role in eliminating the invader from the body [22]. Elevated levels of IgE have been found in the sera of infants who died with IPN [22]. The next stage is to look for precipitation of IgE in the affected vascular beds and tissues and to see whether specific IgE can be found [3]. As pointed out previously [3], at present one can only say that factors prevalent in the environment since the 1960s may be a trigger for the specific host response of MCLS. Whether these factors are new strains of microorganisms or environmental pollutants is unknown. Goldsmith et al. [6] raised the question of whether this syndrome represents a hyperimmune response reflected in the pseudomalignant reaction in the patient's cervical lymph node. Such a phenomenon has been occasionally encountered in association with various known or unknown antigenic stimuli. Kusakawa and Heiner [22] suggest that the brisk IgE response to unidentified immunogens may be genetically predetermined and that children with persistently elevated levels of IgE may be at a greater risk of acquiring the lPN-like disease and cardiovascular complications. Mortimer [23] advocates a systematic epidemiologic investigation divided into four phases to attempt to determine the cause of the disease. Elucidation of the etiology and pathogenesis of MCLS will doubtless increase Our knowledge about IPN and other related vascular diseases. The Japanese MCLS study group has lately adopted the name Kawasaki disease in place of MCLS, thus accepting it as a nosological entity [3]. It seems that MCLS or Kawasaki disease is likely to be identified increasingly and may become an important disease of childhood. HARRIS
D.
RILEY, JR.
Department of Pediatrics Children's Memorial Hospital and University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma
Downloaded from http://jid.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 23, 2015
same age range [3]. However, MCLS can be distinguished from acrodynia clinically, pathologically, and by measurement of mercury in hair, blood, and urine. It is of interest that, before the onset of the illness, the two children described from the New York City area had contact with unlaundered clothes made in Japan and wore clothing manufactured in Hong Kong and Taiwan [6]. Other diseases to be differentiated are measles, rubella, Stevens-Johnson syndrome, juvenile rheumatoid disease, and the staphylococcal scaldedskin syndrome. As mentioned previously, approximately 1%2 % of children succumb, most of whom die suddenly. Studies at autopsy of such cases have revealed an interesting finding: the cause of death was usually myocardial infarction secondary to coronary thromboarteritis. Aneurysmal dilatation of involved arteries was often noted. The pathologists concerned stated that these findings were almost indistinguishable from those of a wellknown but rare entity, infantile polyarteritis nodosa (IPN) [4, 17, 18]. By coronary angiography at various stages of the illness, more than 60% of patients examined were found to have abnormalities in the coronary arteries such as aneurysm, dilatation, stenosis, irregularity of arterial walls, and tortuosity [19]. Kato et al. [19] noted a tendency for the coronary arterial changes to regress with disappearance of the aneurysm during the observation period, but the long-term prognosis remains in question. Brachial, iliac, and aortic aneurysms and stenosis of the retinal and little cerebral arteries have also been reported [4]. Some recent evidence suggests that IPN may be the fatal form of MCLS [20, 21]. A comparative review of the pathologic findings in 19 patients with IPN from the continental United States and of fatal cases of MCLS from Hawaii and Japan was carried out at the Children's Hospital of Los Angeles, Calif. [20]. The pathologic findings were reported to be indistinguishable in the two diseases. In addition, histories of the patients with IPN included clinical features of MCLS, with recovery from the acute disease followed by sudden death several weeks later [8, 20]. A recent finding in patients is an elevated level of serum IgE; it is highest one to two weeks after the onset of illness and declines over one to two
Riley
Editorial
305
References 15.
16.
17.
18.
19.
20.
21.
22.
23.
Downloaded from http://jid.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 23, 2015
1. Kawasaki, T. Acute febrile mucocutaneous syndrome with lymph node involvement with specific desquamation of the fingers and toes in children. I pn. I. ABerg. 16: 177-222, 1967. 2. Kawasaki, T., Kosaki, F., Okawa, S., Shigematsu, I., Yanagawa, H. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan, Pediatrics 54:271-276, 1974. 3. Unsigned editorial. Kawasaki disease. Lancet 1:675676, 1976. 4. Fetterman, G. H., Hashida. Y. Mucocutaneous lymph node syndrome (MLNS): a disease widespread in I apan which demands our attention. Pediatrics 54:268-270, 1974. 5. Melish, M. E., Hicks, P. M., Larson, E. Mucocutaneous lymph node syndrome (MCLS) in the United States. Pediatr. Res. 8:427, 1974. 6. Goldsmith, R. W., Gribetz, D., Strauss, L. Mucocutaneous lymph node syndrome (MLNS) in the continental United States. Pediatrics 57:431-435, 1976. 7. Brown, I. S., Billmeier, C. I., Cox, F., Ibrahim, M., Stepp, N. P., Gibson, R. Mucocutaneous lymph node syndrome in the continental United States. I. Pediatr. 88:81-83, 1976. 8. Robinson, R., Adler, R. Mucocutaneous lymph node syndrome in California. I. Pediatr. 88: 10691070, 1976. 9. Lauer, B. A., Bruhn, F. W., Todd, I. K., Todd, W. A. Mucocutaneous lymph node syndrome in Denver. Am. I. Dis. Child. 130:610-612, 1976. 10. John, T. I., DeBenedetti, C. D., Lee, M. D. Mucocutaneous lymph .node syndrome in Arizona. Am. I. Dis. Child. 130:613-614, 1976. 11. Melish, M. E., Hicks, R. M., Larson, E. I. Mucocutaneous lymph node syndrome in the United States. Am. I. Dis. Child. 130:599-607, 1976. 12. Center for Disease ControL Mucocutaneous lymph node syndrome. Morbidity and Mortality Weekly Rep. 25(20): 157-158, 1976. 13. Radford, D. I., Sondheimer, H. M., Williams, G. I., Fowler, R. S. Mucocutaneous lymph node syndrome with coronary artery aneurysm. Am. I. Dis. Child. 130:596-598, 1976. 14. Hamashima, Y., Kishi, K., Tasaka, K. Rickettsia-
like bodies in infantile acute febrile mucocutaneous lymph-node syndrome. Lancet 2:42, 1973. Hamashima, Y., Kishi, K., Tasaka, K. Discovered and isolation of rickettsia-like bodies from MCLS patients. Progress in Medicine (Tokyo) 87: 189193, 1973. Shishido, A., Adachi, Y. In T. Kawasaki, S. Kusakawa, and I. Shigematsu [ed.]. Progress of research on Kawasaki disease (M.C.L.S.). Tokyo, 1976. Tanaka, N., Naoe, S., Kawasaki, T. Pathological study on autopsy cases of MCLS in childhoodparticularly in relation with periarteritis nodosalike arteritis. I. Jpn, Red Cross Center Hospital 2: 85-94, 1971. Yanagisava, M., Kobayashi, N., Matsuya, S. Myocardial infarction due to coronary thromboarteritis, following acute febrile mucocutaneous lymph node syndrome in an infant. Pediatrics 54: 277-281, 1974. Kato, H., Koike, S., Yamamoto, M., Ito, Y., Yano, E. Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome. I. Pediatr. 86:892-898, 1975. Landing, B. H., Larson, E. I. Apparent identity of infantile periarteritis nodosa with coronary artery involvement (lPN) and fatal mucocutaneous lymph node syndrome (MCLS): comparison of 20 patients from North America to patients from Hawaii and Japan [abstract]. In Proceedings of the second joint meeting of the Pediatric Pathology Club and Paediatric Pathology Society, Toronto, September 25-27, 1975. Jones, M. E., Nihill, M. R., Barrett, F. F., Singer, D. B., Rosenberg, H. S. Infantile periarteritis nodosa: the expanded syndrome of KawasakiFetterman [abstract]. In Proceedings of the second joint meeting of the Pediatric Pathology Club and Paediatric Pathology Society, Toronto, September 25-27, 1975. Kusakawa, S., Heiner, D. C. Elevated levels of immunoglobin E in the acute febrile mucocutaneous lymph node syndrome. Pediatr. Res. 10: 108-111, 1976. Mortimer, E. A., Jr. Mucocutaneous lymph node syndrome. The epidemiologic approach toward finding its causation. Am. J. Dis. Child. 130:593594, 1976.
•
SEPTEMBER 19 6 7
EDITORIAL ~nd
Mucocutaneous Lymph Node Syndrome (I(avvasald Ilisease)
11 deaths (1.7 % ). Epidemiological surveys Japan showed that the incidence in males was higher than that in females (1.5: 1), that the incidence was highest in one-year-old children with four-fifths of the patients younger than four years, that the incidence was highest from May to July, and that the incidence had increased sharply since 1970 [2, 3]. Kawasaki [1] noted some resemblance of MCLS to Stevens-Johnson syndrome and to scarlet fever, but he was confident that MCLS was different from and could be differentiated from these disorders. Examination of biopsy specimens of cervical lymph nodes from three cases in Kawasaki's original series [1] revealed swelling of endothelial cells of postcapillary venules and hyperplasia of reticulum cells. Biopsy specimens of skin taken from seven of Kawasaki's patients showed edema of dermis, dilatation of capillaries, and mild perivascular infiltration of lymphocytes and monocytes. None of these changes was specific. Although appropriate studies were carefully pursued in Kawasaki's series, no evidence for a bacterial or viral etiology could be identified. The possibility that MCLS is a "collagen disease" was considered but not proven [1, 3, 4]. Thus, it appeared highly likely that many cases of a new or previously unrecognized disease of unknown etiology had been described [5]. Outside of Japan the disease has so far been reported from South Korea (eight cases) , Greece (eight), the United States (five to 12), and Canada (13). The first reported instances of the disorder in the United States were in nine children of multiple races in Hawaii; these cases were described in 1974 by Melish et al. [5]. The first case was seen in 1971, and emphasis was placed on MCLS as a distinctive disease. Goldsmith et al. [6] reported a case in a two-year-old boy (August 1974)l residing in the New York City area. A second case with strikingly similar clinical features was subsequently seen in the same area. In III
[3].
With these diagnostic guidelines, the Japanese study group sent surveys to the pediatric units of the larger hospitals. These surveys identified 6,537 cases (5,524 definite and 1,013 probable) Received for publication July 13, 1976. Please address requests for reprints to Dr. Harris D. Riley, Jr., Department of Pediatrics, The University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, Oklahoma 73190.
. 1 Dates in parentheses indicate dates on which patients were first observed to have manifestations compatible with MCLS.
302
Downloaded from http://jid.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 23, 2015
In 1967, Kawasaki [1] described 50 cases in infants and young children of a seemingly selflimited disease syndrome of unknown etiology; the disease was designated as mucocutaneous lymph node syndrome (MCLS). The patients ranged in age from two months to nine years, with the great majority younger than five years of age. The cases had come to Kawasaki's attention during the six-year period from 1961 through 1966 [1, 2]. In 1970 the Japanese Ministry of Health and Welfare established a special MCLS study group [3]. This body defined the principal findings as fever (101 F-I04 F) lasting for longer than five days and not responding to antibiotics; changes of peripheral extremities (reddening and indurative edema of palms and soles and membranous desquamation from fingertips in the convalescent stage); polymorphous exanthema of the trunk without vesicles or crusts; bilateral conjunctival congestion; changes in lips and oral cavity (redness and fissuring of lips, strawberry tongue, and diffuse reddening of oropharyngeal mucosa); and acute, nonpurulent swelling of cervical lymph nodes. Other important signs were tachycardia, gallop rhythm, distant heart sounds, heart murmurs, and electrocardiographic changes; diarrhea; proteinuria and increased leukocytes in urine sediment; leukocytosis with shift to the left, slight anemia, elevated platelet count, increased erythrocyte sedimentation rate, positive C-reactive protein, increased serum u2-globulin, and no increase in titer of antistreptolysin 0; and, rarely, arthralgia, arthritis, aseptic meningitis, and mild jaundice or slight increase of serum transaminase
Editorial
75 %, swelling of cervical lymph nodes [l, 2]. The incidence of these manifestations is similar in patients reported from this country. Other findings compatible with an infection include myocarditis and pericarditis, arthritis, leukocytosis with shift to the left, increased sedimentation rate, abnormal acute-phase reactants, and occasionally aseptic meningitis and jaundice. In his early report, Kawasaki [1, 2] referred to "abnormal host response ... to infection" in patients with MCLS. Goldsmith et al. [6] speculated about the possible occurrence of "a rare but ubiquitous infectious disease which has reached epidemic proportions in Japan and which in time may become common experience elsewhere" and suggested alternatively that MCLS may represent a distinctive exanthematous disease of childhood. Kawasaki and his colleagues [2] mentioned early the clinical resemblance of MCLS to scarlet fever, particularly because of the rash and strawberry tongue. However, hemolytic streptococci have seldom been isolated, and the titer of antistreptolysin 0 is not increased in MCLS. No virus has been found, and there is no strong serological evidence of a viral origin. Hamashima et al. [14] caused excitement when they reported the presence of rickettsia-like bodies identified by electron microscopy of biopsy specimens of skin and cervical lymph nodes from 12 of 23 patients with MCLS. The bodies were located in the cytoplasm of macrophages and endothelial cells of arterioles and clustered inside the vascular lumen. These workers [15] claimed to have isolated Rickettsia from patients' whole blood by inoculation into yolk sacs after successive inoculation in guinea pigs and mice. Shishido and Adachi [16], however, failed to confirm these results. Furthermore, the epidemiological features and the unresponsiveness of the disease to antibiotics are evidence against a rickettsial etiology. Environmental pollutants, unidentified toxic agents, specific patterns of drug therapy, and an allergic reaction to chemical detergents have been considered as possible causes for explanation of the concentration of the syndrome to an as yet limited geographic area [2, 3, 6]. The similarities to another disease caused by an exogenous toxin, acrodynia, are not only clinical; acrodynia, like MCLS, appeared suddenly (at the beginning of this century) and affects persons in much the
Downloaded from http://jid.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 23, 2015
January 1976, Brown et al. [7] reported three cases that occurred in Memphis, Tenn. (November 1974, May 1975, and June 1975). Robinson and Adler [8] reported two cases recently observed in California, a 21-month-old Caucasian boy and a 3.5-year-old MexicanAmerican male. In addition to the usual clinical findings, the older child exhibited a striking polyarticular arthritis. Lauer et at [9] described four children, from eight months to 10 years old, seen in Denver during 1974-1976. None were of Oriental extraction, but one had previously resided in Hawaii. John et al. [10] reported in June 1976 four cases seen in Arizona (November 1972, December 1974, April 1975, and September 1975). Melish et al. [11] have recently described seven additional cases seen in Hawaii between 1971 and t 975. Eight of the 16 patients were Japanese, and all but one had some Oriental ethnic admixture; however, this racial background is representative of the population at the hospital where these patients were seen. In the 12 months before May 28, 1976, 14 suspect cases that have met the diagnostic criteria for the syndrome have been reported to the Center for Disease Control (Atlanta, Ga. ) from Arizona, California, Florida, Hawaii, Iowa, New York, Tennessee, and Washington, D.C. [12]. In addition, a case has been reported recently from Toronto (February 1974) [13]. As mentioned previously, the early reports of the disorder indicated that the disease was seemingly self-limited and that all patients had recovered. However, as the number of cases of MCLS increased, a new but not entirely unexpected feature was added. Fatalities were reported in 1% -2 % of cases. The deaths were more common in young infants and occurred suddenly a short time after apparent recovery from MCLS. At autopsy the cause of death appeared to be cardiovascular in origin. The etiology of MCLS is unknown at present. There are many features that suggest an infectious etiology. In the Japanese patients these features include the following: 95% of the patients have fever; 92%, polymorphous exanthema; 90%, diffuse reddening of oral mucosa; 88 % -94 %, reddening of the palms and soles with subsequent desquamation; 88%, conjunctival congestion; and
303
304
months [22]. This finding is compatible with the view that allergic arteritis plays a major role in the syndrome. If a microbial agent is identified as etiologic in MCLS, the role of IgE will not be diminished; MCLS may be an infection in which IgE plays an important role in eliminating the invader from the body [22]. Elevated levels of IgE have been found in the sera of infants who died with IPN [22]. The next stage is to look for precipitation of IgE in the affected vascular beds and tissues and to see whether specific IgE can be found [3]. As pointed out previously [3], at present one can only say that factors prevalent in the environment since the 1960s may be a trigger for the specific host response of MCLS. Whether these factors are new strains of microorganisms or environmental pollutants is unknown. Goldsmith et al. [6] raised the question of whether this syndrome represents a hyperimmune response reflected in the pseudomalignant reaction in the patient's cervical lymph node. Such a phenomenon has been occasionally encountered in association with various known or unknown antigenic stimuli. Kusakawa and Heiner [22] suggest that the brisk IgE response to unidentified immunogens may be genetically predetermined and that children with persistently elevated levels of IgE may be at a greater risk of acquiring the lPN-like disease and cardiovascular complications. Mortimer [23] advocates a systematic epidemiologic investigation divided into four phases to attempt to determine the cause of the disease. Elucidation of the etiology and pathogenesis of MCLS will doubtless increase Our knowledge about IPN and other related vascular diseases. The Japanese MCLS study group has lately adopted the name Kawasaki disease in place of MCLS, thus accepting it as a nosological entity [3]. It seems that MCLS or Kawasaki disease is likely to be identified increasingly and may become an important disease of childhood. HARRIS
D.
RILEY, JR.
Department of Pediatrics Children's Memorial Hospital and University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma
Downloaded from http://jid.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 23, 2015
same age range [3]. However, MCLS can be distinguished from acrodynia clinically, pathologically, and by measurement of mercury in hair, blood, and urine. It is of interest that, before the onset of the illness, the two children described from the New York City area had contact with unlaundered clothes made in Japan and wore clothing manufactured in Hong Kong and Taiwan [6]. Other diseases to be differentiated are measles, rubella, Stevens-Johnson syndrome, juvenile rheumatoid disease, and the staphylococcal scaldedskin syndrome. As mentioned previously, approximately 1%2 % of children succumb, most of whom die suddenly. Studies at autopsy of such cases have revealed an interesting finding: the cause of death was usually myocardial infarction secondary to coronary thromboarteritis. Aneurysmal dilatation of involved arteries was often noted. The pathologists concerned stated that these findings were almost indistinguishable from those of a wellknown but rare entity, infantile polyarteritis nodosa (IPN) [4, 17, 18]. By coronary angiography at various stages of the illness, more than 60% of patients examined were found to have abnormalities in the coronary arteries such as aneurysm, dilatation, stenosis, irregularity of arterial walls, and tortuosity [19]. Kato et al. [19] noted a tendency for the coronary arterial changes to regress with disappearance of the aneurysm during the observation period, but the long-term prognosis remains in question. Brachial, iliac, and aortic aneurysms and stenosis of the retinal and little cerebral arteries have also been reported [4]. Some recent evidence suggests that IPN may be the fatal form of MCLS [20, 21]. A comparative review of the pathologic findings in 19 patients with IPN from the continental United States and of fatal cases of MCLS from Hawaii and Japan was carried out at the Children's Hospital of Los Angeles, Calif. [20]. The pathologic findings were reported to be indistinguishable in the two diseases. In addition, histories of the patients with IPN included clinical features of MCLS, with recovery from the acute disease followed by sudden death several weeks later [8, 20]. A recent finding in patients is an elevated level of serum IgE; it is highest one to two weeks after the onset of illness and declines over one to two
Riley
Editorial
305
References 15.
16.
17.
18.
19.
20.
21.
22.
23.
Downloaded from http://jid.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 23, 2015
1. Kawasaki, T. Acute febrile mucocutaneous syndrome with lymph node involvement with specific desquamation of the fingers and toes in children. I pn. I. ABerg. 16: 177-222, 1967. 2. Kawasaki, T., Kosaki, F., Okawa, S., Shigematsu, I., Yanagawa, H. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan, Pediatrics 54:271-276, 1974. 3. Unsigned editorial. Kawasaki disease. Lancet 1:675676, 1976. 4. Fetterman, G. H., Hashida. Y. Mucocutaneous lymph node syndrome (MLNS): a disease widespread in I apan which demands our attention. Pediatrics 54:268-270, 1974. 5. Melish, M. E., Hicks, P. M., Larson, E. Mucocutaneous lymph node syndrome (MCLS) in the United States. Pediatr. Res. 8:427, 1974. 6. Goldsmith, R. W., Gribetz, D., Strauss, L. Mucocutaneous lymph node syndrome (MLNS) in the continental United States. Pediatrics 57:431-435, 1976. 7. Brown, I. S., Billmeier, C. I., Cox, F., Ibrahim, M., Stepp, N. P., Gibson, R. Mucocutaneous lymph node syndrome in the continental United States. I. Pediatr. 88:81-83, 1976. 8. Robinson, R., Adler, R. Mucocutaneous lymph node syndrome in California. I. Pediatr. 88: 10691070, 1976. 9. Lauer, B. A., Bruhn, F. W., Todd, I. K., Todd, W. A. Mucocutaneous lymph node syndrome in Denver. Am. I. Dis. Child. 130:610-612, 1976. 10. John, T. I., DeBenedetti, C. D., Lee, M. D. Mucocutaneous lymph .node syndrome in Arizona. Am. I. Dis. Child. 130:613-614, 1976. 11. Melish, M. E., Hicks, R. M., Larson, E. I. Mucocutaneous lymph node syndrome in the United States. Am. I. Dis. Child. 130:599-607, 1976. 12. Center for Disease ControL Mucocutaneous lymph node syndrome. Morbidity and Mortality Weekly Rep. 25(20): 157-158, 1976. 13. Radford, D. I., Sondheimer, H. M., Williams, G. I., Fowler, R. S. Mucocutaneous lymph node syndrome with coronary artery aneurysm. Am. I. Dis. Child. 130:596-598, 1976. 14. Hamashima, Y., Kishi, K., Tasaka, K. Rickettsia-
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