INFECTIOUS DISEASE
The Mucocutaneous
Lymph Node Syndrome
Description of an Affected 21-Month-Old Child in Charles J.
HE
MUCOCUTANEOUS LYMPH NODE SYNDROME (MLNS), originally described in Japan, has now been reported from various parts of the continental United States.1-4 Most of the Japanese observations and investigations have been done within the Ministry of Health and Welfare of the Japanese government.5,6 The etiology of the disease remains unknown, but several studies have suggested either an association with Rickettsiae, or an autoimmune response to an unknown antigen8 Mortality from the disease, estimated at 1 to 2 per cent, mairalyoccurs from coronary aneurysms, coronary artery thrombosis, and myocardial infarction.9>1° We here describe a child with MLNS seen recently at the Children’s Mercy Hospital, Kansas City, Missouri.
Case
Report
A 21-month-c~ld black male
was examined in the emergency room on January 17, 1976 because of subcutaneous swellings behind his ears. He was afebrile. A white blood cell (WBC) count was 14,600/cmm with 69 per cent PMI~is, 22 per cent Ls, 8 per cent Ms, and 1 per cent PMEs. Serum amylase test was not elevated, and the spot test for infectious mononucleosis was negative. The initial impression was streptococcal pharyn-
From the Children’s Mercy Hospital and the Uniof Missouri-Kansas City, School of Medicine, Kansas City. Mo. Correspondence to Herbert A. Wenner, I~I.T)., the Children’s Mercy Hospital, 24th at Gillham Road, Kansas City, Mo 64108.
versity
Siegel, M.D.,
Kansas
City
Herbert A. Wenner, M.D.
gitis with enlarged cerwical lymph nodes. The infant was given an intramuscular injection of 600,000 units of CR bicillin. The throat culture did not yield hemotytic streptococci. On January 19. two days later, he was brought back to the clinic because of fever and progressive cervical lymphadenitis. He was letlrar~ic and complained of~ pain in his neck. An erytheniatous papular rash, generalized in distribution, had begun on the preceding clay. He was admitted to the infectious disease unit c~f’ the hospital. He had no significant previous His I sister. age four years, was reported to have had &dquo;threeday n~errsles&dquo; on about January 1C~, 1976. When examined on January 1~7, he was welldeveloped and wen-nourished but lethargic. His temperature was J9.2 ~~; pulse 90: respiratory rate 30 per minute. The presenting signs included mild’I bilateral conjunctivitis and bright red, swotten pharyngeal tonsiuar tissue without exudate. His lips were hery red. cracked and peeling; his tongue had the strawberry appearance associated with scay-let fever. Prominent, tender lymph nocles were present mainly in the posterior triangte of the neck below the angle of mandible. The heart rate (90 per minute) was regular in sequence, without murmur or gallop. Peripheral pulses were equal and strong. The chest was clear to auscultation. A bright red rash was present over the palms and soles. Elsewhere there was a diffuse ervthematous macuiopapuiar rash, especially prominent on the f’ace, abdomen, and back. On the second day of hospitalization, both the hands and feet were visibly swollen. Excepting f’or the intense redness of lips and oropharyngeat mucosa, no other mucocutaneous lesions developed. By the fifth day, the rash had resc>lved, and the fever was gone by the next day. During the first week of illness, he was querulous, extremely irritable, and cried with pain when his ankles or knees were moved. His condition improved 1105
slowly.
His rash
desquamated.
At the end of the
ship,’ but
second week of 1~«spitalizatic~n, he was sent home. He had received only intravenous fluids and
antipyretics, as supportive therapy. In the hospital his WBC was 21,900/cmm, with 85 per cent P~IfV’s, lymphocytes 10 per cent, monocytes 5 per cent; his hemoglobin was 11.5 gm. Erythrocyte sedimentation rate was 40 mm/hour; blood glucose was 69 per cent; liver function studies (SGOT, bilirrrbin) were normal for age. The CSF contained 5 WBC; with glucose 62 mg/100 m3, and protein 38 mg/100 nil. ASO was 125 Todd units. Urine crzlture was negative for bacteria; analysis showed 25 BVBC/hpf. Tests four fe~rile and cold aggiutinins in the blood stream were
negative.
Fluid aspirated from an enlarged lymph node was cultured on sheep’s blood and chocoiate agar plates; no bacteria were recovered, The serum IgE obtained during the acute phase of illness (seven days after onset) was 65 IlJ/ml (nc~rnraf ‘?6-fi I I Er/nz1). Acute and convalescent sera were nonreactive against four rickettsial antigens. (These tests were performed at the Center for Disease Cc~ntrol, U.S. Department of Health, Education, and Welfare. Atlanta, Georgia.) Similarsera were nonreactive with rubella antigen. Feces, naso- and oropharynx samples were inoculated on tissue cultures; no virus was identified. An EKG on the second day of’ hospitalization showed premature ventricutar contractions; two other EKG’s ciuring the second week were within normal limits. At discharge, the differential leukocyte count was within normal valves; the hemoglobin concentration had f’allen to 8.9 gmll 00 ml. At a recent fo!)ow-up, he was in excellent health.
Comment A continuum of fever (>5 davs) with three of the five following clinical signs-1) conjunctivitis, 2) nonsuppurative cervical lymphadenitis, 3) erythema of the lips or pharynx, 4) reddening or swelling of palms and soles, and 5) polymorphous exanthem of the torsoshould suggest MLNS. Our patient fulfilled these criteria, and manifested additionally, possible mild carditis, sterile pyuria, leukocytosis, anemia and a negative ASO test. All these changes have been observed previously with the MLNS.1.11 A predilection for causing arteritis, especially of the coronary arteries, makes this disease one of the leading causes of myocardial infarction during infancy in Japan. 6,7,9 In this respect, it resembles juvenile periarteritis nodosa. The elevated level of immunoglobulin E may support this relation’
1106
the distinctive feature between the diseases is the rather good prognosis of MLNS. Our patient had transitory premature ventricular contractions but no other signs of cardiac inadequacy. Our patient’s serum seven days following onset of illness did not have a significant elevation of IgE; not all patients do have such rises.’ Both acute and convalescent specimens of’ sera were nonreactive to rickettsial antigens. Our patient differed possibly from those described by others in the generalized desquamation that involved the trunk and extremities.~5 This report is presented to note again the occurrence of MLNS in the United States, and hence further alert practicing physicians to this disease entity. Since its etiology is unknown, therapy should be primarily supportive ; neither antimicrobial agents not steroids appear to be beneficial. two
.
References 1. Brown, J.: Mucocutaneous lymph node syndrome in the continenta) United States. J. Pediatr. 88:
81. 1976. 2. Goldsmith, R. W. et al.: Mucocutaneous Ivmph node syndrome in the continental United States. Pediatrics 57: 431, 1976. 3. Lauer. B. A., Bruhn, F. W., Todd. J. K. and Todd, W. A.: Mucocutaneous lymph node syndrome in Denver. Am. J. Dis. Child. 130: 610, 1976. 4. John. T. J,. DeBenedetti, C. D., and Zee, M. L.: Mucocutaneous lymph node syndrome in Arizona. Am. J. Dis. Child. 130: 6t3, 1976. 5. Kawasaki, T., Kosaki, F., Okawa. S. et al.: A new infantile febrile mucocutaneous lymph node svndrome (MLNS) prevailing in Japan. Pediatrics 54: 271. 1974. 6. Tanaka, N., Sekimoto, K., and Naoe. S.: Kawasaki disease. Arch. Pathol. Lab. Med. 100: 81, 1976. 7. Kusakawa, S., and Heiner, D.: Elevated levels of immunoglobulin E in the acute febrile mucocutaneous lvmph node syndrome. Pediatr. Res. 10: 108. 1976. 8. Hamashima, Y., Kishi, K., and Tasaka. K.: Rickettsialike bodies in infantile acute febrile mucocutaneous lymph-node syndrome. Lancet 2: 42. 1973. 9. Kato, H., et al .: Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome. J. Pediatr. 86: 892, 1975. 10. M.,Kobayashi, N., and Watsuva, S.: Myocardial infarction due to coronary thromboarteritis, following acute febrile mucocutaneous lymph node syndrome (MLNS) in an infant. Pediatrics 54: 277. 1974. 11. Melish. M. E., Hicks, R. M., and Larson. E. J.: Mucocutaneous lymph node syndrome in the United States. Am. J. Dis. Child. 130: 599. 1976.
Yanagisawa.
The Mucocutaneous
Lymph Node Syndrome
Description of an Affected 21-Month-Old Child in Charles J.
HE
MUCOCUTANEOUS LYMPH NODE SYNDROME (MLNS), originally described in Japan, has now been reported from various parts of the continental United States.1-4 Most of the Japanese observations and investigations have been done within the Ministry of Health and Welfare of the Japanese government.5,6 The etiology of the disease remains unknown, but several studies have suggested either an association with Rickettsiae, or an autoimmune response to an unknown antigen8 Mortality from the disease, estimated at 1 to 2 per cent, mairalyoccurs from coronary aneurysms, coronary artery thrombosis, and myocardial infarction.9>1° We here describe a child with MLNS seen recently at the Children’s Mercy Hospital, Kansas City, Missouri.
Case
Report
A 21-month-c~ld black male
was examined in the emergency room on January 17, 1976 because of subcutaneous swellings behind his ears. He was afebrile. A white blood cell (WBC) count was 14,600/cmm with 69 per cent PMI~is, 22 per cent Ls, 8 per cent Ms, and 1 per cent PMEs. Serum amylase test was not elevated, and the spot test for infectious mononucleosis was negative. The initial impression was streptococcal pharyn-
From the Children’s Mercy Hospital and the Uniof Missouri-Kansas City, School of Medicine, Kansas City. Mo. Correspondence to Herbert A. Wenner, I~I.T)., the Children’s Mercy Hospital, 24th at Gillham Road, Kansas City, Mo 64108.
versity
Siegel, M.D.,
Kansas
City
Herbert A. Wenner, M.D.
gitis with enlarged cerwical lymph nodes. The infant was given an intramuscular injection of 600,000 units of CR bicillin. The throat culture did not yield hemotytic streptococci. On January 19. two days later, he was brought back to the clinic because of fever and progressive cervical lymphadenitis. He was letlrar~ic and complained of~ pain in his neck. An erytheniatous papular rash, generalized in distribution, had begun on the preceding clay. He was admitted to the infectious disease unit c~f’ the hospital. He had no significant previous His I sister. age four years, was reported to have had &dquo;threeday n~errsles&dquo; on about January 1C~, 1976. When examined on January 1~7, he was welldeveloped and wen-nourished but lethargic. His temperature was J9.2 ~~; pulse 90: respiratory rate 30 per minute. The presenting signs included mild’I bilateral conjunctivitis and bright red, swotten pharyngeal tonsiuar tissue without exudate. His lips were hery red. cracked and peeling; his tongue had the strawberry appearance associated with scay-let fever. Prominent, tender lymph nocles were present mainly in the posterior triangte of the neck below the angle of mandible. The heart rate (90 per minute) was regular in sequence, without murmur or gallop. Peripheral pulses were equal and strong. The chest was clear to auscultation. A bright red rash was present over the palms and soles. Elsewhere there was a diffuse ervthematous macuiopapuiar rash, especially prominent on the f’ace, abdomen, and back. On the second day of hospitalization, both the hands and feet were visibly swollen. Excepting f’or the intense redness of lips and oropharyngeat mucosa, no other mucocutaneous lesions developed. By the fifth day, the rash had resc>lved, and the fever was gone by the next day. During the first week of illness, he was querulous, extremely irritable, and cried with pain when his ankles or knees were moved. His condition improved 1105
slowly.
His rash
desquamated.
At the end of the
ship,’ but
second week of 1~«spitalizatic~n, he was sent home. He had received only intravenous fluids and
antipyretics, as supportive therapy. In the hospital his WBC was 21,900/cmm, with 85 per cent P~IfV’s, lymphocytes 10 per cent, monocytes 5 per cent; his hemoglobin was 11.5 gm. Erythrocyte sedimentation rate was 40 mm/hour; blood glucose was 69 per cent; liver function studies (SGOT, bilirrrbin) were normal for age. The CSF contained 5 WBC; with glucose 62 mg/100 m3, and protein 38 mg/100 nil. ASO was 125 Todd units. Urine crzlture was negative for bacteria; analysis showed 25 BVBC/hpf. Tests four fe~rile and cold aggiutinins in the blood stream were
negative.
Fluid aspirated from an enlarged lymph node was cultured on sheep’s blood and chocoiate agar plates; no bacteria were recovered, The serum IgE obtained during the acute phase of illness (seven days after onset) was 65 IlJ/ml (nc~rnraf ‘?6-fi I I Er/nz1). Acute and convalescent sera were nonreactive against four rickettsial antigens. (These tests were performed at the Center for Disease Cc~ntrol, U.S. Department of Health, Education, and Welfare. Atlanta, Georgia.) Similarsera were nonreactive with rubella antigen. Feces, naso- and oropharynx samples were inoculated on tissue cultures; no virus was identified. An EKG on the second day of’ hospitalization showed premature ventricutar contractions; two other EKG’s ciuring the second week were within normal limits. At discharge, the differential leukocyte count was within normal valves; the hemoglobin concentration had f’allen to 8.9 gmll 00 ml. At a recent fo!)ow-up, he was in excellent health.
Comment A continuum of fever (>5 davs) with three of the five following clinical signs-1) conjunctivitis, 2) nonsuppurative cervical lymphadenitis, 3) erythema of the lips or pharynx, 4) reddening or swelling of palms and soles, and 5) polymorphous exanthem of the torsoshould suggest MLNS. Our patient fulfilled these criteria, and manifested additionally, possible mild carditis, sterile pyuria, leukocytosis, anemia and a negative ASO test. All these changes have been observed previously with the MLNS.1.11 A predilection for causing arteritis, especially of the coronary arteries, makes this disease one of the leading causes of myocardial infarction during infancy in Japan. 6,7,9 In this respect, it resembles juvenile periarteritis nodosa. The elevated level of immunoglobulin E may support this relation’
1106
the distinctive feature between the diseases is the rather good prognosis of MLNS. Our patient had transitory premature ventricular contractions but no other signs of cardiac inadequacy. Our patient’s serum seven days following onset of illness did not have a significant elevation of IgE; not all patients do have such rises.’ Both acute and convalescent specimens of’ sera were nonreactive to rickettsial antigens. Our patient differed possibly from those described by others in the generalized desquamation that involved the trunk and extremities.~5 This report is presented to note again the occurrence of MLNS in the United States, and hence further alert practicing physicians to this disease entity. Since its etiology is unknown, therapy should be primarily supportive ; neither antimicrobial agents not steroids appear to be beneficial. two
.
References 1. Brown, J.: Mucocutaneous lymph node syndrome in the continenta) United States. J. Pediatr. 88:
81. 1976. 2. Goldsmith, R. W. et al.: Mucocutaneous Ivmph node syndrome in the continental United States. Pediatrics 57: 431, 1976. 3. Lauer. B. A., Bruhn, F. W., Todd. J. K. and Todd, W. A.: Mucocutaneous lymph node syndrome in Denver. Am. J. Dis. Child. 130: 610, 1976. 4. John. T. J,. DeBenedetti, C. D., and Zee, M. L.: Mucocutaneous lymph node syndrome in Arizona. Am. J. Dis. Child. 130: 6t3, 1976. 5. Kawasaki, T., Kosaki, F., Okawa. S. et al.: A new infantile febrile mucocutaneous lymph node svndrome (MLNS) prevailing in Japan. Pediatrics 54: 271. 1974. 6. Tanaka, N., Sekimoto, K., and Naoe. S.: Kawasaki disease. Arch. Pathol. Lab. Med. 100: 81, 1976. 7. Kusakawa, S., and Heiner, D.: Elevated levels of immunoglobulin E in the acute febrile mucocutaneous lvmph node syndrome. Pediatr. Res. 10: 108. 1976. 8. Hamashima, Y., Kishi, K., and Tasaka. K.: Rickettsialike bodies in infantile acute febrile mucocutaneous lymph-node syndrome. Lancet 2: 42. 1973. 9. Kato, H., et al .: Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome. J. Pediatr. 86: 892, 1975. 10. M.,Kobayashi, N., and Watsuva, S.: Myocardial infarction due to coronary thromboarteritis, following acute febrile mucocutaneous lymph node syndrome (MLNS) in an infant. Pediatrics 54: 277. 1974. 11. Melish. M. E., Hicks, R. M., and Larson. E. J.: Mucocutaneous lymph node syndrome in the United States. Am. J. Dis. Child. 130: 599. 1976.
Yanagisawa.
