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Kawasaki syndrome: Report of four cases with acute gallbladder hydrops
Kawasaki Syndrome: Report of Four Cases With Acute Gallbladder Hydrops By Enrique Grisoni, Robert Fisher, and Robert Izant Cleveland, Ohio
O W e studied gallbladder involvement in 19 patients with Kawasaki syndrome who presented over a 4-year period from 1979 to 1982. Diagnosis and follow-up of gallbladder disease were defined by real-time ultrasound. Complete spontaneous resolution of abdominal symptomatology related to the hydropic gallbladder occurred without complication and did not require surgical intervention. W e suggest that the incidence of hydrops of the gallblader in mucocutaneous lymph node syndrome is higher than commonly appreciated, since diagnosis may be missed unless ultrasound is performed. INDEX WORDS: Kawasaki syndrome; hydrops of the gallbladder.
A W A S A K I S Y N D R O M E (KS), also K known as mucocutaneous lymph node syndrome (MLNS), first described in Japan by Tomisaku Kawasaki in 1967, is a febrile illness of undetermined origin that occurs predominantly in children under 5 years of age. Clinical features of the syndrome include prolonged fever, conjunctival injection, oropharyngeal inflammation, peripheral changes on extremities (edema, erythema or desquamation), generalized rash, and lymphadenopathy. Coronary artery aneuryms, pericardial effusion, myocardial infarction, or congestive heart failure may be present in 17% to 31% of cases. It appears to be most prevalent in Japan, where more than 24,000 cases were reported between 1968 and 1982. In the United States more than 700 cases have been reported since 1976. 2 6 Among the spectrum of associated findings reported in MLNS, the incidence of hydrops of the gallbladder, usually occurring in the first 2 weeks of illness, is reported in 5% of cases] Four cases of hydrops of the gallbladder, diagnosed and followed by ultrasound, are reported. Management of these four children was governed by careful and expectant monitoring without the need of surgical intervention. MATERIALS AND METHODS Nineteen cases of MLNS were seen since 1979 with four cases having proven hydrops of the gallbladder. The four patients with gallbladder hydrops ranged in age from 3.5 to 8
Journal of Pediatric Surgery, Vol. 19, No. 1 (February),1984
years. There were two white males, one black male, and one black female. Gallbladder hydrops was verified using real-time ultrasound in the fasting, supine state. All ultrasound studies were performed with Technicore, Toshiba, or Diasonical real-time units with 5.0 MHZ transducers and x-ray recording.
Case Reports
Case 16 An 8-year-old white male developed a tender cervical mass, ear pain, and fever which did not improve on 1 week of oral cephalosporin therapy. Physical examination revealed a febrile (39 ~ irritable child with a 6 • 6 cm tender left posterior cervical mass, conjunctivitis, marked hyperemia of the tongue, and lip desquamation. The abdomen was diffusely tender and a right upper quadrant mass was noted. Pertinent laboratory data are summarized in Table 1. Ultrasound on admission revealed a diffusely enlarged gallbladder, 9.0 cm in its greatest longitudinal dimension, and multiple enlarged lymph nodes in the left cervical chain. Twenty-four hours after admission, he developed congestive heart failure and pulmonary edema requiring digitalization and intensive care monitoring. Echocardiogram revealed left ventricular dilatation and a possible right coronary artery aneurysm. With seven days of supportive and salicylate (100 mg/ kg/d) therapy, the child was clinically well. At 3-months, follow-up ultrasound, echocardiogram, and clinical evaluation revealed a normal child.
Case 17 A 31/2-year-old black female was admitted with a 2-week history of cough, pharyngitis, vomiting, and fever to 103 ~ that had not responded to Amoxicillin. Physical examination on admission revealed a febrile, lethargic child with a macular rash on the torso, meningismus, conjunctiyitis, erythema and edema of the feet, pharyngeal erythema, right submandibular tender adenopathy, and right upper quadrant tenderness. Laboratory values are listed
From the Department o f Surgery, Rainbow Babies and Childrens Hospital, Case Western Reserve University, School o f Medicine, Cleveland, Ohio. Presented in London at the X X X Annual International Congress o f the British Association o f Paediatric Surgeons, 20-22 July, 1983. Address reprint requests to Enrique Grisoni, MD, Department o f Surgery, Cleveland Metropolitan General Hospital, 3395 Scranton Road, Cleveland, OH 44109. 9 1984 by Grune & Stratton, Inc. 0022-3468/84/1901-003501.00/0
9
10
GRISONI, FISHER, AND IZANT
Table 1. Summary of Patient Laboratory Values
Patient Test
16
17
18
19
Hemoglobin (gm/dL) Hematocrit (%) Direct Coombs White Blood Count (thous//zL) Polymorphonuclear cells (%) Lymphocytes (%) Band cells (%) Reticulocyte Count (%) Platelet count (thous/#L) Cultures Throat Blood CSF Urine Bilirubin mg/dL Total Direct Liver function tests 1. Lactate dehydrogenase (#/L) 2. SGOT (/z/L) 3. Alkaline phosphatase (/Z/L) 4. Prothrombin time Serum Amylase (Somogyi units) Serum albumin Total protein Mono screen Antistreptolysin O (Todd units) ANA Rheumatoid factor C3 C4
11.3 33.9 X 49 75 1 17 1.2 593
10.5 32.2 NEG 19.2 16 7 71 1.1 510
10.0 32.5 X 18.9 27 3 57 1.1 400
9 . 3 - 8.7 29.5-27.0 NEG 46.2 63 6 20 X 1896
NEG NEG X NEG
NEG NEG NEG NEG
NEG NEG X NEG
NEG NEG NEG NEG
1.4- .6 . 9 - .2
3.4-1.2 2 . 8 - .7
304 40-72 543 10.0/12 X 1.9-2.4 5.5 6.3 NEG X NEG X X X
356 48 108 10.0/11.6 200 2.5 5.8 NEG X X X X X
1.3 .7 247 19 324 10.O/10.6 X 3.3 6.6 NEG X NEG <20 171 37
4 . 2 - .8 3 . 8 - .5 332-466 64-44 228-288 10.4/10.6 40 1.5-2.8 4.7-7.2 NEG 125 X X X X
X--notperformed 1--95-260/Z/L-nL 2 - - 4 1 /Z/L-nL 3--55-350/Z/L-nL
in Table 1. Ultrasound of the abdomen revealed mild hepatomegaly and a hydropic gallbladder. Four days after admission with salicylate therapy and intravenous fluid support, the child was taking oral feedings and an ultrasound re-examination revealed a gallbladder which was normal in size. Follow-up 7 months later revealed a well child.
Case 18 Five days prior to admission, a 4~/2-year-old white male had fever, malaise, arthralgias, myalgias, conjunctivitis, bilateral cervical adenopathy, diarrhea, and an erythematous, macular nondesquamating rash. Admitting laboratory data are summarized in Table 1. An ultrasound was performed because of right upper quadrant guarding and persistent vomiting. The study revealed a hydropic gallbladder, 9.5 cm in its greatest longitudinal dimension. Within the first hospital day, the patient became afebrile and his appetite improved. Echocardiogram revealed a small posterior pericardial effusion and no coronary artery
pathology. On the third hospital day the child was discharged to home on aspirin (30 mg/kg/d), taking a regular diet. Ten days later he expired suddenly. A limited autopsy revealed hemopericardium from a rupture of a left coronary artery aneurysm and acute posterolateral myocardial infarction.
Case 19 A 6-year-old black male was admitted after a 1-week history of cervical adenopathy, nausea, fever, malaise, lethargy, increasing abdominal pain, and diarrhea not responsive to Amoxicillin therapy. On admission, this febrile (39 ~ listless child had marked conjunctivitis, palmar erythema, red encrusted swollen lips, posterior pharyngeal erythema, "strawberry" tongue, a right posterior cervical 5 x 5 cm tender adenopathy, and a right upper quadrant 5-cm tender mass. Pertinent laboratory values are recorded in Table 1. Ultrasound of the abdomen revealed a hydropic gallbladder, 11.5 cm in its greatest longitudinal dimension. Echocardiography revealed a pericardial effusion with right and left coronary
KAWASAKI SYNDROME: GALLBLADDER HYDROPS
11
artery dilatation. The patient improved with supportive and salicylate (30 mg/kg/d) therapy. Ultrasound examination on the eighth day of admission revealed a resolving gallbladder distention. Follow-up at 1 month has revealed a clinically well child. DISCUSSION
T h e acute diagnosis of hydrops of the g a l l b l a d der associated with M L N S should not be a diagnostic d i l e m m a with the availability o f ultrasonography and previously published references of normal g a l l b l a d d e r size in children. 7 T h e u l t r a s o n o g r a p h i c f e a t u r e of hydrops of the gallbladder, as noted by Slovis et al, 7 is t h a t of e n l a r g e m e n t without c h a n g e in n o r m a l a n a t o m i cal characteristics. All of our four patients with hydrops of the g a l l b l a d d e r had m a r k e d a b d o m i n a l pain in the right upper q u a d r a n t and vomiting that resolved in time with supportive care. All of these patients had a m a r k e d leukocytosis with a left shift, negative cultures, and variable liver function as did the m a j o r i t y of the other 15 patients without g a l l b l a d d e r hydrops. M o r t a l i t y in one case was secondary to c a r d i o v a s c u l a r injury associated
with M L N S and was not related to the gallbladder hydrops. M L N S m a y well be an i m m u n o l o g i c a l l y m e d i a t e d vascular disease initiated by a yet undefined agent as noted by Melish et al 5 and L a p o i n t e et al. 9 T h e pathology of the g a l l b l a d d e r in a patient reported by M a g i l a v y et al 8 revealed an actue i n f l a m m a t o r y process m a r k e d by a vasculitis within the muscularis of vessels in the g a l l b l a d d e r wall. M e r c e r and C a r p e n t e r noted in their series t h a t arteritis could involve any size a r t e r y and operative intervention for the complication of cystic duct obstruction with g a l l b l a d d e r necrosis and bowel infarction was f r a u g h t with a 40% surgical complication rate.~~ W e feel that patients with K a w a s a k i s y n d r o m e and a b d o m i n a l complaints or a b n o r m a l liver function should have u l t r a s o n o g r a p h y for diagnosis and follow-up of g a l l b l a d d e r hydrops, which a p p e a r s to be generally a benign, selflimiting complication as a p p r e c i a t e d in other series. 7'8,~1 S u r g i c a l i n t e r v e n t i o n should be reserved for nonresolving g a l l b l a d d e r obstruction and organ necrosis.
REFERENCES
1. Kawasaki T: MCLS: Clinical observation of 50 cases. Jpn J Allergy 16:178, 1967 2. Bell DM, Brink EW, Nitzkin JL, et al: Kawasaki Syndrome: Description of two outbreaks in the United States. N Engl J Med 304:1568-1575, 1981 3. Sasaguri Y, Kato H: Regression of aneurysms in Kawasaki Disease: A pathological study. J Pediatr 100(2):225-231, 1982 4. Canter CE, Bower RJ, Strauss AW: Atypical Kawasaki Disease with aortic aneurysms. Pediatr 68(6):885-888, Dec 1981 5. Melish ME, Hicks RV, Reddy V: Kawasaki syndrome: An update. Hosp Pract March, 99-106, 1982 6. Chung KJ, Brandt L, Fulton DR, et al: Cardiac and coronary arterial involvement in infants and children from New England with Mucocutaneous Lymph Node Syndrome (Kawasaki Disease): Angiographic-echocardiographic correlations. Am J Cardiol 50: 136-142, 1982
7. Slovis TJ, Hight DW, Phillippart AI, et al: Sonography in the diagnosis and management of hydrops of the gallbladder in children with Mucocutaneous Lymph Node Syndrome. Pediatrics 65(4):789 794, 1980 8. Magilvay DB, Speert DP, Silver TM, et al: Mucocutaneous Lymph Node Syndrome. Report of two cases complicated by gallbladder hydrops diagnosed by ultrasound. Pediatrics 61(5):699-702, 1978 9. Lapointe N, Chad Z, La Croix J, et al: Kawasaki Disease: Association with uveitis in seven patients. Pediatrics 69(3):376-379, 1982 10. Mercer S, Carpenter B: Surgical complications of Kawasaki Disease. J Ped Surg 16(4):444-448, 1981 11. Bradford B, Reid B, Weinstein B, et al: Ultrasonographic evaluation of the gallbladder in Mucocutaneous Lymph Node Syndrome. Pediatr Radiol 142(2):381-384, 1982
O W e studied gallbladder involvement in 19 patients with Kawasaki syndrome who presented over a 4-year period from 1979 to 1982. Diagnosis and follow-up of gallbladder disease were defined by real-time ultrasound. Complete spontaneous resolution of abdominal symptomatology related to the hydropic gallbladder occurred without complication and did not require surgical intervention. W e suggest that the incidence of hydrops of the gallblader in mucocutaneous lymph node syndrome is higher than commonly appreciated, since diagnosis may be missed unless ultrasound is performed. INDEX WORDS: Kawasaki syndrome; hydrops of the gallbladder.
A W A S A K I S Y N D R O M E (KS), also K known as mucocutaneous lymph node syndrome (MLNS), first described in Japan by Tomisaku Kawasaki in 1967, is a febrile illness of undetermined origin that occurs predominantly in children under 5 years of age. Clinical features of the syndrome include prolonged fever, conjunctival injection, oropharyngeal inflammation, peripheral changes on extremities (edema, erythema or desquamation), generalized rash, and lymphadenopathy. Coronary artery aneuryms, pericardial effusion, myocardial infarction, or congestive heart failure may be present in 17% to 31% of cases. It appears to be most prevalent in Japan, where more than 24,000 cases were reported between 1968 and 1982. In the United States more than 700 cases have been reported since 1976. 2 6 Among the spectrum of associated findings reported in MLNS, the incidence of hydrops of the gallbladder, usually occurring in the first 2 weeks of illness, is reported in 5% of cases] Four cases of hydrops of the gallbladder, diagnosed and followed by ultrasound, are reported. Management of these four children was governed by careful and expectant monitoring without the need of surgical intervention. MATERIALS AND METHODS Nineteen cases of MLNS were seen since 1979 with four cases having proven hydrops of the gallbladder. The four patients with gallbladder hydrops ranged in age from 3.5 to 8
Journal of Pediatric Surgery, Vol. 19, No. 1 (February),1984
years. There were two white males, one black male, and one black female. Gallbladder hydrops was verified using real-time ultrasound in the fasting, supine state. All ultrasound studies were performed with Technicore, Toshiba, or Diasonical real-time units with 5.0 MHZ transducers and x-ray recording.
Case Reports
Case 16 An 8-year-old white male developed a tender cervical mass, ear pain, and fever which did not improve on 1 week of oral cephalosporin therapy. Physical examination revealed a febrile (39 ~ irritable child with a 6 • 6 cm tender left posterior cervical mass, conjunctivitis, marked hyperemia of the tongue, and lip desquamation. The abdomen was diffusely tender and a right upper quadrant mass was noted. Pertinent laboratory data are summarized in Table 1. Ultrasound on admission revealed a diffusely enlarged gallbladder, 9.0 cm in its greatest longitudinal dimension, and multiple enlarged lymph nodes in the left cervical chain. Twenty-four hours after admission, he developed congestive heart failure and pulmonary edema requiring digitalization and intensive care monitoring. Echocardiogram revealed left ventricular dilatation and a possible right coronary artery aneurysm. With seven days of supportive and salicylate (100 mg/ kg/d) therapy, the child was clinically well. At 3-months, follow-up ultrasound, echocardiogram, and clinical evaluation revealed a normal child.
Case 17 A 31/2-year-old black female was admitted with a 2-week history of cough, pharyngitis, vomiting, and fever to 103 ~ that had not responded to Amoxicillin. Physical examination on admission revealed a febrile, lethargic child with a macular rash on the torso, meningismus, conjunctiyitis, erythema and edema of the feet, pharyngeal erythema, right submandibular tender adenopathy, and right upper quadrant tenderness. Laboratory values are listed
From the Department o f Surgery, Rainbow Babies and Childrens Hospital, Case Western Reserve University, School o f Medicine, Cleveland, Ohio. Presented in London at the X X X Annual International Congress o f the British Association o f Paediatric Surgeons, 20-22 July, 1983. Address reprint requests to Enrique Grisoni, MD, Department o f Surgery, Cleveland Metropolitan General Hospital, 3395 Scranton Road, Cleveland, OH 44109. 9 1984 by Grune & Stratton, Inc. 0022-3468/84/1901-003501.00/0
9
10
GRISONI, FISHER, AND IZANT
Table 1. Summary of Patient Laboratory Values
Patient Test
16
17
18
19
Hemoglobin (gm/dL) Hematocrit (%) Direct Coombs White Blood Count (thous//zL) Polymorphonuclear cells (%) Lymphocytes (%) Band cells (%) Reticulocyte Count (%) Platelet count (thous/#L) Cultures Throat Blood CSF Urine Bilirubin mg/dL Total Direct Liver function tests 1. Lactate dehydrogenase (#/L) 2. SGOT (/z/L) 3. Alkaline phosphatase (/Z/L) 4. Prothrombin time Serum Amylase (Somogyi units) Serum albumin Total protein Mono screen Antistreptolysin O (Todd units) ANA Rheumatoid factor C3 C4
11.3 33.9 X 49 75 1 17 1.2 593
10.5 32.2 NEG 19.2 16 7 71 1.1 510
10.0 32.5 X 18.9 27 3 57 1.1 400
9 . 3 - 8.7 29.5-27.0 NEG 46.2 63 6 20 X 1896
NEG NEG X NEG
NEG NEG NEG NEG
NEG NEG X NEG
NEG NEG NEG NEG
1.4- .6 . 9 - .2
3.4-1.2 2 . 8 - .7
304 40-72 543 10.0/12 X 1.9-2.4 5.5 6.3 NEG X NEG X X X
356 48 108 10.0/11.6 200 2.5 5.8 NEG X X X X X
1.3 .7 247 19 324 10.O/10.6 X 3.3 6.6 NEG X NEG <20 171 37
4 . 2 - .8 3 . 8 - .5 332-466 64-44 228-288 10.4/10.6 40 1.5-2.8 4.7-7.2 NEG 125 X X X X
X--notperformed 1--95-260/Z/L-nL 2 - - 4 1 /Z/L-nL 3--55-350/Z/L-nL
in Table 1. Ultrasound of the abdomen revealed mild hepatomegaly and a hydropic gallbladder. Four days after admission with salicylate therapy and intravenous fluid support, the child was taking oral feedings and an ultrasound re-examination revealed a gallbladder which was normal in size. Follow-up 7 months later revealed a well child.
Case 18 Five days prior to admission, a 4~/2-year-old white male had fever, malaise, arthralgias, myalgias, conjunctivitis, bilateral cervical adenopathy, diarrhea, and an erythematous, macular nondesquamating rash. Admitting laboratory data are summarized in Table 1. An ultrasound was performed because of right upper quadrant guarding and persistent vomiting. The study revealed a hydropic gallbladder, 9.5 cm in its greatest longitudinal dimension. Within the first hospital day, the patient became afebrile and his appetite improved. Echocardiogram revealed a small posterior pericardial effusion and no coronary artery
pathology. On the third hospital day the child was discharged to home on aspirin (30 mg/kg/d), taking a regular diet. Ten days later he expired suddenly. A limited autopsy revealed hemopericardium from a rupture of a left coronary artery aneurysm and acute posterolateral myocardial infarction.
Case 19 A 6-year-old black male was admitted after a 1-week history of cervical adenopathy, nausea, fever, malaise, lethargy, increasing abdominal pain, and diarrhea not responsive to Amoxicillin therapy. On admission, this febrile (39 ~ listless child had marked conjunctivitis, palmar erythema, red encrusted swollen lips, posterior pharyngeal erythema, "strawberry" tongue, a right posterior cervical 5 x 5 cm tender adenopathy, and a right upper quadrant 5-cm tender mass. Pertinent laboratory values are recorded in Table 1. Ultrasound of the abdomen revealed a hydropic gallbladder, 11.5 cm in its greatest longitudinal dimension. Echocardiography revealed a pericardial effusion with right and left coronary
KAWASAKI SYNDROME: GALLBLADDER HYDROPS
11
artery dilatation. The patient improved with supportive and salicylate (30 mg/kg/d) therapy. Ultrasound examination on the eighth day of admission revealed a resolving gallbladder distention. Follow-up at 1 month has revealed a clinically well child. DISCUSSION
T h e acute diagnosis of hydrops of the g a l l b l a d der associated with M L N S should not be a diagnostic d i l e m m a with the availability o f ultrasonography and previously published references of normal g a l l b l a d d e r size in children. 7 T h e u l t r a s o n o g r a p h i c f e a t u r e of hydrops of the gallbladder, as noted by Slovis et al, 7 is t h a t of e n l a r g e m e n t without c h a n g e in n o r m a l a n a t o m i cal characteristics. All of our four patients with hydrops of the g a l l b l a d d e r had m a r k e d a b d o m i n a l pain in the right upper q u a d r a n t and vomiting that resolved in time with supportive care. All of these patients had a m a r k e d leukocytosis with a left shift, negative cultures, and variable liver function as did the m a j o r i t y of the other 15 patients without g a l l b l a d d e r hydrops. M o r t a l i t y in one case was secondary to c a r d i o v a s c u l a r injury associated
with M L N S and was not related to the gallbladder hydrops. M L N S m a y well be an i m m u n o l o g i c a l l y m e d i a t e d vascular disease initiated by a yet undefined agent as noted by Melish et al 5 and L a p o i n t e et al. 9 T h e pathology of the g a l l b l a d d e r in a patient reported by M a g i l a v y et al 8 revealed an actue i n f l a m m a t o r y process m a r k e d by a vasculitis within the muscularis of vessels in the g a l l b l a d d e r wall. M e r c e r and C a r p e n t e r noted in their series t h a t arteritis could involve any size a r t e r y and operative intervention for the complication of cystic duct obstruction with g a l l b l a d d e r necrosis and bowel infarction was f r a u g h t with a 40% surgical complication rate.~~ W e feel that patients with K a w a s a k i s y n d r o m e and a b d o m i n a l complaints or a b n o r m a l liver function should have u l t r a s o n o g r a p h y for diagnosis and follow-up of g a l l b l a d d e r hydrops, which a p p e a r s to be generally a benign, selflimiting complication as a p p r e c i a t e d in other series. 7'8,~1 S u r g i c a l i n t e r v e n t i o n should be reserved for nonresolving g a l l b l a d d e r obstruction and organ necrosis.
REFERENCES
1. Kawasaki T: MCLS: Clinical observation of 50 cases. Jpn J Allergy 16:178, 1967 2. Bell DM, Brink EW, Nitzkin JL, et al: Kawasaki Syndrome: Description of two outbreaks in the United States. N Engl J Med 304:1568-1575, 1981 3. Sasaguri Y, Kato H: Regression of aneurysms in Kawasaki Disease: A pathological study. J Pediatr 100(2):225-231, 1982 4. Canter CE, Bower RJ, Strauss AW: Atypical Kawasaki Disease with aortic aneurysms. Pediatr 68(6):885-888, Dec 1981 5. Melish ME, Hicks RV, Reddy V: Kawasaki syndrome: An update. Hosp Pract March, 99-106, 1982 6. Chung KJ, Brandt L, Fulton DR, et al: Cardiac and coronary arterial involvement in infants and children from New England with Mucocutaneous Lymph Node Syndrome (Kawasaki Disease): Angiographic-echocardiographic correlations. Am J Cardiol 50: 136-142, 1982
7. Slovis TJ, Hight DW, Phillippart AI, et al: Sonography in the diagnosis and management of hydrops of the gallbladder in children with Mucocutaneous Lymph Node Syndrome. Pediatrics 65(4):789 794, 1980 8. Magilvay DB, Speert DP, Silver TM, et al: Mucocutaneous Lymph Node Syndrome. Report of two cases complicated by gallbladder hydrops diagnosed by ultrasound. Pediatrics 61(5):699-702, 1978 9. Lapointe N, Chad Z, La Croix J, et al: Kawasaki Disease: Association with uveitis in seven patients. Pediatrics 69(3):376-379, 1982 10. Mercer S, Carpenter B: Surgical complications of Kawasaki Disease. J Ped Surg 16(4):444-448, 1981 11. Bradford B, Reid B, Weinstein B, et al: Ultrasonographic evaluation of the gallbladder in Mucocutaneous Lymph Node Syndrome. Pediatr Radiol 142(2):381-384, 1982