Pediatr Cardiol DOI 10.1007/s00246-015-1144-2
CASE REPORT
Incomplete Kawasaki Disease with Coronary Artery Aneurysm and Coronary Sinus Thrombus Guang Song1 • Weidong Ren1 • Zhe Liu2 • Dan Wu1
Received: 3 January 2015 / Accepted: 4 March 2015 Ó Springer Science+Business Media New York 2015
Abstract We describe herein a rare case of coronary artery aneurysm and coronary sinus thrombus due to incomplete Kawasaki disease. To the best of our knowledge, coronary sinus thrombosis has not previously been reported as a complication of this disease. Our patient underwent thrombolytic therapy with a good response. Keywords Incomplete Kawasaki disease Coronary artery aneurysm Coronary sinus thrombus
Introduction Kawasaki disease (KD) is an acute, self-limited vasculitis first described by the Japanese pediatrician Tomisaku Kawasaki in 1967. Recently, KD has become the most common acquired heart disease in the pediatric age group. A total of 80 % of KD occurs in children between 6 months and 4 years of age [6], with 1.67 % occurring in infants \3 months of age [5]. The term ‘‘incomplete KD’’ should be reserved for children who fail to meet the strict definition for classic KD but who have compatible laboratory findings and atypical symptoms, such as shock or pleural effusion, that are not common in classical KD [4]. There must be no other explanation for their illness. The prevalence of incomplete KD is 15–20 % [6].
& Weidong Ren [email protected] 1
Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China
2
Department of Pediatrics Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, China
The etiology of KD is unknown, but activation of the immune system is an evident characteristic. The most reasonable hypothesis is that KD may be caused by an infectious agent that targets vascular tissue, in particular that of the coronary artery [3]; it is extremely rare for the coronary sinus to be involved. The infection leads to the secretion of vascular endothelial growth factor and other proinflammatory cytokines. This immune reaction destroys the intima, the internal and external elastic laminae of the coronary artery are fragmented, and ballooning occurs, leading to an arterial aneurysm. Aneurysms and coronary ectasia are detected in 15–25 % of patients with KD who do not receive treatment [2].
Case Report A 3-month-old, previously healthy male infant developed an upper respiratory tract infection 10 days prior to hospitalization. The patient had a fever and was managed with antibiotics, without good response. He presented to our hospital with a cough and diarrhea. Chest computed tomography demonstrated thickened pulmonary vascular texture and inflammation-like changes in multiple lobes and segments, leading to an initial diagnosis of acute bronchopneumonia. However, the possibility of incomplete KD was considered based on the presence of a difficult-tocontrol fever lasting more than 5 days, cervical lymphadenopathy [1.5 cm in diameter, and the presence of erythema in the hands. We planned to evaluate cardiologic findings to confirm the diagnosis of incomplete KD. On hospital day 1, laboratory testing revealed a sodium level of 132 mmol/L and a C-reactive protein level of 180 mg/L. All laboratory findings are presented in Table 1. The patient was treated with intravenous immunoglobulin,
123
Pediatr Cardiol Table 1 Laboratory findings Day
C-reactive protein (mg/L)
1
180
3
59.5
White blood cells (mm3)
Neutrophils (%)
Hemoglobin (g/L)
Platelets (mm3)
31,100
68.6
83
494,000
28,300
49.4
80
486,000
10
152
28,700
59.2
91
305,000
15
156
22,500
51.8
83
492,000
17
114
10,600
35.0
71
455,000
12,300
43.0
81
536,000 773,000
19
86.3
23
132
11,400
31.2
91
29
156
16,300
43.8
83
861,000
34
96
16,000
44.1
83
701,000
12,600
34.9
94
818,000
40
\3.45
Fig. 1 Echocardiography showing a dilated coronary sinus
Fig. 2 Echocardiography showing a thrombus (arrow) in the coronary sinus
aspirin, and latamoxef for inflammation; yeast capsules to prevent antibiotic-associated diarrhea; and intravenous saline to correct the hyponatremia. On day 3, the patient
123
Fig. 3 Echocardiography showing a dilated coronary sinus without thrombus (arrow)
had a convulsion and was found to have a sodium level of 121.2 mmol/L. With continuous replenishment of sodium, the convulsions resolved by the time of hospital discharge. Although the C-reactive protein level decreased to 59.5 mg/L on day 3, it began rising again and continued to increase until day 15, when it reached 156 mg/L. On this day, the platelet count recovered to 492,000/mm3, after initially decreasing from 494,000 to 305,000/mm3. On day 10, echocardiography revealed a healthy heart, with the right coronary artery measuring 1.8 mm in diameter and the left measuring 1.8 mm; there was no aneurysm. However, on day 15, coronary aneurysms were present on repeat echocardiography. The left coronary artery now measured 4.1 mm, the circumflex branch measured 1.5 mm, and the anterior descending branch measured 3.4 mm, with a fusiform aneurysm measuring 4.3 mm. The right coronary artery measured 4.6 mm, with a fusiform aneurysm measuring 5.4 mm. Intravenous immunoglobulin treatment was repeated for a 2-day course. On day 17, the patient finally achieved a normal body
Pediatr Cardiol Table 2 Echocardiographic findings Day
Left coronary artery (mm)
Circumflex (mm)
Anterior descending (mm)
Right coronary artery (mm)
Coronary sinus (mm)
Ejection fraction (%)
10
1.8
–
–
1.8
–
68
15
4.1
1.4
3.4–4.3
4.6–5.4
2
61
23
5.1
1.7
3.3–4.1
4.6–5.2
2
57
29
4.5
1.5
3.3–4.3
4.6–5.3
7 with thrombus
64
34
3.7
1.3
3.3–4.4
4.4–5.5
6
67
70
3.2
1.3
3.0–4.1
3.8–4.7
4
69
temperature, and the white blood cell count returned to normal. On day 19, the C-reactive protein level decreased to 86.3 mg/L, but rose again by day 23–132 mg/L. The patient was treated with methylprednisolone for 3 days. Echocardiography findings of coronary artery aneurysm remained stable, and the results of anti-neutrophil cytoplasmic antibody (ANCA) testing were negative. On day 29, the patient experienced desquamation of the fingers. Echocardiography showed that the coronary sinus was dilated to 7 mm and contained a thrombus measuring 5.4 9 5.2 mm (Figs. 1, 2). The patient was treated with intravenous low molecular weight heparin sodium for six consecutive days. On day 34, echocardiography showed a dilated coronary sinus without thrombus (Fig. 3). The patient was treated with 5 mg of methylprednisolone for 1 day. On day 40, ANCA testing was repeated and was again negative. The C-reactive protein level returned to normal, although the platelet count remained elevated because of the methylprednisolone treatment. The patient was discharged on this day. One month later, echocardiography showed persistent aneurysms, slightly diminished in size (Table 2).
Discussion The diagnosis of incomplete KD is quite challenging, especially in children younger than 6 months of age, as younger infants are likely to present with fewer clinical features than their older counterparts and are therefore less likely to fulfill the full diagnostic criteria. The optimal time for treatment is within the first 10 days of illness. Aspirin and intravenous immunoglobulin should be given if incomplete KD is suspected, regardless of the echocardiographic findings. In patients who are resistant to
intravenous immunoglobulin, intravenous methylprednisolone is the most accepted treatment. A small prospective study found that following the American Heart Association guidelines, especially the early use of echocardiography, increases the diagnostic sensitivity and treatment rate [2]. The main aim of echocardiography is to assess the presence of coronary artery dilation, aneurysm formation, or pericardial effusion, in addition to evaluating ventricular function. The coronary sinus should always be measured. It is possible that our patient experienced a thrombus in the coronary sinus after the aneurysms appeared because of KD-induced vascular damage and injury to the coronary microcirculation system [1]. Conflict of interest disclose.
The authors have no conflicts of interest to
References 1. Hamaoka K, Onouchi Z, Kamiya Y, Sakata K (1998) Evaluation of coronary flow velocity dynamics and flow reserve in patients with Kawasaki disease by means of a Doppler guide wire. J Am Coll Cardiol 31(4):833–840 2. Heuclin T, Dubos F, Hue V, Godart F, Francart C, Vincent P et al (2009) Increased detection rate of Kawasaki disease using new diagnostic algorithm, including early use of echocardiography. J Pediatr 155(5):695–699 3. Rowley AH, Baker SC, Orenstein JM, Shulman ST (2008) Searching for the cause of Kawasaki diseased-cytoplasmic inclusion bodies provide new insight. Nat Rev Microbiol 6(5):394–401 4. Sa´nchez-Manubens J, Bou R, Anton J (2014) Diagnosis and classification of Kawasaki disease. J Autoimmun 48–49:113–117 5. Tseng CF, Fu YC, Fu LS, Betau H, Chi CS (2001) Clinical spectrum of Kawasaki disease in infants. Zhonghua Yi Xue Za Zhi 64(3):168–173 6. Yim D, Curtis N, Cheung M, Burgner D (2013) An update on Kawasaki disease II: clinical features, diagnosis, treatment and outcomes. J Paediatr Child Health 49(8):614–623
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CASE REPORT
Incomplete Kawasaki Disease with Coronary Artery Aneurysm and Coronary Sinus Thrombus Guang Song1 • Weidong Ren1 • Zhe Liu2 • Dan Wu1
Received: 3 January 2015 / Accepted: 4 March 2015 Ó Springer Science+Business Media New York 2015
Abstract We describe herein a rare case of coronary artery aneurysm and coronary sinus thrombus due to incomplete Kawasaki disease. To the best of our knowledge, coronary sinus thrombosis has not previously been reported as a complication of this disease. Our patient underwent thrombolytic therapy with a good response. Keywords Incomplete Kawasaki disease Coronary artery aneurysm Coronary sinus thrombus
Introduction Kawasaki disease (KD) is an acute, self-limited vasculitis first described by the Japanese pediatrician Tomisaku Kawasaki in 1967. Recently, KD has become the most common acquired heart disease in the pediatric age group. A total of 80 % of KD occurs in children between 6 months and 4 years of age [6], with 1.67 % occurring in infants \3 months of age [5]. The term ‘‘incomplete KD’’ should be reserved for children who fail to meet the strict definition for classic KD but who have compatible laboratory findings and atypical symptoms, such as shock or pleural effusion, that are not common in classical KD [4]. There must be no other explanation for their illness. The prevalence of incomplete KD is 15–20 % [6].
& Weidong Ren [email protected] 1
Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China
2
Department of Pediatrics Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, China
The etiology of KD is unknown, but activation of the immune system is an evident characteristic. The most reasonable hypothesis is that KD may be caused by an infectious agent that targets vascular tissue, in particular that of the coronary artery [3]; it is extremely rare for the coronary sinus to be involved. The infection leads to the secretion of vascular endothelial growth factor and other proinflammatory cytokines. This immune reaction destroys the intima, the internal and external elastic laminae of the coronary artery are fragmented, and ballooning occurs, leading to an arterial aneurysm. Aneurysms and coronary ectasia are detected in 15–25 % of patients with KD who do not receive treatment [2].
Case Report A 3-month-old, previously healthy male infant developed an upper respiratory tract infection 10 days prior to hospitalization. The patient had a fever and was managed with antibiotics, without good response. He presented to our hospital with a cough and diarrhea. Chest computed tomography demonstrated thickened pulmonary vascular texture and inflammation-like changes in multiple lobes and segments, leading to an initial diagnosis of acute bronchopneumonia. However, the possibility of incomplete KD was considered based on the presence of a difficult-tocontrol fever lasting more than 5 days, cervical lymphadenopathy [1.5 cm in diameter, and the presence of erythema in the hands. We planned to evaluate cardiologic findings to confirm the diagnosis of incomplete KD. On hospital day 1, laboratory testing revealed a sodium level of 132 mmol/L and a C-reactive protein level of 180 mg/L. All laboratory findings are presented in Table 1. The patient was treated with intravenous immunoglobulin,
123
Pediatr Cardiol Table 1 Laboratory findings Day
C-reactive protein (mg/L)
1
180
3
59.5
White blood cells (mm3)
Neutrophils (%)
Hemoglobin (g/L)
Platelets (mm3)
31,100
68.6
83
494,000
28,300
49.4
80
486,000
10
152
28,700
59.2
91
305,000
15
156
22,500
51.8
83
492,000
17
114
10,600
35.0
71
455,000
12,300
43.0
81
536,000 773,000
19
86.3
23
132
11,400
31.2
91
29
156
16,300
43.8
83
861,000
34
96
16,000
44.1
83
701,000
12,600
34.9
94
818,000
40
\3.45
Fig. 1 Echocardiography showing a dilated coronary sinus
Fig. 2 Echocardiography showing a thrombus (arrow) in the coronary sinus
aspirin, and latamoxef for inflammation; yeast capsules to prevent antibiotic-associated diarrhea; and intravenous saline to correct the hyponatremia. On day 3, the patient
123
Fig. 3 Echocardiography showing a dilated coronary sinus without thrombus (arrow)
had a convulsion and was found to have a sodium level of 121.2 mmol/L. With continuous replenishment of sodium, the convulsions resolved by the time of hospital discharge. Although the C-reactive protein level decreased to 59.5 mg/L on day 3, it began rising again and continued to increase until day 15, when it reached 156 mg/L. On this day, the platelet count recovered to 492,000/mm3, after initially decreasing from 494,000 to 305,000/mm3. On day 10, echocardiography revealed a healthy heart, with the right coronary artery measuring 1.8 mm in diameter and the left measuring 1.8 mm; there was no aneurysm. However, on day 15, coronary aneurysms were present on repeat echocardiography. The left coronary artery now measured 4.1 mm, the circumflex branch measured 1.5 mm, and the anterior descending branch measured 3.4 mm, with a fusiform aneurysm measuring 4.3 mm. The right coronary artery measured 4.6 mm, with a fusiform aneurysm measuring 5.4 mm. Intravenous immunoglobulin treatment was repeated for a 2-day course. On day 17, the patient finally achieved a normal body
Pediatr Cardiol Table 2 Echocardiographic findings Day
Left coronary artery (mm)
Circumflex (mm)
Anterior descending (mm)
Right coronary artery (mm)
Coronary sinus (mm)
Ejection fraction (%)
10
1.8
–
–
1.8
–
68
15
4.1
1.4
3.4–4.3
4.6–5.4
2
61
23
5.1
1.7
3.3–4.1
4.6–5.2
2
57
29
4.5
1.5
3.3–4.3
4.6–5.3
7 with thrombus
64
34
3.7
1.3
3.3–4.4
4.4–5.5
6
67
70
3.2
1.3
3.0–4.1
3.8–4.7
4
69
temperature, and the white blood cell count returned to normal. On day 19, the C-reactive protein level decreased to 86.3 mg/L, but rose again by day 23–132 mg/L. The patient was treated with methylprednisolone for 3 days. Echocardiography findings of coronary artery aneurysm remained stable, and the results of anti-neutrophil cytoplasmic antibody (ANCA) testing were negative. On day 29, the patient experienced desquamation of the fingers. Echocardiography showed that the coronary sinus was dilated to 7 mm and contained a thrombus measuring 5.4 9 5.2 mm (Figs. 1, 2). The patient was treated with intravenous low molecular weight heparin sodium for six consecutive days. On day 34, echocardiography showed a dilated coronary sinus without thrombus (Fig. 3). The patient was treated with 5 mg of methylprednisolone for 1 day. On day 40, ANCA testing was repeated and was again negative. The C-reactive protein level returned to normal, although the platelet count remained elevated because of the methylprednisolone treatment. The patient was discharged on this day. One month later, echocardiography showed persistent aneurysms, slightly diminished in size (Table 2).
Discussion The diagnosis of incomplete KD is quite challenging, especially in children younger than 6 months of age, as younger infants are likely to present with fewer clinical features than their older counterparts and are therefore less likely to fulfill the full diagnostic criteria. The optimal time for treatment is within the first 10 days of illness. Aspirin and intravenous immunoglobulin should be given if incomplete KD is suspected, regardless of the echocardiographic findings. In patients who are resistant to
intravenous immunoglobulin, intravenous methylprednisolone is the most accepted treatment. A small prospective study found that following the American Heart Association guidelines, especially the early use of echocardiography, increases the diagnostic sensitivity and treatment rate [2]. The main aim of echocardiography is to assess the presence of coronary artery dilation, aneurysm formation, or pericardial effusion, in addition to evaluating ventricular function. The coronary sinus should always be measured. It is possible that our patient experienced a thrombus in the coronary sinus after the aneurysms appeared because of KD-induced vascular damage and injury to the coronary microcirculation system [1]. Conflict of interest disclose.
The authors have no conflicts of interest to
References 1. Hamaoka K, Onouchi Z, Kamiya Y, Sakata K (1998) Evaluation of coronary flow velocity dynamics and flow reserve in patients with Kawasaki disease by means of a Doppler guide wire. J Am Coll Cardiol 31(4):833–840 2. Heuclin T, Dubos F, Hue V, Godart F, Francart C, Vincent P et al (2009) Increased detection rate of Kawasaki disease using new diagnostic algorithm, including early use of echocardiography. J Pediatr 155(5):695–699 3. Rowley AH, Baker SC, Orenstein JM, Shulman ST (2008) Searching for the cause of Kawasaki diseased-cytoplasmic inclusion bodies provide new insight. Nat Rev Microbiol 6(5):394–401 4. Sa´nchez-Manubens J, Bou R, Anton J (2014) Diagnosis and classification of Kawasaki disease. J Autoimmun 48–49:113–117 5. Tseng CF, Fu YC, Fu LS, Betau H, Chi CS (2001) Clinical spectrum of Kawasaki disease in infants. Zhonghua Yi Xue Za Zhi 64(3):168–173 6. Yim D, Curtis N, Cheung M, Burgner D (2013) An update on Kawasaki disease II: clinical features, diagnosis, treatment and outcomes. J Paediatr Child Health 49(8):614–623
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