Hypertension Triggers the Rupture of Coronary Artery Aneurysm in an 8‐Year‐Old Boy With Kawasaki Disease

To the Editor:

Kawasaki disease (KD), first described in 1967, is an acute, life‐threatening vasculitis of unknown etiology with a predilection for the coronary artery. According to an epidemiological survey in Shanghai, China, the annual incidence of KD is about 46 per 100,000 children younger than 5 years. Among them, 4.3% of patients treated with intravenous immunoglobulin (IVIG) will develop coronary artery aneurysm (CAA).1 KD associated‐CAA is prone to rupture in the acute stage and can also lead to stenosis or myocardial infarction later in life.2 However, the potential risk factors for these adverse outcomes remain unclear. In the present report, we encountered a fatal case of KD in a boy with moderate CAA and obvious hypertension.

A previously healthy 8‐year‐old Chinese boy was referred to our department with a 6‐day history of fever, abdominal pain, irritability, cervical lymphadenopathy, and truncal dermatitis. On admission, his blood pressure was 155/110 mm Hg, heart rate 112 beats per minute, axillary temperature 41.0°C, respiratory rate 32 breaths per minute, and oxygen saturation 98%. Physical examination revealed bilateral conjunctival congestion, cracked lips, and edema of the extremities. The maximum diameter of cervical lymph node was approximately 5 cm. Cardiac and pulmonary physical examinations were both unremarkable. The abdomen showed no clinical signs of masses or enlarged organs, except for periumbilical tenderness. Laboratory studies exhibited leukocytosis (white blood cell [WBC] 21.24×10⁹/L], irregular liver function (alanine transaminase activity 251 units/L, aspartate transaminase activity 43 units/L), elevation of acute‐phase reactants (C‐reactive protein [CRP] 90.8 mg/L, erythrocyte sedimentation rate [ESR] 62 mm/h), and positive immunofluorescence for immunoglobulin M to Mycoplasma pneumoniae (MP). Chest x‐ray showed patches of pneumonia at both hilar regions radiating outwards along the course of the bronchovascular markings. Echocardiography showed diffuse dilatation of the left and right coronary arteries to 3.7 mm and 5.2 mm diameter, respectively. Results from the patient's admission blood culture were negative. Abdominal and urinary tract ultrasonography demonstrated no abnormal findings. Based on these above clinical and laboratory findings, the patient was diagnosed with KD and treated with IVIG (2 g/kg) and high‐dose aspirin (30 mg/kg/d). In addition, ramipril (5 mg/d) was administered to lower his blood pressure and erythromycin (30 mg/kg/d) to treat MP infection. Three days later he received another 2 g/kg dose of IVIG plus methylprednisolone (2 mg/kg/d) for persistent fever and systemic inflammation. His blood pressure remained at around 160/120 mm Hg. On the 12th day of illness, our patient experienced cyanosis, irritability, and unconsciousness. He deteriorated rapidly and was declared dead despite aggressive attempts at resuscitation. Postmortem findings showed that a rupture of CAA occurred in the right coronary arteries.

In 2004, the American Heart Association (AHA) published diagnostic criteria for KD, which included fever for at least 5 days and four or more of the following five major clinical features: conjunctival injection, cervical lymphadenopathy, oral mucosal changes, polymorphous eruption, and swelling or redness of the extremities. Although there is no specific diagnostic test for KD, leukocytosis is typical during the acute stage, and approximately 50% of patients have WBC >15×10⁹/L. In addition, elevation of ESR and CRP are nearly universal in KD.3 More importantly, up to 25% of patients with untreated KD and 5% of those treated with IVIG will develop coronary artery abnormalities including lack of tapering, perivascular brightness, and ectasia.4 In the present report, we encountered an 8‐year‐old boy who had persistent fever, cervical lymphadenopathy, truncal dermatitis, bilateral conjunctival congestion, cracked lips, and edema of the extremities with high WBC, ESR, and CRP levels. Echocardiography showed moderate CAA both in the left and right coronary arteries. Therefore, the diagnosis of KD in our patient can be made undoubtedly.

There were four unusual features of this case. First, the patient was 8 years old. KD is predominant in infancy or early childhood, and 84.4% of patients present younger than 5 years, with a peak age incidence of 10 to 12 months in China.1 It is less common in older children. Second, specific serum IgM antibodies for MP were positive in our patient. Although the etiology of KD remains unknown, an infectious agent is strongly suspected based on clinical and epidemiologic features. Clinical research from Korea indicates that 3.35% of children with typical KD have concurrent MP infection.5 Host immune responses such as immune complex–mediated injury, cytotoxic T‐cell–mediated immune responses, and autoimmune reactions are thought to play a crucial role in the onset of KD in our patient with MP infection. Third, our patient presented with stomach pain and hepatic dysfunction. As a systemic vasculitis, KD can affect multiple organs and tissues. Gastrointestinal complaints, such as diarrhea, vomiting, and abdominal pain, occur in approximately one third of patients,1 and mild to moderate elevations in serum transaminases are observed in 27% of patients.6 It is worth noting that, in some cases, these manifestations in the gastrointestinal system may lead to misdiagnosis and delay appropriate treatment. Last, but most important, our patient exhibited obvious hypertension throughout the course of disease. Foster and colleagues7 reported an 18‐month‐old girl who developed severe hypertension and renal dysfunction at 6 months after acute KD, and an ostial stenosis was identified in her right main renal artery. In the present case, findings from urinary tract ultrasonography and renal function were normal; thus the possibility of renovascular hypertension was excluded. We postulated that the hypertension in our patient was mainly caused by endothelial dysfunction. CRP, a nonspecific marker of inflammation, is described as a fundamental biomarker for endothelial dysfunction and increases with hypertension.8 More persuasively, diminished flow‐mediated dilatation and increased carotid artery stiffness index were observed in children with KD.9 In addition, irritability and corticosteroid therapy may also contribute to the onset of hypertension in our patient.

Early recognition and treatment of KD with aspirin and IVIG has been unequivocally shown by randomized controlled trials and meta‐analyses to reduce the occurrence of CAA. However, initial IVIG resistance occurs in up to 20% of cases. Despite controversy, another 2 g/kg dose of IVIG plus a corticosteroid is usually advocated in these circumstances.10 Adachi and colleagues11 administered a corticosteroid plus therapy to five children with IVIG‐resistent KD and found that all of the patients regressed. However, a meta‐analysis reported by Athappan and coworkers12 demonstrated that a corticosteroid plus therapy did not decrease the incidence of CAA or adverse events. In this patient, the corticosteroid plus therapy was undertaken because of persistent fever and systemic inflammation after initial IVIG therapy. Taking into account the existent hypertension, lower‐dose (2 mg/kg) intravenous methylprednisolone was adopted. Unfortunately, he deteriorated and died on the 12th day of the illness. Postmortem findings showed that a rupture of CAA occurred in the right coronary arteries. According to 2004 AHA guidelines for KD,3 there were several risk factors for his sudden death, including being male, being an older child, and having persistent fever and systemic inflammation. In addition, hypertension may act as an important trigger to the rupture of CAA. Therefore, regular blood pressure monitoring should be highlighted in children with KD.

Disclosures

None declared.