ABSTRACT
Kawasaki disease, traditionally classified as medium vessel vasculitis, is known for the preferential involvement of coronary arteries. Infrequently, large systemic arteries might be involved and may affect the prognosis. Here, we present an infant with Kawasaki disease who had extensive involvement of large vessels such as the abdominal aorta and medium vessels of the extremities, along with giant coronary artery aneurysms.
Keywords: Coronary aneurysm, refractory Kawasaki disease, systemic aneurysm, vasculitis
INTRODUCTION
Kawasaki disease is an acute inflammatory vasculitis of unknown etiology predominantly affecting medium sized vessels especially coronary arteries.[1] Systemic arterial involvement (SAA) has been reported in various reports.[2,3,4] Exact incidence of SAA is not known however its association with giant coronary aneurysm has been documented.[2] Here, we present an infant with Kawasaki disease who had extensive involvement of large vessels like abdominal aorta and medium vessels of the extremities, along with giant coronary artery aneurysms.
CASE REPORT
A 5-month-old female infant presented elsewhere with fever and diaphoresis for the preceding 10 days. There was no identifiable focus of infection and significant laboratory parameters showed anemia (hemoglobin 8.5 g/dL), thrombocytosis (5.2 L/mm3), elevated transaminases (serum glutamic oxaloacetic transaminase 76 IU/L and serum glutamate pyruvate transaminase 78 IU/L), elevated C-reactive protein (CRP) (125 mg/dL), erythrocyte sedimentation rate (32 mm at 1 h), and sterile pyuria (leukocytes 20–30/hpf). With a suspicion of incomplete Kawasaki disease, an echocardiography was performed that revealed dilated coronary arteries with normal biventricular function. Intravenous immunoglobulin (IVIG) was administered at 2 g/kg. The child was referred to us for further management. At the time of presentation, the child was afebrile and hemodynamically stable. Echocardiography confirmed aneurysmal dilatation of left as well as right coronary arteries [Figure 1]. In addition, moderate pericardial effusion was noted, although with normal biventricular function. Interestingly, the child had palpable pulsatile swellings in the bilateral axilla [Figure 2], which, on Doppler evaluation, were identified as bilateral subclavian and axillary artery aneurysms. The child was started on aspirin and unfractionated heparin infusion.
Figure 1.
Echocardiographic images in parasternal short axis view (Panel A) at the level of the aortic valve show dilated right coronary artery (1); dilated left coronary artery (2) along with aneurysmal dilatation of left anterior descending artery.(3) The subcostal sagittal view (Panel B) demonstrates aneurysmal dilation (*) of the aorta just below the diaphragm. DTA demonstrated by arrow. AoV: Aortic valve, DTA: Descending thoracic aorta
Figure 2.
Clinical photographs of the child show pulsatile swellings in the right (a) and the left axilla (b). (Reproduced with permission after consent from parents)
A computed tomographic angiography was performed to define the extent of coronary and peripheral artery involvement. Besides massive coronary artery aneurysms [Figure 3], the computed tomography angiography also delineated multiple aneurysms in the thoraco-abdominal aorta, intercostal arteries, bilateral subclavian, axillary, common iliac, and femoral arteries [Figure 4].
Figure 3.
Volume-rendered computed tomography angiographic images in the left anterior oblique view demonstrate aneurysmal involvement of the right coronary artery, left anterior descending artery, and left circumflex artery. RCA: Right coronary artery, LAD: Left anterior descending artery, LCX: Left circumflex artery
Figure 4.
Volume-rendered computed tomography angiographic images in the anterior (a), left anterior oblique (b), posterior (c), and right anterior oblique (d) view demonstrate aneurysmal involvement of the right coronary artery, left anterior descending artery and left circumflex artery, bilateral axillary arteries (indicated by arrowheads), bilateral common iliac arteries, bilateral internal iliac arteries and bilateral common femoral arteries. The juxta diaphragmatic thoracic aorta and abdominal aorta up to the bifurcation (yellow dotted circle) are tortuous and dilated with small saccular aneurysms from the ostio-proximal part of lower intercostal arteries (indicated by yellow arrows). RCA: Right coronary artery, LAD: Left anterior descending artery, LCX: Left circumflex artery, CIA: Common iliac arteries, IIA: Internal iliac arteries, CFA: Common femoral arteries
Although the child was afebrile, persistently elevated inflammatory markers and extensive arterial involvement prompted the administration of infliximab at 10 mg/kg and 3 doses of methylprednisolone at 30 mg/kg over 3 h. The child was then started on oral prednisolone at 2 mg/kg. The inflammatory markers normalized (CRP 6 mg/dL) with no increase in coronary or peripheral aneurysms on ultrasound imaging. However, given the extensive involvement of coronary and peripheral arteries, the child was started on long-term immunosuppression using cyclosporin at 6 mg/kg while steroid therapy was being tapered. Tapering prednisolone, however, led to the resurgence of inflammation. The platelet count measured 5.17 lac/mm3, while CRP was 40.1 mg/dL. This necessitated another dose of Infliximab (10 mg/kg) and oral prednisolone at 1 mg/kg for an additional 2 weeks. We then continued the child on cyclosporine with no increase in inflammatory markers [Figure 5]. Throughout the hospital stay, the coronary and peripheral artery aneurysms remained stable, and the child was discharged home on anticoagulants (low-molecular-weight heparin), antiplatelets (aspirin), statins, and immunosuppressive drugs (cyclosporine 1 mg/kg/day). A week later, the child suddenly became irritable and unresponsive, leading to the death of the child before reaching the hospital. The autopsy was not performed as the parents refused consent.
Figure 5.
Graphical representation of the immunosuppressive therapy and trends of inflammatory markers during hospital stay (C reactive protein)
CASE DISCUSSION
Noninfectious febrile illness with giant coronary artery aneurysms in a young child strongly indicates the possibility of Kawasaki disease. Besides the predominant involvement of coronary arteries, the absence of skin, renal, and other system involvement makes the other medium vessel vasculitis, polyarteritis nodosa, less likely.[1] Similarly, considering the significant involvement of coronary arteries and the conspicuous absence of branch point involvement of arch vessels made large vessel vasculitis such as nonspecific aortoarteritis unlikely. Although classified as medium vessel vasculitis, autopsy studies have shown aortic inflammation in 90% of cases of Kawasaki disease in the acute phase.[2]
Coronary artery involvement is a characteristic feature of Kawasaki disease. Approximately 23% of patients with Kawasaki disease have coronary artery involvement, with 8% developing coronary artery aneurysms.[3] Giant coronary artery aneurysms, defined as Z score >10 or absolute dimension more than 8 mm, are infrequently seen but have serious implications for management and outcome. Infrequently, such patients of Kawasaki disease with giant coronary artery aneurysms also develop systemic artery aneurysms. The exact prevalence of systemic artery aneurysms is not known. Nonetheless, depending upon the timing and method of screening, 2.2%–14% of children with giant coronary artery aneurysms have been shown to develop aneurysms of systemic arteries. With a higher prevalence among infants (mean age 5 months), systemic artery aneurysms possibly indicate a malignant course of Kawasaki disease. The prevalence is also higher among infants, with the mean age being 5 months. These aneurysms are mostly seen in subclavian, brachial, axillary, and iliac arteries.[4,5,6,7] Systemic artery aneurysms are at risk of rupture and thrombosis while also posing the risk of embolization, thus emphasizing the need for clinical and imaging-based screening in all cases with giant coronary artery aneurysms [Table 1].
Table 1.
Summarizes features of reported cases of peripheral artery aneurysms in Kawasaki diseases
| Author, year | Age | Location | outcome | Follow up | Immunosuppression | Coronary |
|---|---|---|---|---|---|---|
| Petrunić M, 2009[8] | 22 years | thoracoabdominal aorta | Surgical repair | 1 year | steroids | h/o kawasaki at 10 years; GCA at follow up |
| Cabrera ND, 2010[9] | 4 months | Unilateral subclavian, brachial a. | Persistent | 5 months | MPS, IVIG | GCA |
| Heran MK, 2011[10] | 5 years | bilateral fusiform common iliac and internal iliac aneurysms | - | - | IVIG, MPS | Kawasaki @10months of age, GCA |
| Hakim K, 2014[11] | 2y4month | Arch of aorta | Surgical repair | - | MPS | Small coronary aneurysm |
| Benson H, 2016[12] | 5 months | B/l axillary, brachial and iliac a. | Hemorrhage, death | - | IVIG, steroids, infliximab | GCA |
| Johnston N, 2017[13] | 2 mo | external, common, and internal iliac a., femoral a., renal a., subclavian, and internal carotid arteries a. | Limb amputation, coronary thrombosis | 2 years | MPS, cyclophosphamide | GCA |
| Arunakumar P, 2018[14] | 3 years | left axillary, right common iliac, and left internal iliac arteries | Persistent | - | - | GCA |
| Ozdemir E, 2019[7] | 2 mo | Axillary and brachial a. | Persistent | 6 month | IVIG, MPS, Infliximab, prednisolone | Small aneurysm |
| Index case | 5mo | B/l axillary a. descending thoracic orta | death | - | IVIG, MPS, Infliximab, cyclosporine | GCA |
IVIG: Intravenous immunoglobulin, MPS: Methyl prednisolone, GCA: Giant coronary aneurysm
Fortunately, systemic artery aneurysms are known to regress spontaneously. The regression rate is inversely related to their size, with smaller aneurysms having a higher chance of regression than larger aneurysms. Unlike coronary artery aneurysms, however, no definite cut-off is known to define a higher risk of nonregression of aneurysms. IVIG administration improves the regression rate from 51% to 85%. However, approximately one-tenth of cases may have persistent systemic artery aneurysms, thus mandating careful evaluation at follow-up. Irrespective of the size and persistence of systemic artery aneurysms, the outcome mostly depends on the status of coronary artery aneurysms.
CONCLUSIONS
Systemic artery aneurysm is an infrequent manifestation of Kawasaki disease, seen almost exclusively among those with giant coronary artery aneurysms. Despite aggressive immunosuppression, large systemic artery aneurysms may persist and adversely affect the clinical outcome. Additional imaging to screen for systemic involvement may be prudent in cases with giant coronary aneurysms, especially with persistent inflammatory marker elevation.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil
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