Introduction
Kawasaki disease (KD) is a paediatric medium-vessel vasculitis that predominantly affects children under 5 years of age. Reference Kawasaki1,Reference Jone, Tremoulet and Choueiter2 It has a predilection for the coronary arteries, causing aneurysms in approximately 25% of untreated children and 5% of those who receive timely treatment. Reference McCrindle, Rowley and Newburger3 It can also cause valvulitis and myocarditis. Reference McCrindle, Rowley and Newburger3,Reference Tsuda, Yashiro and Nakamura4 Giant coronary artery aneurysms are defined as dilations with a Z-score ≥ 10 or an absolute diameter ≥ 8 mm Reference McCrindle, Rowley and Newburger3 and are associated with a higher risk of thrombosis and rupture. Valvular involvement usually occurs during the acute phase, most often affecting the mitral valve with an incidence of 25% Reference McCrindle, Rowley and Newburger3 arising either from direct tissue inflammation or as a consequence of ischaemic complications. Aortic regurgitation is less common and usually secondary to aortic dilation. Reference Jone, Tremoulet and Choueiter2,Reference McCrindle, Rowley and Newburger3 Both of these conditions tend to be transient, as valvular coaptation is promptly restored with improving clinical and inflammatory conditions.
We present the case of a 3-year-old patient who presented with late-onset bivalvular involvement that progressively worsened despite appropriate inflammatory control. This led to severe mitral and aortic regurgitation, seemingly originating from direct valvulitis. Eventually, surgical intervention was required for repair due to the worsening condition.
Case report
A 3-year-old female with no previous medical history presented at her community hospital with a prolonged fever (7 days), cough, and cheilitis. Biological markers found a marked inflammatory response (C-reactive protein 305 mg/L, procalcitonin 0.23 ug/L) and microcytic anaemia (8.2 g/dL). Initial N-terminal pro-B-type natriuretic peptide was elevated at 343 pg/mL, with no concomitant troponin elevation. Microbiological workup only documented Parainfluenzae on respiratory polymerase chain reaction. Initial CT and echocardiography (day 13) showed minimal pericardial effusion.
On day 15, persistent fever despite antibiotics prompted repeat echocardiography, revealing giant coronary artery aneurysms: Reference Friedman, Gauvreau and Hamaoka-Okamoto5 left main coronary artery 8.6 mm (Z + 13.7), left anterior descending artery 4.9 mm (Z + 12.4), right coronary artery 7.5 mm (Z + 12.7)—Z-scores calculated according to Lopez et al. Reference Lopez, Colan and Stylianou6 Mild mitral regurgitation of non-ischaemic origin was noted; wall motion and ventricular function were normal. CT showed aneurysms in both internal iliac arteries and the left renal artery.
Immunosuppressive treatment was initiated with intravenous immunoglobulin (2 g/kg) and a 3-day course of high-dose corticosteroids. Despite initial improvement, fever and inflammatory markers rebounded (CRP 132 mg/L) during the steroid taper, alongside progression of coronary aneurysms. Intravenous methylprednisolone was restarted, and Anakinra was introduced on day 32. Persistent fever and a further CRP increase (310 mg/L) after 72 hours motivated a switch of Anakinra for Tocilizumab (day 35), resulting in rapid clinical and biochemical improvement. The patient was discharged on a tapering oral steroid regimen.
Given the elevated thrombotic risk, anticoagulation therapy was initiated upon discovery of giant coronary artery aneurysms with low-molecular-weight heparin and aspirin, then warfarin (INR 2–3).
Follow-up
As recommended by international guidelines Reference Jone, Tremoulet and Choueiter2 and according to our local practice for patients with giant coronary artery aneurysms, follow-up included clinical evaluation, echocardiography, and angiographic imaging. At 7 months, coronary evolution was favourable under immunosuppressant therapy, with persistent fusiform dilation of the left main coronary artery 6.4 mm (Z + 8.4), right coronary artery 4.1 mm (Z + 4.8), and no focal stenosis. Angiography documented systemic aneurysms in the right and left carotid arteries (12 × 12 mm), abdominal aorta (16 × 65 mm), and coeliac artery, which remained stable on subsequent ultrasound (8 months)—no additional vascular imaging was performed afterwards.
However, at 4 months, the patient developed both aortic and mitral regurgitation on echocardiography (Figure 1). The mitral valve appeared thickened and dysplastic, with moderate regurgitation and no evidence of ischaemia. Aortic insufficiency was secondary to left cusp retraction without aortic dilation. Ventricular function remained normal.
Echocardiography at 4 months. Prolapse of the left aortic cusp (*) with redundant tissue (top), thickened and infiltrated aortic wall (right), and dysplastic, nodular mitral valve (bottom left).
Cardiac MRI at 6 months confirmed worsening aortic (regurgitant fraction 31%) and mitral (RF 26%) regurgitation with ventricular dilation (148 mL/m2). MRI showed moderate aortic wall thickening (2 mm) without T2 hypersignal or contrast enhancement, suggesting no evidence of active aortitis, though low-grade inflammation could not be excluded.
The patient underwent aortic and mitral valve repair 11 months after diagnosis. Perioperative findings (Figure 2) included aortic cusp prolapse, commissural retraction, fenestrations of the left coronary cusp, and a thickened yellow aortic wall (adult hypercholesterolaemia-like appearance, see Supplementary Figure S1). The mitral valve showed a hemmed appearance with dense nodular formations (see Supplementary Figure S2).
Surgical observations and repair of aortic valve lesions. Surgeon’s drawing (by Dr. Régis Gaudin) showing perioperative findings: free-edge retraction, commissural retraction, fenestrations of the left coronary cusp, and corresponding repair steps.
This observation prompted lipid profiling of the patient and her parents, revealing elevated low-density lipoprotein-cholesterol (LDL, 4.4 mmol/L; N < 4). High-density lipoprotein cholesterol, triglycerides, and lipoprotein A were normal. Notably, the mother had combined hyperlipidaemia: total cholesterol 6.4 mmol/L, LDL-cholesterol 4.41 mmol/L, and triglycerides 2.1 mmol/L.
At 17-month follow-up, echocardiography showed mild ventricular dysfunction (ejection fraction 50%), trivial aortic regurgitation, and mild mitral regurgitation with thickened leaflets. Persistent dilation of the descending thoracic aorta was also noted (17 mm). Coronary aneurysms remained stable (left main coronary artery 7.6 mm, Z + 13; right coronary artery 4 mm, Z + 6.3). Anticoagulation and aspirin were continued, and angiotensin-converting enzyme inhibitors were introduced postoperatively to address dysfunction. Dietary measures effectively controlled cholesterol; pharmacologic therapy was not initiated. Immunosuppression was discontinued.
Discussion
This case illustrates several rare and clinically significant features of KD: giant coronary artery aneurysms, progressive bivalvular insufficiency due to direct valvulitis, and extensive extracoronary lesions.
Valvular lesions in KD are typically transient and resolve with systemic inflammation control, but our patient developed severe aortic and mitral regurgitation months after apparent stabilisation, requiring surgery. While ischaemia-induced insufficiency is well documented, Reference Tsuda, Yashiro and Nakamura4 direct valvulitis affecting both valves is rare. Reference Honda, Matsumoto, Mizoguchi, Hamasaki and Sunagawa7,Reference Imakita, Sasaki, Misugi, Miyazawa and Hyodo8 Aortic lesions identical to those observed here—cusp perforation and free-edge retraction—have been reported Reference Chaudhuri, Jose, Shenoi and Tomar9,Reference Yamada, Shikata, Yamamoto, Numata, Yasukochi and Takeuchi10 but remain unpredictable. The delayed, independent progression of valvular disease despite normalised inflammatory parameters and regressing coronary aneurysms supports the idea of subclinical inflammation with active chronic valvulitis, as reported by Gidding et al. Reference Gidding, Shulman, Ilbawi, Crussi and Duffy11 This emphasises the need for long-term echocardiographic surveillance even after apparent remission.
Systemic arterial aneurysms represent another feature of severe KD, occurring almost exclusively in patients with giant coronary artery aneurysms, prolonged inflammation, and treatment resistance. Reference Hoshino, Tsuda and Yamada12,Reference Orr, Fabi and Khoury13 Their true incidence is likely underestimated; targeted screening in subjects with giant coronary artery aneurysms identified systemic arterial aneurysm in up to 14% of cases. Reference Orr, Fabi and Khoury13 Although regression occurs, thrombosis and late stenosis remain a risk, particularly for aneurysms >10 mm, with complication rates of 25% at 20 years. Reference Hoshino, Tsuda and Yamada12 Our patient’s extensive extracoronary involvement underlines the need for systematic vascular imaging and lifelong extracardiac surveillance whenever KD follows a refractory or atypical course.
Although KD remains the leading cause of coronary artery aneurysms in children, clinicians should be alert to alternative diagnoses—including Takayasu arteritis, structural coronary anomalies, autoimmune diseases, and infections—especially when presentation is atypical or accompanied by large-vessel involvement. Reference Lin, Qi, Liu, Wu, Li and Shi14 Takayasu arteritis is a large-vessel vasculitis primarily affecting the aorta and its branches, with coronary lesions in up to 39% of pediatric cases. Reference Xu, Luo and Su15 Risk factors for coronary lesions in Takayasu arteritis include elevated inflammation (high CRP, Tumor necrosis factor-α, and interleukin-2 receptor), thrombocytosis, low age of onset (73% of affected patients aged <36 months in the cohort described by Xu et al.), Reference Xu, Luo and Su15 and prolonged fever—features overlapping with severe KD phenotypes. Our patient presented with extreme inflammation, refractory fever requiring sequential lines of immunosuppressants, and multiple extracoronary lesions. This overlap raises the possibility of a pathogenic continuum of widespread high-level vascular inflammation manifesting with rapidly progressive histological lesions. Although the absence of pulse deficits, renal artery stenosis, and active aortitis on MRI argued against Takayasu arteritis, these similarities highlight the need for comprehensive vascular imaging and individualised immunosuppression strategies. Next-generation sequencing found no autoinflammatory variants in our patient, but recent literature suggests the existence of subgroups of KD patients prone to severe vascular manifestations, Reference Wang, Shimizu and Bainto16 with a potential role of an autoinflammatory predisposition.
Finally, arterial changes resembling hypercholesterolaemia observed perioperatively likely reflect chronic inflammation. Reference Newburger, Burns, Beiser and Loscalzo17 Macroscopic changes to the vasculature encourage caution in long-term management of these patients who will remain at risk for coronary artery disease. Strict cardiovascular risk factor control is essential with LDL targets and medication as needed.
Conclusion
This case highlights the complexities of severe Kawasaki disease. Aside from coronary aneurysms, late progressive valvulitis and systemic arterial aneurysms can develop despite inflammatory control. This underlines the need for comprehensive follow-up with systemic vascular imaging and cardiac monitoring, as such patients are at lifelong risk for cardiovascular complications. Clinicians should maintain a high suspicion for overlapping vasculitic presentations which may lead to individualised therapeutic strategies.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/S1047951126112086.
Financial support
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Competing interests
None.
Ethical standard
Written informed consent was obtained from the patient’s legal guardian for publication of this case report and accompanying images.
