Adult Kawasaki disease: a rare and challenging diagnosis—a case report

Abstract

Background

Kawasaki disease (KD) is an acute systemic vasculitis which predominantly occurs in childhood but rarely in adulthood. Diagnosis relies on the presence of typical clinical features; however, patients may present atypically, increasing the challenge of timely diagnosis for physicians.

Case summary

We report a case of a 40-year-old male presenting with persistent fever, rash, and unilateral neck swelling. Initial investigations were suggestive of necrotizing lymphadenitis, with a presumed infective aetiology. However, extensive microbiology and immunological investigations remained negative. Cardiac injury was evident with elevated troponin T and NT-proBNP; however, left ventricular systolic function was normal. After 4 days, clinical features consistent with KD were noted and the results of a lymph node biopsy supported this diagnosis. Despite timely treatment with intravenous immunoglobulins (IVIG) and high-dose aspirin, follow-up computed tomography (CT) coronary angiography demonstrated two sequential aneurysms (max 6 mm) in the right coronary artery, plus one small subtle aneurysm in the proximal left anterior descending artery (4 mm).

Discussion

Diagnosis of adult KD remains challenging, as symptoms often present sequentially over time rather than simultaneously and many of the clinical features necessary for diagnosis share commonality with other infectious disease processes.

Learning Points.

• Adult Kawasaki disease is a rare diagnosis which is classically diagnosed clinically based on the presence of key clinical findings. However, patients can present atypically and clinical findings can present sequentially, making diagnosis challenging.

• Delayed or misdiagnosis is associated with an increased incidence of coronary artery aneurysm formation and can have devastating long-term impacts due to myocardial ischaemia from coronary artery thrombosis and stenosis.

• Risk stratification and long-term follow-up is advised in those with persistent and regressed coronary aneurysms.

Introduction

Kawasaki disease (KD) is an acute self-limiting febrile illness and systemic vasculitis of unknown aetiology, predominantly affecting children and rarely adults.¹ This systemic arteritis of medium-sized vessels is the leading cause of acquired heart disease in children due to coronary artery aneurysm formation, occurring in up to 30% of untreated patients.² The classical diagnosis of KD is based on the presence of fever for 5 days and at least 4/5 principal clinical findings: bilateral non-exudative conjunctivitis, lip/oral mucosal changes, maculopapular or erythema multiforme–like rash, changes in peripheral extremities with subsequent periungual desquamation in the sub-acute phase, and cervical lymphadenopathy.³ However, diagnosis remains challenging, particularly in adults, as symptoms often present sequentially rather than simultaneously and the clinical findings necessary for a diagnosis of KD share commonality with other infectious diseases.² Delayed or misdiagnosis is associated with an increased incidence of coronary artery aneurysm formation and can have devastating long-term impacts due to myocardial ischaemia from coronary artery thrombosis and stenosis.³ We present a case of a 40-year-old male with KD who presented atypically and critically unwell.

Summary figure

Case presentation

A 40-year-old male presented with a 4-day history of fever, nausea/vomiting, and an enlarging non-tender left neck swelling. The patient was hypotensive, febrile, and confused. Clinical examination demonstrated a unilateral anterior cervical triangle swelling and an erythematous rash on the left side of his neck and anterior chest wall. Electrocardiogram (ECG) demonstrated sinus rhythm with left anterior fascicular block. Treatment was initially with intravenous fluid resuscitation and broad-spectrum antibiotics. Laboratory findings indicated elevated inflammatory markers [C-reactive protein (CRP) 205 mg/L], and a computed tomography (CT) neck and thorax demonstrated an acute inflammatory process of the left submandibular space, unilateral enlarged lymph nodes (largest 4 cm × 2 cm), and evidence of necrotizing lymphadenopathy.

Rapidly, the patient clinically deteriorated, requiring admission to the intensive care unit (ICU) for septic shock. Laboratory findings showed normal haemoglobin (Hb) and neutrophils (Hb 11.1 g/dL; 6.20 10⁹/L) with elevated inflammatory markers [CRP 205 mg/L; erythrocyte sedimentation rate (ESR) 91 mm/h], lymphopoenia (0.21 10⁹/L), thrombocytopoenia (59 10⁹/L), hyponatraemia (127 mmol/L), hepatitis [alanine aminotransferase (ALT) 275 IU/L; aspartate aminotransferase (AST) 51 U/L; bilirubin 23 umol/L], hypoalbuminaemia (27 g/L), coagulopathy [international normalized ratio (INR) 1.8], and myocarditis (troponin T 1104 ng/L; NT-proBNP 48 412 pg/mL). Viral and bacterial investigations were performed but remained negative throughout hospitalization. Additionally, a vasculitis screen returned negative. Transthoracic echocardiogram demonstrated normal left ventricular function and moderate central mitral regurgitation.

Despite ongoing broad-spectrum antibiotics, the patient remained critically unwell and febrile with no definitive aetiology. An ultrasound-guided biopsy of a left anterior cervical lymph node on Day 3 demonstrated features suggestive of suppurative necrotizing lymphadenitis (Figure 1). On Day 4, clinical assessment noted new erythema of the oral mucosa, fissured lips, strawberry tongue, and bilateral conjunctival injection. Coupled with persistent fever, laboratory findings, and lymph node histology, a possible diagnosis of classic KD was made. Treatment with intravenous immunoglobulins (IVIG) and high-dose aspirin (300 mg) commenced, with dramatic clinical improvement noted within 2 days. On Day 10, acute transient left upper limb weakness occurred. This was investigated by CT angiogram and magnetic resonance imaging (MRI) which excluded vertebral artery dissection or stroke.

Figure 1.

Histopathology of lymph node core biopsy. Evidence of areas of necrosis (arrow) which are associated with abundant neutrophils and debris. Occasional fibrin thrombi are noted in small vessels. Features are of suppurative necrotizing lymphadenitis with a wide differential diagnosis including Kawasaki disease.

Given the likely diagnosis of KD, with elevated cardiac enzymes on admission, a computed tomography coronary angiography (CTCA) and cardiac magnetic resonance imaging (CMRI) was undertaken as an outpatient (Figures 2 and 3). A CTCA at 3 months demonstrated two sequential aneurysms (max 6 mm) in the right coronary artery (RCA), with one smaller subtle aneurysm in the proximal left anterior descending (LAD) artery (4 mm). No associated thrombus, mural thickening, coronary plaque, or perivascular fatty changes were noted. Cardiac MRI showed normal left ventricular volumes with preserved function but focal regions of mid-wall fibrosis consistent with previous myocarditis. A follow-up CTCA at 12 months showed resolution of the LAD aneurysm and improvement of the two focal aneurysms in the RCA (3 mm).

Figure 2.

Coronary computed tomography angiography shows aneurysms (marked with asterisk) in the right coronary artery and left anterior descending artery 3 months post discharge (A–C). Interval improvement in size of aneurysms noted on follow-up imaging at 12 months post discharge (D–F) Ao, aorta; RCA, right coronary artery; LAD, left anterior descending artery.

Figure 3.

Cardiac magnetic resonance imaging with post contrast (gadolinium) imaging showing a confluent stripe of mid-wall fibrosis in the inferolateral/lateral wall at the basal level (A) as well as some patchy inferolateral mid-wall fibrosis at the mid-ventricular level (B).

Discussion

Kawasaki disease is a systemic vasculitis, typically affecting young children, and is the leading cause of acquired heart disease in children in developed countries. Aetiology of the disease remains unknown, but current consensus suggests an infectious trigger initiating an abnormal immune response in genetically predisposed persons.⁴ Treatment focuses on prevention of coronary artery aneurysm formation, which occurs in up to 30% of untreated cases and predisposes to stenosis/thrombosis.² It is estimated that 5% of acute coronary syndromes (ACS) in adults < 40 years of age results from coronary artery aneurysms from KD.³ Whilst coronary artery aneurysms receive the majority of attention with regard to cardiovascular complications of Kawasaki disease, myocarditis is more common from a histological perspective and, in a small subset of patients, may result in diffuse myocarditis and fibrosis formation.²

Adult-onset Kawasaki disease is rare and often misdiagnosed or diagnosed late due to the natural history of the disease, the lack of a specific diagnostic test, and clinical similarities to other more common infectious diseases.⁵ According to current guidelines, diagnosis of classic Kawasaki disease requires the presence of fever for 5 days and at least four principal clinical findings.³ However, in patients whose clinical features do not meet the epidemiological case definition, a diagnosis of atypical Kawasaki disease can be made aided by supporting laboratory findings and imaging studies. As in the current case, Kawasaki disease can rarely manifest with fever and cervical adenopathy before the onset of other clinical signs or may even present with adenopathy dominating the presentation.^6,7 Such presentations may be misdiagnosed as bacterial cervical lymphadenitis which may delay a definitive diagnosis of KD and lead to serious cardiac sequale.⁶ Indeed, node-first or node-predominant presentations have represented 9–23% of acute KD admissions in some series.^8,9

Based on current guidelines, echocardiography is the primary imaging modality for cardiac assessment of Kawasaki disease, but the diagnostic yield is reduced in adults due to inadequate visualization of the coronary arteries.³ In an adult population, the incidence of abnormal findings on initial echocardiography is low at 44%.⁵ Thus, other imaging modalities such as CTCA and CMRI may play a vital role in the diagnosis of adult Kawasaki disease and identify patients at risk of future cardiac adverse sequela. Furthermore, due to the long-term damaging effects to coronary artery function, it is recommended that stress CMRI perfusion be carried out during follow-up of persistent and now regressed coronary aneurysms.^3,4

Clinical experience demonstrates that long-term follow-up requires risk stratification to identify those at risk of myocardial ischaemia. This stratification, based on the presence, size, and persistence of aneurysms, allows for individualized long-term management to guide the frequency of clinical follow-up, diagnostic testing, and medical therapy.³ Whilst therapy with aspirin is well established, statins may play a key role in lowering low-density lipoprotein cholesterol in addition to potential pleiotropic effects on inflammation, endothelial function, platelet aggregation, and fibrinolysis.³

Conclusion

Kawasaki disease is a rare presentation in adulthood and may have serious long-term cardiac consequences if misdiagnosed. Diagnosis remains challenging; however, an understanding of the typical clinical features and potential atypical presentations may reduce delays in diagnosis and appropriate treatment.

Lead author biography

Dr Tim O’ Connor is currently a Complex and High-Risk Coronary Intervention Fellow at Beaumont Hospital, Dublin, Ireland. He completed his basic medical degree in 2015 from University College Dublin and is a higher specialist trainee in cardiology accredited by the Royal College of Physicians of Ireland.

Supplementary material

Supplementary material is available at European Heart Journal – Case Reports online.

Consent: The authors confirm that written consent for submission and publication of this case report including images and associated text has been received from the patient in line with the Committee on Publication Ethics (COPE) guidelines.

Funding: None declared.

Data availability

The data underlying this article are available in the article and in its online Supplementary material.