When coronaries speak last; atypical Kawasaki disease beyond the classical criteria – A four-case series

ABSTRACT

Coronary artery aneurysms (CAAs) are the most serious complication of Kawasaki disease (KD). Delayed diagnosis is associated with an increased risk of CAA, particularly in atypical presentations lacking classic mucocutaneous features. We report four children diagnosed with atypical KD only after coronary abnormalities were detected on echocardiography. Initial presentations included acalculous cholecystitis with marked transaminase elevation, aseptic meningitis, and an inflammatory arthritis. None of the cases had fulfilled complete diagnostic criteria at admission. Coronary imaging showed single- or multi-segment aneurysms ranging from small to giant (maximum Z-score +11.7). All received intravenous immunoglobulin and high-dose acetylsalicylic acid; corticosteroids, anticoagulation, or biologic therapy were added as treatment in cases with giant CAA. CAA persisted in patients with giant aneurysms. Early echocardiography is essential to establish the diagnosis in atypical KD and it may prevent irreversible coronary complications.

INTRODUCTION

Atypical or incomplete presentations of Kawasaki disease (KD) that do not fulfill classical criteria at initial evaluation pose a diagnostic challenge. These patients often present with predominant gastrointestinal, neurological, or musculoskeletal findings, leading to misdiagnosis and delayed treatment. We report four children diagnosed with atypical KD over the past 2 years who did not meet clinical criteria at admission but were subsequently diagnosed after echocardiographic detection of coronary abnormalities.

CASE REPORTS

Case 1

A 5-year-old boy was referred with 5 days of high-grade fever, abdominal pain, vomiting, and markedly elevated liver enzymes (aspartate aminotransferase [AST] 1116 U/L and alanine aminotransferase [ALT] 380 U/L). Abdominal ultrasonography revealed acalculous cholecystitis and he was hospitalized in the pediatric gastroenterology unit. After 5 days of broad-spectrum antibiotics, persistent fever prompted echocardiography. Examination revealed isolated, marked nonexudative oropharyngeal hyperemia without other classical features of KD. Echocardiography demonstrated a small left coronary artery (left anterior descending [LAD]) aneurysm (3.5 mm; Z-score +4.65) and trivial mitral regurgitation. There was no evidence of pericardial effusion. Laboratory findings included white blood cell (WBC) 14,300/mm³, C-reactive protein (CRP) 184 mg/L, ALT 210 U/L, hemoglobin 10.5 g/dL, and albumin 2.9 g/dL, supporting the diagnosis. Atypical KD was diagnosed based on a single clinical feature and coronary involvement. Intravenous immunoglobulin (IVIG) 2 g/kg and high-dose acetylsalicylic acid (ASA) were administered, with fever resolution after a single infusion. ASA was reduced to low dose and continued for 8 weeks as per the American Heart Association (AHA)[1] guidelines, then discontinued after regression, which occurred before 8 weeks, despite a coronary aneurysm. Echocardiography showed complete resolution by 3 months. The patient remains clinically stable and asymptomatic.

Case 2

A 3½-year-old girl was admitted with a 20-day history of intermittent high fever (38°C–39°C), headache, arthralgia, and abdominal pain. She had been on colchicine for familial Mediterranean fever (FMF) for 2 years. At a local hospital, she received antibiotics and systemic corticosteroids with transient improvement, and an FMF attack was suspected. Persistent severe headache prompted lumbar puncture, which was consistent with aseptic meningitis. On the hospital day 11, echocardiography performed for persistent fever revealed multiple giant saccular aneurysms of the proximal LAD (5 mm × 6.3 mm; Z-score + 11.76) and distal LAD (5.1 mm; Z-score + 10.16), and the proximal right coronary artery (RCA) [Figure 1a]. There was no evidence of valvular regurgitation or pericardial effusion. Laboratory findings were WBC 10,160/mm³, hemoglobin 10.5 g/dL, platelets 396,000/mm³, ALT 17 U/L, albumin 3.8 g/dL, CRP 2.4 mg/L, and sedimentation (erythrocyte sedimentation rate [ESR]) 10 mm/h; the relatively low acute-phase reactants were attributed to prior corticosteroid use and the late subacute phase. Atypical KD was diagnosed, and IVIG 2 g/kg, corticosteroids, high-dose ASA, and enoxaparin were initiated. Treatment was guided by coronary involvement, with intensified therapy (IVIG plus corticosteroids) reserved for patients with giant aneurysms. Coronary computed tomography angiography (CTA) showed a proximal saccular aneurysm (~5 mm), multiple fusiform RCA aneurysms (largest 6.5 mm) [Figure 1b], and fusiform dilatation of the LAD and circumflex arteries. Fever resolved after a single IVIG dose and corticosteroids. On rheumatology recommendation, anakinra was initiated and enoxaparin was transitioned to oral apixaban due to challenges with subcutaneous administration in a young child. After 4 months, the coronary artery aneurysms remained largely unchanged, and she remains asymptomatic on medical therapy.

Figure 1.

(Case 2) (a) Two-dimensional transthoracic echocardiography in the parasternal short-axis view demonstrates saccular aneurysmal dilatations along the courses of the right coronary artery (RCA) and left anterior descending artery. (b) Cardiac computed tomography imaging reveals aneurysmal dilatations extending along the course of the RCA. RCA: Right coronary artery, LAD: Left anterior descending

Case 3

A 13-year-old boy presented with 5 days of fever and cough. At the local hospital, elevated liver enzymes (AST 209 U/L, ALT 132 U/L) were noticed, and he was referred to our hospital, and hospitalized with a preliminary diagnosis of viral infection or cholestasis. After 5 days, headache and vomiting developed and lumbar puncture findings were consistent with aseptic meningitis. On day nine of illness, echocardiography for persistent fever revealed a medium-sized LAD aneurysm (5.8 mm; Z-score + 7.8) and a small RCA aneurysm (5 mm; Z-score + 4.9) [Figure 2a]. There was no evidence of valvular regurgitation or pericardial effusion. Laboratory values showed WBC 11,080/mm³, hemoglobin 11.5 g/dL, platelets 279,000/mm³, ALT 140 U/L, albumin 3.7 g/dL, CRP 199 mg/L, and ESR 31 mm/h. Atypical KD was diagnosed, and IVIG 2 g/kg, systemic corticosteroids, high-dose ASA, and enoxaparin were initiated. Treatment was guided by coronary involvement, with intensified therapy (IVIG plus corticosteroids) reserved for patients with giant aneurysms. Coronary CTA demonstrated fusiform aneurysm of the LAD (6 mm), mid-circumflex artery, and RCA (4.7 mm) [Figure 2b-e]. Fever resolved after a single IVIG dose. Corticosteroids were tapered and anticoagulation was switched to oral apixaban, and at 18 months, only a small residual LAD aneurysm (4.1 mm; Z-score +3.5) persisted.

Figure 2.

(Case 3) (a) Two-dimensional transthoracic echocardiography in the parasternal short-axis view demonstrates aneurysmal dilatation of the left anterior descending (LAD) artery and the right coronary artery (RCA). (b-e) Coronary computed tomography angiography reveals long-segment dilatation of the LAD beginning at its origin, with a maximal diameter of 6 mm. A proximal fusiform dilatation is also identified in the first diagonal (D1) branch. The circumflex artery (Cx) demonstrates a short-segment fusiform dilatation in its mid portion. The RCA, beginning approximately 2 mm distal to its origin, exhibits a long-segment fusiform dilatation with focal segments approaching normal caliber; the maximal diameter measures 4.7 mm. The arrows indicate the aneurysmal and dilated coronary artery segments. RCA: Right coronary artery, LAD: Left anterior descending

Case 4

A 2-year-old boy presented with 8 days of fever, refusal to bear weight, knee and ankle pain, upper extremity tenderness, and abdominal pain. He had received ibuprofen for presumed arthritis at an outside center with partial response and was referred for persistent fever. Physical examination revealed oral mucosal changes and conjunctivitis without other classical KD features. On day 10, echocardiography showed LAD dilatation (2.2 mm; Z-score +2.36) and trivial mitral regurgitation. There was no evidence of pericardial effusion. Laboratory findings included WBC – 21,000/mm³, hemoglobin – 9.8 g/dL, platelets –984,000/mm³, ALT – 12 U/L, albumin – 3.1 g/dL, CRP – 50 mg/L, and ESR – 67 mm/h. Atypical KD was diagnosed, and IVIG 2 g/kg with high-dose ASA was initiated. Fever resolved after a single IVIG dose. ASA was tapered and discontinued at week 8. The patient remains clinically stable and asymptomatic on follow-up.

At discharge, all patients were clinically stable and afebrile, received low-dose ASA (with additional anticoagulation in selected cases), and were scheduled for close cardiology follow-up with serial echocardiography.

DISCUSSION

KD is a systemic vasculitis that may present in complete, incomplete, or atypical forms and remains the leading cause of acquired heart disease in childhood. The current guidelines from the AHA and Japanese Circulation Society recommend echocardiographic evaluation in children with ≥ 5 days of unexplained fever and laboratory evidence of systemic inflammation, even when full clinical criteria are not met.[1,2] Recent recommendations, including those from international and regional guidelines, emphasize the early recognition of incomplete KD to prevent coronary artery complications.[3,4]

Atypical KD remains a diagnostic challenge due to its heterogeneous clinical presentation and its ability to mimic other inflammatory conditions. Patients are frequently evaluated in noncardiology pediatric settings, which may delay appropriate cardiac assessment. In our series, all patients presented with prolonged fever but lacked complete mucocutaneous criteria. Instead, atypical features such as acalculous cholecystitis with marked transaminase elevation, aseptic meningitis, and inflammatory arthritis-like manifestations were predominant. Consistent with previous reports, diagnostic delay was observed in all cases, and coronary involvement was detected only after echocardiographic evaluation.

Importantly, our findings reinforce that coronary artery abnormalities may develop even in the absence of classical clinical criteria. Notably, two of our patients developed giant coronary aneurysms despite initially incomplete clinical presentations, underscoring the clinical consequences of delayed recognition. In line with emerging evidence and recent guideline updates, our observations support a more proactive cardiac evaluation strategy.

Our case series adds to the existing literature by demonstrating that atypical KD may initially present with organ-specific manifestations, leading to diagnostic delay and severe coronary involvement despite incomplete clinical criteria.

Our key message is that echocardiographic assessment should be strongly considered in children with persistent fever and even a single compatible clinical feature of KD, particularly when accompanied by laboratory evidence of inflammation, in order to prevent coronary artery complications. This approach may facilitate earlier diagnosis and timely treatment in atypical cases.

CONCLUSION

Our case series highlights the diagnostic challenges of atypical KD and emphasizes that coronary artery involvement may develop despite incomplete clinical presentations. We propose that echocardiographic evaluation should be performed in children with persistent fever and even minimal clinical suspicion, rather than relying strictly on classical diagnostic criteria, to enable early diagnosis and prevent coronary artery complications.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.