Recurrent Intravenous-Immunoglobulin-Resistant Kawasaki Disease Within 14 Weeks Despite High-Risk Intensification: A Case Report

Introduction

Kawasaki disease (KD) is an acute, self-limited vasculitis that predominantly affects children under five years of age. Standard therapy consists of intravenous immunoglobulin (IVIG) and aspirin, which reduces the incidence of coronary artery aneurysms to less than five percent [1]. Recurrence occurs in approximately four percent of patients, with additional risk factors including age under 1 year, IVIG resistance, and coronary involvement during the initial episode [2].
The 2017 AHA guidelines recommend treating recurrent KD as a first episode with IVIG and aspirin [1]. The 2024 update provides further detail on treatment intensification in high-risk patients, including those with baseline coronary dilation, for whom adjunctive therapies such as corticosteroids or infliximab may be appropriate [3]. However, no specific guidance exists for patients who experience recurrent KD that is again IVIG-resistant.
We present a case of an infant with prior GI prodrome preceded IVIG-resistant KD and coronary artery aneurysms who developed a second, GI prodrome preceded IVIG-resistant recurrence of KD within 14 weeks. This case demonstrates the gaps in the current guidelines for addressing recurrent resistant KD and highlights the need for individualized escalation strategies.

Case Presentation

The patient first presented on day one at 11 months of age with four days of fever, erythematous rash, swelling of hands and feet, conjunctivitis, oral mucous membrane changes with erythematous lips, and GI prodrome of nausea, vomiting, diarrhea, poor oral intake, and dilated bowel loops on x-ray. His initial labs were significant for an elevated C-reactive protein (CRP) of 32mg/dL and he was treated for incomplete Kawasaki disease with high dose aspirin (40 mg/kg/day divided over every six hours) and IVIG (2g/kg), as recommended by the 2024 AHA treatment guidelines. His labs later showed leukocytosis (16.9 k/uL), thrombocytosis (488 k/uL), and low albumin (2 g/dL). His initial echocardiogram (ECHO) was unremarkable. He had recurrence of fever on day two, more than 36 hours after the first treatment, and IVIG was repeated. He remained afebrile and was discharged on hospitalization day five. His outpatient ECHO on week three from initial presentation showed dilation of proximal coronary arteries (z scores 3.6, 4.2, 3.8). He was therefore readmitted to the hospital and treated with infliximab and prednisolone. His outpatient ECHO on week four showed improvement in coronary artery dilation (z scores 2.3, 4.0, 3.7).
He returned to the hospital 14 weeks after initial presentation with symptoms of fever, conjunctivitis, rash, swelling of hands and feet and was diagnosed with recurrent Kawasaki disease. He received IVIG, high dose aspirin (had been maintained on low-dose aspirin at home prior), and Infliximab. He remained febrile for longer than 36 hours after IVIG and therefore was started on a five-day course of methylprednisolone. During that hospitalization, ECHO demonstrated normal coronary artery measurement (.81, 3.3, 2.1).
At cardiology follow-up two months later, he remained well on aspirin with no recurrence of fever or coronary involvement. Given the short interval between episodes and the prolonged gastrointestinal prodrome and poor appetite preceding both illnesses, a predisposition to systemic inflammation was suspected so he was referred to rheumatology for further evaluation.

Discussion

This case illustrates recurrent KD occurring at an unusually short interval (14 weeks). Large cohort data place the recurrence rate of KD at about four percent with a median interval of 18 months [2]. In contrast, our patient recurred within 14 weeks. The shortest interval to recurrence that had been previously reported was five months [4]. Thus, to our knowledge, our case demonstrates the shortest reported interval for recurrence. Furthermore, our case represents a clinical scenario not clearly described in the current literature: recurrent, resistant KD in a high-risk patient. The 2017 AHA guidelines recommend treating recurrent KD as a first episode with IVIG and aspirin [1], while the 2024 update specifies that high-risk patients, including those with baseline coronary artery dilation, may benefit from early intensification with adjunctive therapies such as corticosteroids or infliximab [3]. However, neither AHA statement provides explicit direction for recurrent KD that is again resistant to first-line therapy. When our patient presented with recurrent KD, he was appropriately categorized as high-risk due to baseline coronary abnormalities and was treated with IVIG, aspirin, and Infliximab; despite early intensification of therapy, he again experienced resistant KD and further escalation with corticosteroids was indicated.
Findings from the KIDCARE trial, a multicenter comparative-effectiveness trial, support the use of infliximab over repeat IVIG for resistant KD due to faster defervescence and fewer adverse effects [5], but data specific to recurrent resistant KD is sparse. Corticosteroids are also supported for resistant disease [6], but their role in recurrent resistant KD has not been well studied. In this patient, layering corticosteroids promptly after evidence of IVIG and infliximab resistance was associated with favorable coronary outcomes, indicating that this escalation strategy should be further investigated as a potential improvement to the current treatment guidelines.
In addition to exhibiting resistance to IVIG in both episodes, this patient also experienced a prolonged gastrointestinal prodrome before both episodes; this could suggest a distinct inflammatory phenotype that may warrant early, multi-agent therapy in similar patients. While speculative, recognition of such prodromal features may have implications for anticipating recurrence in high-risk children and guide subsequent follow-up. For example, in our patient’s case, the decision was made to refer to rheumatology for further evaluation.
In summary, this case shows that KD recurrence can occur as early as 14 weeks after initial episode, even after aggressive initial therapy. It also brings attention to a potential gap in KD treatment guidelines, which currently recommend standard therapy for recurrence (2017 AHA) and intensification for high-risk patients (2024 AHA), but do not provide a stepwise approach for recurrent resistant KD due to lack of available data. Furthermore, prodromal gastrointestinal symptoms and appetite changes before both episodes may reflect a predisposed inflammatory phenotype, warranting rheumatology evaluation.

Consent

Written consent was obtained from parents on behalf of the participating minor.

Conflicts of Interest

The authors declare no conflicts of interest. No funding was received for this case report.