Atypical Kawasaki disease with giant coronary artery aneurysms in a 2-month-old boy: a case report

Abstract

Background

Kawasaki disease is an acute inflammatory disorder primarily affecting medium-sized blood vessels, especially in infants and young children under 5 years old, characterized by inflammation of the arterial walls, including coronary arteries. While predominantly affecting young children, rarely Kawasaki disease is seen in adults. Reporting this case is crucial due to the patient’s very young age and the disease’s unusual presentation following vaccination, contributing to the limited literature on Kawasaki disease in very young infants.

Case presentation

A full-term, 2-month-and-10-day-old Iranian boy presented with persistent fever unresponsive to treatment, beginning 5 days after receiving the 5-in-1 vaccine. Although physical examination results were normal, his medical history included maternal hypothyroidism during pregnancy and neonatal jaundice that did not require hospitalization. Initial laboratory tests revealed bicytopenia, thrombocytosis on the complete blood count, and elevated erythrocyte sedimentation rate and C-reactive protein levels. Echocardiography identified giant coronary artery aneurysms. The patient was diagnosed with atypical Kawasaki disease and treated with intravenous immunoglobulin, methylprednisolone, infliximab, and aspirin, which resolved his fever.

Conclusions

This case emphasizes the importance of considering Kawasaki disease as a differential diagnosis in infants with persistent, treatment-resistant fever and abnormal complete blood count findings. Early diagnosis and timely intervention are essential to prevent severe complications, such as coronary artery aneurysms and possible mortality. It underscores the need for heightened awareness and vigilance among healthcare providers in similar clinical scenarios.

Introduction

Kawasaki disease (KD) is a febrile systemic vasculitis first described in 1967 by Dr. Tomisaku Kawasaki in Japan, with cardiac complications being identified about 3 years later [1]. This acute disorder primarily affects children under 5 years old, targeting medium-sized blood vessels. Research has shown that KD is approximately 1.5 times more prevalent in boys than in girls [2, 3]. Although the etiology of KD is not fully understood, its higher incidence in children of East Asian and Pacific Islander descent, even among families who have migrated, suggests a potential genetic component in KD’s pathogenesis [4, 5].

While the exact cause of KD remains unknown, some studies suggest that vaccination might trigger KD by strongly activating innate and adaptive immune pathways. However, there is no conclusive evidence linking vaccination to KD development [6,7,8,9].

Typically, around 5 days after fever onset, KD presents with distinct clinical features, including prolonged fever, bilateral non-purulent conjunctivitis, inflammation of the oral mucosa (characterized by dryness and a ‘‘strawberry’’ tongue), extremity changes, skin rashes, and cervical lymphadenopathy (often unilateral and ≥ 1.5 cm in diameter). The diagnosis of classic KD requires a fever lasting five or more days, accompanied by at least four of these five signs, with no other explanation for the symptoms.

In contrast, ‘‘atypical KD’’ refers to cases that do not meet the full diagnostic criteria and may exhibit unusual clinical features. Atypical KD can also present in children outside the typical age range [3]. While KD commonly affects children between 6 months and 5 years of age [9], there have been only a few reported cases in neonates [10].

One of the most serious complications of KD is coronary artery aneurysm (CAA). KD is prevalent among children in developed countries [11] and may even pose a risk factor for myocardial infarction later in adulthood [12]. Factors contributing to CAA development include young age and delayed treatment [13]. Research in Japan, where KD incidence is high, has shown that early treatment with intravenous immunoglobulin (IVIG) can reduce the incidence of CAA by 15–25% [14,15,16].

Atypical KD, which often occurs in children younger than 6 months or older than 5 years, carries a higher risk of CAA and other complications [3, 17]. One severe complication of KD is macrophage activation syndrome (MAS), characterized by excessive activation of macrophages and T lymphocytes, leading to elevated levels of cytokines such as IFN-gamma and GM-CSF. MAS occurs in 1.1–1.9% of KD cases but can be challenging to distinguish from severe KD itself (24). MAS arises from persistent macrophage activation and is associated with autoimmune or inflammatory disorders, including KD [19].

In KD, the presence of symptoms such as persistent fever, hyperferritinemia, thrombocytopenia, splenomegaly, and elevated aspartate aminotransferase (AST) raises suspicion for MAS. Confirming an MAS diagnosis typically requires a thorough evaluation of clinical and laboratory criteria [20].

In this study, we present the case of a 2-month-old boy with atypical KD, who developed aneurysms in the right and left coronary arteries.

Case report

A previously healthy, full-term 2-month-and-10-day-old Iranian boy developed a persistent fever 5 days after receiving the 5-in-1 vaccine. Initially, the fever responded temporarily to treatment with oral acetaminophen at home, but high fever recurred, accompanied by an occasional dry cough. This prompted a visit to a primary care hospital, where he was evaluated, diagnosed with pneumonia, and started on cefotaxime. Due to the continued fever, 6 days later, he was admitted to our hospital for further assessment.

On admission, the patient’s vital signs included a temperature of 38.8 °C, heart rate of 156 bpm, blood pressure of 92/63 mmHg, respiratory rate of 50 breaths per minute, and oxygen saturation of 99%. There were no signs of conjunctivitis, skin rash, or peripheral edema. Examination of the pharynx, as well as auscultation of the heart and lungs, was unremarkable, with no abnormal findings. His past medical history revealed that his mother had hypothyroidism during pregnancy, and he had experienced neonatal jaundice that did not require hospitalization. The patient’s height was 61 cm, and his weight was 7 kg. The remainder of the general and systemic examination was within normal limits.

Management

The patient was initially admitted to the General Children’s Service with a diagnosis of viral pneumonia and was treated with ceftriaxone and nebulized epinephrine.

Initial investigations revealed a C-reactive protein (CRP) level of 116 mg/dL, erythrocyte sedimentation rate (ESR) of 15 mm/hour, white blood cell count (WBC) of 3.12 × 10⁹/L (66% neutrophils, 34% lymphocytes), hemoglobin (Hb) of 7.5 g/dL, and a platelet count of 595 × 10⁹/L. Blood and urine cultures showed no growth of pathogens, and a catheterized urinalysis was normal. The initial chest X-ray (CXR) was also unremarkable.

On day 3 of admission (day 9 of illness), nebulized epinephrine was discontinued, and azithromycin syrup was prescribed for a 5-day course. By day 5, due to persistent fever (38.9˚C) and worsening laboratory results (ESR = 60 and CRP = 136), meningitis was suspected, and vancomycin was added to the antibiotic regimen. Given the decrease in hemoglobin, 70 cc of packed red blood cells were administered. Lumbar puncture analysis showed protein levels of 76 mg/dL, glucose of 44 mg/dL, red blood cell count (RBC) of 18, and WBC of 5 (totally polymorphonuclear cells). Abdominal and pelvic ultrasounds showed no abnormalities.

On day 9 of admission, a brain ultrasound was conducted, which was unremarkable. On day 10, ampicillin was added to the antibiotic regimen due to ongoing fever. However, the fever persisted, and repeated blood tests showed leukocytosis, along with elevated ESR and CRP levels. On day 17, ampicillin and ceftriaxone were discontinued, and meropenem was initiated.

After 18 days, given the patient’s persistent fever and lack of response to antibiotics, suspicion for atypical Kawasaki disease increased. An echocardiogram was performed, revealing coronary artery dilation [left main coronary artery (LMCA) > 6 mm and right coronary artery (RCA) > 4 mm]. Following the diagnosis of atypical Kawasaki disease, the patient was transferred to the Pediatric Intensive Care Unit (PICU) for specialized management.

Treatment was initiated with intravenous immunoglobulin (IVIG) at 2 g/kg over 12 hours, methylprednisolone at 2 mg/kg/day, and aspirin at 50 mg/kg/day divided into four doses.

On day 20, due to elevated prothrombin time–international normalized ratio (PT-INR), the patient received 100 cc of fresh frozen plasma (FFP) along with the first pulse of methylprednisolone. On day 22, a coronary computed tomography angiogram (CTA) was performed, which revealed significant aneurysms in the coronary arteries: RCA ≤ 6.5 mm, LMCA = 6.5 mm, proximal left anterior descending artery (LAD) = 6.5 mm, with significant stenosis in the distal RCA. The second pulse of methylprednisolone was administered (Fig. 1).

Fig. 1

An axial cut of computed tomography angiography (CTA) showing aneurysm in the left coronary artery (A) and right coronary artery (B). Arrows point towards the aneurysm

On day 23, the patient received a third pulse of methylprednisolone, along with 40 cc of packed red blood cells due to low hemoglobin levels. On day 24, treatment with infliximab was initiated.

On day 26, a color Doppler ultrasound of the abdominal aorta and its branches was conducted, revealing normal arterial findings.

On day 28, methylprednisolone injections were discontinued, and oral prednisolone was started. On day 30, meropenem and vancomycin were also discontinued.

On day 33, on the basis of the Z-score calculated from echocardiography and the lack of reduction in coronary artery aneurysm size, enoxaparin was prescribed. After 5 days, enoxaparin was stopped, and the patient was discharged with a regimen including warfarin and aspirin.

Discussion and conclusions

According to the 2017 guidelines from the American Heart Association, Kawasaki disease (KD) is diagnosed when a child presents with a fever lasting more than 5 days and at least four of the primary clinical features. If a child has a fever for more than 5 days, exhibits two or three primary clinical features, and has evidence of coronary artery dilatation, an incomplete diagnosis of KD may be considered. It is important to recognize that certain findings, such as ulcerative stomatitis, splenomegaly, bullous or vesicular rash, exudative pharyngitis, systemic lymphadenopathy, or exudative conjunctivitis, may argue against a KD diagnosis [18].

Approximately 10% of KD cases occur in infants under 6 months of age. Diagnosing KD in infants aged 3 months or younger is particularly challenging [21], as only a limited number of cases (about 24%) meet four out of the five classic clinical criteria. Since delayed diagnosis or treatment is a risk factor for developing coronary artery aneurysms (CAA) [13], infants with KD under 6 months are at higher risk for cardiac complications. To minimize the risk of cardiac issues, IVIG treatment should ideally begin within 10 days of illness onset, and preferably by day 7 [21]. If untreated, KD can lead to coronary artery aneurysms in 15–25% of cases, with approximately 2–3% of untreated children succumbing to coronary-vasculitis-induced myocardial ischemia, which can present years later [22].

In this paper, we present the case of a 2-month-and-10-day-old boy with atypical KD. The patient did not exhibit the classic criteria for KD aside from persistent fever lasting more than 5 days. The delay in diagnosis, therefore, led to the development of coronary artery dilatation. Initially, viral pneumonia was suspected, and broad-spectrum antibiotics were administered; however, this treatment proved ineffective, indicating the absence of an infection, at least during hospitalization. Despite the patient’s continued clinical decline, a definitive diagnosis remained uncertain until day 18, when echocardiography confirmed atypical Kawasaki disease. Treatment with IVIG, methylprednisolone, and aspirin was promptly initiated. IVIG, aspirin, and infliximab remain the cornerstone of KD management [21].

Our patient did not exhibit lymphadenopathy, a feature typically seen in 75% of pediatric KD cases [1]. Laboratory findings consistent with KD-included neutrophilia (though not leukocytosis), anemia, thrombocytosis, and elevated ESR and CRP levels. In this case, the anemia was severe enough to require a blood transfusion. The possibility of macrophage activation syndrome (MAS) was also considered due to persistent fever and thrombocytopenia, although MAS was not definitively diagnosed.

This case underscores the importance of considering Kawasaki disease in infants presenting with prolonged, antibiotic-resistant fever, even though KD is uncommon in children younger than 6 months. Prompt diagnosis and timely treatment—preferably within 10 days of symptom onset—are essential to prevent potentially life-threatening complications, such as coronary artery aneurysms.

Further research is needed to better understand the underlying causes and mechanisms of KD, which may ultimately lead to more effective treatment approaches and improved follow-up protocols.