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GIANT CORONARY ANEURYSM IN A 6 WEEK OLD INFANT, AN UNUSUAL FINDING?

Palacios Argueta Jorge Roberto MD., (1,A,ⴕ) . Sanchez Manubens Judith MD., PhD., (2,A,ⴕ,3,Ω) Zuccarino Flavio (5,π,D, Ω) MD., PhD.,. Teodoro Marin Silvia (1,A, ⴕ) MD., Prada Martinez Freddy H MD., (4,C,Ω).

Pediatric Cardiology Unit. (1) Pediatric Medicine Service (A). Corporacion Sanitaria del Parc Tauli, Sabadell, Universitat Autónoma de Barcelona. Barcelona, Spain (ⴕ).

Pediatric Rheumatology Unit (2). Pediatric Medicine Service (A) . Corporacion Sanitaria del Parc Tauli. Sabadell, Associate professor of Pediatrics, Universitat Autónoma de Barcelona. Barcelona, Spain (ⴕ). Pediatric Rheumatology Service (3). Hospital Sant Joan de Deu, Universitat de Barcelona. Barcelona, Spain ( Ω).

Pediatric Cardiology Service (4). Hosital Sant Joan de Deu, Universitat de Barcelona. Barcelona, Spain (Ω).

Department of Radiology (5). Hospital Sant Joan de Deu, Univesitat de Barcelona, Barcelona, Spain (Ω). Department of Radiology, Head of Cardio-Thoracic Radiology section, Hospital del Mar. Barcelona, Spain (D).  Associate professor of Radiology, Universidad Autonoma de Barcelona. Barcelona, Spain (π).

Corresponding Author: Jorge Roberto Palacios Argueta. Pediatric Cardiology Unit.Pediatric Medicine Service. Corporacion Sanitaria del Parc Tauli, Sabadell, Universitat Autónoma de Barcelona. Barcelona, Spain. Tel. 00 (34)937231010. Ext. 21006. E-mail: jrpalacios@tauli.cat

KEY WORDS.

Kawasaki disease. coronary aneurysms. Infant. Fever.

ABSTRACT.

Kawasaki disease (KD) is a self-limited vasculitis with significant morbidity and even mortality if

not treated early. The diagnosis and timely treatment in children younger than 3 months is

challenging, most of them have an incomplete or atypical presentation. Coronary artery

abnormalities are frequent in this type of patients. We present a 6-week-old female infant

with Kawasaki disease who developed a giant coronary aneurysm. The timely

diagnosis and promptly treatment as well as the echocardiographic and multimodality

follow-up allowed us to improve our clinical approach and management.

INTRODUCTION.

Kawasaki disease (KD) is a self-limited acute febrile illness of unknown cause that

predominates in children under 5 years of age. When initially described, the potential for

coronary artery complications was not appreciated. KD is now the most common cause of

acquired heart disease in children in developed countries. (1). Since its first

description in Japan in 1967 by Tomisaku Kawasaki , KD has been increasingly

reported worldwide. KD is a great concern among predisposed children it is

likely to result in grave clinical consequences (2). Diagnosis is based on

clinical findings of its signs and symptoms. Complete KD is diagnosed with > 5 days of

fever and 4 of 5 clinical features, including bilateral conjunctival injection without

exudates, polymorphous exanthema, erythematous changes in the lips and the oral cavity,

swelling and erythema of the hands and feet, and cervical lymphadenopathy (>1.5cm).

Incomplete KD should be considered in patients with unexplained fever for > 5 days and with 2

or 3 of the clinical features of KD. The peak incidence of KD is from 6 months to 2 years of age.

However, there are fewer cases in infants younger than 6 months that can be difficult to

diagnose because these patients are more likely to have an incomplete clinical

presentation ( 3).Approximately 30-50% of patients with KD developed transient coronary

artery dilatation in the acute stage and about 25% progress to have serious

coronary artery abnormalities such as coronary artery aneurysm and ectasia, if left untreated

(2 ). We present the case of a 6 weeks-old female infant who consults to

our center due to 12 hour fever and clinical deterioration, and is admitted for suspicion

of invasive bacterial infection. During its evolution at pediatric ward, the patient presented

clinical signs compatible with KD and progressive changes in the

diameter of the left coronary artery was documented during her hospitalization and her

follow up.

CASE.

A 6-week-old female infant with 12 hour high fever and irritability was admitted in the

Pediatric Ward with the suspicion of bacterial invasive infection. Blood test, Blood culture,

Urine culture and Lumbar Puncture were performed on the day of admission. The weight:

4130 grams. Height: 53 centimeters. On the 3^rd day she presented torpid evolution with

marked irritability, persistence of high fever and a generalized morbiliform rash with cranio-

caudal progression . During the next 2 days, limbs edema , strawberry tongue and non-

secretory ocular redness with right eye predominance was appreciated.

Blood test showed the elevation of acute phase reactants, C Reactive Protein ( CRP) 25

mg/dl and Procalcitonin(PCT) 1.2ng / ml, hypoalbuminemia of 23.5 g / dl and platelet

44,000 stand out. Given the clinical and analytical findings and age of the patient a Kawasaki

Disease with incomplete presentation (5-day fever + 3 clinical criteria: Rash, limbs edema and

conjunctivitis) was diagnosed. On day 5^th of admission a first dose of IV

Gamma globulins (IVIG) 2g/ kg was administered. An echocardiogram on day 5th ( figure 1).

was normal. A slight clinical improvement of the rash after IVIG was observed, but with

worsening of blood parameters (plaquetopenia of 9000 and anemia of 7.9g/dL).

Despite the IVIG treatment, the patient persists with fever on the 8th day , so is decided to

start with a second dose of IVIG and IV methylprednisolone 30mg / kg / d for 3 days.

The acute phase reactants improve, although the fever persisted, so on 12th day

It started 3rd line of treatment for Kawasaki Disease with Anakinra (Anti IL-1)

2mg / kg / day subcutaneously.

The patient presents analytical improvement with the appearance of significant

desquamation on the feet in the second week. But the fever persisted so on day

16 th of admission a new course of methylprednisolone 30 mg/kg/day by 3 days was

administrated and anakinra was increased to 4 mg/kg/day.

Echocardiogram follow-up was performed every 48 to 72 hours. A progressive dilatation in the

diameter of the descendent anterior left coronary artery with an aneurysm formation was

diagnosed. The clinical and analytical response to treatment was good and remained afebrile

from day 22 of admission. Given a good evolution, the patient was discharged on the 28th day

of admission. The 12^th day after discharge the patient was admitted again due to worsening

of cardiac aneurysms and analytical blood test parameters. Abciximab infusion, IV

Methylprednisolone 3 days course , cyclosporine and clopidogrel were started.

The treatment with subcutaneous Anakinra (2mg / kg / day) and Aspirin (5mg / kg / day)

was maintained. After 5 days in the pediatric intensive care unit and due to clinic and blood

test parameters stability the patient was transferred to the pediatric ward. Anticoagulation

with enoxaparin was started adjusted according to factor Xa levels. Serial controls were

performed with echocardiograms and Electrocardiogram (EKG). They showed an

increase in the size of the anterior descending left coronary artery with an aneurysm + 11,53

Z score and an enlargement from the proximal portion of the left coronary

artery with a + 5.57 Z score . A 12 Lead EKG showed pathological Q waves on the DII, DIII and

AVf (predominantly DIII). The patient was asymptomatic the blood test showed

normalization of acute phase reactants parameters. The steroids were progressively reduced

in the next 15 days and the patient was discharged from the pediatric ward after 14 days of

the 2^nd admission. On 5^th day after discharge a CT Scan was performed ( fig 4).

A development of giant coronary aneurysm from the left anterior descending coronary artery

was diagnosed. She has continued her follow up in the outpatient clinic of Pediatric

rheumatology and Pediatric cardiology Units and has not required any hospital admissions

since then. In the ambulatory controls after 2 months of the second admission the

medications were progressively withdrawn. Enoxaparin, Aspirin and

Clopidrogel were maintained . Regular echocardiographic follow up has showed a

progressive improvement of the aneurysm of the left anterior descending coronary artery.

A diagnostic cardiac catheterization was performed after 2 years of diagnosis and the

aneurysm of the left anterior descending coronary artery has disappeared (fig. 5), the patient

has a normal development and has fulfilled her milestones for her age.

DISCUSSION.

We present a case of a 6 week old female with diagnosis of complete KD

defined as the presence of fever and all clinical criteria (1,4) that developed a resistant form of

KD. A resistant KD is defined by failure in the response to the initial therapy with IVIG (5). Our

Patient, despite an adequate and timely treatment, developed a giant left anterior descending

coronary aneurysm according the 2017 criteria of American Heart Association guidelines.

This classification of coronary involvement is based on raw dimensions and Z score. No

involvement: Always Z score < 2. Dilatation only 2 to < 2.5; or if initially < 2, a decrease in Z-

score during follow-up > 1. Small aneurysm> 2.5 to < 5. Medium aneurysm:> 5 to < 10, and

absolute dimension <8 mm. Large or giant aneurysm> 10, or absolute dimension > 8 (1, 6).

It is evident that recognition of coronary artery lesions is important in KD for

prediction of late complications and treatment modification. (7). The most common

complications of KD include coronary artery dilatation and aneurysms caused by coronary

artery vasculitis. Patients younger than 3 months of age who did not fulfil the diagnostic

criteria have higher coronary involvement and a higher rate of severe coronary artery lesions

(8). Our case showed that although a high degree of clinical suspicion, timely diagnosis,

promptly and correct treatment with first line, second line and third line treatments, coronary

artery complications still occur and are worrisome with high morbidity and mortality. This

type of clinical scenario reminds us the importance of the multidisciplinary approach as well as

the echocardiographic and multimodality imaging follow-up to better characterize this type of

lesions, improving the clinical prognosis of this patients in the short, mid, and long term like we

have been described in our patient.

FIGURES.

COMPLIANCE WITH ETHICAL STANDARDS.

Funding: The authors have not declared any specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Patient consent Parental/guardian consent obtained

AUTHOR CONTRIBUTIONS.

Jorge Palacios designed the manuscripts, conceptualized, drafted and revised the article. Judith Sanchez Manubens conceptualized and critically revised the article. Flavio Zuccarino, Freddy Prada and Silvia Teodoro approved the manuscript and participated in the imaging collection and interpretation. All authors fully approve the manuscript as submitted.

REFERENCES.

FIGURE LEGENDS.

FIG 1. Trans Thoracic Echocardiogram with a parasternal short-axis view at the level of the aortic valve ( AV), Right ventricle outflow tract ( RVOT), Right Atrium ( RA). Left coronary descending artery ( DA) with normal diameter. Echocardiogram on day 5^th

FIG 2. Trans Thoracic Echocardiogram with a parasternal short-axis view at the level of the aortic valve (AV), Right Atrium ( RA), Right Ventricle Outflow Tract ( RVOT) showed the progressive dilatation of left coronary and left descending coronary artery ( DA) in the serials echocardiograms at the end of second week of illness.

FIG 3. Trans Thoracic Echocardiogram with a parasternal short-axis view at the level of the aortic valve (AV), showed a giant aneurysm of the left anterior descending coronary artery (DA).

FIG 4. Thoracic CT: Volume rendering reformation (A) shows ascending aorta and LAD (both displayed in red). LAD fusiform aneurysm (length of 13 mm) affecting proximal and middle LAD, is clearly defined (Asterisk). Short axis reformation (B) perpendicular to LAD aneurysm depicts a maximum transverse diameter of 5.8 mm (red circle). DA distal to aneurysm has a small-caliber (2.5mm diameter).

FIG 5. Left coronary angiogram at 2 years of age with normalization in diameter of her anterior descending coronary artery.