National Consensus On The Cardiological Treatment and Follow-Up of Kawasaki Disease
National Consensus On The Cardiological Treatment and Follow-Up of Kawasaki Disease
National Consensus On The Cardiological Treatment and Follow-Up of Kawasaki Disease
ARTICLE IN PRESS
An Pediatr (Barc). 2018;xxx(xx):xxx---xxx
www.analesdepediatria.org
a
Cardiología infantil, Servicio de Pediatría, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain
b
Sociedad Española de Cardiología Pediátrica y Cardiopatías Congénitas, Spain
c
Cardiología infantil, Servicio de Pediatría, Hospital Universitario Río Hortega, Valladolid, Spain
d
Cardiología infantil, Servicio de Pediatría, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
e
Unidad de Enfermedades Infecciosas, Servicio de Pediatría, Hospital Materno Infantil Doce de Octubre, Madrid, Spain
f
Sociedad Española de Infectología Pediátrica, Spain
g
Unidad de Reumatología Pediátrica, Servicio de Pediatría, Hospital Parc Taulí, Sabadell, Barcelona, Spain
h
Sociedad Española de Reumatología Pediátrica, Spain
i
Cardiología infantil, Servicio de Pediatría, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain
KEYWORDS Abstract Kawasaki disease is a self-limiting acute vasculitis that affects small and medium-
Kawasaki disease; sized vessels, and is the most common cause of acquired heart disease in children in our
Mucocutaneous lymph environment. Up to 25% of untreated patients develop coronary aneurysms. It is suspected
node syndrome; that an infectious agent may be the trigger of the disease, but the causative agent is still
Vasculitis; unknown. Based on the previous evidence, recommendations are proposed for the diagnosis,
Arteritis; treatment of acute disease, and the long-term management of these patients, in order to unify
Coronary aneurysm; criteria. The diagnosis must be quick, based on easy-to-use algorithms and with the support of
Coronary vessels; complementary tests. This document includes the indication of available imaging techniques,
Aneurysm; as well as the planning of cardiological examinations based on the initial involvement. Intra-
Immunoglobulins; venous immunoglobulin is the basis of the initial treatment. The role of corticosteroids is still
Intravenous; controversial, but there are studies that support its use as adjuvant treatment. A multidisci-
Steroids; plinary working group has developed a scheme with different treatment guidelines depending
Consensus on the risk factors at diagnosis, the patient’s clinical situation, and response to previous
夽 Please cite this article as: Tascón AB, Malfaz FC, Sombrero HR, Fernández-Cooke E, Sánchez-Manubens J, Pérez-Lescure Picarzo J,
et al. Consenso nacional sobre diagnóstico, tratamiento y seguimiento cardiológico de la enfermedad de Kawasaki. An Pediatr (Barc). 2018.
https://doi.org/10.1016/j.anpedi.2018.04.003
夽夽 This document is endorsed by the following scientific societies: Asociación Española de Pediatría (AEP); Sociedad Española de Cardiología
(SEC); Sociedad Española de Infectología Pediátrica (SEIP); Sociedad Española de Reumatología Pediátrica (SERPE); Asociación Española de
Pediatría de Atención Primaria (AEPap).
∗ Corresponding author.
2341-2879/© 2018 Asociación Española de Pediatrı́a. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Aetiology, pathogenesis and genetics Table 1 Diagnostic criteria for classic Kawasaki disease.
Although clinical and laboratory findings and the epidemi- Fever of at least 5 days together with
ologic characteristics of the disease hint at an infectious 4 of the 5 principal clinical criteria. In the presence of ≥ 4
cause or trigger, a specific aetiological agent has not been principal clinical criteria, particularly when redness and
identified to date. Previous studies have also been unable swelling of the hands and feet are present, the diagnosis of
to prove an association between the development of KD KD can be made with 4 days of fever (in rare cases,
and exposure to certain drugs or the immune response to experienced clinicians may establish the diagnosis with as
a superantigen.12 few as 3 days of fever)
One of the theories that is currently most widely Not all criteria need to be present at the same time. The
accepted is that KD is caused by an infectious agent that is feature may have resolved by the time of evaluation
inhaled and infects medium-size ciliated bronchial epithe- In cases where the clinical criteria for KD are not fully met,
lial cells.13 Recent studies based on the analysis of the the presence of coronary abnormalities confirms the
large epidemics of KD in Japan suggest that the causative diagnosis
agent could be an environmental agent borne by tropo- Principal criterion Description/comments
spheric winds, possibly a fungal toxin.14 At the same time,
the high incidence in Asian communities and the increased 1. Changes in the lips Erythema, cracking or
risk of siblings of cases suggest that host genetic factors and/or oral mucosa bleeding of lips,
are important in the pathogenesis of KD. A few genome- strawberry tongue with
wide association studies (GWAS) in patients with KD11 have prominent papillae,
been published that identified several loci implicated in and/or erythema of oral
inflammation, the immune response and cardiovascular or pharyngeal mucosa in
involvement. Thus, a reasonable hypothesis is that KD is the absence of compatible
caused by an infectious agent yet to be identified that pro- exudate or lesions
duces disease only in genetically predisposed individuals, 2. Bulbar nonexudative Typically spares the
especially those of Asian descent. Its low incidence in the conjunctival injection limbus.
first months of life and in adults suggests that this is an Subconjunctival
agent to which adults have developed immunity and new- haemorrhage and
borns are passively protected against thanks to maternal punctate keratitis are
antibodies. occasionally observed
3. Maculopapular Without vesicles/bullae,
eruption, diffuse petechiae or scabs.
erythroderma. Accentuation in the groin
Diagnosis of disease
Urticarial or micropustular with early desquamation
eruptions may also be is a characteristic feature
The diagnosis is based on clinical criteria and is
observed
supported by serum values of inflammatory markers
4. Palmar and plantar The induration may be
(Table 1). The identification of aneurisms in the coro-
erythema and swelling painful in some cases.
nary arteries or other locations confirms the diagnosis;
during the acute stage and Beau’s lines (transverse
however, coronary aneurisms are not usually detected
periungual peeling during grooves in nails) may be
until the first week from onset, so a normal echocar-
subacute stage observed at 1---2 months
diographic examination early on does not rule out the
5. Cervical adenopathy May be associated with
diagnosis.11
with diameter ≥1.5 cm, retropharyn-
The diagnosis of atypical or incomplete KD should be con-
usually unilateral geal/parapharyngeal
sidered in patients with prolonged fever of unknown origin
oedema
that meet fewer than 4 of the main clinical criteria and
have compatible laboratory or echocardiographic findings Features that support the diagnosis: elevation of
(Fig. 1).11 inflammatory markers (CRP, ESR, PCT, leucocytosis with
Infants aged less than 6 months are more likely to have neutrophilia), hyponatremia and hypoalbuminemia,
prolonged fever with no additional manifestations of KD and elevated transaminase levels and sterile pyuria.
are at higher risk of developing coronary complications. Thrombocytosis is a characteristic feature starting from the
second week from onset.
CRP, C-reactive protein; ESR, erythrocyte sedimentation rate;
Cardiovascular involvement in Kawasaki PCT, procalcitonin.
disease
Cardiovascular manifestations and complications (Table 2) Recent microscopy studies have identified 3 vasculo-
are the main cause of morbidity and mortality in KD, both pathic processes: the first is a self-limited process that
in the acute stage and in the long term. Patients experience ends about 2 weeks from onset, a necrotising arteri-
inflammation at the level of the pericardium, myocardium, tis produced by infiltration of activated neutrophils into
endocardium (including the heart valves) and the coronary the adventitia that causes aneurisms. The second pro-
arteries. cess is a subacute/chronic vasculitis with infiltration of
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4 A. Barrios Tascón et al.
CRP < 30 mg/L and ESR < 40 mm/h CRP ≥ 30 mg/L and ESR ≥ 40 mm/h
1: Clinical criteria in Table 1. The following findings are NOT indicative of KD: exudative
conjunctivitis, oral ulcers, vesicular or bullous rash, generalised lymphadenopathy,
leukopaenia with lymphocytosis or splenomegaly or normal ESR, CRP level and platelet count
after the 7th day of disease
3. If the echocardiogram is positive, treatment should be given within 10 days of fever onset
or after the tenth day of fever in case of elevated acute phase reactants
lymphocytes, plasma cells, eosinophils and macrophages pericardial/pleural effusion and valve regurgitation in the
that starts 2 weeks from onset and may continue for months acute stage of KD. Table 3 proposes a protocol for car-
or even years in some patients. The third is luminal myofi- diovascular assessment in KD that takes into account the
broblastic proliferation of the medial smooth muscle cells abnormalities described most frequently in the current
that starts in the first 2 weeks and persists for months or literature.11,16
years and can eventually cause arterial stenosis.15
In the acute stage, features may include a hyperdynamic precordium and tachycardia. Patients may present with a gallop
rhythm suggestive of diastolic dysfunction secondary to myocardial inflammation and oedema. The presence of a pericardial
rub or signs of pericardial tamponade is rare (if there is pericardial effusion, it is usually small). A pansystolic murmur may be
heard on auscultation in children with mitral regurgitation. A diastolic murmur associated with aortic regurgitation is rare.
Signs and symptoms of myocardial ischaemia are atypical and nonspecific in children.
Lesion Incidence Characteristics
Coronary abnormalities Up to 25% in untreated patients. The risk drops They are a primary determinant of prognosis.
to <5% with IVIG treatment. In 50% of patients, and depending on the size,
Retrospective phase of KAWARACE study: they resolve within 2 years. Patients with
incidence of coronary aneurisms, 9.6% large/giant aneurisms do not have
cardiovascular manifestations except for
development of myocardial ischaemia due to
severe changes in blood flow or thrombosis.
The risk of coronary aneurism rupture is very
low. It may occur during the acute phase due
to rapid growth of the aneurism
Myocarditis Nearly universal (case series that used labelled It develops prior to coronary artery
WBC heart scans found myocardial abnormalities and without concurrent
involvement in 50%-70% of cases) ischaemic damage. It does not lead to cellular
disruption or myocyte necrosis: the
myocarditis is transient and responds quickly
to anti-inflammatory treatment.
Assessment of ventricular systolic and diastolic
function is necessary in all patients
Cardiogenic shock It is the initial presentation in approximately Thrombocytopaenia and coagulopathy are
5% of patients common in these cases. Patients with this
presentation are at higher risk of IVIG
resistance, coronary involvement and
prolonged myocardial dysfunction
Valvulitis
Mitral regurgitation In the acute stage in up to 25% of patients. In the early course of KD, it is usually of
moderate severity, and it does not appear to
persist on follow-up. It has been correlated
with other laboratory markers of inflammation
Its development seems to be associated with
the pancarditis or the shared inflammatory
process that takes place during the acute stage
of KD.
Aortic regurgitation Much less frequent (1%) It is associated with aortic root dilation in the
early course of illness, and has been reported
in 10% of patients during the acute stage of KD.
Its presence has been associated with coronary
artery dilation
Pericarditis 6---24% of patients In most patients it is limited to the acute stage
of disease, and it is usually mild and transient.
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Table 3 Evaluation of cardiovascular abnormalities in Kawasaki disease.
The cardiovascular evaluation should include: history taking, physical examination, electrocardiogram and echocardiogram
Abnormality Assessment
Coronary Echocardiogram:
abnormalities Use the highest-frequency transducer possible, reduce the window to the region under study, focusing on the area of interest. Compress 50---60 and gain
60---65%. Measure inner edges of coronary arteries excluding points of branching. Coronary abnormalities typically start to develop in the proximal segments
and extend distally
1. Size (z-score):
No involvement Dilation/ectasia Small aneurisms Midsized aneurisms Giant aneurisms
z-score: <2 z-score ≥2 and z-score ≥2.5 and z-score ≥5 and <10 and diameter <8 mmz-score ≥10 and/or diameter ≥8 mm
<2.5 <5
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2. Location: identify the affected coronary artery and segment (proximal, medial or distal)
Echocardiographic views:
- Left main coronary artery: precordial short axis at level of aortic valve; precordial long axis of left ventricle (superior tangential); subcostal ventricular
long axis
- Left anterior descending: precordial short axis at level of aortic valve; precordial superior tangential long axis of left ventricle; precordial short axis of left
ventricle
- Circumflex branch: precordial short axis at level of aortic valve, apical 4-chamber
- Right coronary artery: precordial short axis at level of aortic valve; precordial long axis (inferior tangential) of left ventricle; subcostal short axis at level of
atrioventricular groove; subcostal coronal projection of right ventricular outflow tract
- Posterior descending: apical 4-chamber (inferior), precordial long axis (inferior tangential), subcostal (inferior)
3. Morphology:
- Saccular: when axial and lateral diameters are nearly equal
- Fusiform: when coronary dilation is symmetrical with progressive proximal and distal tapering of luminal diameter
Electrocardiogram:
Depending on the involvement, the infarction may be:
- Subepicardial: T-wave changes
- Subendocardial: ST changes
- Transmural: pathologic Q waves
During acute illness, it can be used to monitor the changes that usually occur in this type of lesions
Approximate localisation of coronary artery involvement during acute illness:
Proximal ADCA ST elevation in V1-V6, aVL, RBBB
Medial ADCA Distal to first septal branch and proximal to diagonal branch ST elevation in V1-V4, aVL
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Table 3 (Continued)
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- Tissue doppler (mitral valve, tricuspid valve and interventricular septum) in 4 chambers: S,
E , A waves, isovolumic contraction time, isovolumic relaxation time and ejection time
Electrocardiogram: rule out sinus node and atrioventricular abnormalities, prolonged PR
interval, pathologic Q waves, prolonged QT interval, low-voltage waves, ST-T abnormalities,
arrhythmias and repolarization abnormalities
Mitral regurgitation Echocardiogram: assess presence or absence of valvular regurgitation and its severity by
colour flow and pulsed-wave Doppler in the apical 4-chamber view
Electrocardiogram: rule out left atrial enlargement in severe cases
Aortic regurgitation Echocardiogram: assess for aortic root dilation in the precordial long axis view, and assess for
valvular regurgitation and its severity by colour flow and pulsed-wave Doppler in the
precordial long axis and apical 5-chamber views
Electrocardiogram: in cases of moderate to severe regurgitation, assess for left ventricular
hypertrophy, and in cases of advanced disease, ST-T wave abnormalities due to ischaemia
Pericarditis Echocardiogram: assess presence and severity of pericardial effusion in apical and subcostal
4-chamber views
Electrocardiogram: Stage I: elevation of ST segment with positive T wave and PR or PQ
interval depression. Stage II: flattening of ST segment and T wave. Stage III: T wave inversion.
Stage IV: normalised T wave
ADCA, anterior descending coronary artery; RBBB, right bundle branch block; RCA, right coronary artery; RV, right ventricle.
Electrocardiogram frontal plane leads: I, II, III, aVR, aVF, aVL. Precordial leads: V1-V8.
7
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8 A. Barrios Tascón et al.
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Treatment of acute illness
First-line drugs
Drug Dose Adverse reactions/precautions Pharmaceutical form
IVIG Single dose: 2 g/kg IV Associated with a high infusion rate at beginning of Vials, 50 mg/mL:
treatment, in 5---15%: fever, chills, headache, myalgia, 0.5 g, 1 g, 2.5 g, 5 g, 10 g,
nausea, vomiting. During or up to 1---2 days after 20 g.
infusion. An anaphylactic reaction may occur in children Vials, 100 mg/mL:
with IgA deficiency due to the development by the 1 g, 2 g, 2.5 g, 5 g, 10 g,
recipient of anti-IgA antibodies during previous 20 g.
treatment with IVIG. In these cases, select the Vials, lyophilised
preparation with the least amount of IgA of those powder: 2.5 g, 5 g, 10 g
available. Measles, mumps, rubella and varicella
immunizations should be deferred for 11 months after
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IVIG administration
Infusion rate: always monitor the first infusion of IVIG for
the first 30 min. Initial rate for 5% solution: 0.5 mL/kg/h
in the first 30 min. For 10% solution: 0.25 ml/kg/h. The
rate can be increased progressively until reaching the
maximum specified by the manufacturer (consult
summary of product characteristics). Usually given over
12 h. The first time IVIG is given to a patient it must be
prepared as a 5% solution
Anti-inflammatory: 30---50 mg/kg/day every At anti-inflammatory doses, it may cause mild chronic Tablets: 100, 125, 150,
ASA
6 h, p.o. salicylate intoxication, which is characterised by 250, 300 and 500 mg
tinnitus and hearing loss. Discontinue treatment if these
symptoms appear. Hypoprothrombinaemia, rhinitis,
paroxysmal bronchospasm, gastrointestinal changes and
bleeding
Antiaggregant: Concomitant administration of ibuprofen antagonises
3---5 mg/kg/day in 1 dose, p.o. the irreversible platelet inhibition effect of ASA, so
ibuprofen is contraindicated in these patients
Use caution if patient has an active varicella or influenza
infection on account of the risk of Reye syndrome. If the
patient has an influenza infection in the acute stage of
KD, aspirin must be avoided (use paracetamol for fever
reduction and another antiplatelet agent, such as
clopidogrel, for at least 2 weeks). Children aged > 6
months should receive the inactivated influenza
vaccine. In case of exposure to varicella, ASA must be
discontinued and replaced by a different antiplatelet
agent. After vaccination against varicella, consider
switching ASA to an alternative antiplatelet agent for 6
weeks. However, there is no evidence of an association
of ASA with Reye syndrome at doses of 3---5 mg/kg/d
9
10
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Table 5 (Continued)
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Infliximab 6 mg/kg IV over 2 h Very frequent (>1/10): risk of infection, headache, Powder for concentrate
1---2 doses (if 2 doses, administer 1 nauseas, abdominal pain. for solution for infusion:
dose/week) Frequent (1/10---1/100): neoplasia, neutropenia, 100 mg
leukopenia, anaemia, lymphadenopathies, respiratory
allergy symptoms, depression, insomnia, conjunctivitis,
hypotension, hypertension, ecchymosis, hot flashes,
facial redness, liver failure, urticaria, eruption,
pruritus, hyperhidrosis, dry skin, fungal dermatitis,
eczema, alopecia, arthralgia, myalgia, back pain
Anakinra 2---6 mg/kg/day subcut, 15 days Infections, neutropenia, thrombocytopenia, headache, 100 mg solution for
local reaction at injection site, hypercholesterolaemia injection in pre-filled
syringe
Etanercept 0.8 mg/kg/dose IV weekly (3 doses) Local reaction at injection site, risk of infection, allergic 10 mg powder and
reaction, development of autoantibodies, fever, pruritus solvent for solution for
injection for paediatric
use
Ciclosporin 3 mg/kg/day IV every 12 h Very frequent (>1/10): hyperlipidaemia, Soft capsules: 25, 50,
4---8 mg/kg/day p.o. every 12 h hypercholesterolaemia, high blood pressure, tremors, 100 mg
headache, renal failure Solution, 100 mg/mL.
Frequent (1/10---1/100): skin rash, oedema, convulsive Ampoules: 50 g/mL,
seizures, hirsutism, hyperkalaemia, hypomagnesemia, 250 mg/5 mL
hyperuricemia, diabetes, cholestasis, gingival
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Table 5 (Continued)
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anticoagulant drugs or drugs with an antiplatelet effect
(omega 3 fatty acids and vitamin E, NSAIDs and valproic
acid).
Increases the levels and amplifies effect of: adenosine,
and its -blocker effect (bradycardia)
Dampens effect of cholinesterase inhibitors
Clopidogrel - Newborns and <2 years: 0.2 mg/kg/day Pruritus, gastrointestinal bleeding, epistaxis Tablets: 75 mg, 300 mg
very 24 h p.o. Increases risk of haemorrhage in combination with drugs Compounded
- >2 years: that cause changes in haemostasis preparation: 5 mg/mL
1 mg/kg/day p.o. titrated to maximum Reduced effect in CYP2C19 poor metabolizers oral suspension
response. 75 mg
Administer with or without food
Abciximab Loading dose: 0.25 mg/kg as IV bolus given Risk of haemorrhage that increases with other drugs or Solution for injection
over 10---60 min, followed by continuous factors that affect haemostasis (4---17%) and infusion, 2 mg/mL
infusion at 0.125 g/kg/min (maximum Other (>10%): hypotension, chest pain, lumbar pain,
10 g/min over 12 h IV) nausea. May cause hypersensitivity reactions.
Concentration of solution for adults: Administer through access in a compressible site. Do not
28.8 g/mL or 36 g/mL diluted in dextrose administer in case of recent history (<6 weeks) of
saline or physiological saline abdominal bleeding, surgery or major injury, stroke,
thrombocytopenia (<100 000/L). Monitor platelet count
at 2---4 h from initial bolus and at 12 h from initiation.
Onset of action at 10 min, duration of antiplatelet effect
of 72 h up to 7 days
11
12
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Table 5 (Continued)
Low molecular weight In paediatrics, do not administer every 24 h Major adverse reactions: anaphylactic shock, Solution in pre-filled
heparin (enoxaparin due to faster clearance of drug haemorrhage, thrombocytopenia, thrombosis syringes,
sodium) - <12 months: Treatment dose: 0.5 --- 1 U/mL 100 mg/mL
Treatment: Prophylaxis dose: 0.1--- 0.3 U/mL Different preparations:
3 mg/kg/day subcut every 12 h Adjust subsequent doses based on anti-factor Xa activity 10 000 IU/mL and
Prophylaxis: and specific nomogram. 15 000 IU/mL
1.5 mg/kg/day subcut every 12 h. Adjust dosage in case of severe renal failure
- Children and adolescents: Risk of hyperkalaemia
Treatment:
2 mg/kg/day subcut every 12 h
Prophylaxis:
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1 mg/kg/day every 12 h
Unfractionated Loading dose: 75 U/kg as IV bolus over High risk of haemorrhage.
heparin sodium 10 min Difficult management. Limited experience in paediatric
Maintenance: use
<1 year: 28 IU/kg/h IV High variability between patients
>1 year: 20 IU/kg/h IV Measure aPTT at 6 h,
target: 60---85 s
Acenocoumarol First dose: Increased risk of haemorrhage. Discontinue if INR > 4 Tablets: 1 and 4 mg.
- Newborns: Effects may be affected by dietary intake of vitamin K
0.2 mg/kg p.o.
- <1 year:
0.1 mg/kg/day p.o.
- 1---5 years:
0.06 mg/kg day p.o. Adjust based on INR
value (target, 2---3)
Peak action at 36---48 h
Alteplase IV thrombolysis: High risk of haemorrhage. Cholesterol crystal Powder and solvent for
Standard dose: 0.5 mg/kg/h embolisation. Lingual angioedema solution for injection
(0.1---0.6 mg/kg/h for 6 h. Low dose: and infusion: vials of
0.03---0.06 mg/kg/h for 12---48 h 10 mg, 20 mg and 50 mg
Maximum 2 mg/h to prepare 1 mg/mL
solution
Urokinase IV thrombolysis: High risk of haemorrhage Powder and solvent for
as second-line treatment in these patients, as noted above. Prevention and treatment of thrombosis in
It appears that long courses of oral corticosteroids may sup- patients with coronary aneurisms
press vascular inflammation, but there have been no clinical
trials comparing different corticosteroid regimens. In addition to rupture of a coronary artery aneurism, which
Two retrospective studies and one randomised multicen- is a rare occurrence, thrombotic occlusion of a coronary
tre study have compared the use of infliximab in patients aneurism followed by secondary myocardial infarction is the
resistant to IVIG to administration of a second dose of IVIG.32 most frequent complication in the acute stage of KD.
Treatment with infliximab was associated with a reduc- Coronary thrombosis should be suspected in patients with
tion in length of stay and in the duration of fever, but rapid deterioration of ventricular function or electrocar-
not in the incidence of cardiovascular sequelae or adverse diographic changes. In case of coronary aneurisms with a
events. There are 3 published case reports describing the progressive increase in diameter, the use of antiplatelet
successful use of anakinra, an interleukin-1 (IL-1) receptor agents should be considered (for example, adding clopido-
antagonist, in patients with KD highly refractory to con- grel to ASA), as inadequate thromboprophylaxis in patients
ventional treatment, and clinical trials that evaluate its with coronary abnormalities is the strongest predictor of a
efficacy in acute KD are currently underway.33---36 Anakinra poor outcome during the acute stage of disease.
has been associated with a decrease in the duration of The management in this section has been extrapolated
fever and serum marker levels as well as improved short- from clinical practice in adults with coronary or cerebrovas-
term coronary outcomes, so its use should be considered cular disease (Tables 4 and 5).
for rescue of patients that do not respond to conventional
treatment.
Ciclosporin seems to reduce the length of stay and Risk stratification and follow-up
duration of fever, but not the incidence of coronary
complications. A clinical trial of ciclosporin in combina- Patients with KD are stratified into different groups accord-
tion with IVIG is currently in progress.37 Cyclophosphamide, ing to coronary involvement regardless of the stage of
which is widely used to treat other types of vasculitis, should disease. In addition to the size of aneurisms, the risk fac-
be reserved for very severe cases on account of its side tors for ischaemia that need to be considered are: extent
effects, as should plasma exchange. of maximal involvement, distal location, absence of collat-
There are cases where diagnosis is delayed (past 10 days eral vessels, obstruction, prior history of thrombosis, acute
from onset) and the fever and elevation of acute phase reac- myocardial infarction (AMI), revascularisation or presence of
tants have already resolved. In these cases, treatment with ventricular dysfunction. The greater the extent of coronary
low-dose ASA for an antiplatelet effect (3---5 mg/kg/day) involvement, the higher the risk of developing ischaemia,
should be initiated and maintained until the end of the acute so the management and follow-up will vary between groups
stage of disease (6---8 weeks), verifying the normalisation of (Table 6). The long-term management protocol should be
echocardiographic features and platelet count before dis- initiated at the end of the acute stage (4---6 weeks) when
continuation. coronary artery luminal diameters are no longer enlarging.
Based on the current evidence, this consensus docu- The cardiovascular risk of patients without aneurisms is
ment proposes different treatment regimens according to similar to that of the general population, so these patients
the presence of risk factors at diagnosis, the clinical condi- may be discharged from follow-up in the cardiology depart-
tion of the patient and the response to previous conventional ment after verifying the normalisation of coronary artery
and steroid treatment (Fig. 2). features, with an emphasis on the evaluation of cardiovas-
Note: our working group recommends consultation with cular risk factors.2
an expert/team of experts to make treatment decisions if In cases where aneurisms develop, the latter resolve in
there is any uncertainty or in particularly complex cases. the first 3 months in 15% of patients, and there is regression
from initial measurement in most patients within the next
2 years, depending on the extent of involvement.38 Despite
regression, the aneurismal area may narrow progressively
as a result of luminal myofibroblastic proliferation. For this
Treatment of cardiomyopathy/shock during acute reason, patients that develop aneurisms in the acute stage
stage of KD require long-term cardiologic follow-up, regardless of
regression.
Myocardial function usually recovers after treatment with Patients with severe coronary artery involvement do not
IVIG, as the latter curbs inflammation and systemic man- usually develop cardiologic symptoms unless they suffer
ifestations. In cases with mild haemodynamic instability, myocardial ischaemia secondary to obstruction and throm-
patients usually respond to treatment with diuretic and bosis.
vasopressor agents. Shock may have a cardiogenic, dis- The signs and symptoms of AMI may be atypical and
tributive or mixed cause, with a pathophysiology similar to nonspecific in children, especially in infants. Few cases of
that of septic shock, with vasodilation produced by inflam- myocardial ischaemia have been reported in children due to
matory factors, absolute and relative hypovolaemia and the development of collateral vessels, and they have been
myocardial dysfunction. In these cases, treatment with IVIG associated with the rupture of aneurisms during acute illness
should be combined with the use of inotropic and vasopres- due to their rapid growth.
sor agents (dobutamine, epinephrine, norepinephrine and In cases where there is evidence of inducible myocar-
dopamine).11 dial ischaemia, performance of invasive angiography is
14
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Table 6 Cardiology followup based on risk in patients with Kawasaki disease.
Risk level Cardiology followupa Followup tests Pharmacological treatment Nonpharmacological
treatment and physical
activity recommendations
1. No coronary involvement Not needed. Discharge at 6 - Not needed. ASA (3---5 mg/kg) until 6 Restriction of physical
at any point weeks from onset. - Prevention of weeks from onset of KD activity is not recommended
(z-score always <2) Consider checkup at 12 cardiovascular risk factorsb No need of ASA thereafter beyond 6---8 weeks
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months
2. Dilation Discharge at 12 months Consider continuing ASA
(z-score always 2---2.5) (If dilation persists, (3---5 mg/kg) if dilation
checkup every 2---5 years) persists
3. Small aneurism (z-score ≥ 2.5 to <5)
3.1 Persistent 6 and 12 months (first year), - Cardiac stress testc every ASA (3---5 mg/kg) until < 11 years: restriction of
once a year thereafter 2---3 years or if patient aneurisms regress physical activity is not
exhibits symptoms of Consider statins recommended beyond
ischaemia or signs of 6---8 weeks
ventricular dysfunction > 11 years: consider
- Consider angiographyd restriction of physical
every 3---5 years activity based on results
- Prevention of of cardiac stress test and
cardiovascular risk factorsb functional testing
3.2 Decreased to dilation 1---3 years - Cardiac stress testc every
or normal luminal dimension 3---5 years or if patient
exhibits symptoms of
ischaemia or signs of
ventricular dysfunction
- Consider angiographyd in
case of inducible ischaemia
- Prevention of
+Model
Table 6 (Continued)
ARTICLE IN PRESS
ischaemia or signs of therapy 6---8 weeks
ventricular dysfunction (Acenocoumarol/LMWH) > 11 years: consider
- Consider angiographyd or dual antiplatelet restriction of physical
every 2---5 years therapy (clopidogrel) if activity based on results
- Prevention of aneurisms persist of cardiac stress test and
cardiovascular risk factorsb functional testing
4.2 Decreased to small 1 year - Cardiac stress testc every Consider dual
aneurism 2---3 years or if patient antiplatelet therapy If anticoagulation is
exhibits symptoms of (add clopidogrel) if used, avoid contact
ischaemia or signs of aneurisms regress sports
ventricular dysfunction Consider statins
- Consider angiographyd
every 3---5 years
- Prevention of
cardiovascular risk factorsb
4.3 Decreased to dilation 1---2 years - Cardiac stress testc every
or normal luminal dimension 2---4 years or if patient
exhibits symptoms of
ischaemia or signs of
ventricular dysfunction
- Angiographyd in case of
inducible ischaemia
- Prevention of
cardiovascular risk factorsb
15
16
+Model
Table 6 (Continued)
ARTICLE IN PRESS
ischaemia or signs of acenocoumarol or LMWH functional testing
ventricular dysfunction if aneurism persists or If anticoagulation is
- Consider angiographyd at decreases to medium used, avoid contact
6---12 months and every 1---5 size sports
years Consider if aneurism
- Prevention of decreases to small size,
cardiovascular risk factorsb discontinue if aneurism
5.2. Decreased to 6---12 months - Cardiac stress testc every regresses
medium aneurism year or if patient exhibits
symptoms of ischaemia or Consider dual
signs of ventricular antiplatelet therapy
dysfunction (ASA + clopidogrel), with
- Consider angiographyd anticoagulation if
every 2---5 years aneurism persists, or in
- Prevention of place of anticoagulation
cardiovascular risk factorsb if aneurism decreases or
5.3 Decreased to small 6---12 months - Cardiac stress testc every regresses
aneurism 1---2 years or if patient
exhibits symptoms of Consider treatment with
ischaemia or signs of beta blockers
ventricular dysfunction Consider statins
- Consider angiographyd
every 2---5 years
+Model
Table 6 (Continued)
ARTICLE IN PRESS
ventricular dysfunction
- Angiographyd in case of
inducible ischaemia
- prevention of
cardiovascular risk factorsb
Stenosise and/or Every 6 months - Cardiac stress testc yearly Anticoagulants Cardiac catheterization in
thrombosis - Angiography at intake and Beta blockers cases with severe stenosis
during followup based on in 5 coronary arteries
patient progress Coronary artery bypass in
cases with severe occlusion
in left coronary artery or
involvement of 2 or 3
vessels, as long as there is
viable myocardium
a The cardiologic assessment includes history and physical examination, electrocardiogram and echocardiogram (the latter is not essential in patients with normalisation of the coronary
arteries, unless they exhibit symptoms of ischaemia, ventricular dysfunction or inducible ischaemia).
b Primary prevention of cardiovascular risk factors includes: measurement of blood pressure, monitoring of body mass index (BMI) and waist circumference, education on healthy dietary
habits and prevention of smoking and sedentary lifestyles. In patients with a history of aneurism, performance of a lipid profile every 5 years. Follow-up may be carried out by the primary
care paediatrician.
c Cardiac stress tests: stress echocardiography, stress magnetic resonance imaging (MRI), stress nuclear medicine (NM) perfusion imaging or positron-emission tomography (PET). The
choice of method will be made by each facility based on its experience and minimising patient risk. In children aged <6 years who are asymptomatic, have no symptoms of ischaemia or
signs of ventricular dysfunction, consider non-invasive coronary artery imaging at rest.
d Coronary angiography can be performed through non-invasive methods (PET, MRI, CT) or invasively (catheterization). In case of inducible ischaemia, catheterization is the method of
choice. Coronary angiography should not be performed during the acute stage: defer until at least 6 months from diagnosis.
e Severe stenosis is defined as a ≥75% narrowing of the lumen (>50% in case of the left main trunk).
17
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ARTICLE IN PRESS
18 A. Barrios Tascón et al.
IVIG 2 g/kg + ASA (30-50 mg/kg) in 4 doses/24 h2 + corticosteroid regimen 1. IVIG 2 g/kg + ASA (30-50 mg/kg) in 4 doses/24 h2. Corticosteroid regimen 2
Perform cardiologic assessment (Table 2) without delaying initiation of treatment Perform cardiologic assessment (Table 2) without delaying initiation of treatment
CORTICOSTEROID REGIMENS:
1. Methylprednisolone boluses: 30 mg/kg/day IV for 3 days followed by methylprednisolone/prednisolone/prednisone (2 mg/kg/day) IV/p.o. based on clinical condition of patient. If IV treatment is required, switch to oral route when fever resolves and
CRP level decreases.5 Maintain 2 mg/kg/day dose until CRP normalizes. Taper over 2-3 weeks to discontinuation.3 semanas.
2. Methylprednisolone at 2 mg/kg/day IV until fever resolves and CRP level decreases,5 followed by prednisolone/prednisone (2 mg/kg/day) p.o. until CRP normalizes. Taper over 2-3 weeks to discontinuation.
1: Rule out sensorineural hearing loss and presence of anterior uveitis (helps diagnosis in uncertain cases), iridocyclitis, vitreous opacities, subconjunctival haemorrhage, punctate keratitis, papilloedema. 2: some patients require nonsteroidal anti-inflammatory
agents, such as ibuprofen, that interfere with the antiplatelet effect of ASA. Consider an alternative antiplatelet agent in these patients (Table 6). 3: Consider if there is evidence of myocarditis, myocardial infarction or pericardial effusion of at least moderate
severity. 4: CRP ≥ 90 mg/L, ESR ≥ 80 mm/h, thrombocytosis ≥ 900 000/mm3. 5: CPR decrease, at least 30% of previous value.
recommended to assess for coronary stenosis, even if the followed by the left main trunk and the circumflex artery,
patient is asymptomatic. distal segments of the right coronary artery and the poste-
rior descending artery, with a predominance of involvement
at branching points.
Adult patients with Kawasaki disease The long-term mortality of Japanese patients with a his-
tory of KD and cardiovascular sequelae is higher compared
Acute-stage KD does not usually occur in adults. Patients to the general population.39 Recent studies have suggested
with KD have usually been discharged or are those that a high incidence of adverse events associated with KD in
have developed sequelae. Their follow-up is planned young adults. In the United States, 5% AMIs in individuals
according to the presence and severity of coronary involve- aged less than 40 years occur in patients with a known
ment, past and present, focusing on abnormalities in the or suspected history of KD (1.5% and 3.5%, respectively).40
coronary arteries, valve function and myocardial abnor- In Japan, up to 9% of AMIs and sudden cardiac deaths
malities (function, perfusion and presence of scar tissue) in young adults are attributable to a previous history of
(Table 6). KD.16
Coronary aneurysms are located at the epicardial level, The AHA recommends transitioning to adult cardiology
and the most frequent locations are the proximal segments care at age 18---21 years.11 Adult cardiologists must be
of the anterior descending artery and right coronary artery, aware of this growing cohort of young adults at risk of
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ARTICLE IN PRESS
National consensus on Kawasaki disease 19
cardiovascular sequelae from their childhood disease, which de Mallorca, Mallorca, Spain), Paola Arévalo (Hospital San
makes the collaboration between paediatric and adult car- Francisco de Asís, Madrid, Spain), August Armengol Rofes (El
diologists essential. Vendrell, Tarragona, Spain), María Arroyas Sánchez (Hospital
Note: to participate in the KAWA-RACE study, contact Severo Ochoa, Leganés, Madrid, Spain), Enrique José Bal-
kawasaki.kawarace@gmail.com. bacid Domingo (Hospital La Paz, Madrid, Spain), Antonio
Baño Rodrigo (Hospital Universitario Niño Jesús, Madrid,
Spain), María Silvina Barcudi Abbona (Hospital Univer-
Conflict of interest sitario de Mutua Terrassa, Tarrasa, Barcelona, Spain),
Isabel Barranco Fernández (Hospital Universitario Príncipe
The authors have no conflicts of interest to declare. de Asturias, Alcalá de Henares, Madrid, Spain), Ana
Barrios Tascón (Hospital Universitario Infanta Sofía, San
Sebastián de los Reyes, Madrid, Spain), Clara María
Acknowledgments
Bernáldez Torralva (Hospital Perpetuo Socorro, Las Palmas
de Gran Canaria, Las Palmas, Spain), Enrique Blanca
We thank Dr Masaru Miura, adjunct physician of the Car-
Jover (Hospital Clínico San Carlos, Madrid, Spain), Car-
diology Department of the Tokyo Metropolitan Children’s
olina Blanco Rodríguez (Centro de Salud Infanta Mercedes,
Medical Center, for his invaluable help in the drafting and
Madrid, Spain), Sonia Blázquez Trigo (Hospital Univer-
editing of this article.
sitario de Cruces, Barakaldo, Vizcaya, Spain), María
Jose Bravo Sayago (Hospital Costa del Sol, Marbella,
Appendix A. Authors Málaga, Spain), María Jesús Caldeiro Díaz (Hospital Infanta
Elena, Valdemoro, Madrid, Spain), María Teresa Cantero
Members of the Working Group on Clinical Cardiology of the Tejedor (Hospital Río Carrión, Palencia, Spain), José Ignacio
Sociedad Española de Cardiología Pediátrica y Cardiopatías Carrasco Moreno (Hospital Universitario y Politécnico La
Congénitas (Spanish Society of Paediatric Cardiology and Fe, Valencia, Spain), Carmen Carreras Blesa (Hospital
Congenital Heart Defects [SECPCC]): Universitario Virgen de las Nieves, Granada, Spain), Juan
Manuel Carretero Bellón (Hospital Sant Joan de Déu,
Members that contributed directly to the development of Barcelona, Spain), María Pia Cassanello (Hospital Uni-
this document versitari General de Catalunya, Sant Cugat del Vallés,
Leticia Albert de la Torre (Hospital Materno Infantil Doce de Barcelona, Spain), Fernando Centeno Malfaz (Hospital
Octubre, Madrid, Spain). Universitario Río Hortega, Valladolid, Spain), Adela Cristina
Carlos Alcalde Martín (Hospital Universitario Río Hortega, Cis Spoturno (Centro Médico Mediterráneo, Almería, Spain),
Valladolid, Spain). Rosa Collell Hernández (Hospital Universitario Sant Joan,
María Álvarez-Fuente (Hospital Ramón y Cajal, Madrid, Reus, Tarragona, Spain), Juan Antonio Costa Orvay (Hospital
Spain). can Misses, Ibiza, Spain), David Crespo Marcos (Hospital
Carolina Blanco Rodríguez (Centro de Salud Infanta Mer- Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain),
cedes, Madrid, Spain). Héctor Augusto Cuéllar Manotas (Hospital Ciudad de Coria,
Gemma Giralt García (Hospital Materno Infantil de Vall Cáceres, Spain), Lucas Alberto Degano Iglesias (Hospital Vall
d’Hebrón, Barcelona. Sociedad Española de Cardiología, D’Hebron, Barcelona, Spain), Lucía Deiros Bronte (Hospital
Spain). Universitario La Paz, Madrid, Spain), Beatriz del Pozo
Federico Gutiérrez-Larraya (Hospital Universitario La Paz, Menéndez (Hospital Universitario 12 de Octubre, Madrid,
Madrid. Sociedad Española de Cardiología, Spain). Spain), Laura del Rey Megías (Complejo Hospitalario
Libertad Latorre Navarro (Hospital Universitario Infanta Universitario de Albacete, Albacete, Spain), Juan José
Sofía, San Sebastián de los Reyes, Madrid, Spain). Díez Tomás (Centro Médico de Asturias, Oviedo, Asturia,
Antonio Sánchez Andrés (Hospital Universitario y Politécnico Spain), Paola Dolader Colina (Hospital Vall D’Hebron,
La Fe, Valencia. Sociedad Española de Cardiología, Spain). Barcelona, Spain), Olga Domínguez García (Hospital Virgen
Belén Toral Vázquez (Hospital Materno Infantil Doce de de la Salud, Toledo, Spain), María Nieves Domínguez
Octubre, Madrid. Sociedad Española de Cardiología, Spain). Garrido (Fundación Jiménez Díaz, Madrid, Spain), Paula
Paula de Vera McMullan (Hospital Universitario Fundación Domínguez Manzano (Hospital Universitario 12 de Octubre,
Alcorcón, Alcorcón, Madrid, Spain). Madrid, Spain), Jesús Duque Bedoya (Hospital Don Benito-
Villa-Nueva, Don Benito, Badajoz, Spain), Javier Echeverría
Espinosa (Hospital General Universitario Gregorio Marañon,
Working Group on Clinical Cardiology of the Sociedad Madrid, Spain), Fidel Ernesto Echeverría Nava (Hospital
Española de Cardiología Pediátrica y Cardiopatías Con- Virgen de la Peña, Fuerteventura, Las Palmas, Spain),
génitas (SECPCC): Hemir David Escobar Pinela (Hospital Universitario de
Georges Akel Pérez (Hospital de Nens de Barcelona, Torrejón, Torrejón, Madrid, Spain), María Esquivias
Barcelona, Spain), Francisco Javier Alados Asenjo (Hospital Universitario Ramón y Cajal, Madrid,
Arboledas (Complejo Hospitalario de Jaén, Jaén, Spain), Spain), Ana Patricia Fariña Ruiz (Hospital Universitario
Carlos Alcalde Martín (Hospital Universitario Río Hort- Nuestra Señora de Candelaria, Santa Cruz de Tenerife,
ega, Valladolid, Spain), Josune Alegría Echauri (Hospital Spain), Javier Fernández Aracama (Hospital Universitario
Universitario Marqués de Valdecilla, Santander, Cantabria, Central de Asturias, Oviedo, Asturias, Spain), Javier
Spain), Patricia Aparicio García (Hospital Son LLàtzer, Palma Fernández Sarabia (Hospital Universitario de Canarias,
+Model
ARTICLE IN PRESS
20 A. Barrios Tascón et al.
La Laguna, Santa Cruz de Tenerife, Spain), María Teresa Universitario Sant Joan, Reus, Tarragona, Spain), Ismael
Fernández Soria (Hospital Universitario Infanta Cristina, Martín de Lara (Hospital General Universitario de Alicante,
Parla, Madrid, Spain), Natalia Fernández Suárez (Hospital Alicante, Spain), María Martínez del Villar (Hospital Gen-
Universitario de Cruces, Barakaldo, Vizcaya, Spain), Aina eral Universitario de Alicante, Alicante, Spain), María
Ferré Belda (Hospital del Vinalopó, Elche, Alicante, Spain), Isabel Martínez Lorente (Hospital Rafael Méndez, Lorca,
Sergio Flores Villar (Hospital Universitari Mutua de Terrassa, Murcia, Spain), Patricia Martínez Olorón (Hospital Virgen
Terrasa, Barcelona, Spain), Julio Fontenla García (Complejo del Camino, Pamplona, Navarra, Spain), María Isabel
Hospital Universitario de Ourense, Ourense, Spain), Martínez Soto (Complejo Hospitalario Universitario de
Antonia Pastora Gallego García de Vinuesa (Hospital Santiago, Santiago de Compostela, La Coruña, Spain),
Maternoinfantil Teresa Herrera, A Coruña, Spain), Marta Laura Marzo Checa (Clínica del Vallés, Sabadell, Barcelona,
Gambra Arzoz (Hospital del Sureste, Arganda, Madrid, Spain), Miguel Ángel Matamala Morillo (Hospital General
Spain), Francisco García Angleu (Hospital infantil Virgen Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain),
del Rocío, Sevilla, Spain), Estefanía García Cerro (Hospital Constancio Medrano López (Hospital Universitario Gregorio
Universitario Príncipe de Asturias, Alcalá de Henares, Marañón, Madrid, Spain), Paula Méndez Abad (Hospital
Madrid, Spain), María Elvira Garrido-Lestache Rodríguez- Universitario Virgen del Rocío, Sevilla, Spain), Francisco
Monte (Hospital Universitario Ramón y Cajal, Madrid, Meza Ortiz (Hospital Nuestra Señora del Prado, Talavera de
Spain), Nuria Gil Villanueva (Hospital Universitario Infanta la Reina, Toledo, Spain), Ángeles Ortega Montes (Complejo
Leonor, Madrid, Spain), Maribel Giner Crespo (Hospital Hospitalario Torrecárdenas, Almería, Spain), Alfonso Orti-
Universitario y Politécnico La Fe, Valencia, Spain), Gema gado Matamala (Hospital Universitario de Guadalajara,
Giralt García (Hospital Vall D’Hebron, Barcelona, Spain), Guadalajara, Spain), Almudena Ortiz Garrido (The Royal
María Ersilia González Carrasco (Hospital Universitario Brompton Hospital, Londres, Reino Unido, Spain), Ignacio
Severo Ochoa, Leganés, Madrid, Spain), María Aránzazu Oulego Erroz (Complejo Asistencial Universitario de León,
González Marín (Hospital General de Ciudad Real, Ciudad León, Spain), Jorge Roberto Palacios Argueta (Corporación
Real, Spain), Cristina González Menchén (Hospital Clínico Sanitaria del Parc Tauli, Sabadell, Barcelona, Spain),
San Carlos, Madrid, Spain), Fernando Gran Ipiña (Hospital Laura Parra Agüera (IMED Elche/CS Babel, Alicante,
Universitario Vall d’Hebron, Barcelona, Spain), Inmacu- Spain), Esteban Peiró Molina (Hospital Universitario
lada Guillén Rodríguez (Hospital Virgen de Valme, Sevilla, Politécnico La Fe, Valencia, Spain), Julio Ernesto Peralta
Spain), María Teresa Guixeres Esteve (Hospital Universi- Salas (Hospital del Tajo, Aranjuez, Madrid, Spain), César
tario y Politécnico La Fe, Valencia, Spain), Manuel Haro Jorge Perera Carrillo (Hospital Universitario de Canarias,
Gómez (Hospital Universitario Virgen Macarena, Sevilla, La Laguna, Santa Cruz de Tenerife, Spain), Dolores Pérez
Spain), Aida Hernández Blanco (Hospital Internacional Med- Campos (Hospital Universitario de Fuenlabrada, Fuen-
imar, Alicante, Spain), Yolanda Herranz Sánchez (Hospital labrada, Madrid, Spain), Verónica Pérez Herrera (Consorci
de la Marina Baixa, Villajoyosa, Alicante, Spain), Carmen Sanitari del Maresme --- Hospital de Mataró, Barcelona,
Herrera del Rey (Hospital Universitario Virgen del Rocío, Spain), María Ángeles Pérez Moneo Agapito (Hospital
Sevilla, Spain), Aleida Ibañez Fernández (Hospital Uni- Universitario La Paz, Madrid, Spain), Alejandro Pérez
versitario Central de Asturias, Oviedo, Asturias, Spain), Muñuzuri (Hospital Clínico Universitario, Santiago de Com-
Gema Iñigo Martín (Hospital Virgen de la Salud, Toledo, postela, La Coruña, Spain), Ana María Pérez Pardo (Hospital
Spain), Ignacio Izquierdo Fos (Hospital General Univer- General de Cataluña, Sant Cugat del Vallés, Barcelona,
sitario de Elche, Elche, Alicante, Spain), María Ángeles Spain), José María Pérez Roldán (Hospital Universitario
Izquierdo Riezu (Hospital Universitario Donostia, San de Cruces, Barakaldo, Vizcaya, Spain), Francisco Javier
Sebastián, Spain), María Soledad Jiménez Casso (Hospital Pérez-Lescure Picarzo (Hospital Universitario Fundación
general de Segovia, Segovia, Spain), Lorenzo Jiménez Alcorcón, Alcorcón, Madrid, Spain), María Rosa Pérez-
Montañés (Hospital Miguel Servet, Zaragoza, Spain), Car- Piaya Moreno (HM Universitario Montepríncipe, Madrid,
los Labrandero de Lera (Hospital Universitario La Paz, Spain), Francesca Perin (Hospital Universitario Virgen de
Madrid, Spain), Libertad Latorre Navarro (Hospital Uni- las Nieves, Granada, Spain), Isabel Pinto Fuentes (Hospital
versitario Infanta Sofía, San Sebastián de los Reyes, Universitario Severo Ochoa, Leganés, Madrid, Spain),
Madrid, Spain), Bernardo López Abel (Hospital Clínico Beatriz Plata Izquierdo (Hospital Universitario de Sala-
Universitario, Santiago de Compostela, La Coruña, Spain), manca, Salamanca, Spain), María Portoles Morales (Hospital
María Lozano Balseiro (Hospital Maternoinfantil Teresa de la Plana, Villareal, Castellón, Spain), María Ángeles
Herrera, A Coruña, Spain), José Luaces González (Hospital Puigdevall Dalmau (Hospital Universitario Doctor Josep
Marcide-Novoa Santos, Ferrol, A Coruña, Spain), Nazaret Trueta, Gerona, Spain), Erika Pulido Ovalle (Hospital Uni-
Macías Julián (Hospital UPS Marbella, Málaga, Spain), versitario Infanta Elena, Valdemoro, Madrid, Spain), María
Jesús Antonio Mairal Cazcarra (Hospital de Terrassa, Teresa Raga Poveda (Hospital Universitario Infanta Sofía,
Barcelona, Spain), María José Maldonado Toral (Hospital San Sebastián de los Reyes, Madrid, Spain), Sara Rellán
General de Villalba, Villalba, Madrid, Spain), Alejandra Rodríguez (Hospital Clínico Universitario de Valladolid,
Manchola Linero (Hospital Universitaru Vall D’Hebron, Valladolid, Spain), Susana María Rey García (Complexo
Barcelona, Spain), Begoña Manso García (Hospital Uni- Hospitalario Universitario de Ourense, Orense, Spain),
versitario Vall d’Hebron, Barcelona, Spain), MaríMaravall Erika Rezola Arcelus (Hospital Universitario Donostia, San
Llagaria (Hospital General de Valencia, Valencia, Spain), Sebastián, Spain), Bibiana Riaño Méndez (Hospital Univer-
Sonia Marcos Alonso (Hospital Maternoinfantil Teresa Her- sitario San Pedro, Logroño, La Rioja, Spain), Andrés Rico
rera, A Coruña, Spain), Cristina Marimón Blanch (Hospital Armada (NE22HS, Newcatle Upon Tyne, Reino Unido, Spain),
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ARTICLE IN PRESS
National consensus on Kawasaki disease 21
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