Kawasaki Disease Flashcards
Kawasaki disease
- by Dr. Tomisaku Kawasaki
- Acute vasculitic syndrome of unknown etiology
- Primarily affects infants + young children
- Most common acquired heart disease in children in developed countries
Clinical features:
1. Cervical lymphadenopathy
2. Conjunctival congestion
3. Red, eroded, fissured lips
4. Strawberry tongue
5. Swollen / Indurated extremities
6. Rash followed by desquamation
- Scarlet fever-like rash: thighs
- Erythema-like rash: auricles, Hands, feet, chest, back, arm, legs
Other clinical features:
1. CVS: heart failure, myocarditis, pericarditis, valvulitis (causing MR, AR)
2. GI: diarrhoea, vomiting, hepatitis, pancreatitis, hydrops of gallbladder
3. CNS: irritability, aseptic meningitis
4. Lungs: pneumonitis
5. Others: erythema and induration at BCG inoculation site (BCGitis: thought to be cross-reactivity between mycobacteria and human heat shock protein), desquamating rash in groin
Risk factors:
- Ethics difference: East > West
- Family history of KD (Siblings, Parents)
- Genetic polymorphism: ITPKC, FCGR2A, BLK, CD40
Etiology:
- Unclear
- Infectious agents triggering off an immunologic cascade
—> A seasonal peak of KD in the winter / spring months in most geographic areas
—> Epidemics with a clear epicentre
—> Peak incidence in toddler but only rare cases in infants <3 months old + in adults (suggesting a role for transplacental Ab conferring protection coupled with asymptomatic infection in most individuals with development of protective Ab)
—> The similarity of many of clinical features of KD to other infectious disease e.g. adenovirus infection, scarlet fever
Diagnosis (Clinical):
1. Fever persisting >=5 days
2. Presence of >=4 of 5 principal features (眼口頸手皮膚):
- Bilateral bulbar conjunctival injection (without exudate)
- Changes in lips and oral cavity: Erythema, Lips cracking, Strawberry tongue
- Cervical lymphadenopathy: >1.5cm diameter, usually unilateral
- Changes in extremities: Erythema of palms, soles; Edema of hands, feet; Periungual peeling of fingers, toes in subacute phase
- Polymorphous exanthem
Suspected incomplete KD:
- Fever persisting >=5 days + 2 or 3 Clinical criteria
—> Other clinical features consistent with KD —> Laboratory investigations + Echo
—> Less consistent / inconsistent features (Exudative conjunctivitis, Exudative pharyngitis, Intraoral lesions, Bullous / Vesicular rash, Generalised lymphadenopathy) —> Consider alternative diagnosis
Laboratory investigations:
1. ↑ CRP, ESR
2. Anaemia (Anaemia of inflammation / Haemolysis)
3. WBC >=15
4. Plt >=450 (Reactive thrombocytosis)
5. ↑ ALT
6. Albumin <=30
7. Urine WBC >=10 per high power field
Echo:
1. Coronary artery
- Dilation
- Aneurysms on ectasia
- Perivascular brightness (∵ inflammation of coronary artery)
-
Myocardium
- Impaired LV function -
Valve
- MR (∵ valvulitis) -
Pericardium
- Pericardial effusion (∵ pericarditis)
Echo should always be considered in infants <6 months with:
- >=7 days fever
- Laboratory evidence of systemic inflammation
- Absence of other explanations
Genetic polymorphism
- ITPKC
- Act as negative regulator of calcineurin / NFAT pathway in T cells
- C allele of ITPKC may enhance T-cell activation - FCGR2A
- Stratifies individuals into either strong / weak responders to IgG subclasses
- Affects binding affinity to IgG
- Influence clinical phenotypes of infection and inflammation - BLK
- Encodes B-lymphoid tissue kinase that transduces signals downstream of B-cell receptor - CD40
- Expressed in APC
- Increased CD40 ligand cell surface expression + Increased serum levels of soluble CD40L in acute phase of KD
DDx of Kawasaki disease
- Viral infections (e.g. measles, adenovirus, enterovirus, EB virus)
- Scarlet fever (by Streptococcus pyogenes)
- Toxic shock syndrome (by Streptococcus pyogenes / Staphylococcus aureus)
- Staphylococcal scalded skin syndrome (by Staphylococcus aureus)
- Bacterial cervical lymphadenitis
- Drug hypersensitivity reactions
- Stevens-Johnson syndrome (SJS)
- Juvenile RA
- Leptospirosis
Lifelong CVS complications
- Coronary artery aneurysms
—> Thrombotic occlusion —> Permanent occlusion / Recanalisation
or
—> Layered mural thrombus / Luminal myofibroblastic proliferation
—> Stenosis (causing myocardial ischaemia) / Remodeled to normal lumen with abnormal arterial wall
or
—> Regression of aneurysms - Aneurysms in axillary arteries, iliac arteries
Acute management of Kawasaki disease
Standard treatment regimen:
1. IVIG
- 2 g/kg as a single infusion
- preferably to be given within 7-10 days to minimise coronary artery aneurysm formation
- dose-response effect
-
Aspirin (High dose)
- High dose 80-100 mg/kg/day in 4 doses (varying from 30-100 mg/kg/day)
- variable duration (usually reduced when afebrile for 48-72 hours / until 14 days)
- to continue at a low dose (3-5 mg/kg/day) till 6-8 weeks (if coronary arteries appear normal)
Non-responder:
- ~10-15% of KD patients have persistent / recrudescent fever >36 hours after end of initial IVIG infusion
—> Rule out other causes
—> Retreatment with IVIG
Refractory KD (Failure of IVIG retreatment) (no standard treatment):
1. Third dose of IVIG
2. IV Methdylprednisolone
3. IV Infliximab single infusion
4. Cyclosporin
5. Oral methotrexate
6. Plasma exchange
Risk stratification of coronary artery involvement
Class 1: No involvement at any timepoint (Z score always <2)
Class 2: Dilation only (Z score 2-2.5)
Class 3: Small aneurysm (Z score 2.5-5)
Class 4: Medium aneurysm (Z score 5-10, absolute dimension <8mm)
Class 5: Large + giant aneurysm (Z score >=10 or absolute dimension >=8mm)
Z score 2.5: 99th percentile of normal coronary artery dimension
Z score significance:
1. FU strategy (coronary artery imaging, assessment of myocardial ischaemia)
2. Counselling
3. Prognosis
Monitoring of CVS health
Echo at the time of diagnosis
—> Low risk patients (No aneurysms / Dilation only)
—> 2 weeks
—> 6-8 weeks
—> May discharge by 1 year of FU
—> High risk patients (Coronary abnormalities (small / medium / large aneurysm), Ventricular dysfunction, IVIG resistance)
—> Need for long-term cardiac FU + further assessment
Further assessment:
1. Assessment for inducible Myocardial ischaemia
- Stress echo
- Stress MRI
- Stress nuclear medicine
- PET
- Cardiology assessment
- CT
- MRI
- Invasive angiography - CV risk assessment
- BP
- Fasting lipid profile
- BMI
- Waist circumference
- Dietary + activity assessment
Stress perfusion imaging / Myocardial perfusion scintigraphy
- Exercise / Drug-induced stress
- Radiotracers: Thallium-201, 2x 99mTc-labelled radiopharmaceuticals, Sestamibi, Tetrofosmin
Long-term management of Kawasaki disease
- Medical treatment
No involvement of coronary artery:
- Low-dose aspirin: 6-8 weeks then discontinue
- Anticoagulation (Warfarin / LMWH): Not indicated
- DAPT (Aspirin + Clopidogrel): Not indicated
- β-blocker: Not indicated
- Statin: Not indicated
Small aneurysm (current):
- Low-dose aspirin: Continue (prevent thrombosis)
- Anticoagulation (Warfarin / LMWH): May be considered
- DAPT (Aspirin + Clopidogrel): May be considered as an alternative to anticoagulation
- β-blocker: Not indicated
- Statin: Empirical therapy may be considered
Medium aneurysm (current / persistent):
- Low-dose aspirin
- Anticoagulation (Warfarin / LMWH)
- DAPT (Aspirin + Clopidogrel): May be considered as an alternative to anticoagulation
- β-blocker: Not indicated
- Statin: Empirical therapy may be considered
Large + Giant aneurysm:
- Low-dose aspirin: Continue
- Anticoagulation (Warfarin / LMWH): Reasonably indicated
- DAPT (Aspirin + Clopidogrel): May be considered as an alternative to anticoagulation
- β-blocker: May be considered
- Statin: Empirical therapy may be considered
Statin:
- ∵ Atherogenic lipid profile in KD patients
- Lowering of LDL cholesterol
- Potential beneficial pleiotropic effects on inflammation, endothelial function, oxidative stress, platelet aggregation, coagulation, fibrinolysis
-
Catheter-based therapy
- Ischaemic symptoms caused by significant coronary artery stenosis (>=75% luminal diameter)
- Significant stenosis (>=75% luminal diameter) without ischaemic symptoms during activities / daily living, but with ischaemic findings during stress testing -
Coronary bypass surgery
- Viability evaluated based on presence / absence of angina + findings of exercise ECG, thallium myocardial scintigraphy, 2D echo, left ventriculography (regional wall movement), and other techniques
- Important angiographic findings
—> Severe occlusive lesions in left main
—> Severe occlusive lesions in multiple vessels (2/3 vessels)
—> Severe occlusive lesions in proximal LAD
—> Jeopardised collaterals - Promotion of CVS health (∵ KD predispose to premature vascular aging)
- CVS risk assessment (obesity, HT, dyslipidaemia, glucose intolerance)
- Screen for dyslipidaemia
- Healthy lifestyle
