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Kawasaki Disease
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Kawasaki Disease
, Kawasaki's Disease, Mucocutaneous Lymph Node Syndrome, Infantile Polyarteritis
See Also
Multisystem Inflammatory Syndrome
(
MIS-C
)
Epidemiology
Incidence
First described in Japan, 1967
Kawasaki (1967) Arerugi 16(3): 178-222 [PubMed]
Overall U.S.: 19 per 100,000 children <5 years (2000 U.S. cases/year)
Japanese descent: 150 per 100,000 children <5 years
Asian american children 2.5 times more likely than white children
Black american children 1.5 times more likely than white children
Age of onset
Most cases (75-80%) occur by age 5 years old
Peak age of onset: 1 to 2 years old
Rare under 4 months of age
Gender: Boys more often affected (by ratio of 1.5 to 1)
More common in winter and spring (typically between January and March)
Most common cause of acquired
Coronary Artery Disease
in children
Pathophysiology
Inflammatory response to a trigger in a genetically susceptible host
Idiopathic
Vasculitis
Affects small and medium sized vessels
Inflammatory
Cytokine
s (e.g. TNF, IL-6) promote
Leukocyte
mediated endothelial injury
Postulated associations
Retrovirus
Rickettsia
Coronaviruses
Precautions
Prolonged Fever
should trigger consideration of Kawasaki Disease
Culture negative shock
Exudative Pharyngitis
and
Lymphadenopathy
not responding to typical management
Infants under 6 months of age often present atypically, and have the highest risk of
Coronary Artery
complications
Have a high index of suspicion in unexplained or
Prolonged Fever
, irritability,
Aseptic Meningitis
Concurrent
Viral Infection
exam and lab findings do not exclude Kawasaki Disease
Viral Infection
s are identified in up to 30-40% of cases
Symptoms
Fever
for 5 days or more
Significant Irritability
Diagnosis
Requires fever and 4 other criteria
Fever
prolonged more than 5 days (100%)
Fever
>102.2 F (often >104 F) with abrupt onset
Duration: Averages 11 days untreated
Polymorphous skin eruption on trunk (80-96%)
Starts within first five days with a 7 day duration
Involves extremities, trunk and perineal region
May appear maculopapular,
Scarlatina
-form or
Erythema Multiforme
-like
May appear morbiliform or
Urticaria
l
No bullae or vessicles
Conjunctivitis
(84-89%%)
Bilateral
Conjunctiva
l injection (bulbar)
No
Ciliary Flush
(no limbus injection)
No photophobia
No
Eye Pain
Non-purulent, non-exudative
May be associated with painless
Anterior Uveitis
Acute
Lymphadenopathy
Typically a single, unilateral, minimally to non-tender node >1.5 cm (73%)
Cervical Lymphadenopathy
is most common
Changes in hands and feet
Edema
or induration of hands and feet (65%)
May be painful (e.g. refusal to walk)
Red palms and soles (69%)
Sharp demarcation at ankles and wrists
Desquamation
of fingertips (80%)
Late sign occurs at 2-3 weeks after fever onset
Starts at periungual area
Fingernail
s may develop
Beau Lines
(transverse grooves)
Mucus mebrane changes (92-96%)
Dry, red, fissured, or vertically cracked lips
Strawberry
Tongue
(erythematous
Tongue
with prominent papillae)
Diffuse reddening of the oropharynx
No focal lesions, exudates,
Vesicle
s or ulcers
Diagnosis
Incomplete Kawasaki Disease (met by 9.6% of cases, esp. young infants and older children)
Fever
for at least 5 days AND
Two or three main criteria above (incomplete criteria) AND
Erythrocyte Sedimentation Rate
(ESR) >40 mm/h or
C-Reactive Protein
>=3 mg/dl AND
One of the two following criteria
Coronary Artery Abnormalities
on
Transthoracic Echocardiogram
OR
Three or more laboratory findings
Anemia
for age
Thrombocytosis
with
Platelet Count
>450,000 after day 7 of fever
Hypoalbuminemia <= 3 g/dl
Alanine
Transaminase (ALT) increased
Leukocytosis
with
White Blood Cell Count
>15,000/uL
Sterile pyuria with >10
White Blood Cell
s on urine microscopy
Findings
Other Associated
Urethritis
with sterile pyuria (75%)
Polyarthralgia
Aseptic Meningitis
(25%)
Rhinorrhea
and cough may be present in some cases
Gastrointestinal Symptoms
Abdominal Pain
and
Diarrhea
(25%)
Obstructive Jaundice
with acute gallbladder hydrops
Vomiting
Cardiac Disease (20%)
Pericardial Effusion
Congestive Heart Failure
Arrhythmia
s (e.g.
Tachycardia
)
Valvular dysfunction (25%)
Mitral Regurgitation
(most common)
Aortic root dilatation
Coronary Artery
anomalies (see below)
Gallup Rhythm
Accentuated flow murmur
Differential Diagnosis
Juvenile Rheumatoid Arthritis
Hypersensitivity Reaction
Medication allergy
Mercury Poisoning
Serum Sickness
Stevens-Johnson Syndrome
Bacterial Infection
Leptospirosis
Rocky Mountain Spotted Fever
Scarlet Fever
Staphylococcal Scalded Skin Syndrome
Toxic Shock Syndrome
Meningitis
Viral Infection
Mononucleosis
Measles
Adenovirus
Parvovirus B19
Labs
Complete Blood Count
with differential cell count
Anemia
Leukocytosis
(>15,000/uL)
Thrombocytosis
(>500,000/uL)
Often delayed until 2-3 weeks after fever onset
Erythrocyte Sedimentation Rate
>40 mm/hr (may be >100)
C-Reactive Protein
(CRP) >3 mg/dl
Preferred (unlike ESR, CRP is not altered with IVIG administration)
Basic chemistry panel
Hyponatremia
Liver Function Test
s
Increased liver enzymes (esp. serum transaminases AST and ALT, and GGT)
Hypoalbuminemia may predict a more prolonged, severe course
Blood Culture
Throat Culture
Antistreptolysin-O Titer (
ASO Titer
)
Urinalysis
Sterile pyuria in >33% of cases
Consider
Lumbar Puncture
if
Meningitis
suspected
Pleocytosis
may be seen in Kawasaki's
Diagnostics
Electrocardiogram
(EKG)
May demonstrate strain pattern (ST and
T Wave
changes)
Chest XRay
Observe for cardiomegaly
MRI
Coronary Angiography
May be used when
Echocardiogram
is non-diagnostic (esp. circumflex, distal vessels)
May demonstrate
Coronary Artery
stenosis, thrombi or intimal hyperplasia
Imaging
Echocardiogram
Coronary Artery
evaluation
Initial
Echocardiogram
at presentation
Follow-up
Echocardiogram
at 2 weeks and 6-8 weeks
Indications for
Echocardiogram
at 6-12 months
Abnormalities on prior
Echocardiogram
s
AHA guidelines currently recommend in all patients
However no benefit if prior
Echocardiogram
s normal
Tuohy (2001) Am J Cardiol 88:328-30 [PubMed]
Measurements
Coronary Artery
lumen diameter is compared with BSA to generate a
Z-Score
Z-Score
>2.5 are suggestive of Kawasaki Disease
Vessels
Left anterior descending branch
Proximal right
Coronary Artery
Findings
Coronary Artery
changes
Acute: Tapering, perivascular brightness, ectasia
Late:
Coronary Artery
aneurysm
Other variable changes
Decreased ventricular function
Pericardial Effusion
Evaluation
Diagnostic criteria met (five days of fever and 4 of the 5 other findings present)
Treat as Kawasaki Disease
May also treat at 4 days if criteria otherwise met
Also see alternative criteria listed above
Diagnostic criteria not met (five days of fever with only 2-3 other findings)
CRP <3 mg/dl and ESR <40 mm/h
Discharge home with follow-up
Repeat labs and evaluation if fever persists an additional 2 days
Obtain
Echocardiogram
if peeling occurs (regardless of fever resolution)
CRP >3 mg/dl or ESR >40 mm/h
Obtain additional criteria (requires 3 or more)
Serum Albumin
<3 g/dl
Anemia
Serum ALT
increased
White Blood Cell Count
>12,000
Platelet Count
>450,000
Sterile pyuria
Three or more additional criteria present
Treat as Kawasaki Disease
Obtain
Echocardiogram
Less than three additional criteria
Obtain
Echocardiogram
If
Echocardiogram
positive, treat as Kawasaki Disease
If
Echocardiogram
negative, but fever persists, repeat the
Echocardiogram
Management
Admission
Hydration
Obtain Rheumatology and Cardiology
Consultation
Observe for and treat
Congestive Heart Failure
Cardiac monitoring in all patients
Start treatment as soon as possible
Especially within 10 days of onset
Do not delay for
Echocardiogram
if diagnostic criteria are met
Aspirin
Postulated to reduce inflammation and thrombus formation
However does not reduce coronary aneurysm formation
Dosing
Initial: 20-25 mg/kg every 6 hours
Later: 3-5 mg/kg/day once daily for 6-8 weeks
Start after fever has resolved at least 2 days OR
14 days passes since onset of illness
Longterm
May be indicated indefinately if coronary anomalies are identified
Precautions should be taken against
Reye Syndrome
if longterm
Aspirin
is used
Influenza Vaccine
Varicella Vaccine
Post-exposure precautions
Intravenous Gamma Globulin (IVIG)
Dose: 2 g/kg infused over 8-12 hours
Must be given early in disease to be efficacious
Consider repeating for a second dose if still febrile after first dose
Risk of
Hypotension
and
Seizure
s
Avoid live virus
Vaccine
s for 11 months after IVIG
Efficacy
Effect likely based on reducing
Cytokine
s, antibodies and
T-Cell
activity
Reduces
Coronary Artery
anomaly risk from 25% to 5%
Reduces giant aneurysm risk to <1%
Corticosteroid
s
May be used in combination with IVIG to reduce the risk of coronary anomalies
Corticosteroid
s independently lower risk of coronary anomalies (NNT 10)
Most indicated in the 10-20% of cases refractory to IVIG and
Aspirin
(see below)
Considered in patients at high risk for IVIG resistance
Coronary Artery
Aneurysm at diagnosis
Age <12 months
Kawasaki
Shock
Syndrome
Kawasaki Disease with
Macrophage
activation syndrome
References
Beck (2023) Am Fam Physician 107(1): 20-1 [PubMed]
Chen (2013) Heart 99(2): 76-82 [PubMed]
Green (2022) Cochrane Database Syst Rev (5): CD011188 [PubMed]
Refractory cases (10-20%, fever persists or recurs 36 hours after initial IVIG)
Repeat IVIG 2 g/kg
Consider
Corticosteroid
s
Variable evidence for
Infliximab
(
Remicade
)
Tremoulet (2014) Lancet 383(9930): 1731-8 [PubMed]
Complications
Gene
ral
Early complications
Myocarditis
Pericarditis
Valvular insufficiency (esp. mitral insufficiency, and to a lesser extent
Aortic Insufficiency
)
Arrhythmia
(esp.
Tachycardia
)
Kawasaki Disease
Shock
Syndrome (7% of cases)
Presents with
Tachycardia
and
Hypotension
Cardiovascular collapse often refractory to IVIG
Manage with volume expanders and
Vasopressor
s
Late complications (>1-2 weeks)
Coronary Artery
aneurysm (see below)
Complications
Coronary Artery
aneurysm
Incidence
Occurs in 15-20% of untreated Kawasaki's Disease
Occurs in 2-5% of treated Kawasaki's Disease
Mechanism:
Coronary Artery
Vasculitis
Occurs 2-4 weeks after onset of illness
Most aneurysms regress in 1-2 year
Spontaneously resolve in 33-66% of cases
Most common coronary arteries affected
Proximal left anterior descending artery
Proximal right
Coronary Artery
Associated Risks
Subsequent stenosis
Thrombosis leading to
Myocardial Infarction
Sudden Death
Risk Stratification
Based on
Echocardiogram
results (see above)
Risk Level 1: Normal coronary arteries on imaging
May stop
Aspirin
at 8 weeks following onset
No
Physical Activity
restrictions after first 6-8 weeks
Life-long counseling on
Cardiac Risk Factor
s every 5 years
Long-term endothelial dysfunction risk
Risk Level 2: Transient coronary ectasia, dilation (resolves in first 6-8 weeks)
Same approach as Risk Level 1
Risk Level 3: Coronary aneurysms 3-6 mm (
Z-Score
3-7)
Aspirin
3-5 mg/kg daily for >8 weeks and until aneurysm regresses
Stress Test every 2 years before sports if age >10
Annual cardiology follow-up
Echocardiogram
and
Electrocardiogram
Avoid contact or high-impact sports if on antiplatelet agents
Risk Level 4: coronary aneurysms >6 mm (large) or multiple
Long-term
Aspirin
Warfarin
(INR 2-2.5) or
LMWH
(Xa 0.5-1) for giant aneurysms
Annual cardiac stress test
Cardiology follow-up with
Echocardiogram
and
Electrocardiogram
every 6 months
Cardiac angiogram 6-12 months after illness
Avoid
Collision Sport
s
Risk Level 5: Obstructed
Coronary Artery
aneurysms
Includes recommendations for risk level 4
Beta Blocker
References
Claudius in Majoewsky (2012) EM:Rap 12(11): 8-9
Pacheco and Rawani-Patel (2019) Crit Dec Emerg Med 33(5): 3-11
Darby (2021) Am Fam Physician 104(3): 244-52 [PubMed]
Dummer (2004) Progress Pediatr Cardiol 19:129-35 [PubMed]
Freeman (2006) Am Fam Physician 74:1141-50 [PubMed]
Newburger (2004) Pediatrics 114:1708-33 [PubMed]
Newburger (2004) Circulation 110(17): 2747-71 [PubMed]
Saguil (2015) Am Fam Physician 91(6): 365-71 [PubMed]
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