Kawasaki Disease Flashcards
1
Q
- Formerly called “mucocutaneous lymph node syndrome”, “infantile polyarteritis nodosa
- Acute febrile illness in childhood, highest occurring in Asian children
- Self-limited systemic inflammatory disorder manifesting vasculitis or inflammation around or in blood vessels
- 85% of affected children are <5 yrs old with an average age of 2 yrs old
- is a self-limited acute systemic vasculitis of unknown cause
- 85% of affected children are <5 yrs old with an average age of 2 yrs old
- In Japan, the highest incidence occurs between 9 and 11 months old in boys, and between 3 and 8 months old in girls
A
KD
2
Q
Etiology of KD
A
- The cause is unknown
- Postulated to be infectious in origin
• Observations:
o young age group affected
o self-limited nature of the disease
o infrequent occurence in infants <3 mos old due to the
presence of maternal antibodies
o rare in adults, result of prior exposure of these adults
with subsequent immunity - Genetic role due to higher risk of KD in Asian children regardless of
their country of residence and higher risk in siblings with a history of
KD
3
Q
Genetic Background
A
- In Japan, 1% of patients with KD have a history of affected sibling
- Concordance for KD was 13.3% in dizygotic twins and 14.1% in
monozygotic twins - The exact genetic factors that may underlie the disorder are unknown
- Affected twin pairs who became ill within two weeks of each other
however suggests also an important role for (an) environmental
agent(s), they could have been exposed with the same infectious
trigger - Risk stratification model that are at highest risk for Coronary Artery
Aneurysm (CAA):
• young age
• male gender
• persistent fever
• poor response to IVIG
• neutrophilia
• thrombocytopenia
• transaminitis
• increase BNP
• hyponatremia
• increase CRP
• hypoalbuminemia - Asian, Pacific Islander, and Hispanic ethnicity are risk factors for CAA
- Kobayashi score (by Japanese) for IVIG resistance
4
Q
Pathology
A
- Vascular inflammation that affects medium size arteries
- Three phases to the process of arteriopathy:
(a) neutrophilic necrotizing arteritis;
o Occurs in the first 2 weeks of illness that begins in the
endothelium and moves through the coronary wall
o Saccular aneurysms might form from these arteritis
o 3 ways in this stage:
§ No coronary artery changes
§ Mild transient dilatation that resolves
between 4-6weeks
§ Becomes necrotizing arteritis or becomes an
aneurysm
(b) subacute/ chronic vasculitis driven by lymphocytes, plasma cells
and eosinophils;
o Which may weeks to years and results in fusiform
aneurysms
(c) smooth muscle cell myofibrobroblast formation
o Causes progressive stenosis
o Thrombi may form in the lumen and obstruct blood flow
5
Q
- 1-2 weeks
- fever, LAD, oropharyngeal changes, peripheral extremity changes
- MYOCARDITIS dominant cardiac manifestation (manifested as
tachycardia) - 2DE: pericarditis with small pericardial effusion
A
Acute Febrile Phase
6
Q
- 2-4 weeks
- fever subsides, conjunctival injection may persist
- desquamation, thrombocytosis
- CORONARY ARTERY ANEURYSM (≥8mm internal diameter) poses
risk for rupture
A
Subacute Phase
7
Q
- 4-8 weeks
- ESR and CRP return to normal
A
Convalescent Phase
8
Q
Criteria for the Diagnosis of Kawasaki Disease (1967)
A
- Fever for more than five days (four days if treatment with IVIG eradicates fever) PLUS at least four of the following clinical signs not
explained by another disease process - bilateral conjunctival injection
- changes in the oropharyngeal mucous membranes, including one or more of injected and/or fissured lips, strawberry tongue, injected
pharynx - changes in the peripheral extremities, including erythema and/or
edema of the hands and feet (acute phase) or periungal desquamation (convalescent phase) - polymorphous rash, primarily truncal; nonvesicular
- cervical lymhadenopathy with at least one node >1.5 cm
Note: Patients with fever at least 5 days and < 4 criteria can be diagnosed with KD when coronary artery abnormalities are detected
by 2Decho or angiography
9
Q
CORONARY ARTERY ANEURYSM
A
- Will develop in 20-25% of untreated patients
- In giant artery aneurysm (z score ≥10 or ≥8mm internal diameter),
IVIG treatment decreases its incidence by >95% - Will develop in 5% of patients despite successful treatment
- 10-20% relapse rate
10
Q
- persistent fever but fewer than four clinical features
- Supplemental laboratory criteria include albumin ≤3.0 g/dL, anemia
for age, elevation of alanine aminotransferase, platelet count after 7
days ≥450,000/ mm3, white blood cell count ≥15,000/mm3, and
urine white blood cell count ≥10 /high-power field - Echocardiogram findings are considered positive (Echo +) if any of 3
conditions are met: - z score of left anterior descending coronary artery (LAD) or right
coronary artery (RCA) ≥2.5mm - coronary arteries meet Japanese Ministry of Health criteria for
aneurysms - ≥3 other suggestive features exist, including perivascular
brightness, lack of tapering, decreased left ventricle (LV) function,
mitral regurgitation, pericardial effusion, or z scores in LAD or RCA of
2-2.5mm - Echocardiogram should be performed at diagnosis and after 1-2
week of illness. If results are normal, repeat at 6-8 weeks
A
ATYPICAL/INCOMPLETE KAWASAKI
11
Q
Treatment of Kawasaki Disease
Acute Stage:
A
- IVIG 2g/kg over 10-12 hr AND aspirin 30-50 mg/kg/day (LOW) or 80-
100 mg/kg/day (HIGH) divided every 6 hr until patient is afebrile for
at least 48 hours
12
Q
Treatment of Kawasaki Disease
Convalescent Stage:
A
- Aspirin 3-5mg/kg once daily orally until 6-8 wk after illness if with
normal coronary findings thoughout the course
13
Q
Long-Term Therapy for patients with coronary abnormalities:
A
Aspirin 3-5mg/kg/day orally; Clopidogrel 1mg/kg/day (maximum
75mg/day); Warfarin or LMWH
Children identified high risk for IVIG resistance using Kobayashi score (≥4) is
treated with prednisolone (2mg/kg/day) plus IVIG
14
Q
- Inhibits platelet adhesion by suppressing platelet release of
thromboxane A2 Does not reduce the frequency of coronary artery
abnormalities - Anti-inflammatory dose: high dose ASA 80-100mg/kg/day: low dose
ASA 30-50mg/ kg /day - Anti-platelet dose (3-5mg/kg/day) should be administered after
patient has been afebrile at 48 hours
A
ASPIRIN
15
Q
- IVIG is most effective in reducing the risk of coronary artery disease
when administered within 10 days of the onset of fever - The mechanism of action of IVIG is uncertain: induction of neutrophil
apoptosis and reversal of inhibited lymphocyte apoptosis - The response is generally prompt, and temperature returns to
normal in most children even before the end of the IVIG infusion
A
Intravenous Immunoglobulin (IVIG)
16
Q
- Found in 10% to 20% of children
- Fever returns within 48 hours of treatment with IVIG
- Indicates failure to suppress the underlying inflammatory process
- Because prolonged fever is an independent risk factor for the
development of coronary artery aneurysms, these children should be
retreated with a second dose of IVIG (2 gm/kg) - If second treatment fails, they should be treated in rapid succession
with intravenous methylprednisolone (30 mg/kg/day for one to three
days) or with infliximab (anti-TNF) (5 mg/kg) - Treatment should continue until fever resolves and the CRP is
normal, and frequent evaluations of the coronary arteries should be
pursued until children have fully recovered
A
TREATMENT RELAPSE
17
Q
Monitoring cardiac status
A
- There is no universal agreement about the timing and frequency of
echocardiographic monitoring of patients with KD - It is recommended that the initial echocardiogram should be
obtained at the time a diagnosis of KD is suspected and that each
child with KD should have a second echocardiogram obtained six to
eight weeks after onset of the disease - Patients should also have repeated clinical examinations during the
first 2 months to detect dysrhythmias, congestive heart failure,
valvular insufficiency, or myocarditis
18
Q
Follow up Recommendations
A
- America Heart Association (AHA) recommends performing
echocardiography at diagnosis, and then 2 weeks and 6–8 weeks
after the initial illness for uncomplicated cases - Referral for earlier coronary artery bypass graft (CABG) in children
with giant coronary aneurysms and myocardial ischemia, resulted in
better post-operative results (95% survival rates at 20–25 years postop)
and cardiac event- free rates that progressively declined to 60%
at 25 years
19
Q
Complications and Prognosis
A
- Although standard therapy with IVIG and aspirin given within the
first 10 days of illness greatly improves outcomes, approximately 5%
of children still develop coronary artery aneurysms, and coronary
artery ectasia - The mortality rate is about 0.1% in the U.S. and Japan
- Recurrent disease after full recovery from a first episode of KD is rare
but does occur - In Japan, the recurrence rate is 2.9%, with a higher incidence of
cardiac complications during the second - Patients undergoing long term aspirin therapy should receive
annual influenza vaccination to reduce the risk of Reye syndrome - IVIG interferes with immune response to live virus vaccines (MMR
and varicella) and should be delayed until 11 months after IVIG
administration. Nonlive vaccines do not need to be delayed.
(NELSON)
