3. 7 year old , quetta resident, previously healthy boy landed in ER
with c/o
High grade Fever - 7 days
Headache 7 days
Rashes 4 days
B/L Eye swelling 4 days
PRESENTING COMPLAINTS
4. HOPC:
According to the patient attendant the child was in his usual
state of health until he developed fever 1 week back which was
initially low grade intermittent associated with rigors and chills
there is also history of headache associated with fever origin
and site not specified.
Patient also has complain of neck pain from last 7 days. There
is also history of rashes from last four days of which attendants
are not aware of progression pattern.
5. GPE
HEIGHT : 121 CM
WEIGHT: 18KG
BP: 70/35 below 50th centile
H/R: 115 B/M
R/R: 32 B/M
TEMP : 101 F
Sats: 97% ON ROOM AIR
6. SYSTEMIC EXAM:
CNS : GCS 15/15
Irritable
CHEST: B/L equal air entry
CVS: S1+S2+0
Pulses palpable but weak, regular rythym
ABD: soft + non tender , no visceromegaly
B/L hand and feet edema
B/L swollen and red eyes
Cracking of lips
RASH: diffuse maculopapular rash
10. HOSPITAL COURSE
Patient was admitted in ICU set up.
Baseline workup was sent and echo done which showed
LV enlargement, mild dysfunction, EF 56%, mildly dilated
coronary artery, z score RCA + 2.9 LCA +2.3, mild pericardial
effusion, max 9mm. Trace to mild MR. Shiny hyperechoic
endothelium.
IVIG 2G/KG was administered on day 1.
Iv ceftriaxone started.
LASIX infusion started due to oliguria
DOPAMINE 10 mics due to low bp.
Pre renal AKI managed.
11. Patient also had right leg swelling, reported pain on 2nd day of
admission, which was suspected as septic arthritis/DVT.
TLC count reported to be increased.
Vancomycin added.
U/s doppler done which was normal.
Fever persisted 72HRS post IVIG.
Methylprednisolone given for 3 days then tapered.
Symptoms improved after methyl prednisolone.
Albumin transfused for 3 days.
Infusions stopped
12. COVID PCR negative but antibodies positive
PEDS ID taken on board
Advise against isolation hence Stepped down to ward
Discharged on LOW DOSE aspirin .
13. LAB WORKUP
DATE HB/PCV TLC N L PLT
6/8 9.3/28 18.6 85 6.8 237
8/8 7.8/24 30 86 6 LOW
NORMAL
10/8 6.55/20 13.60 74 22 102
11/8 6.11/18.5 10.90 74 15 217
15. DATE CRP BLOOD
6/8/20 24 NO GROWTH
11/8/20 8.68
DATE 6/8 8/8 9/8 10/8
ALBUMIN 2.23 1.76 3.03
NT PRO BNP 9533 10879
CPK 442
16. DATE 6/8 9/8 10/8
ALT 22 28
FERRITIN 7909 4645
LDH 385
CPK
D DIMER 11.56
SAR COV NEG
COVID AB POSITIVE
MPICT -VE
17. URINE DR
Color Yellow
Quantity 30 ml
Specific Gravity 1.015
pH 5.0
Nitrite Negative
Protein 25 mg/dl
Glucose Negative
Ketones Negative
Urobilinogen Normal
Bilirubin Negative
Microscopic Examination
RBC Negative
Pus Cells 4-6 /HPF
Epithelial Cells 3-5 /HPF
Casts Granular 2-3 /LPF
Crystals NIL
18. Echo;
LV enlargement mild dysfunction, EF 56%, mildly
dilated coronary artery, Z score RCA + 2.9 LCA
+2.3. Mild pericardial effusion, max 9mm. Trace
to mild MR. Shiny hyperechoic endothelium
Review echo;
EF 55% mildly dilated coronary arteries
Review echo;
Cardiac function improved. RCA 3 LAD 2.2 LM 2
TR 50 mildly dilated LV
19. Venous color doppler right leg:
Mildly enlarged benign inguinal lymph nodes
Normal venous color doppler sonography of right
lower limb
No evidence of DVT
U/S both kidneys:
Minimal bilateral effusion
Minimal ascites seen
Both kidneys mildly echogenic
20. FINAL DIAGNOSIS
1. KAWASAKI DISEASE
2. QUERY FOR MULTISYSTEM INFLAMMATORY
SYNDROME IN CHILDREN (MIS-C )
3. MULTI ORGAN DAMAGE (RESOLVED)
4. ACUTE KIDNEY INJURY (RESOLVED)
23. •History of KD/Epidemiology
•2017 Guidelines
- Diagnosis –
• Classic cases
• The challenges of diagnosis
• Echocardiography in KD
• Need for additional imaging
- Treatment
• The future of initial KD therapy
• IVIG resistance - Knowing when to retreat
• Complex cases
• KDSS
• KD with severe coronary artery aneurysms
• Persistent features without fever
• Thromboprophylaxis in KD
- Follow-up
• When to follow-up
• Immunizations after IVIG for KD
Pediatric Cardiology
Outline
25. What is Kawasaki Disease (KD)?
Kawasaki disease (KD) is an acute, self-limiting disease of
unknown etiology. It involves both small and medium-sized
vessels of various organs with predilection for the coronary
arteries. It is mainly a childhood illness, predominantly in
<5years old, occuring in all races around the world
Pediatric Cardiology
mucocutaneous lymph node syndrome and infantile polyarteritis nodosa.
26. •Coronary artery aneurysms or ectasia develop in20 % to 25%
of untreated children and can lead to
•ischemic heart disease or
•Sudden death
27. •Annual US incidence ~25 per 100,000 children <5yrs old
•The incidence was highest among Asians and Pacific Islanders (30.3 per
100 000 children <5 years of age)
• in Japan, the annual incidence IS 264.8 per 100 000
Pediatric Cardiology
Epidemiology
28. •Japan:
•10x increased risk with an affected sibling
•2x increased risk with a previously affected parent
Pediatric Cardiology
29. •80-90% of cases occur in children <5yrs old
•Peak 18-24 mo
•Rare beyond late childhood
•Older children may experience delays in diagnosis
•Boys > Girls (1.5:1)
•Worldwide, KD occurs in two peak seasons of summers and winters
30.
31. • 1st phase - neutrophilic necrotizing arteritis in the 1st 2 wk of
illness that begins in the endothelium, moves in the coronary walls
and progressively destroys the arterial wall into the adventitia,
causing aneurysms.
32. • 2nd phase – subacute/chronic vasculitis driven by lymphocytes,
plasma cells, and eosinophils, which may last weeks to years and
results in fusiform aneurysms.
33. • 3rd phase - smooth muscle cell myofibroblasts develop
which causes progressive stenosis. Thrombi may form in
the lumen and obstruct blood flow.
46. KD can be divided into 3 clinical phases.
The acute febrile phase is characterized by fever and the other
acute signs of illness and usually lasts 1-2 wk.
The subacute phase is associated with desquamation,
thrombocytosis, the development of CAA, the highest risk of sudden
death in patients in whom aneurysms have developed, and generally
lasts about 3 wk.
The convalescent phase begins when all clinical signs of illness have
disappeared and continues until the erythrocyte sedimentation rate
(ESR) returns to normal, typically about 6-8 week after onset of
illness.
47. •The signs are common
•There is no gold standard lab test
•The stakes are high
•A missed diagnosis may manifest years (or decades)
later
•However, are we over-diagnosing?
The Challenges of Diagnosis
Pediatric Cardiology
57. •Any of 3 conditions are met:
- Z score of LAD or RCA≥2.5
- Coronary artery aneurysm
- ≥3 other suggestivefeatures:
•decreased left ventricular function
•mitral regurgitation
•pericardial effusion
•Z scores in the LAD or RCA of 2 to
2.5
Pediatric Cardiology
2017 Guidelines –
What Defines a Positive Echocardiogram?
58. •Z-Score Classification – Risk Level
1. No involvement: Always <2
2. Dilation only: 2 to <2.5; or if initially <2, a decrease in Z
score during follow-up ≥1
3. Small aneurysm: ≥2.5 to <5
4. Medium aneurysm: ≥5 to <10, and absolute dimension
<8 mm
5. Large or giant aneurysm: ≥10, or absolute dimension ≥8
mm
A z score ≥10 is considered giant and hence defines the
threshold at which anticoagulation should be initiated.
Pediatric Cardiology
Coronary Artery Involvement
61. Giant Aneurysms and Prognosis
Pediatric Cardiology
•Patients with giant aneurysms have worst
prognosis
•30 year survival- 90%
•Only 36% cardiac event free
(Tsuda et al AM Heart J 2014; 167: 249-58)
(Manlhoit/PHN Pediatr Cardiol 2010)
62. • Echocardiography should be performed at diagnosis and again after 2-3 wk of
illness
• If the results are normal, a repeat study should be performed 6-8 wk after
onset of illness.
• If results of either of the initial studies are abnormal or the patient has
recurrent fever or symptom,
more frequent echocardiography or other studies may be necessary.
• In patients without coronary abnormalities at any time during the illness,
performance of echocardiography and a lipid profile is recommended 1 year
later.
• After this time, periodic evaluation for preventive cardiology some experts
recommend cardiologic follow-up every 5 yr.
63.
64. •It is reasonable to obtain advanced imaging studies
- computed tomographic angiography(CTA)
- cardiac magnetic resonance imaging(CMRI)
- invasiveangiography
•Recommended on patients with:
- severe proximal coronary artery abnormalities
- when management decisions depend on visualization ofdistal
segments
- difficult to be seen byechocardiography
•Other vasculature can be imaged simultaneously
Pediatric Cardiology
2017 Guidelines –
Advanced Imaging in KD
65. •MR in KD
-Demonstrates distal aneurysms
-Viability/delayed enhancement
-Myocardial perfusion
-See extracardiac dilation
-Frequently need anesthesia
•CT in KD
-Better than MR for thrombus
evaluation
-Smaller slices than MRI
-Down side: Radiation
68. •2017 Guideline states
-IVIG
•“Patients with complete and incomplete KD should be
treated with high-dose IVIG (2 g/kg)”
-Aspirin:
•“Administration of moderate (30 – 50 mg/kg/day) to high
dose (80 – 100 mg/kg/day) ASA is reasonable until the
patient is afebrile, although there is no evidence that it
reduces coronary artery aneurysms”
Pediatric Cardiology
The Future of Initial KD Treatment
69. •What about steroids?
- Traditionally has been a controversial topic
- But should we consider steroids as part of initialtherapy?
Pediatric Cardiology
The Future of Initial KD Treatment
70. •2017 Guideline states
-“Single-dose pulse methylprednisolone should not be
administered with IVIG as routine primary therapy”
-“A longer course of corticosteroids (tapering over 2 – 3
weeks), together with IVIG and ASA may be considered for
treatment of high-risk patients when such high risk can be
identified in patients before initiation of treatment”
Pediatric Cardiology
The Future of Initial KD Treatment
71. •2017 Guideline states…
-“Approximately 10 – 20% of patients with KD develop
recrudescent or persistent fever at least 36 hours after the
end of their IVIG infusion and are termed IVIG resistant.”
Pediatric Cardiology
When to Retreat?
72. 2017 Guidelines - IVIG Resistance
Brian W.McCrindle et al. Circulation. 2017;135:e927-e999
Pediatric Cardiology
1. Second dose of IVIG (2 g/kg) after 36 hours
OR
2. Methylprednisolone 20–30 mg/kg IV x 3 days, +/- taper
of oral steroids
OR
Second dose of IVIG (2 g/kg), IV steroids x 3 days, +/-
taper of oral steroids
OR
3. Second dose of IVIG (2 g/kg) with prolonged oral taper
of prednisolone/prednisone
OR
4. Infliximab (5 mg/kg) instead of 2nd IVIG or corticosteroids
73. 5. Cyclosporine in those who have failed above
6. Highly refractory patients
- Anakinra
- Cyclophosphamide
- Plasma exchange
Brian W.McCrindle et al. Circulation. 2017;135:e927-e999
Pediatric Cardiology
2017 Guidelines - IVIG Resistance
74. Problems with 2017 Guidelines
Pediatric Cardiology
•No robust data from clinical trials for IVIG resistance
•No guidelines for sickest patients: children < 1 year of
age, KD shock syndrome, severe CA abnormalities or
macrophage activation syndrome
•Persistent disease (worsening labs, persistent to
worsening symptoms) in the absence of fever
75. Kawasaki Disease Shock Syndrome
(KDSS)
Pediatric Cardiology
•“Kawashocki”
- Hypotension plus KDsymptoms
- Incidence of ≈ 7%
•Compared to typical KD patients
- Higher CRP, hyponatremia, hypoalbuminemiaand
thrombocytopenia
- ↑IVIGresistance
- ↑rates of CAabnormalities
- Increased risk of MR and prolonged myocardialdysfunction
Kanegaye JT, et al. Pediatrics. 2009;123:e783–e789.
76. KDSS
2017 Guidelines
•Initial IVIG and ASA
•Guidelines hint that KDSS
are IVIG resistant
•If IVIG resistant proceed
with options 1,2, 3 or 4,
etc
Additional therapy driven by clinical
course
TCH
Initial IVIG and ASA w/ IV
methylprednisolone 30 mg/kg x (3
pulses) w/ oral steroid taper
2nd dose of IVIG if IVIG resistant[2]
Pediatric Cardiology
77. KD with Severe CA Abnormalities
2017 Guidelines
•No guidelines
•Only case reports with
limited outcomes
•Worrisome since these
patients are at greatest
risk of morbidity and
mortality
TCH
Initial IVIG andASA
+/- 2nd dose of IVIG [1] if IVIG
resistant
IV methylprednisolone 30 mg/kg
x (3 pulses) w/ oral steroid taper
and infliximab vs other anakinra
Pediatric Cardiology
78. Persistent Features w/o Fever
2017 Guidelines
•No guidelines outside of
initial therapy
TCH
Additional therapy driven by
clinical course
IV methylprednisolone 30
mg/kg x (~3 pulses) w/ oral
corticosteroid taper [2]
Initial IVIG andASA
Pediatric Cardiology
79. •Most common in first 45 days
•Contributing factors:
-thrombocytosis
- increased plateletadhesion
-inflammation
- endothelialdysfunction
- abnormal flowconditions
Pediatric Cardiology
Thromboprophylaxis in KD
80. •Aspirin – low dose until
coronary artery
normalization
•Clopidogrel - increased risk
of thrombosis or aspirin non-
responder
•Lovenox - the anti-
inflammatory actions and
anticoagulant effects
Thromboprophylaxis in KD
Pediatric Cardiology
81.
82.
83.
84. 2017 Guidelines - Echo Surveillance
• Twice weekly while
rapidly expanding
• First 45 days: weekly
• First 3 months:
monthly
• Every 3 months for
first year
Prevention and Treatment of Thrombosis in Pediatric
and Congenital Heart Disease: A Scientific Statement
from the AHA. 2013; Circulation
Pediatric Cardiology
92. Rheumatology Follow Up
Pediatric Cardiology
•Children < 1 year or any child with a complicated KD
course
•Follow up labs (i.e., CBC, LFTs, inflammatory markers,
albumin, sodium) and clinical course
•Tapering of corticosteroids and other therapies if
necessary, are based on improvement of labs and
collaboration with cardiology
93. •Defer live virus vaccines for 11 months
-MMR
-Varicella
-Flumist
-Rotavirus
-Zoster
-Smallpox
- Yellowfever
Pediatric Cardiology
2017 Guidelines –
Immunizations After IVIG in KD
