محاضرة مؤتمر شبين ال25 لعام 2017

1. 1
BY:
Dr, WALAA SALAH MANAA
SPECIALEST OF PEDIATRIC
‫ـستشفى‬‫م‬‫ـفر‬‫ك‬ ‫ـيات‬‫م‬‫ح‬‫ـيخ‬‫ش‬‫ال‬
Kawasaki Disease

4. Introduction
• Acute multi system disease affecting
infants & children with prominent
vasculitis of large & medium sized vessels
• Acute vasculitis of childhood,
characterized by
Fever
Bilateral non exudative conjunctivitis
Erythema of the lips and oral mucosa
Changes in the extremities
Rash
Cervical lymphadenopathy17-Nov-17

5. • KD -The leading cause for
acquired heart disease in children
• Coronary artery aneurysms or
ectasia develop in 15% to 25% of
untreated children & can lead to
– ischemic heart disease or
– sudden death
17-Nov-17
Why?

6. History
• 1967 - Tomisaku Kawasaki reports a series of 50
patients and establishes the clinical criteria for diagnosis
(in Japanese)
• 1974 - first English language report of Kawasaki
syndrome by Kawasaki
• 1976 - first series of American patients reported by
Melish, Hawaii
• 1977 - landing and Larson establish that Kawasaki
disease and infantile polyarteritis nodosa are
pathologically indistinguishable
• 1988 - American academy of pediatrics endorses high
does IVGG plus ASA as recommended therapy for
Kawasaki disease17-Nov-17

7. Tomisaku Kawasaki (centre right) at the 8th
International Kawasaki Disease Symposium, 2005

8. Epidemiology
• More prevalent in Japan and in children
of Japanese ancestry (annual incidence
of 112 cases per 100 000 children <5
years old).
• Age of onset -
– Peak age - 2 to 5 yrs
– 80 - 85 % < 5 yrs
– Rare > 11 yrs
17-Nov-17

9. Aetiology
• Aetiology remains unknown, (although
clinical and epidemiological features
strongly suggest an infectious cause).
17-Nov-17
Theories :
1-Immunologic response
2-Infectious etiology
3-Genetic factors

10. • Immunologic response:
– Affects medium-sized arteries
– Inflammatory cell infiltration into KD
vascular tissue vascular damage
– Stimulus for this inflammatory
infiltration has not been identified

11. Infectious etiology:
• Similarities between KD and other pediatric infectious
conditions suggest that KD is caused by a transmissible
agent include:
– Febrile exanthem with lymphadenitis and mucositis
– Seasonal increase in disease incidence in the winter
and summer
• No studies have identified a specific virus, bacteria or
bacterial toxin, or other pathogen associated with KD

12. Genetic factors:
– Increased frequency of the disease in Asian
and Asian-American populations and among
family members

13. • Its rarity in the first few months of life and in
adults suggests an agent to which the latter are
immune and from which very young infants are
protected by passive maternal antibodies
• Little evidence exists of person-to-person
transmission.
• Hypothesis assumes that most infected children
experience asymptomatic infection with only a
small fraction developing overt clinical features
of Kawasaki disease.
• The genetic basis of susceptibility is currently
unknown
17-Nov-17

15. Pathology
• Generalized systemic vasculitis involving
blood vessels throughout the body.
• Aneurysms may occur in other
extraparenchymal muscular arteries
(celiac, mesenteric, femoral, iliac,
renal, axillary, and brachial arteries).
• Media of affected vessels demonstrate
edematous dissociation of the smooth
muscle cells
17-Nov-17

16. • Endothelial cell swelling and subendothelial
edema are seen, but the internal elastic lamina
remains intact
• Influx of neutrophils is found in the early
stages (7 to 9 days after onset), with a rapid
transition to large mononuclear cells in concert
with lymphocytes (predominantly CD8+ T cells)
and IgA plaasma cells
• Destruction of the internal elastic lamina and
eventually fibroblastic proliferation
• Active inflammation is replaced over several
weeks to months by progressive fibrosis, with
scar formation
17-Nov-17

17. 17-Nov-17

18. 17-Nov-17
Clinical Features

19. 17-Nov-17

21. – First day of fever is considered first day of
illness, although other features may develop
first
– High-spiking (~40 C) and remittent
– Fever of ≥5 days generally distinguishes KD from
self-limiting viral infections.
– Untreated the fever usually lasts 1-2 weeks.
– Defervescence within 1-2 days of treatment
with IVIG17-Nov-17
1: Fever in KD

22. – Begins shortly after the
fever
– Resolves rapidly.
– Non-purulent
– Bulbar conjunctivitis with
limbic sparing
– Anterior uveitis may occur
17-Nov-17
2: Conjunctivitis

23. – Erythema, dryness, swelling
and peeling of lips
lipstick sign
– Lips may bleed
– Erythema of oropharyngeal
mucosa
– Strawberry tongue.
– No Koplik’s spots or oral
ulceration or exudates.
17-Nov-17
3:Oropharyngeal changes

24. – Oedema of hands and feet, especially in
infants
– Peeling of fingers and toes (often
periungual) is NOT a feature of the
acute presentation
– Peeling of hands and feet in sub acute
phase (1-2 weeks)
– Beau’s lines in nails; occasionally nail is
lost
17-Nov-17
4:Changes in the extremities

25. – occurs with onset of fever and fades within
a week
– erythematous plaques at flexor creases.
– Erythema and desquamation of the
inguinal/perineal area
– Occurs early (desquamation of hands and
feet is a later sign)
–NOpetechiae or purpura, vesicles or
bullae, crusting, pruritis.
17-Nov-17
5: Polymorphous rash

26. – 50-80% of cases
– >1.5cm, usually more obvious
– May be unilateral single node
– May be erythematous, but
non-fluctuant and no pus
17-Nov-17
6: Lymphadenopathy

27. 17-Nov-17

28. 17-Nov-17

29. Other clinical features
– Aseptic meningitis (Irritability)
(~25% ) (CSF - ↑ lymph's, N glucose/protein)
– Arthritis - probably less common since IVIG
treatment
– Hydrops of the gallbladder
– Sterile pyuria, urethritis and diarrhoea
– Pulmonary infiltrates or pneumonitis
Inflammation at site of BCG scar
– Cross-reactivity of T cells in KD patients between
specific epitopes of Mycobacterial and human heat
shock proteins
17-Nov-17

30. Kawasaki disease - diagnostic criteria
Fever of ≥ 5 days duration + four of five criteria
– Oropharyngeal changes (90%)
– Changes in peripheral extremities (90%)
– Cervical lymphadenopathy (~75%)
– Polymorphous rash (95%)
– Bilateral non-purulent conjunctivitis (90%)
17-Nov-17

31. Challenge in diagnosis

32. – Most common in infants
– greatest risk of CAA
– Children may have fever and 3 clinical signs
– Reports of coronary AN with 2 diagnostic features
– Occasionally only prolonged fever is present, and
diagnosis is only made after an ECHO
17-Nov-17
1-Atypical or incomplete KD

33. – Recognition is difficult
– KD should be in the DD of prolonged fever
in infants
– Sequential clinical features: incomplete
becomes complete Use other clues
(irritability, BCG scar indurations etc.)
– Balance between risk of KD and risk of
IVIG
17-Nov-17

34. – Much rarer than parents or clinicians think
– 2% in Japanese; ~<1% in UK and N America
– Must fulfil diagnostic criteria again in full
– Skin peeling with subsequent febrile
illnesses is common
– Increased rate of heart damage in second
episode of KD
17-Nov-17
2-Recurrent Kawasaki Disease

35. differential diagnosis

42. Investigation
No laboratory
test specific
for KD

43. CBC :
Leukocytosis, and a left-shift.
Thrombocytosis: may reach to 1,000,000/mm3
Normocytic, normochromic anemia
[CRP,ESR] Increased of acute phase reactants
Urine: white blood cells (Pyuria ) is often of urethral origin
LFT Abnormal because of intrahepatic congestion
Echocardiography : study of choice to evaluate CAA
ECG

44. Complications
• Irritability and aseptic meningitis
• Gallbladder hydrops
• Hepatitis
• Otitis media
• Pancreatitis
• Myositis
• Pericarditis and myocarditis
• Aneurysm formation can lead to peripheral
gangrene, cerebral infarction and cardiac arterial
aneurysm (this may lead to thrombosis, myocardial
infarction and dysrrhythmia)
17-Nov-17

45. Cardiac complications
• 20–40% of untreated KD patients develop coronary
artery abnormalities
• 50% of these lesions regress within five years, and
in most with mild CAA (3–4 mm) regression occurs
within two years
• Giant aneurysms (>8 mm) are unlikely to resolve,
and some may develop stenosis with risk of
coronary thrombosis, myocardial infarction, and
death.
• mortality rate of 3.7% in the UK for KD
17-Nov-17

46. 17-Nov-17
Newburger, J. W. et al. Circulation 2004;110:2747-2771
Coronary angiogram demonstrating giant aneurysm of the LAD with obstruction and giant
aneurysm of the RCA with area of severe narrowing in 6-year-old boy

47. Recommended guideline for the management of
Kawasaki disease in the UK

48. Recommended guideline for the management of
Kawasaki disease in the UK
• Establish diagnosis
– (1) Complete Kawasaki disease (any age)
– (2) Incomplete Kawasaki (<1 year)
• Treatment
– IVIG 2 g/kg as a single infusion over 12 hours
– Aspirin 30–50 mg/kg/day in 4 divided doses for 2 weeks (7.5 – 12.5 mg/kg QDS)
– Echocardiography and ECG
– Aspirin 2–5 mg/kg/day when fever settled ,continuing for a minimum of 6
weeks
17-Nov-17

49. 17-Nov-17
Disease defervescence:
Repeat echocardiography at 2 and 6 weeks
No CAA CAA <8 mm, no stenoses CAA > 8 mm and/or stenoses
Stop aspirin at 6
weeks
Continue aspirin Lifelong aspirin 2–5 mg/kg/day
Lifelong follow up at
least every 2 years
Repeat echocardiography and
ECG at 6 monthly intervals
Consider warfarin
Discontinue aspirin if resolves Consider coronary aneurysm
angiography and exercise stress
testing
Consider exercise stress test if
multiple aneurysms
Repeat echocardiography and ECG at
6 monthly intervals
Specific advice on minimizing
atheroma risk factors
Specific advice on minimizing
atheroma risk factors
Lifelong follow up Lifelong follow up
No disease defervescence within 48 hours, or disease recrudescence within 2
weeks:
Seek expert advice to consider:
• Second dose of IVIG at 2 gm/kg/day
• Pulsed methylprednisolone at 600 mg/m2 twice daily for 3 days or
prednisolone 2 mg/kg/day once daily, weaning over 6 weeks

50. ● Treatment can be started before full 5 days of fever if
sepsis excluded
● Treatment should also be given if the presentation is
>10 days from fever onset
● Incomplete cases >1 year old treated at discretion of
clinician--seek expert advice
● Refer to paediatric cardiologist
17-Nov-17

51. Take home message
• Kawasaki disease should be considered in the DD of every
child with prolonged fever accompanied by rash and non-
purulent conjunctivitis
– especially in children < 1 year old and in adolescents, in whom
the diagnosis is frequently missed
• Diagnostic pitfalls include mistaking:
– rash and mucosal changes for an antibiotic reaction
– sterile pyuria for partially treated urinary tract infection
– cerebrospinal fluid (CSF) pleocytosis for viral meningitis
17-Nov-17

52. • The diagnosis is guided by:
– the number of positive clinical criteria
– the age of the child (those under 6 months with persistent
fever for seven days and evidence of inflammation
needing an echocardiogram even in the absence of
positive clinical criteria)
– the absence of clinical features suggesting another
diagnosis, and
– the laboratory (CRP) and (ESR) results
17-Nov-17

53. Vaccination post KD
• IVIG can block replication of live viral vaccines &
subsequent actively acquired immunity
• Current recommendation - live vaccines be
deferred for at least three months following
treatment with IVIG
• Autoimmune diseases including the systemic
vasculitis flare in response to live and non-live
vaccine preparations
• Defer immunisation with all vaccines for at least 3
months following an episode of KD
17-Nov-17

54. CONCLUSION:
High index of
suspicion is
mandatory for
early diagnosis of
Kawasaki disease
Delayed diagnosis
may lead to
coronary lesions