محاضرة لى بفضل الله ونعمة منه تم القاءها فى مؤتمر حميات شبين الكوم 2017 نوفمبر

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

3. Introduction
• Acute multi system disease affecting
infants & children with prominent
vasculitis of large & medium sized vessels
• Acute self-limited vasculitis of childhood,
characterized by
Fever
Bilateral non exudative conjunctivitis
Erythema of the lips and oral mucosa
Changes in the extremities
Rash
Cervical lymphadenopathy13-Feb-18

4. • KD –famous 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
13-Feb-18
Why?

5. 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 disease13-Feb-18

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

7. 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
13-Feb-18

8. Aetiology
• Aetiology remains unknown, (although
clinical and epidemiological features
strongly suggest an infectious cause).
13-Feb-18
Theories :
1-Immunologic response
2-Infectious etiology
3-Genetic factors

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

10. Etiology
• 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 convincingly identified a specific virus,
bacteria or bacterial toxin, or other pathogen associated
with KD

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

12. • 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
13-Feb-18

14. 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
13-Feb-18

15. • 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 cellsin concert
with lymphocytes (predominantly
CD8+ T cells) and IgA plasma 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
13-Feb-18

17. 13-Feb-18

18. Clinical Features
13-Feb-18

19. – 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
Kawasaki disease from self-limiting viral
infections.
– Untreated the fever usually lasts 1-2 weeks.
– Defervescence within 1-2 days of treatment
with IVIG
13-Feb-18
1: Fever in KD

20. 13-Feb-18

21. – Begins shortly after the
fever
– Resolves promptly
– Non-purulent
– Bulbar conjunctivitis with
limbic sparing
– Anterior uveitis may
occur (in up to 80%)
13-Feb-18
2: Conjunctivitis

22. – 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.
13-Feb-18
3: Oropharyngeal changes

23. – 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
13-Feb-18
4: Changes in the extremities

24. – 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)
– The presence of - petechiae or
purpura, vesicles or bullae, crusting,
pruritis - search for an alternative
diagnosis
13-Feb-18
5: Polymorphous rash

25. – 50-80% of cases
– >1.5cm, usually more
obvious
– May be unilateral single
node
– May be erythematous, but
non-fluctuant and no pus
13-Feb-18
5: Lymphadenopathy

26. 13-Feb-18

27. 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
13-Feb-18

28. 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%)
13-Feb-18

29. Diagnostic problems in Kawasaki
disease
• Atypical or incomplete cases
– Most common in infants - greatest risk of CAA
– Children may have fever and < 4 clinical signs
– Reports of coronary AN with 3 diagnostic
features
– Occasionally only prolonged fever is present, and
diagnosis is only made after an ECHO
13-Feb-18

30. • Atypical or Incomplete KD
– 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
13-Feb-18

31. • Recurrent Kawasaki Disease
– 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
13-Feb-18

32. differential diagnosis

39. Investigation
No laboratory test specific for KD

40. CBC :
Leukocytosis, and a left-shift in the white blood cell count
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
Abnormal liver function test because of intrahepatic congestion
Echocardiography : study of choice to evaluate for coronary
artery aneurysms
ECG

41. 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)
13-Feb-18

42. 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
13-Feb-18

43. 13-Feb-18
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

44. 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 (disease
defervescence) continuing for a minimum of 6 weeks
13-Feb-18

45. 13-Feb-18
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

46. ● Treatment can be commenced 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
13-Feb-18

47. KEY PRACTICE POINTS
• 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
13-Feb-18

48. • 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
13-Feb-18

49. 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
three months following an episode of KD
13-Feb-18

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