IVIG Resistant
Kawasaki Disease:
Xenia Katrina Lucero
• Patient A
• 2 years old
• Male
• Filipino
• R. Catholic
• born on April 7, 2009
• from 17 Little Tagaytay, Marulas Valen...
Chief Complaint
History of Present Illness
Day of Illness
Paracetamol
History of Present Illness
Day of Illness
Val Gen: UTI
Cefuroxime
Ibuprofen
History of Present Illness
Day of Illness
Red lips
Dysuria
vomiting
History of Present Illness
Day of Illness
Red lips
Dysuria
vomiting
VGHVGH
History of Present Illness
Day of Illness
vomiting
Swelling
on LE
History of Present Illness
Day of Illness
vomiting
Swelling
on LE
History of Present Illness
Day of Illness
vomiting
History of Present Illness
Day of Illness
A
KD
History of Present Illness
History of Present Illness
SE Post
correction
Na+ 135.7
K+ 4.76
History of Present Illness
Acute
phase
reactants
Result
ESR 62
CRP 108
Urinalysis 4/17
Color yellow
Characteristics clear
...
History of Present Illness
Day of Illness
A ASA
(30)
History of Present Illness
A
2D-Echo
4/17
Trivial MR
Left Atrial Enlargement
Normal coronary artery size
Proximal Distal
R...
History of Present Illness
Day of Illness
A
ASA
History of Present Illness
Blood GS/CS 4/21/2012
Heavy Growth S. coagulase negative
organism
Sensitive Resistance
Chloramp...
History of Present Illness
Day of Illness
A
History of Present Illness
Day of Illness
A
ASA
History of Present Illness
Day of Illness
A
ASA
History of Present Illness
Day of Illness
A
ASA
MGH
ASA (5)
History of Present Illness
Day of Illness
A
ASA
MGH
ASA (5)
History of Present Illness
Day of Illness
A
ASA
MGH
ASA (5)
Swelling of LE,
painful extremities
Red Lips
Perianal
desquama...
History of Present Illness
Day of Illness
A
ASA
MGH
ASA (5)
Swelling of LE,
Painful extremities
Red lips
Perianal desquama...
 (-) AGE
 (-) Pneumonia
 (-) Measles
 (-) PTB
 (-) Bronchial Asthma
o (+) Hypertension: Maternal
o (-) Diabetes
o (-) Bronchial Asthma
o (-) Heart Disease
o (-) Cancer
• only child of the couple
• Father: 25 year-old, HS graduate, factory worker
• Mother: 23 year-old HS graduate, housewife...
• Born to a 21 year old G1P1 (1001)
• Live
• Fullterm
• via NSD
• Chinese General Hospital
• (-) fetomaternal complications
• (+) regular PNCU c/o CGH starting 2 mos
AOG
• (+) regular intake of MVS and FESO4, FA
• (+) maternal URTI: 9mos AOG: Amo...
• fullterm,
• cephalic,
• NSD
• Chinese General
Hospital.
• BW : 2900g
• (+) good suck
• (+) good cry
• (+) spontaneous
ac...
• Breastfed: up to 1 week, per demand
• bottle-fed with Promil at 1:1 dilution
• Complementary feeding: 6mos with
cereals
...
Growth and
Development
• 1month: social smile
• 3 months: controls head
• 5 months: rolls over
• 7 months: crawls
• 10 mon...
Immunization History
1 BCG
3 DPT
OPV
Hepa B
measles
General: no weight loss, decreased in appetite
Respiratory: no difficulty of breathing, no cough, no
colds
Cardiovascular:...
Physical Examination:
• Vital signs:
• HR- 136bpm
• RR- 38/min
• Temp- 38.8 C
• BP- 100/70mmHg
• Weight: 9.5kg
• Height: 8...
• Skin:
warm to touch, good skin turgor
• HEENT:
anicteric sclerae, pink palpebral conjunctiva,
no nasoaural discharge, no...
• Heart:
adynamic precordium, normal rate, regular
rhythm, PMI at 4th ICS L MCL, no murmur
• Abdomen:
slightly globular, n...
Neurologic exam: awake, active, GCS 15
CN I – able to smell
CN II - pupils 1-2mm equally reactive to light, (+)
ROR
CN III...
Salient features
• 2 yo male
• Previously admitted with a diagnosis of KD
– given IVIG on 11 day of illness
– Afebrile pha...
Differential Diagnosis
TB
Typhoid
fever
HRCI
(Sepsis)
IVIG
Resistant KD
Recurrent KD
Differential Diagnosis
Rule IN Rule OUT
Prolonged fever No hepatosplenomegaly
(+) CLAD No weight loss
Swelling and joint p...
Differential Diagnosis
TB
Typhoid
fever
HRCI
(Sepsis)
IVIG
Resistant KD
Recurrent KD
Differential Diagnosis
Infectious
TB
Rule IN Rule OUT
Fever No cough
Loss of appetite Weight loss
CLAD No exposure
(-) CXR
Differential Diagnosis
Infectious
Typhoid fever
Rule IN Rule OUT
Fever (-) diarrhea/
constipation
Loss of appetite (-)Abdo...
Differential Diagnosis
Infectious
Health Care Related Infection (Sepsis)
Rule IN Rule OUT
Admitted for 14 days
(+) recurre...
Differential Diagnosis
Connective Tissue Disease
Recurrent Kawasaki Disease
Rule IN Rule OUT
13 days post IVIG,
Recurrence...
Differential Diagnosis
Connective Tissue Disease
IVIG-Resistant Kawasaki Disease
Rule IN Rule OUT
(+) IVIG transfusion
Afe...
Course
in
the
Ward
Course
in
the
Ward
CBC 5/2/1
2
ABO A­­+
Hgb 85
Hct 0.28
RBC 3.62
WBC 15.72
Neutro 65.8
Lympho 27.2
Platelet 665
Urinalysis 5/2/212
Color L. y...
Acute phase reactants
5/6/2012 Result NV
ESR 142 0-9
CRP >384 <6 mg/l
5HD
Swelling of LE
Perianal
desquamation
Red lips
D1...
Culture and
sensitivity
Final result
Urine (5/7) No growth
6HD
Swelling of LE
Perianal
desquamation
Red lips
5/8/2012
Trivial MR
Left Atrial Enlargement
Normal coronary artery size
Proximal Distal
RCA 0.21/0.4/.37 0.17/0.24/0.29
LC...
Culture and
sensitivity
Final result
Blood (5/9) No growth
8HD
Swelling of LE
Perianal
desquamation
Red lips
IVIG
ordered
...
11HD
Swelling of LE
Perianal desquamation
Red lips
IVIG
DISCUSSION
• “A self-limited vasculitis of unknown
etiology that predominantly affects
children younger than 5 years. It is now
the m...
• 1967: Dr Tomisaku Kawasaki
– 50 cases of a distinctive illness in children at
Tokyo Red Cross Medical Center in Japan.1
...
Leading cause of acquired heart disease in
children in the developed world
In the US, KD has surpassed acute rheumatic
fev...
Kawasaki Disease
• Leading cause of acquired
heart disease
• disease of childhood
• 80%: < 5 years of age
• Boys: girls 1....
• US: ˜3,000 annually
Japan: 200,000
cases since the 1960s
– One case report in the literature documents a
35-day-old infant who developed Kawasaki
disease after his second hepatiti...
• 2007: FDA
– required the makers of RotaTeq rotavirus
vaccine to report in the package insert that 9
cases of Kawasaki di...
Pathology
vasculitis
Med-sized
arteries
Med-sized
arteries
Coronary
Arteries
Acute/subacute:
Edema of endothelial smooth m...
Pathology
Severe:
involves all layers, with destruction of internal elastic
lamina
Vessel
wall
weakens
dilatation
• high (≥101F)
• Unremitting
• unresponsive to antibiotics
without treatment is generally 1-2
weeks but may persist for 3-...
Five principal clinical criteria of KD
Clinical Manifestations
Initial Phase - lasts 2 weeks
• 101° temperature for
5 days
• Red eyes
• Sore throat
• Swollen lymph nodes
Skin Reactions
Skin Reactions
Rashes on the body
Skin Reactions
• Palms of hands swell
• Soles of feet swell
• Red - purple in color
• Palms of hands swell
• Soles of feet...
Phase 2 – Lasts 2 Weeks
• Thrombocytosis
• Desquamation
• Swollen and joint
pains
• Devt of coronary
aneurysms
• Highest r...
Phase 3 – convalescent
• All clinical
signs
disappeared
• ESR returns to
normal (6-8
weeks)
Associated Signs and Symptoms
Respiratory
Rhinorrhea, cough, pulmonary infiltrate
GI
Diarrhea, vomiting, abdominal pain, h...
Diagnostic Test
Laboratory findings
• WBC: normal to elevated with neutrophilic
predominance
• Elevated ESR, CRP, may persist for 4–6 wk
•...
• The incidence of KD refractory to initial IVIG
therapy increased to 38 percent in 2006 from a
range of 10 to 20 percent ...
• Risk factors associated with the need for
retreatment included:
• Initial treatment at or before the fifth day
of illnes...
Risk Factors for unresponsiveness
to IVIG
• Young patient age, < 1 yo
• Early diagnosis, with initial treatment < 4DOL
• E...
• In a study done by Young-Sun Do, et.al, they found out
that IVIG resistant group has significantly longer febrile
period...
Complications
Coronary Artery
Aneurysm
commonest
Most life threatening
25% untreated KD
6-8 wks from onset of
illness
Complications
Coronary Artery
Aneurysm
Coronary
thrombosis
death
M I
Complications
Coronary Artery
Aneurysm
Size
Small = <5 mm diameter
Medium = 5-8 mm
Giant = ≥ 8 mm
Highest risk for sequela...
Echocardiography
Onset of DX
2–3 wks of
illness
N
6-8 wks of
illness
(-) CAA/
ESR: Normal
2D- echo:
optional
Coronary Artery Changes
• 15% to 25 % of untreated patients develop
coronary artery changes
• 3-7% if treated in first 10 ...
Echocardiographic Findings
•Myocarditis with dysfunction
•Pericarditis with an effusion
•Valvar insufficiency
•Coronary ar...
The HARADA score
• 1) WBC count: >12 ×103
/μl,
• 2) Platelet count: < 35×104
/μl,
• 3) CRP: > 4 mg/dl,
• 4) Hematocrit: <3...
treatment
1. IVIG 2g/kg as a single infusion
over 12H
2. Aspirin 30-50 mg/kg/day in four
doses (in USA 80-100mg/kg/day
in ...
treatment
1. Second dose of IVIG 2 g/kg
2. Third dose of IVIG or
3. Methylprednisolone 30mg/kg for
3 days or prednisolone ...
• Patients receiving long-term aspirin therapy
– annual influenza vaccination
– Varicella vaccination
• Patients treated w...
prognosis
Recovery is complete and without apparent long-term
effects for patients who do not develop coronary
disease
In ...
prognosis
Recurrence of the disease has been previously noted with
reported rates varying between 0.8% in the United State...
KT H A N
YOU!!!
IVIG resitant kawasaki
IVIG resitant kawasaki
IVIG resitant kawasaki
IVIG resitant kawasaki
IVIG resitant kawasaki
IVIG resitant kawasaki
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IVIG resitant kawasaki

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  • Kawasaki disease was first described in 1967 by Dr Tomisaku Kawasaki, who reported 50 cases of a distinctive illness in children seen at the Tokyo Red Cross Medical Center in Japan.1 In 1976, Melish et al first reported Kawasaki disease in the United States, in a group of 12 children from Honolulu examined from 1971-1973.2 Kawasaki disease is now recognized worldwide, although the greatest number of cases has been in Japan. It is the leading cause of acquired heart disease in children in the developed world and may be a risk factor for adult ischemic heart disease. In the United States, Kawasaki disease has surpassed acute rheumatic fever as the leading cause of acquired heart disease in children younger than 5 years.3
  • It is the leading cause of acquired heart disease in children in the developed world and may be a risk factor for adult ischemic heart disease. In the United States, Kawasaki disease has surpassed acute rheumatic fever as the leading cause of acquired heart disease in children younger than 5 years.3
  • Kawasaki disease is predominantly a disease of childhood although cases have been reported in adults. Around 80% of cases occur in children under 5 years of age. It occurs more often in boys than girls with a male/female ratio of about 1.5:1. An estimated 3,000 cases are diagnosed annually in the United States. In Japan, almost 200,000 cases have been reported since the 1960s.
  • The etiology of Kawasaki disease remains unknown. Over the years, multiple infectious agents have been implicated; however, to date, no single microbial agent has surfaced as the prevailing cause.4 However, autoimmune reactions and genetic predisposition have been suggested as possible etiologic factors.
  • KD is a vasculitis that predominantly affects the medium-sized arteries, with a striking predilection for the coronary arteries. Pathologic examination of fatal cases in the acute or subacute stages reveals edema of endothelial and smooth muscle cells with intense inflammatory infiltration of the vascular wall. In the most severely affected vessels, inflammation involves all three layers of the vascular wall, with destruction of the internal elastic lamina.
  • In the most severely affected vessels, inflammation involves all three layers of the vascular wall, with destruction of the internal elastic lamina. Loss of structural integrity weakens the vessel wall and results in dilation (ectasia) or saccular or fusiform aneurysm formation.
  • Fever is characteristically high (≥101F), unremitting, and unresponsive to antibiotics. The duration of fever without treatment is generally 1-2 weeks but may persist for 3-4 weeks.
  • In the absence of treatment, 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 weeks. The subacute phase is associated with desquamation, thrombocytosis, the development of coronary aneurysms, and the highest risk of sudden death in patients in whom aneurysms have developed, and generally lasts about 2 weeks. 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 weeks after the onset of illness.
  • The complete list of associated symptom is too long to go into in detail here,but virtually every organ system can be involved. Patients can have cough, rhinorrhea, or a pulmonary infiltrate. They can have diarrhea, vomiting, abdominal pain, hydrops of gallbladder, mild jaundice, and mild increase of serum transaminase levels. They can have striking irritability and an aseptic meningitis with a mononuclear pleocytosis in cerebrospinal fluid as well as a facial palsy and hearing loss. Finally, they can develop myositis, arthralgias, and arthritis.
  • There is no diagnostic test for Kawasaki disease. Primarily, it is diagnosed based on the presence of characteristic clinical signs. For classic Kawasaki disease, the diagnostic criteria require the presence of fever for at least 5 days and at least four of five of the other characteristic clinical features of illness. In atypical or incomplete Kawasaki disease, the patient has persistent fever but with fewer than four other features of the illness while IVIG resistant Kawasaki disease is defined as persistent or recrudescent fever 36 hours after completion of the initial IVIG infusion and occurs in approximately 15% of patients.
  • Kawasaki disease has certain characteristic laboratory findings. The leukocyte count is normal to elevated with a predominance of neutrophils and immature forms. Elevated ESR, CRP, and other acute phase reactants are almost universally present in the acute phase of illness and may persist for 4–6 wk. Normocytic, normochromic anemia is common. The platelet count is generally normal in the 1st week of illness and rapidly increases by the 2nd–3rd week of illness, sometimes exceeding 1,000,000/mm3. Tests for antinuclear antibody and rheumatoid factor are negative. Sterile pyuria, mild elevations of the hepatic transaminases, and cerebrospinal fluid pleocytosis may be present.
  • Risk Factors for IVIG Resistance The incidence of KD refractory to initial IVIG therapy increased to 38 percent in 2006 from a range of 10 to 20 percent between 1998 and 200510. This increase did not appear to be related to any changes in the formulations of IVIG used. In comparison, in 2006, the incidence of refractory KD in Boston was 8 percent. The same IVIG brands and lots administered in San Diego to treat patients with KD were also used in Boston.
  • Retrospective studies have identified potential factors that predict which patients will require further therapy for refractory disease. The first study utilized the database of patients treated in 2003 and 2004 included in the 18th nationwide survey of KD in Japan11. Of the 15,940 patients with KD, 20 percent did not respond to initial IVIG therapy. Risk factors associated with the need for retreatment included: • Initial treatment at or before the fifth day of illness • Recurrent episodes of KD • Male sex
  • Other retrospective studies have reported that the following clinical factors increased the likelihood of patient’s nonresponsiveness to initial IVIG therapy12: • Young patient age, children less than one year of age • Early diagnosis, with initial treatment at or before the 4th day of illness • Elevated C-reactive protein (≥10 mg/dL or ≥8 mg/dL) • Elevated liver enzymes (aspartate aminotransferase, AST and alanine aminotransferase, ALT) • Platelet count ≤300,000/mm2 • Elevated band count • Serum sodium ≤133 mmol/L • Low serum albumin
  • In a study done by Young-Sun Do, et.al, the found out that IVIG resistant group has significantly longer febrile period and hospital days than those IVIG-responsive groups. Serum levels of albumin and sodium were significantly lower in the IVIG-resistant group. Fewer lymphocytes was observed during the subacute phase in the IVIG-resistant group. Coronary arterial dilatations (CADs) were observed in 10.9% (7/64) of IVIG-responders and 38.5% (5/13) of IVIG-resistant patients.
  • The commonest and potentially most life threatening complication of KD is the development of CAA. In untreated KD, up to 25% of patients develop CAA and in a small number this may result in coronary thrombosis, myocardial infarction and death14. Most aneurysms will develop within 6–8 weeks from the onset of the illness.
  • In untreated KD, up to 25% of patients develop CAA and in a small number this may result in coronary thrombosis, myocardial infarction and death14.
  • Aneurysms are classified as small, medium and giant. Giant aneurysms have the greatest risk for complications and have an incidence of 0.8 % in the latest Japanese survey. The aneurysms are also classified as saccular, if they have axial and lateral dimensions being of about equal size, or fusiform, if there is dilation with proximal and distal tapering.
  • The most useful test to identify and monitor potential development of coronary artery abnormality is by two-dimensional echocardiography. It should be performed on the onset of diagnosis and again after 2–3 weeks of illness. If both are normal, a repeat study should be performed 6–8 wk after onset of illness. If coronary abnormalities are not detected by 6–8 wk after onset of illness, and after the ESR has normalized, additional follow-up studies are optional.
  • Ectasia is defined as coronary artery size larger than normal for age but without discrete aneurysm.
  • Echocardiographic finding include myocarditis and depressed function, pericarditis with an effusion, valvular insufficiency, or coronary artery changes. The most common finding is mild coronary artery changes. Echo is 80-90% sensitive for the diagnosis of proximal coronary artery aneurysms
  • The score The Harada score was developed in the early 1990s to select patients who were at higher risk of developing CAA. This scoring is based on; 1) WBC count: equal to or more than 12 ×103/μl, 2) Platelet count: less than 35×104/μl, 3) CRP: equal to or more than 4 mg/dl, 4) Hematocrit: less than 35%, 5) Serum albumin: less than 3.5 g/dl, 6) Gender: male, 7) Age: equal to or less than 12 months. When the patient with KD satisfies 4 or more of the above 7 criteria within the 9th day of illness, treatment with IVIG should be started, hence, this patient has a high risk of developing coronary artery lesions.
  • Patients with acute Kawasaki disease should be treated with intravenous immunoglobulin (IVIG) and high-dose aspirin as soon as possible after diagnosis and, ideally, within 10 days of disease onset. The mechanism of action of IVIG in Kawasaki disease is unknown, but treatment should result in rapid defervescence and resolution of clinical signs of illness in 85–90% of patients. With therapy, the CRP normalizes much more quickly than the ESR, which will often increase immediately after IVIG therapy. IVIG reduces the prevalence of coronary disease from 20–25% in children treated with aspirin alone to 2–4% in those treated with IVIG and aspirin within the 1st 10 days of illness. Consideration should even be given to treatment of patients diagnosed after the 10th illness day if fever has persisted, because the anti-inflammatory effect may be helpful, although the effect of such therapy on the risk of developing coronary aneurysms is unknown. The dose of aspirin is decreased from anti-inflammatory to antithrombotic doses (3–5 mg/kg/day as a single dose) on the 14th illness day or after the patient has been afebrile for at least 3–4 days. Aspirin is continued for its antithrombotic effect until 6–8 wk after onset, when the ESR has normalized in patients that have not developed abnormalities detected by echocardiography.
  • Patients with acute Kawasaki disease should be treated with intravenous immunoglobulin (IVIG) and high-dose aspirin as soon as possible after diagnosis and, ideally, within 10 days of disease onset. The mechanism of action of IVIG in Kawasaki disease is unknown, but treatment should result in rapid defervescence and resolution of clinical signs of illness in 85–90% of patients. With therapy, the CRP normalizes much more quickly than the ESR, which will often increase immediately after IVIG therapy. IVIG reduces the prevalence of coronary disease from 20–25% in children treated with aspirin alone to 2–4% in those treated with IVIG and aspirin within the 1st 10 days of illness. Consideration should even be given to treatment of patients diagnosed after the 10th illness day if fever has persisted, because the anti-inflammatory effect may be helpful, although the effect of such therapy on the risk of developing coronary aneurysms is unknown. The dose of aspirin is decreased from anti-inflammatory to antithrombotic doses (3–5 mg/kg/day as a single dose) on the 14th illness day or after the patient has been afebrile for at least 3–4 days. Aspirin is continued for its antithrombotic effect until 6–8 wk after onset, when the ESR has normalized in patients that have not developed abnormalities detected by echocardiography.
  • Patients receiving long-term aspirin therapy are candidates for annual influenza vaccination to reduce the risk of Reye syndrome. Varicella vaccination should be strongly considered, since the risk of Reye syndrome in children who take salicylates and who receive varicella vaccine is likely to be lower than with wild-type varicella. Patients treated with 2 g/kg IVIG should have measles-mumps-rubella and varicella vaccinations delayed for 11 mo because the specific antiviral antibody in IVIG may interfere with the immune response to live-virus vaccines.
  • IVIG resitant kawasaki

    1. 1. IVIG Resistant Kawasaki Disease: Xenia Katrina Lucero
    2. 2. • Patient A • 2 years old • Male • Filipino • R. Catholic • born on April 7, 2009 • from 17 Little Tagaytay, Marulas Valenzuela • admitted for the 2nd time in JRRMMC (May 2, 2012)
    3. 3. Chief Complaint
    4. 4. History of Present Illness Day of Illness Paracetamol
    5. 5. History of Present Illness Day of Illness Val Gen: UTI Cefuroxime Ibuprofen
    6. 6. History of Present Illness Day of Illness Red lips Dysuria vomiting
    7. 7. History of Present Illness Day of Illness Red lips Dysuria vomiting VGHVGH
    8. 8. History of Present Illness Day of Illness vomiting Swelling on LE
    9. 9. History of Present Illness Day of Illness vomiting Swelling on LE
    10. 10. History of Present Illness Day of Illness vomiting
    11. 11. History of Present Illness Day of Illness A KD
    12. 12. History of Present Illness
    13. 13. History of Present Illness SE Post correction Na+ 135.7 K+ 4.76
    14. 14. History of Present Illness Acute phase reactants Result ESR 62 CRP 108 Urinalysis 4/17 Color yellow Characteristics clear pH 8.5 SG 1.010 Sugar/Protein (-) RBC - WBC -
    15. 15. History of Present Illness Day of Illness A ASA (30)
    16. 16. History of Present Illness A 2D-Echo 4/17 Trivial MR Left Atrial Enlargement Normal coronary artery size Proximal Distal RCA 0.18/0.2 0.17cm/0.2 LCA 0.16 0.16 Normal PAP by PAT Good LV systolic function with EF of 72% Left sided aortic arch Minimal pericardial Effusion
    17. 17. History of Present Illness Day of Illness A ASA
    18. 18. History of Present Illness Blood GS/CS 4/21/2012 Heavy Growth S. coagulase negative organism Sensitive Resistance Chloramphenicol Clindamycin Erythromycin Oxacillin Tetracycline Penicillin Vancomycin
    19. 19. History of Present Illness Day of Illness A
    20. 20. History of Present Illness Day of Illness A ASA
    21. 21. History of Present Illness Day of Illness A ASA
    22. 22. History of Present Illness Day of Illness A ASA MGH ASA (5)
    23. 23. History of Present Illness Day of Illness A ASA MGH ASA (5)
    24. 24. History of Present Illness Day of Illness A ASA MGH ASA (5) Swelling of LE, painful extremities Red Lips Perianal desquamation
    25. 25. History of Present Illness Day of Illness A ASA MGH ASA (5) Swelling of LE, Painful extremities Red lips Perianal desquamation
    26. 26.  (-) AGE  (-) Pneumonia  (-) Measles  (-) PTB  (-) Bronchial Asthma
    27. 27. o (+) Hypertension: Maternal o (-) Diabetes o (-) Bronchial Asthma o (-) Heart Disease o (-) Cancer
    28. 28. • only child of the couple • Father: 25 year-old, HS graduate, factory worker • Mother: 23 year-old HS graduate, housewife • lives in two-storey semi-concrete house • no rooms, portions are divided only by cabinets • 1 pour-flush toilet • Water supply: NAWASA • garbage is collected 2x a week.
    29. 29. • Born to a 21 year old G1P1 (1001) • Live • Fullterm • via NSD • Chinese General Hospital • (-) fetomaternal complications
    30. 30. • (+) regular PNCU c/o CGH starting 2 mos AOG • (+) regular intake of MVS and FESO4, FA • (+) maternal URTI: 9mos AOG: Amoxicillin • (-) exposure to radiation/ intake of teratogenic drugs
    31. 31. • fullterm, • cephalic, • NSD • Chinese General Hospital. • BW : 2900g • (+) good suck • (+) good cry • (+) spontaneous activity • (-) jaundice • (-) cyanosis
    32. 32. • Breastfed: up to 1 week, per demand • bottle-fed with Promil at 1:1 dilution • Complementary feeding: 6mos with cereals • Currently: milk, rice, meat and vegetables
    33. 33. Growth and Development • 1month: social smile • 3 months: controls head • 5 months: rolls over • 7 months: crawls • 10 months: sit and stands with support • 11 months: walks with support • 1 yr 4 months: walks alone
    34. 34. Immunization History 1 BCG 3 DPT OPV Hepa B measles
    35. 35. General: no weight loss, decreased in appetite Respiratory: no difficulty of breathing, no cough, no colds Cardiovascular: no easy fatigability, no orthopnea Gastrointestinal: no diarrhea, no constipation Genitourinary: no hematuria, no frequency, no oliguria Neurological: no seizures, no loss of consciousness, Review of Systems
    36. 36. Physical Examination: • Vital signs: • HR- 136bpm • RR- 38/min • Temp- 38.8 C • BP- 100/70mmHg • Weight: 9.5kg • Height: 85 cm •Z scores: •Height-for-age: below -1 – -2 (Normal) •Weight- for-age: below -3 (severely underweight) •BMI-for-age: below -3 (severely wasted) awake, comfortable, not in cardio-respiratory distress
    37. 37. • Skin: warm to touch, good skin turgor • HEENT: anicteric sclerae, pink palpebral conjunctiva, no nasoaural discharge, no cervical lympadenopathy, no tonsillo-pharyngeal congestion, with red dry lips • Lungs: symmetric lung expansion, no retractions, clear breath sounds
    38. 38. • Heart: adynamic precordium, normal rate, regular rhythm, PMI at 4th ICS L MCL, no murmur • Abdomen: slightly globular, normoactive bowel sounds, soft, nontender, with perianal desquamation • Extremities: grossly normal, no cyanosis, with edema on lower extremities, grade I, CRT <3s
    39. 39. Neurologic exam: awake, active, GCS 15 CN I – able to smell CN II - pupils 1-2mm equally reactive to light, (+) ROR CN III, IV, VI – intact extraocular muscle movements CN V – no facial asymmetry CN VII – no facial asymmetry with facial expressions CN VIII – able to hear CN IX, X – good gag CN XI – good shoulder shrug CN XII – no tongue deviation Motor Sensory DTR
    40. 40. Salient features • 2 yo male • Previously admitted with a diagnosis of KD – given IVIG on 11 day of illness – Afebrile phase noted 5 days post IVIG • 3 days post discharge/ 13 days post IVIG – Recurrence of fever – Recurrence of swelling on LE, perianal desquamation and red lips
    41. 41. Differential Diagnosis TB Typhoid fever HRCI (Sepsis) IVIG Resistant KD Recurrent KD
    42. 42. Differential Diagnosis Rule IN Rule OUT Prolonged fever No hepatosplenomegaly (+) CLAD No weight loss Swelling and joint pains No bleeding tendencies Malignancy
    43. 43. Differential Diagnosis TB Typhoid fever HRCI (Sepsis) IVIG Resistant KD Recurrent KD
    44. 44. Differential Diagnosis Infectious TB Rule IN Rule OUT Fever No cough Loss of appetite Weight loss CLAD No exposure (-) CXR
    45. 45. Differential Diagnosis Infectious Typhoid fever Rule IN Rule OUT Fever (-) diarrhea/ constipation Loss of appetite (-)Abdominal pain vomiting (-) Blood culture
    46. 46. Differential Diagnosis Infectious Health Care Related Infection (Sepsis) Rule IN Rule OUT Admitted for 14 days (+) recurrence of fever 3 days post discharge
    47. 47. Differential Diagnosis Connective Tissue Disease Recurrent Kawasaki Disease Rule IN Rule OUT 13 days post IVIG, Recurrence of: Recurrence of fever 13 days post IVIG transfusion fever no available criteria which defines recurrent KD Perianal desquamation Majority of cases recurs at 2 years post IVIG Red lips Edema of LE
    48. 48. Differential Diagnosis Connective Tissue Disease IVIG-Resistant Kawasaki Disease Rule IN Rule OUT (+) IVIG transfusion Afebrile phase noted 5 days post IVIG 13 days post IVIG: (+) fever (+) red lips (+) edema of LE (+) perianal desquamation
    49. 49. Course in the Ward Course in the Ward
    50. 50. CBC 5/2/1 2 ABO A­­+ Hgb 85 Hct 0.28 RBC 3.62 WBC 15.72 Neutro 65.8 Lympho 27.2 Platelet 665 Urinalysis 5/2/212 Color L. yellow Characteristics S. turbid pH 6.5 SG 1.020 Sugar/Protein (-) RBC 0-2 WBC 10-25 Antibiotics ASA (30) 1HD Swelling of LE Perianal desquamation Red lips
    51. 51. Acute phase reactants 5/6/2012 Result NV ESR 142 0-9 CRP >384 <6 mg/l 5HD Swelling of LE Perianal desquamation Red lips D1 AntibioticsD1 Antibiotics D2 Antibiotics D2 Antibiotics
    52. 52. Culture and sensitivity Final result Urine (5/7) No growth 6HD Swelling of LE Perianal desquamation Red lips
    53. 53. 5/8/2012 Trivial MR Left Atrial Enlargement Normal coronary artery size Proximal Distal RCA 0.21/0.4/.37 0.17/0.24/0.29 LCA 0.2/0.3 0.2/0.31 cm Normal PAP by PAT Fair LV systolic function with EF of 55% Left sided aortic arch Minimal pericardial Effusion 7HD Swelling of LE Perianal desquamation Red lips D3 AntibioticsD3 Antibiotics
    54. 54. Culture and sensitivity Final result Blood (5/9) No growth 8HD Swelling of LE Perianal desquamation Red lips IVIG ordered IVIG ordered
    55. 55. 11HD Swelling of LE Perianal desquamation Red lips
    56. 56. IVIG
    57. 57. DISCUSSION
    58. 58. • “A self-limited vasculitis of unknown etiology that predominantly affects children younger than 5 years. It is now the most common cause of acquired heart disease in children in the United States and Japan.” • *Burns, J. Adv. Pediatr. 48:157. 2001. Kawasaki Disease: Mucocutaneous Lymph Node Syndrome
    59. 59. • 1967: Dr Tomisaku Kawasaki – 50 cases of a distinctive illness in children at Tokyo Red Cross Medical Center in Japan.1 • 1976: Melish et al – United States, in a group of 12 children from Honolulu examined from 1971-1973.2 1. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Arerugi. Mar 1967;16(3):pp 178-222. 2. Melish ME, Hicks RM, Larson EJ. Mucocutaneous lymph node syndrome in the United States. Am J Dis Child. Jun 1976;130(6):599-607.
    60. 60. Leading cause of acquired heart disease in children in the developed world In the US, KD has surpassed acute rheumatic fever as the leading cause of acquired heart disease in children younger than 5 years Newburger JW, et al. Summary and abstracts of the Seventh International Kawasaki Disease Symposium: December 4-7, 2001, Hakone, Japan. Pediatr Res. Jan 2003;53(1):pp 153-7
    61. 61. Kawasaki Disease • Leading cause of acquired heart disease • disease of childhood • 80%: < 5 years of age • Boys: girls 1.5:1 • Highest incidence in Japan
    62. 62. • US: ˜3,000 annually Japan: 200,000 cases since the 1960s
    63. 63. – One case report in the literature documents a 35-day-old infant who developed Kawasaki disease after his second hepatitis B vaccination. 6 6. Miron D, Fink D, Hashkes PJ. Kawasaki disease in an infant following immunization with hepatitis B vaccine. Clin Rheumatol. Dec 2003;22(6):pp 461-3.
    64. 64. • 2007: FDA – required the makers of RotaTeq rotavirus vaccine to report in the package insert that 9 cases of Kawasaki disease had occurred in children who had received the vaccine. • However, most believe that there is no connection between the vaccine and the disease. 5 5. Hua W, Izurieta HS, Slade B, Belay ED, Haber P, Tiernan R, et al. Kawasaki disease after vaccination: Pediatr Infect Dis J. Nov 2009;28(11):pp 943-7.
    65. 65. Pathology vasculitis Med-sized arteries Med-sized arteries Coronary Arteries Acute/subacute: Edema of endothelial smooth muscle cells with intense inflammatory infiltration of the vascular wall Severe: involves all layers, with destruction of internal elastic lamina
    66. 66. Pathology Severe: involves all layers, with destruction of internal elastic lamina Vessel wall weakens dilatation
    67. 67. • high (≥101F) • Unremitting • unresponsive to antibiotics without treatment is generally 1-2 weeks but may persist for 3-4 weeks. Clinical presentation
    68. 68. Five principal clinical criteria of KD
    69. 69. Clinical Manifestations
    70. 70. Initial Phase - lasts 2 weeks • 101° temperature for 5 days • Red eyes • Sore throat • Swollen lymph nodes
    71. 71. Skin Reactions
    72. 72. Skin Reactions Rashes on the body
    73. 73. Skin Reactions • Palms of hands swell • Soles of feet swell • Red - purple in color • Palms of hands swell • Soles of feet swell • Red - purple in color
    74. 74. Phase 2 – Lasts 2 Weeks • Thrombocytosis • Desquamation • Swollen and joint pains • Devt of coronary aneurysms • Highest risk of sudden death
    75. 75. Phase 3 – convalescent • All clinical signs disappeared • ESR returns to normal (6-8 weeks)
    76. 76. Associated Signs and Symptoms Respiratory Rhinorrhea, cough, pulmonary infiltrate GI Diarrhea, vomiting, abdominal pain, hydrops of the gallbladder, jaundice Neurologic Irritability, aseptic meningitis, facial palsy, hearing loss Musculoskeletal Myositis, arthralgia, arthritis
    77. 77. Diagnostic Test
    78. 78. Laboratory findings • WBC: normal to elevated with neutrophilic predominance • Elevated ESR, CRP, may persist for 4–6 wk • Normocytic, normochromic anemia • platelet count: normal- 1st week, rapidly increases by the 2nd–3rd week (1,000,000/mm3) • ANA/rheumatoid factor: Negative • Sterile pyuria • mild elevations of the hepatic transaminase
    79. 79. • The incidence of KD refractory to initial IVIG therapy increased to 38 percent in 2006 from a range of 10 to 20 percent between 1998 and 2005. – This increase did not appear to be related to any changes in the formulations of IVIG used. Tremoulet AH, Best BM, Song S, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr 2008; 153:117
    80. 80. • Risk factors associated with the need for retreatment included: • Initial treatment at or before the fifth day of illness • Recurrent episodes of KD • Male sex Tremoulet AH, Best BM, Song S, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr 2008; 153:117.
    81. 81. Risk Factors for unresponsiveness to IVIG • Young patient age, < 1 yo • Early diagnosis, with initial treatment < 4DOL • Elevated C-reactive protein (≥10 mg/dL ) • Elevated liver enzymes (AST/ALT) • Platelet count ≤300,000/mm2 • Elevated band count • Serum sodium ≤133 mmol/L • Low serum albumin Sundel, Robert, Treatment of refractory Kawasaki disease, UpToDate, June 17, 2011
    82. 82. • In a study done by Young-Sun Do, et.al, they found out that IVIG resistant group has significantly longer febrile period and hospital days than those IVIG-responsive groups. • Serum levels of albumin and sodium were significantly lower in the IVIG-resistant group. • Fewer lymphocytes was observed during the subacute phase in the IVIG-resistant group. • Coronary arterial dilatations (CADs) were observed in 10.9% (7/64) of IVIG-responders and 38.5% (5/13) of IVIG-resistant patients.
    83. 83. Complications Coronary Artery Aneurysm commonest Most life threatening 25% untreated KD 6-8 wks from onset of illness
    84. 84. Complications Coronary Artery Aneurysm Coronary thrombosis death M I
    85. 85. Complications Coronary Artery Aneurysm Size Small = <5 mm diameter Medium = 5-8 mm Giant = ≥ 8 mm Highest risk for sequelae Shape Size Small = <5 mm diameter Medium = 5-8 mm Giant = ≥ 8 mm Highest risk for sequelae Shape
    86. 86. Echocardiography Onset of DX 2–3 wks of illness N 6-8 wks of illness (-) CAA/ ESR: Normal 2D- echo: optional
    87. 87. Coronary Artery Changes • 15% to 25 % of untreated patients develop coronary artery changes • 3-7% if treated in first 10 days of fever with IVIG • Most commonly proximal, can be distal • Left main > LAD > Right
    88. 88. Echocardiographic Findings •Myocarditis with dysfunction •Pericarditis with an effusion •Valvar insufficiency •Coronary arterial changes
    89. 89. The HARADA score • 1) WBC count: >12 ×103 /μl, • 2) Platelet count: < 35×104 /μl, • 3) CRP: > 4 mg/dl, • 4) Hematocrit: <35%, • 5) Serum albumin: < 3.5 g/dl, • 6) Gender: male, • 7) Age: equal to or less than 12 months. > 4 :high risk of developing coronary artery lesions
    90. 90. treatment 1. IVIG 2g/kg as a single infusion over 12H 2. Aspirin 30-50 mg/kg/day in four doses (in USA 80-100mg/kg/day in 4 doses) until afebrile for 2-3 days 3. Aspirin 3-5 mg/kg/day once daily for 6-8 weeks minimum
    91. 91. treatment 1. Second dose of IVIG 2 g/kg 2. Third dose of IVIG or 3. Methylprednisolone 30mg/kg for 3 days or prednisolone 2 mg/kg/day orally and tailored based on clinical/ inflammatory marker improvement Fever persists after 48H or recrudescent fever within 2 weeks 4. Cyclophosphamide, cyclosporin, plasmapheresis and monoclonal antibodies to TNFalpha have been reported Tizard E.J., Complications of Kawasaki disease, Current Pediatrics, 2005 Volume 15, pp 62-88
    92. 92. • Patients receiving long-term aspirin therapy – annual influenza vaccination – Varicella vaccination • Patients treated with 2 g/kg IVIG  delay measles-mumps-rubella and varicella vaccinations delayed for 11 mo
    93. 93. prognosis Recovery is complete and without apparent long-term effects for patients who do not develop coronary disease In Japan, fatality rates are very low, about 0.01%. Overall, 50% of coronary artery aneurysms resolve as assessed by echocardiogram 1–2 yr after the illness.
    94. 94. prognosis Recurrence of the disease has been previously noted with reported rates varying between 0.8% in the United States to 3% in Japan. The proportion of patients suffering a recurrence increases with age, while the majority of recurrences occur within 2 years of the initial attack. 9. Pemberton1, I M Doughty2, R J Middlehurst3 & M H Thornhill4, British Dental Journal 186, 270 - 271 (1999), Case study: Recurrent Kawasaki disease
    95. 95. KT H A N YOU!!!

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