In life

puzzled countless illnesses

Most important

oblivion

Never to lose heart Breaks the Heart

the real worry Fever left hidden

Brave Heart

OBJECTIVES
To present a case of atypical Kawasaki Disease that evolves to complete KD To present the differential diagnoses of Kawasaki Disease To review the management and prognosis of Kawasaki Disease

GENERAL DATA GENERAL DATA

M.L. 2 year old Female Filipino Pampanga, Davao City

CHIEF COMPLAINT

FEVER

HISTORY OF PRESENT ILLNESS

5 days PTA

2 days PTA

CBC:
Hgb: 111 WBC: 9.1 Neut: 84 Mono: 16 Plt: 220 Hct: 37 Advised to consult a cardiologist if with persistence of fever

1 days PTA
AM PTA

PERSONAL/MEDICAL HISTORY

REVIEW OF SYSTEMS
GENERAL: (+) irritability and decreased in appetite, (-) seizures SHEENT: (+) hx of headache. No history of any head injury No history of otorrhea, tinnitus or otalgia No history of epistaxis, gum bleeding, or difficult swallowing NECK: No history pain, stiffness or limitation in movement RESPIRATORY: No hx of dyspnea or postnasal drip No history of TB exposure CARDIO: No cyanosis, palpitations or easy fatigability GASTRO: No abdominal pain, tenderness or changes in bowel habit URINARY: No dysuria, polyuria or tea-colored urine PERIPHERAL: No phlebitis, pallor or edema MUSCULOSKELETAL: No limitations in movement or no weakness

PHYSICAL EXAM
Awake, afebrile, comfortable, not in respiratory distress
Vital Signs: BP: 90/60mmHG CR: 120bpm Temp: 35.6C RR: 28cpm

Measurement: Wt: 12.73 kg Ht: 90cm HC: 48cm

PHYSICAL EXAM
50th Percentile 25th Percentile 50th percentile 50th Percentile

PHYSICAL EXAM

SHEENT

Skin brown, smooth, warm to touch, w/ good turgor Atraumatic and normocephalic head AS w/ PPC; no conjunctival injection, PERRLA Dry lips with fissuring and chapping; moist tongue, uvula at midline, no tonsillopharyngeal congestion

Neck was supple with bilateral submandibular lymphadenopathy approximately 1x1 cm in size.
NECK

PHYSICAL EXAM
Equal chest expansion, Clear breath sounds. No retraction or deformities
CHEST

HEART

Adynamic precordium with distinct heart sounds NRRR No murmurs, thrills or heaves Abdomen flat, soft, and non-tender with NABS Tympanitic on percussion except on areas of liver dullness No masses or organomegaly

ABDOMEN

PHYSICAL EXAM
Pulses were strong on all extremities with CRT < 2secs. No edema, desquamation or rashes.
EXTREMITIES

MUSCULOS KELETAL

No deformities and atrophy noted, no limitation on range of motion; no paralysis; no joint instability

Intact cranial nerve functions No pathologic reflexes

NEURO

SALIENT FEATURES
2 years old Female Moderate to high grade fever for 5 days Bilateral submandibular lymphadenopathies 1x1 chapping lips
Irritability headache Cough & coryza LBM Macular rashes on the trunk and upper extremities Redness of both eyes

DIFFERENTIAL DIAGNOSIS
Dengue Fever
Measles

Fever

Scarlet Fever Roseola Infantum

Kawasaki Disease

DENGUE FEVER

Hematocrit 38 33

Platelet count

379

377

MEASLES

SCARLET FEVER

ROSEOLA INFANTUM

KAWASAKI DISEASE

Fever + 4 Clinical Criteria = Complete Kawasaki Disease Fever + 2 or 3 Clinical Criteria = Incomplete Kawasaki

ADMITTING IMPRESSION

LABS OF ADMISSION
Day of Admission (5TH DOI)
CBC WBC RBC Hgb Hct Plt Neutro Lympho Mono 15 Eo Baso

7.6 4.8 12.8 38 379 33 52 0 0

U/A Yellow, slightly cloudy, acidic Sp. Gravity: 1.010 Albumin: trace Pus cells: 15-20/hpf Mucus: +++

C-Xray: Normal Stool Exam: Negative

MEDICATIONS
Paracetamol 250mg/5ml 3.5ml q 4
Sildenafil 50mg tablet tab + 5ml water, 5ml BID

Aspirin 300mg 1tab + in 5 ml water, 5 ml TID (70.7mkd) Al HO2/Mg (Maalox) syrup 5ml TID 30 mins before ASA
IVIG 250grams (2mg/kg) Diphenhydramine 13 mg IVTT 30 min prior IVIG

1ST HD, 6th DOI

S/O (+) Febrile Episodes (-) Active losses Fair appetite Erythematous lips, cracking Bilateral cervical lymphadenopathies 1x1 P Paracetamol given for fever Sildenafil 50mg tablet tab + 5ml water, 5ml BID Aspirin 300mg 1tab + in 5 ml water, 5 ml TID Maalox syrup 5ml TID 30 mins before ASA Repeat U/A requested

A
Kawasaki Disease, Incomplete

Repeat U/A Pus cells: 8-10/hpf Epithelial: + Mucus: ++

2nd HD, 7th DOI

S/O (-) Febrile episodes Comfortable Stable vital signs Erythematous, cracked lips Cervical lympadenopathies of about 1.5 x 1.5 P Paracetamol given for fever Sildenafil 50mg tablet tab + 5ml water, 5ml BID Aspirin 300mg 1tab + in 5 ml water, 5 ml TID Maalox syrup 5ml TID 30 mins before ASA Repeat CBC requested CBC WBC RBC Hgb Hct Plt 7.4 4.0 10.8 33 377

A Kawasaki Disease, Complete

Neutro Lympho Mono Eo Baso

39 51 10 0 0

3rd HD, 8th DOI

S/O (-) Febrile Episodes x 35 (-) Active losses Good appetite Bilateral cervical lymphadenopathies 1x1 P MGH with home medications: Sildenafil 50mg tablet tab + 5ml water, 5ml BID Aspirin 300mg 1tab + in 5 ml water, 5 ml TID Maalox syrup 5ml TID 30 mins before ASA Follow up with cardiologist after 1week For repeat 2D-echo after 2 weeks

A Kawasaki Disease, Complete

KAWASAKI DISEASE
Dr. Tomisaku Kawasaki Mucocutaneous lymph node syndrome Infantile polyarteritis nodosa an acute Febrile Vasculitis of childhood UNKNOWN CAUSE

Nelson Textbook of Pediatrics 18th Edition

EPIDEMIOLOGY
Prevalent in Japan
Children of Japanese ancestry 80% of children less than 5 years old; median age of illness 2-3 y/o Americans of Asian and Pacific Island descent

Boys > girls = ~1.5 to 1.7:1

Winter and spring
Newburger JW, Takahashi M, Gerber MA, et al: Diagnosis, treatment, and long-term management of Kawasaki disease. Pediatrics 2004;114:17081733. Nelson Textbook of Pediatrics 19th Edition

EPIDEMIOLOGY
Average: 408 cases/year M:F Ratio 1.6:1 Age distribution:

28 days-1 year 20-25% 1-4 years old 50%

Philippine Pediatric Society May 2006- December 2008 (2.5 years)

PATHOGENESIS
Clinical and epidemiologic features suggests an INFECTIOUS cause Hypothesis: 1. Infectious cause manifesting in genetically predisposed individuals 2. Bacterial superantigenic toxin 3. Antigen driven 4. immune response to different microbial agents
Newburger JW, Takahashi M, Gerber MA, et al: Diagnosis, treatment, and long-term management of Kawasaki disease. Pediatrics 2004;114:17081733.

Discussion

Discussion PATHOGENESIS
Acute or Subacute stages Edema of endothelial and smooth muscle cells Inflammatory infiltration of the vascular wall polymorphonuclear cells Macrophages lymphocytes (primarily CD8 T cells) plasma cells IgA plasma cells - prominent in the inflammatory infiltrate
Nelson Textbook of Pediatrics 18th Edition

Discussion PATHOGENESIS
In Severely affected vessels:
Inflammation of 3 layers of the vascular wall

Destruction of the internal elastic lamina Vessels weaken

Aneurysm formation

Thrombi Blood Flow Obstruction

Nelson Textbook of Pediatrics 18th Edition

PATHOGENESIS
Healing Phase
Fibrotic vascular wall

Stenotic occlusion of the vessel

Nelson Textbook of Pediatrics 18th Edition

PATHOGENESIS
Acute Kawasaki disease - an inflammatory infiltrate present in certain nonvascular tissues host immune response Myocardium Upper respiratory tract Pancreas Kidney Biliary tract

CLINICAL FEATURES
Fever of at least 5 days duration plus 4 0f 5 criteria plus lack of another known disease process to explain the illness

Current Opinion in Infectious Diseases 2008, 21:263270

CRITERIA
Changes of the the extremities: peripheral edema,respiratory mucous membranes of the Changes of Polymorphous rash - upper peripheral 80% Cervical adenopathy tongue Bilateraland periungual desquamation85% 90% conjunctival injection40% 75% tract: injected, fissured lips; strawberry erythema,

Current Opinion in Infectious Diseases 2008, 21:263270

PHASES
I. Acute Febrile Phase
II. Subacute Phase

III. Convalescent Phase

Nelson Textbook of Pediatrics 19th Edition

PHASES
I. Acute Febrile Phase High grade Fever Irritable Bilateral conjunctivitis and rash Erythema and edema of hands and feet Red and cracked tongue and oral mucosa Cardiac complications: myocarditis and pericarditis
Parillo, Steven J., DO, FACOEP, FACEP. Pediatric Kawasaki Disease Follow-up. emedicine.medscape.com/article/804960-followup#showall. March 18, 2010

PHASES
II. Subacute Phase Fever and other signs have abated End by the 4th week persistent irritability Anorexia Conjunctival injection Risk of cardiac complications Thrombocytosis develops Desquamation of the fingertips and toes Aneurysm formation Greatest risk of sudden death
Parillo, Steven J., DO, FACOEP, FACEP. Pediatric Kawasaki Disease Follow-up. emedicine.medscape.com/article/804960-followup#showall. March 18, 2010

PHASES
III. Convalescent Phase begins when all signs of illness have disappeared ESR and CRP level return to normal presence of coronary artery aneurysms

Parillo, Steven J., DO, FACOEP, FACEP. Pediatric Kawasaki Disease Follow-up. emedicine.medscape.com/article/804960-followup#showall. March 18, 2010

PHASES
IV. Chronic Phase For patients who have cardiac complications

Parillo, Steven J., DO, FACOEP, FACEP. Pediatric Kawasaki Disease Follow-up. emedicine.medscape.com/article/804960-followup#showall. March 18, 2010

CLINICAL FINDINGS
Cardiovascular findings Musculoskeletal System Gastrointestinal Tract Central Nervous System Genitourinary System

Nelson Textbook of Pediatrics 18th Edition

LABORATORY FINDINGS
Primary Laboratory Findings - markers of systemic inflammation 1. ESR > 40 mm/hr 2. CRP > 3 mg/dl Echocardiogram - recommended for all patients who meet 1 or both of these criteria
Newburger JW, Takahashi M, Gerber MA, et al: Diagnosis, treatment, and long-term management of Kawasaki disease. Pediatrics 2004;114:17081733.

LABORATORY FINDINGS
Supplemental Laboratory Findings: 1. Albumin < 3 g/ d 2. Anemia for age 3. Increased alanine aminotransferase (ALT) 4. Platelet count > 450 X 103 /l after 7 days of fever 5. WBC > 15 X 103 / L 6. Urine WBC > 10/hpf
Newburger JW, Takahashi M, Gerber MA, et al: Diagnosis, treatment, and long-term management of Kawasaki disease. Pediatrics 2004;114:17081733.

A patient who meets 3 supplementary criteria qualifies for treatment Treatment may precede performance of echocardiogram

Newburger JW, Takahashi M, Gerber MA, et al: Diagnosis, treatment, and long-term management of Kawasaki disease. Pediatrics 2004;114:17081733.

TREATMENT
2. Aspirin Anti-inflammatory dose in acute phase: 80-100 mg/kg/day given every 6 hours
Antiplatelet / anti-thrombotic dose: 3-5 mg/kg/day single dose, 2-3 days after the fever lyses; given for 6 weeks and continued indefinitely if coronary abnormalities are observed
Scheinfeld, Noah S. MD, JD, FAAD, et. al. Intravenous Immunoglobulin. emedicine.medscape.com/article/210367-overview#aw2aab6b7. May 9, 2011.

TREATMENT
3. Heparin/ Warfarin- anticoagulants

4. Corticosteroids

Others: Pentoxyfylline, Ulinastatin, Abciximab

Scheinfeld, Noah S. MD, JD, FAAD, et. al. Intravenous Immunoglobulin. emedicine.medscape.com/article/210367-overview#aw2aab6b7. May 9, 2011.

Risk Level

Pharmacological Therapy

Physical Activity No restrictions beyond 1st 6-8 wks

Follow-up and Diagnostic Testing

Invasive Testing

I. No coronary artery changes at any stages of illness II. Transient coronary artery Ectasis Disappears within 1st 68wks III. 1 small medium coronary artery aneurysm/major coronary artery

None beyond 1st 6-8 wks

Cardiovascular None risk assesment, recommended counseling at 5 yr intervals Cardiovascular None risk assesment, recommended counseling at 3 to 5 yr intervals

None beyond 1st 6-8 wks

No RISK Levelrestrictions I beyond 1st 6-8

wks No coronary Artery changes at any stages of illness Pt <11 yo, no Low dose aspirin (3-5 mkD), at least until aneurysm regression documented
restriction beyond 1st 6-8 wks Pt 11-20yo,P.A guided by biennal stress test, evaluation of myocardial perfusion scan

Annual cardiology follow-up with echocardiogram +ECG, combined with cardiovascular risk assesment, counseling; biennal stress test,eval.myocardial perfusion scan

Angiography, if noninvasive test suggest ischemia

Risk Level

Pharmacological Therapy

Physical Activity No restrictions beyond 1st 6-8 wks

Follow-up and Diagnostic Testing

Invasive Testing

I. No coronary artery changes at any stages of illness II. Transient coronary artery Ectasis Disappears within 1st 68wks III. 1 small medium coronary artery aneurysm/major coronary artery

None beyond 1st 6-8 wks

Cardiovascular None risk assesment, recommended counseling at 5 yr intervals Cardiovascular None risk assesment, recommended counseling at 3 to 5 yr intervals

None beyond 1st 6-8 wks

No restrictions beyond 1st 6-8 wks

RISK Level II
Pt <11 yo, no Low dose Transient restriction beyond aspirin (3-5 6-8 wks mkD), at least artery coronary 1st11-20yo,P.A Pt until aneurysm guided by biennal Ectasia disappears regression stress test, documented1st 6- 8wks within evaluation of myocardial perfusion scan Annual cardiology follow-up with echocardiogram +ECG, combined with cardiovascular risk assesment, counseling; biennal stress test,eval.myocardial perfusion scan

Angiography, if noninvasive test suggest ischemia

Risk Level

Pharmacological Therapy

Physical Activity

Follow-up and Diagnostic Testing

Invasive Testing

I. No coronary artery changes at any stages of illness II. Transient coronary artery Ectasis Disappears within 1st 68wks III. 1 small medium coronary artery aneurysm/major coronary artery

None beyond 1st 6-8 wks

No RISK Levelrestrictions III beyond 1st 6-8

wks 1 small medium coronary artery None beyond No restrictions aneurysm/major 6-8 1st 6-8 wks beyond 1st coronary artery wks

Cardiovascular None risk assesment, recommended counseling at 5 yr intervals Cardiovascular None risk assesment, recommended counseling at 3 to 5 yr intervals

Low dose aspirin (3-5 mkD), at least until aneurysm regression documented

Pt <11 yo, no restriction beyond 1st 6-8 wks Pt 11-20yo,P.A guided by biennal stress test, evaluation of myocardial perfusion scan

Annual cardiology follow-up with echocardiogram +ECG, combined with cardiovascular risk assesment, counseling; biennal stress test,eval.myocardial perfusion scan

Angiography, if noninvasive test suggest ischemia

Risk Level

Pharmacological Therapy Long-term antiplatelet therapy and warfarin or low molecular-weight heparin, should be combine in giant aneurysm

Physical Activity

Follow-up and Diagnostic Testing Biannual follow up with echocardiogram +ECG; annual stress test/evaluation of myocardial perfusion scan

Invasive Testing 1st angiography at 6-12 mo or sooner if clinically indicated; repeated angiography if noninvasive test, clinical or laboratory findings suggest ischemia;electiv e repeat angiography Angiography recommended to address therapeutic options

IV. 1 large or giant coronary artery aneuryms, or multiple or complex aneuryms in same coronary artery, without obstruction

RISK Level IV
V. Coronary artery obstruction Long-term lowdose aspirin; warfarin or lowmolecular-weight heparin if giant aneurysm persists ; consider use of

1 large or giant coronary Contact or high artery aneuryms, or multiple or impact sports Biannual follow-up complex should be aneuryms in with avoided because echocardiogram same coronary artery, without of risk of and ECG; annual bleeding; other obstruction activity stress physical test/evaluation of
recommendations guided by stress myocardial perfusion scan

Contact or high impact sports should be avoided because of risk of bleeding; other physical activity recommendations guided by stress test/evaluation of myocardial perfusion scan outcome

Risk Level

Pharmacological Therapy Long-term antiplatelet therapy and warfarin or low molecular-weight heparin, should be combine in giant aneurysm

Physical Activity

Follow-up and Diagnostic Testing Biannual follow up with echocardiogram +ECG; annual stress test/evaluation of myocardial perfusion scan

Invasive Testing 1st angiography at 6-12 mo or sooner if clinically indicated; repeated angiography if noninvasive test, clinical or laboratory findings suggest ischemia;electiv e repeat angiography Angiography recommended to address therapeutic options

IV. 1 large or giant coronary artery aneuryms, or multiple or complex aneuryms in same coronary artery, without obstruction

RISK Level V

Coronary artery obstruction

Contact or high impact sports should be avoided because of risk of bleeding; other physical activity recommendations guided by stress test/evaluation of myocardial perfusion scan outcome

V. Coronary artery obstruction

Long-term lowdose aspirin; warfarin or lowmolecular-weight heparin if giant aneurysm persists ; consider use of

Contact or high impact sports should be avoided because of risk of bleeding; other physical activity recommendations guided by stress

Biannual follow-up with echocardiogram and ECG; annual stress test/evaluation of myocardial perfusion scan

COMPLICATIONS
Myocardial Infarction Development and Rupture of Coronary artery aneurysms

American Heart Association, 2001

PROGNOSIS
Depends on : Severity of coronary artery involvement as a risk for myocardial ischemia Without proper treatment of IVIG: Risk to develop abnormalities in coronary arteries is 20-25%

With proper treatment of IVIG : Risk to develop abnormalities in their coronary arteries is 2-4%
American Heart Association, 2001

PROGNOSIS
In general, the risk of death from cardiac complications is about 1% to 2% most commonly during the first 2-12 weeks of illness

American Heart Association, 2001