Kawasaki Disease

In life…

Brave Heart

oblivion …

countless illnesses Most important

Breaks the Heart

the real worryleft hidden…

puzzled

Never to lose heart

Fever

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

M.L.2 year old

FemaleFilipino

Pampanga, Davao City

GENERAL DATA

CHIEF COMPLAINT

FEVER

HISTORY OF PRESENT ILLNESS

• Remittent moderate to high grade fever, highest temperature at 40˚C and lowest at 38˚C with Paracetamol syrup at 11.7mkdose q4hours

• Headache, coryza, and non-productive cough

• Loose watery stool, yellowish, non-mucoid, non-blood streaked ~ ¼ cup/episode • Persistence of fever

• Redness of both eyes

• Erythematous non-pruritic macular rashes on the trunk and upper extremities

5 days PTA

2 days PTA CBC:Hgb: 111WBC: 9.1Neut: 84Mono: 16Plt: 220 Hct: 37

Advised to consult a

cardiologist if with

persistence of fever

1 days PTA

• 2D echo = moderate pulmonary hypertension with minimal pericardial effusion

• ESR = 61mm/hr

• CRP positive (>6mg/L)

• Given Maalox, Sildenafil, and Aspirin

• Refused admission

AM PTA

PERSONAL/MEDICAL HISTORY

REVIEW OF SYSTEMS

GENERAL: (+) irritability and decreased in appetite, (-) seizuresSHEENT: (+) hx of headache. No history of any head injury

No history of otorrhea, tinnitus or otalgiaNo history of epistaxis, gum bleeding, or

difficult swallowingNECK: No history pain, stiffness or limitation in movementRESPIRATORY: No hx of dyspnea or postnasal drip

No history of TB exposureCARDIO: No cyanosis, palpitations or easy fatigabilityGASTRO: No abdominal pain, tenderness or changes in bowel habitURINARY: No dysuria, polyuria or tea-colored urinePERIPHERAL: No phlebitis, pallor or edema MUSCULOSKELETAL: No limitations in movement or no weakness

PHYSICAL EXAMAwake, afebrile, comfortable, not in

respiratory distress

Vital Signs:BP: 90/60mmHGCR: 120bpmTemp: 35.6˚CRR: 28cpm

Measurement:Wt: 12.73 kgHt: 90cmHC: 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

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

PHYSICAL EXAM

CHEST

• Equal chest expansion, Clear breath sounds.

• No retraction or deformities

• Adynamic precordium with distinct heart sounds

• NRRR• No murmurs, thrills or heavesHEART

• Abdomen flat, soft, and non-tender with NABS

• Tympanitic on percussion except on areas of liver dullness

• No masses or organomegalyABDOMEN

PHYSICAL EXAM

EXTREMITIES

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

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

MUSCULOSKELETAL

• 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

Fever

DIFFERENTIAL DIAGNOSIS

Scarlet Fever

Dengue Fever

Measles

Roseola InfantumKawasaki Disease

DENGUE FEVER

Hematocrit 38 33

Platelet count 379 377

MEASLES

SCARLET FEVER

ROSEOLA INFANTUM

KAWASAKI DISEASE

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

ADMITTING IMPRESSION

Day of Admission (5TH DOI)

LABS OF ADMISSION

CBCWBC 7.6RBC 4.8Hgb 12.8Hct 38Plt 379Neutro 33Lympho 52Mono 15Eo 0Baso 0

C-Xray: NormalStool Exam: Negative

U/AYellow, slightly cloudy, acidicSp. Gravity: 1.010

Albumin: trace Pus cells: 15-20/hpfMucus: +++

MEDICATIONS

Paracetamol 250mg/5ml 3.5ml q 4

Sildenafil 50mg tablet ¼tab + 5ml water, 5ml BID

Diphenhydramine 13 mg IVTT 30 min prior IVIG

Al HO2/Mg (Maalox) syrup 5ml TID 30 mins before ASA

Aspirin 300mg 1tab + in 5 ml water, 5 ml TID (70.7mkd)

IVIG 250grams (2mg/kg)

1ST HD, 6th DOIS/O•(+) Febrile Episodes•(-) Active losses•Fair appetite•Erythematous lips, cracking•Bilateral cervical lymphadenopathies 1x1

AKawasaki Disease,

Incomplete

P•Paracetamol given for fever•Sildenafil 50mg tablet ¼tab + 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

Repeat U/APus cells: 8-10/hpfEpithelial: +Mucus: ++

S/O•(-) Febrile episodes•Comfortable•Stable vital signs•Erythematous, cracked lips•Cervical lympadenopathies of about 1.5 x 1.5

AKawasaki Disease,

Complete

P•Paracetamol given for fever•Sildenafil 50mg tablet ¼tab + 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

Neutro 39Lympho 51Mono

10Eo 0Baso 0

2nd HD, 7th DOI

3rd HD, 8th DOIS/O•(-) Febrile Episodes x 35˚•(-) Active losses•Good appetite•Bilateral cervical lymphadenopathies 1x1

AKawasaki Disease,

Complete

P•MGH with home medications:•Sildenafil 50mg tablet ¼tab + 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

Dr. Tomisaku Kawasaki Mucocutaneous lymph

node syndrome Infantile polyarteritis

nodosa an acute Febrile

Vasculitis of childhood UNKNOWN CAUSE

Nelson Textbook of Pediatrics 18th Edition

KAWASAKI DISEASE

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

EPIDEMIOLOGY

Newburger JW, Takahashi M, Gerber MA, et al: Diagnosis, treatment, and long-term management of Kawasaki disease. Pediatrics 2004;114:1708–1733.Nelson Textbook of Pediatrics 19th Edition

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)

EPIDEMIOLOGY

Discussion

Clinical and epidemiologic features suggests an INFECTIOUS cause

Hypothesis:1.Infectious cause manifesting in genetically predisposed individuals2.Bacterial superantigenic toxin3.Antigen driven4.immune response to different microbial agents

PATHOGENESIS

Newburger JW, Takahashi M, Gerber MA, et al: Diagnosis, treatment, and long-term management of Kawasaki disease. Pediatrics 2004;114:1708–1733.

Discussion

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

PATHOGENESIS


Discussion

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

PATHOGENESIS


Healing Phase

Fibrotic vascular wall

Stenotic occlusion of the vessel

PATHOGENESIS


Acute Kawasaki disease- an inflammatory infiltrate present in certain nonvascular tissues host immune response

MyocardiumUpper respiratory tractPancreasKidneyBiliary tract

PATHOGENESIS

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, 21:263–270

CLINICAL FEATURES

Bilateral conjunctival injection – 85%

Current Opinion in Infectious Diseases 2008, 21:263–270

CRITERIA

Changes of the mucous membranes of the upper respiratory tract: injected, fissured lips;

strawberry tongue – 90%

Polymorphous rash - 80%Changes of the extremities: peripheral edema, peripheral erythema, and periungual desquamation – 75%

Cervical adenopathy – 40%

I. Acute Febrile Phase

II. Subacute Phase

III. Convalescent Phase

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

pericarditisParillo, 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

PHASES

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

III. Convalescent Phase begins when all signs of illness

have disappeared ESR and CRP level return to normal presence of coronary artery

aneurysms

PHASES


IV. Chronic Phase For patients who have cardiac

complications

PHASES


Cardiovascular findingsMusculoskeletal SystemGastrointestinal Tract

Central Nervous SystemGenitourinary System


CLINICAL 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


LABORATORY FINDINGS

Supplemental Laboratory Findings:

1. Albumin < 3 g/ d2. Anemia for age3. Increased alanine aminotransferase

(ALT)4. Platelet count > 450 X 103 /µl after

7 days of fever5. WBC > 15 X 103 / µL6. Urine WBC > 10/hpf


LABORATORY FINDINGS

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;114:1708–1733.

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

TREATMENT

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

3. Heparin/ Warfarin- anticoagulants

4. Corticosteroids

Others: Pentoxyfylline, Ulinastatin, Abciximab

TREATMENT

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

Follow-up and Diagnostic

Testing

Invasive Testing

I. No coronaryartery changesat any stagesof illness

II. Transientcoronary arteryEctasisDisappearswithin 1st 6-8wks

III. 1 smallmediumcoronary arteryaneurysm/majorcoronary artery

None beyond 1st 6-8 wks


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

No restrictions beyond 1st 6-8 wks


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

Cardiovascular risk assesment, counseling at 5 yr intervals

Cardiovascular risk assesment, counseling at 3 to 5 yr intervals

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

None recommended

None recommended

Angiography, if noninvasive test suggest ischemia

Newburger et al. Diagnosis, treatment and long-term management of KD. American Academy of Pediatrics.2004

RISK Level INo coronaryArtery changesat any stagesof illness


Physical Activity


Testing

Invasive Testing













None recommended

None recommended


RISK Level IITransientcoronary arteryEctasia disappearswithin 1st 6- 8wks



Physical Activity


Testing

Invasive Testing













None recommended

None recommended


RISK Level III1 small mediumcoronary arteryaneurysm/majorcoronary artery



Physical Activity Follow-up and Diagnostic

Testing

Invasive Testing

IV. ≥ 1 large orgiant coronaryartery aneuryms,or multiple orcomplexaneuryms insame coronaryartery, withoutobstruction

V. Coronaryarteryobstruction

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

Long-term low-dose aspirin; warfarin or low-molecular-weight heparin if giant aneurysm persists ; consider use of β

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

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

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

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

1st angiography at 6-12 mo or sooner if clinically indicated; repeated angiography if noninvasive test, clinical or laboratory findings suggest ischemia;elective repeat angiography

Angiography recommended to address therapeutic options

RISK Level IV ≥ 1 large or giant coronaryartery aneuryms, or multiple or

complex aneuryms insame coronary artery, without

obstruction


Physical Activity Follow-up and Diagnostic

Testing

Invasive Testing

IV. ≥ 1 large orgiant coronaryartery aneuryms,or multiple orcomplexaneuryms insame coronaryartery, withoutobstruction

V. Coronaryarteryobstruction

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

Long-term low-dose aspirin; warfarin or low-molecular-weight heparin if giant aneurysm persists ; consider use of β

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

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

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

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

1st angiography at 6-12 mo or sooner if clinically indicated; repeated angiography if noninvasive test, clinical or laboratory findings suggest ischemia;elective repeat angiography

Angiography recommended to address therapeutic options

RISK Level V Coronary artery obstruction

Myocardial Infarction

Development and Rupture of Coronary artery aneurysms

American Heart Association, 2001

COMPLICATIONS

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%


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


PROGNOSIS

Documents

Kawasaki Disease