KAWASAKI DISEASE Kaushal Raj KafleIntern Department Of Paediatrics

INTRODUCTION Acute febrile illness of children Vasculitis with predilection to Coronary artery

EPIDEMIOLOGY Leading Cause of Acquired heart disease in Developed Countries Median Age : 2-3yrs (80% cases < 5yrs) 17.1/100,000 in children <5 yr of age 39/100,000 children of Asian and Pacific Islander background Compared with 19.7/100,000 black 13.6/100000 hispanic 11.4/100000 white non hispanic

200000 cases in Japan since 1960s

ETIOLOGY Unknown Infectious : no single infectious etiologic agent has been successfully identified, Young age group Epidemic with geographic spread Fever with rash, exanthem, conjunctivitis, cervical lymphadenopathy Not in < 3mo : likely maternal Antibody Not in adults : Prior exposure and immunity KD assosciated antigen

Genetic: Higher risk of KD in Asian children regardless of country of residence siblings and children of individuals with a history of KD susceptibility loci

ETIOLOGY superantigen activity subacute phase of illness, levels of all immunoglobulins (Igs) are elevated

PATHOLOGY Vasculitidis of Medium sized artery Predilectioon to coronary artery

Infiltration of vascular wall with PML Followed by macrophage, Lymphocyte (CD 8+ T cells) and plasma cells (Ig A)

Edema of endothelium smooth musclesAll layers inflammation Destruction of internal elastic laminaLoss of structural Integrity Saccular and Fusiform DilatationsThrombus formation Obstruction

Progressive fibrosis with marked intimal proliferationArterial stenosis or occlusion

CLINICAL FEATURES: PRINCIPLE FEATURES Fever high (≥101°F), unremitting, and unresponsive to antibiotics. Conjunctivitis : Bilateral nonexudative bulbar conjunctival injection with limbal sparing; Rash :Polymorphous exanthem (maculopapular, erythema multiforme, or scarlatiniform) with accentuation in the groin area Edema and erythema: of the hands and feet Adenopathy: nonsuppurative cervical lymphadenopathy, unilateral, size >1.5 cm Mucosa Erythema : oral and pharyngeal mucosa with strawberry tongue and dry, cracked lips;

DIAGNOSIS Fever at least 5 days

+ < 4 principal criteria

+ coronary artery abnormalities detected by 2D

echocardiography or angiography. In the presence of ≥4 principal criteria, Kawasaki disease diagnosis can be made on day 4 of illness. Experienced clinicians who have treated many patients with Kawasaki disease may establish diagnosis before day 4.

CARDIOVASCULAR FINDINGSMyocarditis (Tachycardia out of proportion to Fever and left systolic dysfunction)

Congestive heart failure: Shock (Severe left ventricular systolic dysfunction )

Pericarditis with mild pericardial effusion Valvular regurgitation mild MR in ¼ patient regresses over time

Aneurysms of medium-sized Coronary artery in 25% of untreated cases (2-3rd week ) Giant coronary artery aneurysms (≥8 mm internal diameter): greatest risk for rupture, thrombosis or stenosis, and MI

noncoronary arteries: Axillary, popliteal, iliac Localised pulsating massesRaynaud phenomenonPeripheral gangrene

OTHER FINDINGS Musculoskeletal systemArthritis, arthralgias Gastrointestinal tract: (65%)Diarrhea, vomiting, abdominal pain

Hepatic dysfunctionHydrops of gallbladderRespiratory System: (35%)Interstitial Infiltrates And effusion

Central nervous system:Extreme irritabilityAseptic meningitisSensorineural hearing loss Genitourinary system:Urethritis/meatitis with sterile pyuria

Other findings:Erythema, induration at bacille Calmette-Guérin inoculation site

Anterior uveitis (mild)Desquamating rash in groin

FINDINGS NOT FAVORING KAWASAKI DISEASE exudative conjunctivitis exudative pharyngitis generalized lymphadenopathy discrete oral lesions bullous, pustular, or vesicular rashes.

NATURAL HISTORY OF DISEASE Acute Febrile Phase : Fever and acute signs of illness lasts 1-2 week.

Subacute Phase : Desquamation, thrombocytosis, development of coronary aneurysms, highest risk of sudden death lasts about 2 week.

Convalescent phase: all clinical signs of illness have disappeared Continues until the erythrocyte sedimentation rate (ESR) returns to normal,

Lasts 6-8 week.

INVESTIGATION No Diagnostic Test Blood Counts: ↑ TC with Neutrophilia and Immature form PBS: Normochromic Normocytic Anemia Platelets : Normal (1st week ) ↑↑ (> 10 lakhs in 2nd and 3rd week ) Acute Phase Reactants: ↑ ESR and ↑ CRP (Universally) LFT : Mild Elevated Liver Enzymes, ↑ TB, ↑ GGT , ↓ Albumin RFT : ↓ Na+

Abnormal Lipid Profile Urine : Sterile Pyuria CSF : Pleocytosis Synovial Fluid : Leukocytosis

INVESTIGATION : 2D ECHOCARDIOGRAPHY Frank aneurysms :rare in early illness, brightness of the arterial walls and lack of normal tapering of the vessels are typical

Japanese Ministry of Health Classification of Aneurysm Small: <5 mm internal diameter Medium : 5-8 mm internal diameter Giant: >8 mm internal diameterRepeat Echo : 2-3 wks of illness and follow-up according to the patients’ coronary status. No finding in Initial Echo : Repeat after 1 year with Lipid Profile and then every 5 year

Coronary Angiogram

DIFFERENTIAL DIAGNOSIS

Viral Infections

Adeno virus Exudative pharyngitis and exudative conjunctivitis

Enterovirus Measles Koplick Spot and Exduative conjunctivitis

Rash arising from the face, hairline, behind the ears Leukopenia

Epstein-Barr Virus

Bacterial Infections

Scarlet Fever Rapid response to Antibiotic in 24-48 hrs

Rocky mountain Spotted Fever

pronounced myalgias, headache at onset, centripedal rash, and petechiae on the palms and soles

Leptospirosis Exposure to water infected with animal urine Biphasic illness: initial period of fever and headache late phase with renal and hepatic failure

Bacterial cervical lymphadenitis

DIFFERENTIAL DIAGNOSIS RHEUMATOLOGIC DISEASE

Systemic Onset JRA

diffuse lymphadenopathy Hepatosplenomegalycoagulopathy, elevated fibrin degradation product values, hyperferritinemia.

OTHER

Toxic Shock Syndrome

Renal Insufficiency , Coagulopathy Pancytopenia, Myositis

Staphylococcal Scalded Skin SyndromeDrug Hyper sensitivity reaction

Periorbital edema, oral ulcerations, and a normal or minimally elevated ESR

Steven Johnson Syndrome

Similar to Drug reaction

TREATMENT ACUTE STAGE • Intravenous immunoglobulin 2 g/kg over 10-12 hr AND • Aspirin 80-100 mg/kg/day divided every 6 hr orally until patient is afebrile for

at least 48 hr

CONVALESCENT STAGE • Aspirin 3-5 mg/kg once daily orally until 6-8 wk after illness onset

POOR OUTCOME PREDICTOR Young age Male Asian and Pacific Islanders Prolonged Fever Lab Investigations

Neutrophilia Thrombocytopenia Elevated Liver Enzymes↓ Na+

↑ CRP↓ Albumin

COMPLICATION small solitary aneurysm: continue aspirin indefinitely larger or numerous aneurysms: Additional Antiplatelet therapy Acute thrombosis: Thrombolytic therapy

COMPLICATION : TREATMENT LONG-TERM THERAPY FOR PATIENTS WITH CORONARY ABNORMALITIES

• Aspirin 3-5 mg/kg once daily orally • Clopidogrel 1 mg/kg/day (max 75 mg/day) • Most experts add warfarin or low-molecular-weight heparin for those patients

at particularly high risk of thrombosis

ACUTE CORONARY THROMBOSIS • Prompt fibrinolytic therapy with tissue plasminogen activator or other

thrombolytic agent under supervision of a pediatric cardiologist

PROGNOSIS Acute KD recurrence: 1-3% Risk of Coronary Artery aneurysm in timely treated case < 5% Fatality rate < 1% 50% of Coronary artery aneurysm (Smaller: Better) regress to normal in 1-2 year

Giant aneurysm : unlikely to resolve : Thrombosis and stenosis Significant compromise in myocardial Perfusion : CABG with Arterial Graft and rarely heart transplant

No established relation with atherosclerosis in Children with KD