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Kawasaki Disease in Children Evidence-Based Guideline

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Kawasaki Disease in Children Evidence-Based Guideline DATE: September 2019 TEXAS CHILDREN’S HOSPITAL EVIDENCE-BASED OUTCOMES CENTER Diagnosis and Management of Kawasaki Disease in Children Evidence-Based Guideline Definition: Kawasaki disease (KD), also known as Inclusion Criteria mucocutaneous lymph node syndrome, is an acute, self- Patients <18 years of age limiting vasculitic syndrome of unknown etiology that primarily Prolonged febrile illness (≥5 days) in a patient with ≥2 of the affects children younger than 5 years of age. (1) First described principal clinical features of Kawasaki disease. in Japan in 1967 by Tomisaku Kawasaki, KD is the leading Patients with fever and ≥4 principal clinical features (2) cause of acquired heart disease in children. The most Infants with fever for ≥7 days without other explanation common and dangerous long-term sequelae of KD are coronary artery abnormalities (aneurysms or ectasia) that Exclusion Criteria develop in up to 25% of untreated children and may lead to Patients ≥18 years of age (3) sudden death or ischemic heart disease. Classic or Complicating existing diagnoses: complete KD is defined by the Centers for Disease Control - Immunologic (CDC) as an illness characterized by fever of 5 or more days - Rheumatologic disease duration and the presence of at least 4 of the following 5 - Major chronic inflammatory diseases clinical criteria: rash; cervical lymphadenopathy (at least 1.5 - Significant congenital heart disease cm in diameter); bilateral conjunctival injection; oral mucosal Macrophage activation syndrome (MAS) changes; and peripheral extremity changes. Incomplete KD is KD shock syndrome (KDSS) an atypical presentation of Kawasaki disease which should be - A rare, potentially life-threatening complication of KD considered in any infant or child with prolonged unexplained characterized by systolic hypotension for age, sustained fever, fewer than 4 of the principal clinical findings, and systolic hypotension (decrease in blood pressure ≥20% compatible laboratory or echocardiographic findings. from baseline) or clinical signs of poor perfusion (7) Epidemiology: According to the CDC, the estimated overall - Laboratory findings annual incidence of KD is approximately 25 per 100,000 . Higher levels of inflammatory markers children younger than five years in the United States. (2) This . Lower albumin levels information was collected via passive national reporting to the . Anemia CDC, private insurance databases, or administrative . Consumptive coagulopathy databases (i.e., Pediatric Hospital Information Service). There . Bandemia is prominent ethnic variation in the KD incidence rate for the . Hyponatremia United States with higher rates among Pacific Islanders and - Clinical Findings Japanese Americans (30 per 100,000), intermediate among . More severe skin rash non-Hispanic African Americans (17 per 100,000) and . Myocardial dysfunction Hispanics (16 per 100,000), and lowest among Caucasians (12 . More severe coronary artery involvement per 100,000). (4) Males are more commonly affected than . Poor response to IVIG - females, and 90% of the cases occur in children younger than *If shock is suspected, exit KD guideline/algorithm five years. Disease occurrence is most common in winter and and treat accordingly (consider Septic Shock early spring in North America. Guideline) (8) Etiology: KD is an acute systemic inflammatory disease of Differential Diagnosis unknown etiology. Several theories have attempted to Infectious and noninfectious conditions: determine whether the source of KD is infectious, genetic or a Viral infections [*In a child with clinical findings compatible host immune response. However, none of the etiological with classic KD, the detection of respiratory viruses such as agents have been found to be causative. The seasonality of respiratory syncytial virus, metapneumovirus, coronaviruses, parainfluenza viruses, or influenza viruses KD is associated with increased incidence in geographic areas (9) and may suggest a transmissible factor. Studies are ongoing to does not exclude the diagnosis of KD ] determine the etiology of KD. (5) - Adenovirus - Epstein Barr Virus Pathophysiology: KD is an acute, self-limiting, multisystem - Influenza vasculitis. The innate immune system plays a vital role in the - Measles pathogenesis of Kawasaki's disease. Neutrophils are important - Mononucleosis factors in the initial inflammatory response on coronary artery - Roseola infantum walls. Recent studies also demonstrate increased expression - Rubella of innate immunity associated genes during the acute phase of Bacterial infections Kawasaki's disease. (6) Impaired immune regulation has been - Lyme Disease found to also play a role in pathogenesis of KD as studies of - Leptospirosis acute and subacute sera from KD patients have shown a - Meningococcemia decrease in the population of T regulatory cells in the acute - Retropharyngeal abscess phase with normalization following treatment with IVIG. The - Rocky Mountain Spotted Fever role of B cells has not been clearly defined; IgA plasma cells - Staphylococcal infection (e.g., Staphylococcal Scalded have been found in coronary artery lesions from fatal cases of Skin Syndrome [SSSS]; Toxic Shock Syndrome [TSS]) KD. Their specific role is unknown. - Streptococcal infection (e.g., rheumatic fever, scarlet fever, TSS like syndrome) © Evidence-Based Outcomes Center 1 Texas Children’s Hospital DATE: September 2019 Autoimmune disorders - Anemia may develop with more prolonged active - Systemic juvenile rheumatoid arthritis inflammation. - Systematic lupus erythematosus - Thrombocytosis is rare in the 1st week of illness but Multi-organ system disorders may appear in the 2nd week (peaking in the 3rd-4th - Infantile Polyarteritis Nodosa week) with a mean peak platelet count of ≈ 700,000/ Drug hypersensitivity reactions mm3. - Stevens-Johnson Syndrome (SJS) Complete metabolic panel - Toxic Epidermal Necrolysis (TEN) - Hyponatremia can be noted. - Mild to moderate elevations in serum transaminases Diagnostic Evaluation occur in ≤40% of patients. History: Assess for presence of fever and principal clinical - Mild hyperbilirubinemia can occur in ≈ 10% of patients. features - Hypoalbuminemia is common and is associated with Fever: more severe and prolonged acute disease. - Onset (≥5 days of fever with ≥2 clinical criteria or 4 days Liver enzymes including aspartate transaminase (AST), with all 5 clinical criteria) alanine transaminase (ALT), and albumin - Response to antipyretics - Abnormal results common in patients with acute - How high was the temperature (typically high spiking; Kawasaki disease and are associated with IVIG >39°C to 40°C, remittent) resistance. Bilateral bulbar conjunctival injection without exudate C-reactive protein (CRP) Oral mucous membrane changes, including injected or - Elevation of CRP is seen but should return to normal by fissured lips, injected pharynx, or strawberry tongue 6-10 weeks after onset of illness. Rash: maculopapular, diffuse erythroderma, or erythema Erythrocyte sedimentation rate (ESR) multiforme-like (often worse in groin area) - Elevation of acute phase reactants is nearly universal in Peripheral extremity changes, including erythema and Kawasaki disease. Elevation of ESR (but no of CRP) edema of hands and feet (acute phase), and periungual can be caused by IVIG therapy; therefore, ESR should desquamation (convalescent phase) not be used as the sole determinant of the degree of Cervical lymphadenopathy (at least one lymph node >1.5 inflammatory activity in IVIG-treated patients. cm in diameter), usually unilateral Urinalysis - Urinalysis reveals intermittent mild to moderate sterile History: Assess for other clinical findings pyuria in ≈ 33% of patients. Cells originate in the urethra Cough, increased work of breathing, sore throat and a catheterized specimen may not contain these Vomiting cells. Diarrhea D-dimer History of illnesses - Elevated D-dimer can signify endothelial damage and fibrinolysis which is associated with systemic vasculitis Review of current medications and may help predict coronary artery involvement Family history of autoimmune disease Physical Examination Optional laboratory tests Vital signs Consider obtaining NT-pro BNP - Temperature - Can be used as an adjunctive marker to assist with the - Heart rate diagnosis of patients in the acute phase of Kawasaki - Respirations disease - Blood pressure - Oxygen saturations Echocardiogram Assess for presence of diagnostic criteria: Transthoracic echocardiography is highly sensitive and - Bilateral bulbar conjunctival injection without exudate specific for the diagnosis of coronary artery involvement. It - Oral mucous membrane changes, including injected or is important to ensure that the timing or results of the fissured lips, injected pharynx, or strawberry tongue echocardiogram do not delay initial treatment of Kawasaki - Rash: maculopapular, diffuse erythroderma, or disease, and that the diagnosis is made predominantly on erythema multiforme-like (often worse in groin area) clinical findings. - Peripheral extremity changes, including erythema and Echocardiogram is considered positive if any of 3 edema of hands and feet (acute phase), and periungual conditions are met: desquamation (convalescent phase) - Z score of LAD or RCA ≥2.5 - Cervical lymphadenopathy (at least one lymph node - Coronary arteries meet criteria for aneurysms >1.5 cm in diameter), usually unilateral - 3 other suggestive features exist, including decreased LV function, mitral
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