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Kawasaki Disease, Emergency Medicine

Basics

Description

- Stages: - Acute (lasts 1 " “2 wk): - Fever - Oral mucosal erythema - Conjunctival injection - Erythema and edema of hands and feet - Cervical adenopathy - Aseptic meningitis - Hepatic dysfunction - Diarrhea - Myocarditis - Pericardial effusion (20 " “40%) - No aneurysms by ECHO

- Subacute (when fever, rash, and lymphadenopathy resolve until about 4 wk): - Anorexia - Irritability - Desquamation of hands and feet - Thrombocytosis - Coronary artery aneurysms (20% if untreated) - Risk for sudden death is highest

- Convalescent phase (about 6 " “8 wk): - Clinical signs are absent - ESR normalizes

- Epidemiology: - 80% of cases occur in children <4 yr old; peak at 1 " “2 yr; rare in infants <3 mo old - Adult cases have been reported - Asians are at highest risk - Males > females 1.5:1

- Risks for nonresponse to standard therapy (10 " “15%): - Elevated band count - Low albumin level - Abnormal initial ECHO

- Risks for development of coronary artery aneurysms: - Extremes of age - Male gender - Prolonged fever - Persistent fever after treatment - Delay in diagnosis - Increased WBC and/or band count - Low hematocrit - Significant increase in CRP and/or ESR

- Unknown " ”believed to be infectious based on manifestations of disease, epidemics, and increased numbers of cases in winter and early spring - Current theory: - Activation of immune system in response to infection - Genetically susceptible host - May explain why certain ethnicities have higher incidence of disease - More prominent in Asian countries

- Classic diagnostic criteria: - Fever for 5 days + 4 of the 5 following criteria: - Bilateral conjunctival injection - Changes in oral mucosa - Polymorphous erythematous rash - Changes in hands or feet " ”edema, erythema, desquamation - Cervical lymphadenopathy >1.5 cm (least common)

- Atypical cases can be seen without meeting diagnostic criteria - Fever for >5 days + 2 or 3 clinical criteria with ESR >40 and CRP >3 - If >3 of the below can diagnose incomplete Kawasaki disease - Albumin <3 - Anemia for age - ALT elevation - WBC > 15,000 - Urine >10 WBC per high power field - Platelets >450,000 after 7 days

- Cardiac: - Shortness of breath - Chest pain

- HEENT: - Eyes: - Conjunctivitis - Photophobia

- Skin rash - Musculoskeletal: - Neurologic: - GI: - Diarrhea - Vomiting - Abdominal pain

- HEENT: - Eyes: - Bilateral conjunctival injection without exudates - Bulbar conjunctiva is more frequently involved than palpebral conjunctiva - Usually within 2 days of onset of fever and lasting 1 " “2 wk - Photophobia, uveitis, iritis

- Neurologic: - Skin: - Rash, primarily on the trunk - May be maculopapular, scarlatiniform, or erythema multiforme " “like; erythroderma - Changes in the hands or feet " ”erythema, edema (acute phase); unwilling to bear weight - Desquamation (subacute phase) of the tips of fingers and toes 2 " “3 wk after onset of illness

- CBC: - WBC " ”normally elevated with shift to left in acute phase - Normocytic anemia - Leukopenia and thrombocytopenia are rare - Suspect viral infection - Thrombocytopenia is a risk factor for development of coronary artery disease

- Urinalysis: - Sterile pyuria - Proteinuria

- Bacterial infection: - Scarlet fever (responds rapidly to penicillin) - Staphylococcal scalded-skin syndrome - Rickettsial disease, including Rocky Mountain Spotted Fever and leptospirosis - Cervical adenitis

- Immune-mediated: - Stevens " “Johnson syndrome - Erythema multiforme - Serum sickness - Connective tissue disease (i.e., Lupus) - Other forms of vasculitis

- Aspirin: 80 " “100 mg/kg/d PO q6h until about day 14 when fever has resolved; then 3 " “5 mg/kg/d PO daily for 6 " “8 wk. Do not exceed 4g/24 h (peds: Do not exceed 120 mg/kg/24 h): - Anti-inflammatory - Antiplatelet - Potentiates the action of IVIG - Reduces the occurrence of aneurysms when given with IVIG - Alternative dosing at 30 mg/kg/d during acute and subacute phases

  • Acute inflammatory process involving multiple organs
  • Leading cause of childhood-acquired heart disease in developed countries
  • Vasculitis is most severe in medium-sized arteries
  • Acute cardiac sequelae:Coronary artery aneurysm:Often lead to stenosis after healingGiant aneurysm:MyocarditisPericarditis
  • Stages:Acute (lasts 1 " “2 wk):FeverOral mucosal erythemaConjunctival injectionErythema and edema of hands and feetCervical adenopathyAseptic meningitisHepatic dysfunctionDiarrheaMyocarditisPericardial effusion (20 " “40%)No aneurysms by ECHOSubacute (when fever, rash, and lymphadenopathy resolve until about 4 wk):AnorexiaIrritabilityDesquamation of hands and feetThrombocytosisCoronary artery aneurysms (20% if untreated)Risk for sudden death is highestConvalescent phase (about 6 " “8 wk):Clinical signs are absentESR normalizesEpidemiology:80% of cases occur in children <4 yr old; peak at 1 " “2 yr; rare in infants <3 mo oldAdult cases have been reportedAsians are at highest riskMales > females 1.5:1
  • Genetics:Possible genetic predisposition
  • Risks for nonresponse to standard therapy (10 " “15%):Elevated band countLow albumin levelAbnormal initial ECHO
  • Risks for development of coronary artery aneurysms:Extremes of ageMale genderProlonged feverPersistent fever after treatmentDelay in diagnosisIncreased WBC and/or band countLow hematocritSignificant increase in CRP and/or ESR

Etiology

  • Unknown " ”believed to be infectious based on manifestations of disease, epidemics, and increased numbers of cases in winter and early spring
  • Current theory:Activation of immune system in response to infectionGenetically susceptible hostMay explain why certain ethnicities have higher incidence of diseaseMore prominent in Asian countries

Diagnosis

  • Classic diagnostic criteria:Fever for 5 days + 4 of the 5 following criteria:Bilateral conjunctival injectionChanges in oral mucosaPolymorphous erythematous rashChanges in hands or feet " ”edema, erythema, desquamationCervical lymphadenopathy >1.5 cm (least common)
  • Atypical cases can be seen without meeting diagnostic criteriaFever for >5 days + 2 or 3 clinical criteria with ESR >40 and CRP >3If >3 of the below can diagnose incomplete Kawasaki diseaseAlbumin <3Anemia for ageALT elevationWBC > 15,000Urine >10 WBC per high power fieldPlatelets >450,000 after 7 days
  • ThrombocytosisChanges in hands or feet " ”edema, erythema, desquamationCervical lymphadenopathy >1.5 cm (least common)

Signs and Symptoms

History

  • Temperature >38.5 ‚ °C (often spiking) for at least 5 days:Begins abruptly and may last >2 wk
  • Cardiac:Shortness of breathChest pain
  • HEENT:Eyes:ConjunctivitisPhotophobiaMouth:ErythemaDry and fissured lips
  • Skin rash
  • Musculoskeletal:
  • Neurologic:
  • GI:DiarrheaVomitingAbdominal pain

Physical Exam

  • Cardiac:Evidence of congestive heart failureEvidence of pericarditisEvidence of valvular disease
  • HEENT:Eyes:Bilateral conjunctival injection without exudatesBulbar conjunctiva is more frequently involved than palpebral conjunctivaUsually within 2 days of onset of fever and lasting 1 " “2 wkPhotophobia, uveitis, iritisMouth:Erythema, dry and fissured lips, strawberry tongue, pharyngeal erythemaLymph:Cervical lymphadenopathy (node diameter >1.5 cm)
  • Neurologic:
  • Skin:Rash, primarily on the trunkMay be maculopapular, scarlatiniform, or erythema multiforme " “like; erythrodermaChanges in the hands or feet " ”erythema, edema (acute phase); unwilling to bear weightDesquamation (subacute phase) of the tips of fingers and toes 2 " “3 wk after onset of illness
  • Genitourinary:
  • GI:Hydrops of the gallbladder

Essential Workup

Must think of the diagnosis in a febrile child with rash ‚

Diagnosis Tests & Interpretation

Lab

  • CBC:WBC " ”normally elevated with shift to left in acute phaseNormocytic anemiaLeukopenia and thrombocytopenia are rareSuspect viral infectionThrombocytopenia is a risk factor for development of coronary artery disease
  • Urinalysis:Sterile pyuriaProteinuria
  • ESR elevated from 1st wk until 4 " “6 wk
  • Increased C-reactive protein
  • CSF pleocytosis
  • Cultures: Negative blood, urine, CSF, throat
  • Increased transaminases and bilirubin

Imaging

  • ECHO to evaluate for coronary artery aneurysm:Acute phase (baseline)2 " “3 wk6 " “8 wk
  • CXR

Diagnostic Procedures/Surgery

  • ECG if concern about MI or pericarditis
  • Slit-lamp exam " ”uveitis

Differential Diagnosis

  • Viral infections:AdenovirusEnterovirusMeaslesEpstein " “Barr virusRubellaRubeolaInfluenza
  • Bacterial infection:Scarlet fever (responds rapidly to penicillin)Staphylococcal scalded-skin syndromeRickettsial disease, including Rocky Mountain Spotted Fever and leptospirosisCervical adenitis
  • Immune-mediated:Stevens " “Johnson syndromeErythema multiformeSerum sicknessConnective tissue disease (i.e., Lupus)Other forms of vasculitis

Treatment

Pre-Hospital

Initial Stabilization/Therapy

ABCs with focus on cardiovascular system ‚

Ed Treatment/Procedures

  • Initiate IV gammaglobulin (IVIG) and aspirin therapy:Do not generally need to monitor salicylate levels because of decreased absorption and increased clearance
  • Treatment within the 1st 10 days of illness reduces cardiac sequelae from range of 20 " “25% to range of 2 " “4%.
  • Cardiology consultation
  • Treatment of MIs as in adults

Medication

First Line

  • IVIG: 2 g/kg IV over 10 " “12 hr; retreatment may be required for persistent (>48 " “72 hr) or recrudescent fever:Requires close cardiac monitoringShould be started within the 1st 10 days of illness3 " “4% failure rate after 2 doses
  • Aspirin: 80 " “100 mg/kg/d PO q6h until about day 14 when fever has resolved; then 3 " “5 mg/kg/d PO daily for 6 " “8 wk. Do not exceed 4g/24 h (peds: Do not exceed 120 mg/kg/24 h):Anti-inflammatoryAntiplateletPotentiates the action of IVIGReduces the occurrence of aneurysms when given with IVIGAlternative dosing at 30 mg/kg/d during acute and subacute phases

Second Line

If no response to 2nd dose of IVIG ‚

  • Corticosteroids:Methylprednisolone 30 mg/kg over 3 hrMay improve outcome in conjunction with IVIG

May also consider: ‚

  • Infliximab
  • Cyclosporine A
  • Methotrexate

Follow-Up

Disposition

Admission Criteria

  • Admit all patients who fulfill diagnostic criteria for Kawasaki disease
  • Admit toxic-appearing patients who do not yet meet the criteria for Kawasaki disease

Discharge Criteria

  • Nontoxic children who do not fulfill diagnostic criteria
  • Close follow-up is required

Issues for Referral

Cardiology consultation for all patients ‚

Pearls and Pitfalls

  • Prompt diagnosis and therapy can prevent coronary aneurysms in 95%
  • Aspirin and IVIG are mainstays of therapy
  • Must consider the diagnosis in febrile children presenting to the ED for multiple visits
  • Restrict steroids to children with 2 IVIG failures

Additional Reading

  • Ashouri ‚ N, Takahashi ‚ M, Dorey ‚ F, et al. Risk factors for nonresponse to therapy in Kawasaki disease. J Pediatr. 2008;153:365 " “368.
  • Gerding ‚ R. Kawasaki disease: A review. J Pediatr Health Care. 2011;25:379 " “387.
  • Harnden ‚ A, Takahashi ‚ M, Burgner ‚ D. Kawasaki disease. BMJ. 2009;338:b1514.
  • Kuo ‚ HC, Yang ‚ KD, Chang ‚ WC, et al. Kawasaki disease: An update on diagnosis and treatment. Pediatr Neonatol. 2012;53:4 " “11.
  • Newburger ‚ JW, Sleeper ‚ LA, McCrindle ‚ BW, et al. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007;356:663 " “675.
  • Newburger ‚ JN, Takahashi ‚ M, Gerber ‚ MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A statement forhealth professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004;114:1708 " “1733.
  • Scuccimarri ‚ R. Kawasaki disease. Pediatr Clin N Am. 2012;59:425 " “445
  • Tacke ‚ CE, Burgner ‚ D, Kuipers ‚ IM, et al. Management of acute and refractory Kawasaki disease. Expert Rev Anti Infect Ther. 2012;10:1203 " “1215.

See Also (Topic, Algorithm, Electronic Media Element)

Myocardial Infarction ‚

Codes

ICD9

  • 429.0 Myocarditis, unspecified
  • 446.1 Acute febrile mucocutaneous lymph node syndrome [MCLS]
  • 447.6 Arteritis, unspecified
  • 420.90 Acute pericarditis, unspecified

ICD10

  • I51.4 Myocarditis, unspecified
  • I77.6 Arteritis, unspecified
  • M30.3 Mucocutaneous lymph node syndrome [Kawasaki]
  • I31.9 Disease of pericardium, unspecified

SNOMED

  • 75053002 Acute febrile mucocutaneous lymph node syndrome (disorder)
  • 31996006 Vasculitis (disorder)
  • 50920009 Myocarditis (disorder)
  • 3238004 Pericarditis (disorder)