Kawasaki disease

Background

• Also known as: mucocutaneous lymph node syndrome
• Vasculitis of unknown etiology
  • Likely a combination of genetic, infectious, and regional factors
• Peaks at 18-24 months
  • Rare in <4mo, >5yr
• Leading cause of acquired heart disease in children
• Coronary aneurysm more common in incomplete than in classic KD
• MIS-C has a number of overlapping clinical features, but appears to be a separate diagnosis at this time.

Vasculitis Syndrome Types

• Large vessel
  • Takayasu arteritis
  • Giant cell arteritis (temporal arteritis)
• Medium-vessel
  • Kawasaki disease
  • Polyarteritis nodosa
  • Thromboangiitis obliterans (Buerger's disease)
  • Primary angiitis of the central nervous system
• Small-vessel
  • Henoch-Schönlein purpura
  • ANCA-associated vasculitides
    • Granulomatosis with polyangiitis (Wegner's)
    • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
    • Microscopic polyangiitis
  • Cutaneous leukocytoclastic angiitis (“hypersensitivity vasculitis”)
  • Essential cryoglobulinemia, cryoglobulinemic vasculitis due to hepatitis C
  • Behçet's disease]
• Secondary vasculitides and other/miscellaneous
  • Drug-induced vasculitis
  • Serum sickness
  • Vasculitis associated with other rheumatic diseases (e.g. SLE)

Clinical Features

Strawberry tongue.

Kawasaki disease signs

(a) Strawberry tongue; (b) Conjunctival injection; (c) Periungual desquamation.

• Fever that is high, abrupt. Anyone with a fever >5 days should be considered for a Kawasaki workup.
• Rash accompanies onset of fever
  • Often seen in perineum. Presents as erythema and desquamation
  • Later there are macular and morbilliform lesions on the trunk, arms, and legs
  • No vescicles or bullae
  • Maculopapular most common; vesicles not seen
• Conjunctivitis
  • Bilateral and non-exudative in 90% of patients
  • Anterior uveitis with cell and flare in 70% of patients but is more specific and suggestive of KD
• Mucositis: Cracked lips and strawberry tongue. Vesicles or ulcers suggest a pathology other than KD
• Edema of the hands and feet
  • Desquamation around the nails in ~90%
• Lymphadenopathy is the least consistent finding in 50-75% of children
  • Usually anterior cervical
  • Less common in those under one year of age
• Cardiac complications develop early on
  • Coronary artery aneurysm development is most prevalent as fever lessens
• KD shock syndrome (7%)

Associated Symptoms

• Cardiac
  • Coronary aneurysm
    • Most develop during 3-4th week of illness
    • May lead to MI (leading cause of death)
  • Myocarditis/pericarditis
  • Pericardial effusion
  • LV dysfunction
  • Valvular dysfunction
  • Dysrhythmias
• Aseptic meningitis
• Urethritis
• Anemia
• RUQ pain, large gallbladder (hydrops on US)

Differential Diagnosis

Pediatric fever

• Upper respiratory infection (URI)
• UTI
• Sepsis
• Meningitis
• Febrile seizure
• Juvenile rheumatoid arthritis
• Pneumonia
• Acute otitis media
• Whooping cough
• Unclear source
• Kawasaki disease
• Neonatal HSV
• Specific virus
  • COVID-19 (peds)
    • MIS-C

Erythematous rash

• Positive Nikolsky’s sign
  • Febrile
    • Staphylococcal scalded skin syndrome (children)
    • Toxic epidermal necrolysis/SJS (adults)
  • Afebrile
    • Toxic epidermal necrolysis
• Negative Nikolsky’s sign
  • Febrile
    • Toxic shock syndrome
    • Kawasaki disease
    • Scarlet fever
    • DRESS syndrome
    • Cellulitis
    • Acute generalized exanthematous pustulosis
  • Afebrile
    • Alcohol intoxication
    • Anaphylaxis
    • Cellulitis
    • Dermatitis (multiple types)
    • Drug rash
    • Erysipelas
    • Erythema multiforme
    • Exfoliative erythroderma
    • Scombroid
    • Vancomycin infusion reaction

Evaluation

Work-Up

• CBC
  • Leukocytosis
  • Thrombocytosis
• Labs
• LFTs- elevated
• ESR, CRP- elevated
• Blood culture
• Urinalysis
• ECG
• Viral panel: A positive viral PCR does not exclude KD
  • 42% of children with KD had a +viral respiratory panel on initial presentation
• TTE (Coronaries, LV, valves)
  • Consider if f ESR≥ 40, CRP≥ 3, or if desquamation occurs
• Red Top "Kawasaki Serum to CBR"

Evaluation

• Clinical diagnosis

Classic Kawasaki Disease	Fever for 5 days or more plus four of the following symptoms
	1. Bilateral nonexudative conjunctivitis
	2. Mucous membrane changes (erythema, peeling, cracking of lips, "strawberry tongue," or diffuse oropharyngeal mucosal erythema)
	3. Changes of the extremities (erythema or swelling of hands/feet, peeling of finger tips/toes in the convalescent stage)
	4. Rash
	5. Cervical adenopathy (more than one node >1.5 cm unusually unilateral anterior cervical)
Incomplete Kawasaki Disease	Fever for 5 days and two to three clinical criteria of classic Kawasaki disease plus
	C-reactive protein 3.0 milligrams/L and/or erythrocyte sedimentation rate 40 mm/h plus positive echocardiogram or three or more of the following:
	1. Albumin <3 grams/dL
	2. Anemia
	3. Elevated alanine aminotransferase (ALT)
	4. Platelets >450,000/mm3 7d after fever onset
	5. White blood cell count >12,000/mm3
	6. Pyuria

Management

Assess risk for IVIG resistance (There are 4 scoring systems):

Scoring System	Nation	Enrolled patients	IVIG resistance	Sensitivity	Specificity	Risk Factors	Point	Predicted risk (score)
Egami	Japan	320	41	78	76	Age <6 mo	1	Low risk (0-2)
						Illness <4 days	1
						CRP 8+ mg/dL	1	High risk (3+)
						ALT 80+ mg/dL	2
						Platelets < 300	1
Kobayashi	Japan	528	148	86	68	Age <12 mo	1	Low risk (0-3)
						Illness days <4 days	2
						CRP >10 mg/dL	1	High risk (4+)
						ALT >100 mg/dL	2
						Platelets < 300	1
						Na <133	2
						Neutrophils >80%	2
San Diego	US	362	60	73.3	61.9	Illness <4 days	1	Low risk (0-1)
						GGT 60+ IU/L	1
						zHgb < -2	1	High risk (2+)
						Bands >20	2
Formosa	Taiwan	248	29	86.2	81.3	Lymphadenopathy	1	Low risk (0-2)
						Neutrophils >60%	2	High risk (3+)
						Albumin <3.5g/dL	1

• IVIG 2gm/kg over 12hr
  • Requires inpatient monitoring for allergic reaction
  • May increase ESR as IGs are positively charged which increases RBC sedimentation[1]
• Aspirin
  • 30-100mg/kg/day divided 4 times a day is often used
  • Has not been shown to prevent coronary artery aneurysms
  • 3-5mg/kg/day is appropriate for anti-platelet activity
  • Reye Syndrome has not been reported in association with KD treatment with aspirin
• Steroids
  • For high-risk patients
  • Decreases CAA formation if started with IVIG
  • Using it as a rescue for IVIG-resistant patients is less effective

Disposition

• Admit
• Follow-up cardiac evaluation for coronary aneurysm screening

See Also

• Pediatric fever
• MIS-C

External Links

• CDC: Kawasaki Disease

References

1. PMID: 24678327