Kawasaki Disease aka Mucocutaneous Lymph Node syndrome
(CHLA Kawasaki Map),
Evaluation flowsheet of atypical disease
Table 1. Principal Diagnostic Criteria for Kawasaki Disease
Fever x 5 days + 4 of the following 5. Fever is abrupt onset, high-spiking, remittent. Duration is 11 days without treatment, resolves within 2 days with treatment.
B/L conjunctival injection; starts early, hours after fever onset. Limbic sparing (except if has associated uveitis); painless; do not get discharge
Mucous: erythema of mouth/pharynx, strawberry tongue (hyperpapillated), red, bleeding, cracked lips; do not get discrete ulcers or exudate; also within hours to a day after fever onset
Cutaneous: induration/swelling of hands/feet, erythema of palms/soles; early in the febrile state. (desquamation first seen around nail beds of fingers, then toes and seen in subacute stage 2-3 weeks later, not acute); Beau's lines - growth arrest lines; transverse grooves across nails 1-2 mos after disease.
Rash (polymorphous exanthem, truncal, maculopapular, erythema multiforme, scarlatiform; NO vesicles or bullae; petechiae are rare); starts within 3 to 5 days of fever onset; "bad diaper rash";
Cervical LAD (>1.5 cm, nonfluctuant); only in 50% of patients. Enlarged, unilateral, tender. Cervical, submandibular; like eyes and oral cavity, NOT purulent. Resolves with resolution of fever.
Table 2. Associated Clinical Features of Kawasaki Dz
Clinical
·
Extreme irritability
·
Arthralgia, arthritis
·
Aseptic meningitis
·
Cardiac disease
·
Hepatic dysfunction
·
Gallbladder hydrops
·
Diarrhea
·
Otitis media, pneumonia
Laboratory
·
Neutrophilia with immature forms
·
Elevated ESR, CRP
·
Thrombocytosis (nl in week 1, >1
million in week 2-3), normocytic anemia
·
Proteinuria
·
Sterile pyuria (week 1: 1/3 of pt
have sterile pyuria of urethral origin, may be intermittent)
·
Elevated levels of serum
transaminases. ANA neg. RF neg.
…a
generalized vasculitis of unknown cause that is a leading
cause of acquired heart disease in children who live in the United States.
Consider Kawasaki in febrile children with cervical adenitis,
unresponsive to ABX, without alternative ABX.
1 . Epidemiology. Approximately 80% of patients are younger than 4 years of age; median age 2 y.o.; the occurrence of this disease after 8 years of age is unusual. Less than 2-3% of patients have recurrences, siblings 2%. Children of Asian ancestry experience the highest incidence. The greatest number of cases occur in the winter and spring, and epidemics have been reported. Person‑to‑person transmission has not been documented. Rare in age < 3 mos, due to protective maternal AB.
2. Etiology. The cause remains unknown. Clinical and epidemiologic characteristics suggest an infectious agent. Infection may lead to an immune‑mediated disease in certain genetically predisposed children. ?ubiquitous infectious agent hitting genetically predisposed individuals (adults immune, young infants protected by maternal ab)
3. Clinical features. The diagnosis is established by the presence of fever and at least four of the five other principal clinical criteria when no other explanations for the illness exist (Table 1). Atypical cases that do not fulfill clinical criteria but are associated with risk of coronary artery aneurysms have been described. Atypical disease is more common under 1 year of age. Other clinical and laboratory findings associated with Kawasaki disease are presented in Table 2. Young adults may present with ischemic heart disease, as sequela of unrecognized disease in childhood.
Cardiovascular: EKG changes (arrythmias, abn Q waves, prolonged PR and QT, low voltage, poor contractility)
GI: V/D/abd pain, hydrops of gallbaladder, mild jaundice
Joints: Arthralgia/ Arthritis
Neuro: IRRITABILITY is striking! CN 7 palsy, asceptic meningitis
Pulm infiltrates/ pneumonitis
Clinical Phases
1-2 weeks - acute febrile phase (fever, conjuctivae, oral, hand/foot, rash, LAD, meningits, diarrhea, myocarditis common at this time +/- pericardial effusion. Coronary arteritis may be active, but aneurysms are generally not visible by echo
subacute phase: from fever onset to 1 month: fever, rash, LAD resolve. Thrombocytosis, digit desquam, coronary artery aneurysms usually develop at this time
convalescent stage, ends by 6-8 weeks: clinical signs are gone. ESR still abnormal.
4. Diagnosis and differential diagnosis. No specific diagnostic test is available. The differential diagnosis includes scarlet fever (responds rapidly to PCN, no elevated ESR, CRP, GABHS+ strep throat (although pt may also be a carrier)), staphylococcal scalded skin syndrome,toxic shock syndrome, Rocky Mountain spotted fever, leptospirosis, Stevens‑Johnson syndrome, drug reactions (periorbital edema), and juvenile rheumatoid arthritis, measles (exudative conjunctivitis, Koplik, severe cough, rash is behind ears, confluent as fades, residual brownish hue, also has swelling of hands, feet. Get measles IgM titer.). Also in ddx, rare: Macrophage Activation Syndrome
Labs are not diagnostic. Helpful studies include: ESR, CRP, Chem panel, CBC/diff, UA
ESR and CRP: Primary markers for ongoing inflammation. Elevation of these is nearly UNIVERSAL, and returns to normal at 6-10 weeks. ESR >40 or CRP >3 is significant. These are REALLY useful in the incomplete cases…
UA: sterile pyuria from urethritis
CSF: aseptic meningitis picture
Chem 14: hyponatremia, elev ALT and GGT, decr albumin, cholesterol, HDL, apolipoprotein A1
CBC: WBC >15. Hb > anemia of chronic disease.
Platelets (by week):
normal
elevated
peaks at 700K
normal again in weeks 4 to 8.
Common pitfalls in diagnosis
F, unilateral LA, started on abx, then rash. Rash thought to be allergic rxn
F, rash, CSF WBC elevated. Thought to be viral meningitis rather than KD.
Any child with F/ rash/ non-purulent pink eye, ALWAYS consider KD.
Incomplete KD (formally called “atypical KD”)
More common in young infants <1 y/o and older kids/ adolescents
They are therefore more at risk of CAA due to delay in diagnosis
Evaluation flowsheet of atypical disease
Red Flags that this may not be Kawasaki Disease…
Kawasaki dz vs Viral (very general): In viral infection, ESR/CRP often normal, platelets normal by day 7 (in Kawasaki >450), WBC nl with lymphocyte dominance (vs elev WBC and left shift in Kawasaki's).
Platelets not elevated after day 7 (in the absence of DIC)
ESR/ CRP not elevated after day 7
Low WBC or predominance of Lymphs
Exudative process of the eyes, oral cavity, or lymph nodes
Discrete oral lesions
Vessicular/ bullous skin eruption
Generalized lymphadenopathy
5. Therapy. High doses of aspirin are given during the acute phase to counter inflammation. After the child is afebrile, low doses of aspirin are given for their antithrombotic effect. Intravenous gamma globulin administered within the first 10 days of illness can significantly reduce the risk of coronary artery abnormalities.
Aspirin
During acute phase 80-100mg/kg/d in 4 divided doses
Switch to low dose when afebrile x 48-72 hours. Some institutions also wait until 14 days after onset of illness.
Low dose 3-5mg/kg/d until at least 6-8 wks
D/C if no Coronary artery aneurysm at that time, or continue possibly indefinitely
2g/kg single infusion in first 7-10 days of illness
If after 10 days, still give it IF: Still has fever without other cause, Has (+) Coronary artery disease and high CRP/ ESR
Retreat with IVIG in 36 hours if still febrile
Long term treatment
None needed if (-) ECHO at 6-8 week f/u visit
Only antiplatelet therapy if solitary small aneurysm
Add warfarin if have large or multiple aneurysms for antithrombotic effect
Add B-blocker if have coronary artery occlusion and at higher risk of MI
6. Complications. Occasional recurrences (3%), or cases in siblings (2%). Kawasaki disease is usually self‑limited, but coronary artery abnormalities including aneurysms, develop in 15-20% of untreated patients. Coronary dilatation is first detectable by day 10, usually within 4 weeks of onset; aneurysms between day 19-25 (weeks). Fate of coronary aneurysms: 50% resolve angiographically 5-18 mos. If persistent 50% get smaller, 1/3 have no aneurysms. Fatalities are rare and occur with myocardial infarctions secondary to thrombosis within a coronary artery aneurysm, during week 3-4. Young infants are at greatest risk of cardiac disease. You may also see aneurysms of the middle sized arteries, most notably the axillary and iliac arteries, but also celiac, femoral, renal, brachial.May also see pancarditis, poor LV function, mitral valve regurgitation.
Followup
50% of aneurysms regress
F/U ECHO at 6-8 weeks
If no CA disease at the 6-8 weeks visit, then reassess CV risk factors every 3-5 years
If has small CA lesion at the 6-8 week visit: normal activity, stress test at 10y/o and then Q 2yrs, Cont with ASA low dose
If has larger CA lesions: Cards eval with ECG Q 6 months, Annual stress testing, Cardiac cath 6-12 months after diagnosis; Antiplatelet therapy with warfarin
Risk Stratification
1.No coronary artery changes
2.Transient ectasia for only 6-8 weeks
3.One small-medium aneurysm
4.One or more large aneurysms
5.Coronary artery obstruction
Things to think about in KD kids who got IVIG and Aspirin
IVIG: Need 11 months after IVIG for live vaccines to “take” (can give the vaccines in less than 11 months, but should repeat it again after that time to ensure immunity)
ASA: Watch for risk of Reyes Syndrome
ASA: No high-impact collision sports due to risk of bleeding
ASA: Avoid ibuprofen because it will counter the antiplateleteffect of ASA
Take home points –areas of focus previously on Boards
Know the criteria COLD
Know the algorithm for incomplete KD (new)
Use the labs, CRP and ESR in unclear cases
Know the treatment in cases that are delayed in diagnosis (the pt who presents with aneurysms but is now 14 days out and afebrile…)
Know when to go from high to low dose ASA
Know criteria that make KD less likely (exudative pharyngitis…)
Review questions
5 month old with fever x7 days, of unknown etiology, no other symptom.
2 y/o in day #12 of fever with peeling extremities and 2cm unilateral cervical LN. Had h/o resolved conjuncitivitis and red lips.
3 y/o with h/o recent febrile illness that lasted 10 days, now 2 days later afebrile. Had rash, and now has peeling extremities
4.Name the 7 “Red Flags” that point the diagnosis away from Kawasaki Disease.
Name the order in which the criteria appear.
Name 3 additional labs besides ESR/ CRP that can influence the decision to treat KD in patients who have incomplete disease, high ESR/ CRP, but normal ECHO.
Answers
Check ESP/ CRP. If + check ECHO
Do ECHO. IVIG since still febrile. High dose aspirin until AF for 48-72 hours, then change to low dose.
ESR, CRP, platelets (all should be elevated). ECHO. If both are positive (pt has elevated ESR/ CRP and has CAA), then give IVIG. Low dose aspirin since now afebrile for 48 hours.
NMS Pediatrics
Pediatric Annals 34(1) Jan 2005
CHLA Board review 2005 (AAP/ AHA Endorsed Clinical Report “Diagnosis, Treatment,
and Long-Term Management of Kawasaki Disease for Health Professionals From the
Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on
Cardiovascular Disease in the Young, American Heart Association” Pediatrics,
Vol. 114 No.6 December 2004)
Commentary by
Mobeen H. Rathore MD, FAAP
Pediatric Infectious Diseases and Immunology, University of Florida Health
Science Center, Jacksonville, FL
Prior studies of the use of corticosteroids for KD have produced conflicting results.1-5 They have, however, been flawed by retrospective, non-randomized, non-blinded design and non-standard IVIG dosing. The current investigation is the first randomized (although not blinded) study of corticosteroid use in combination with the standard treatment of KD (IVIG/ASA). Although the number of subjects was small, detrimental effects were not noted whereas benefits of corticosteroids, including shorter hospital stay and duration of fever, were seen. The clinical significance of the lower mean temperature during the first day of IVMP therapy and lower acute phase reactants (ESR, CRP) 6 weeks after IVMP therapy, however, require further clarification. No differences in coronary dimensions were noted between the 2 treatment groups at the 6-week visit. The accompanying editorial cautions against the use of corticosteroids as a routine management strategy and supports a second dose of IVIG as the preferential rescue therapy.6 This seems to be the prudent strategy until large, multicenter, prospective, randomized, blinded studies confirm or refute the benefit of corticosteroid use in the management of KD. Until that time, corticosteroids should be used as adjunctive therapy of unusual and severe cases of KD,7 and not routinely used for initial management
References