A four year old Japanese male was brought into Emergency with 5 days of fevers, non-exudative bilaterally injected sclerae, erythematous pharynx and irritability.
Wondering about the possibility of Kawasaki Disease, I turned to check the 2017 update of the American Heart Association Scientific Statement, focusing on considering a diagnosis of Incomplete Kawasaki Disease.
- Unchanged diagnostic criteria of complete Kawasaki Disease (KD)
- Refined algorithm for evaluation of suspected incomplete KD (15-20% of cases)
- Recommended ECHO at diagnosis, and repeated at 1-2 weeks and 4-6 weeks after treatment
- Unchanged acute management– Intravenous immunoglobulin (IVIG) single dose 2g/kg over 10-12 hours. Ideally prior to day 10. Some countries continue to use high dose aspirin for varying durations.
- Additional therapeutic options are outlined for the 10-20% with persistent or recurrent fever
- New model of KD vasculopathy
What is Kawasaki Disease?
An acute, self-limited febrile illness of unknown cause, predominantly in children <5 years. It is the most common cause of acquired heart disease in developed countries. Without pathognomonic tests, we need to detect it clinically!
- Most common in Japan (where it was first described) with an annual incidence of 264.8 per 100 000 children in 2012. Estimated incidence in North America is 25 cases per 100 000 children <5 years of age per year. Australia has one of the lowest reported rates (3.7 per 100 000 <5 years of age), equivalent to 50–60 cases Australia-wide per year. It is likely that the current Australian incidence is higher.
- Highest relative risk is in Asian children, especially of Japanese ancestry
- Ratio of males to females is 1.5:1
- Predominantly affects children 6months to 4 years
- Predisposing factors have been reported inconsistently
- In Japan, the recurrence rate is 3%, and the relative risk in siblings is ten-fold higher
What is the aetiology?
We have no idea why…. BUT the resultant systemic inflammation leads to associated clinical findings: liver (hepatitis), lung (interstitial pneumonitis), gastrointestinal tract (abdominal pain, vomiting, diarrhoea, gallbladder hydrops), meninges (aseptic meningitis, irritability), heart (myocarditis, pericarditis, valvulitis), urinary tract (pyuria), pancreas (pancreatitis), and lymph nodes (lymphadenopathy).
A new model of KD vasculopathy involves three processes impacting muscular arteries. The first is a necrotising arteritis, followed by subacute/chronic vasculitis. The final process is luminal myofibroblastic proliferation.
How do we diagnose it in Australia?
Fever for 5 days or more (typically high spiking (>39°C to 40°C) and remittent)
Plus 4/5 of:
- polymorphous rash (usually within 5 days of fever onset)
- bilateral (non purulent) conjunctival injection (usually begins shortly after fever onset and often spares the limbus, an avascular zone around the iris)
- mucous membrane changes, e.g. reddened or dry cracked lips, strawberry tongue, diffuse redness of oral or pharyngeal mucosa (Oral ulcers and pharyngeal exudates are not consistent with KD)
- peripheral changes, e.g. erythema of the palms or soles, oedema of the hands or feet, and in convalescence desquamation
- cervical lymphadenopathy (> 15 mm diameter, usually unilateral, single, non-purulent and painful in anterior cervical chain)
Trickily, these children may have a concurrent viral infection, often adenovirus. Adenovirus is more likely with exudative pharyngitis and conjunctivitis and positive PCR assay. KD is more likely with erythema/swelling of hands and feet, strawberry tongue, and a desquamating groin rash. Inflammation and crusting of a recent Bacille-Calmette-Guérin (BCG) injection site may occur. Consider an alternative diagnosis to KD if there is exudative conjunctivitis, exudative pharyngitis, ulcerative intraoral lesions, bullous or vesicular rash, generalised adenopathy, or splenomegaly. What is Incomplete Kawasaki Disease? Scarily, this is so easily missed. They make up 15-20% of all cases!! Consider KD if: In addition, findings can provide support when considering Incomplete Kawasaki Disease – refer to the above algorithm. Pitfalls: What is the treatment? Coronary artery abnormalities What is the prognosis? In Summary:
Patients with incomplete KD, particularly those <6 months of age and older children, may experience significant delays in diagnosis and these children are at high risk of developing coronary artery abnormalities.
Fever and pyuria in an infant or young child may be diagnosed as a urinary tract infection, with subsequent development of rash, red eyes, and red lips attributed to an antibiotic reaction. Irritability and a culture-negative pleocytosis of the cerebrospinal fluid in an infant with prolonged fever suggestive of aseptic meningitis (or if antibiotics have been given, partially treated meningitis) may cause a diagnosis of KD to be overlooked. Cervical lymphadenitis as the primary clinical manifestation can be misdiagnosed as having bacterial adenitis. Gastrointestinal symptoms are considered for surgical causes, other physical findings of KD can be overlooked.
We’re aiming to prevent important coronary artery abnormalities. Timely (as soon as possible, ideally within 10 days) IVIG treatment reduces the incidence of coronary artery aneurysms (defined from absolute luminal dimensions) from 25% to 4%. Studies with additional therapies to IVIG have not substantially reduced this residual risk of 4%. Adverse effects are rare but include Coomb’s positive haemolytic anaemia and aseptic meningitis. The measles, mumps, and varicella vaccine should be deferred for 11 months unless at high risk (seek advice, may need repeat vaccination). If diagnosis is delayed, IVIG should still be given (after the tenth day of illness) IF there is presence of fever, or continued elevation of ESR or CRP>3, indicating ongoing inflammation. Aspirin is used with the theoretical rationale of reducing coronary artery aneurysms (although there is no well established evidence for this). In Australia, a dose of 3-5mg/kg daily from diagnosis until cardiology review at 6 weeks is routine. The newly released statement advises the administration of moderate to high-dose (80–100 mg/kg/day) aspirin is reasonable until the patient is afebrile. PAtients should receive a seasonal influenza vaccination.
Fever usually resolves within 36 hours after IVIG infusion has been completed; if not, the patient is considered to have resistance to IVIG. 10-20% of patients will not respond to the single IVIG treatment dose. There is minimal data to support therapeutic agents for the child with IVIG resistance. Repeating the IVIG dose, 3 days of high-dose pulse steroids, or 2-3 weeks of tapering prednisolone are all options. There are lower levels of evidence for infliximab and cyclosporine.
An angiographic study of 1100 patients showed coronary artery lesions in 24%, with aneurysms in 8% and a number of patients with stenoses and occlusions. Valvular regurgitation is usually mild to moderate in severity and resolves prior to follow-up. MR can occur after the acute stage from myocardial ischaemia. Patients after KD have been shown to have functional and anatomic abnormalities of the aorta with unknown long-term implications. Myocarditis is common during the acute illness but complete resolution is expected. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalised as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up.
Trickily, these children may have a concurrent viral infection, often adenovirus. Adenovirus is more likely with exudative pharyngitis and conjunctivitis and positive PCR assay. KD is more likely with erythema/swelling of hands and feet, strawberry tongue, and a desquamating groin rash.
Inflammation and crusting of a recent Bacille-Calmette-Guérin (BCG) injection site may occur.
Consider an alternative diagnosis to KD if there is exudative conjunctivitis, exudative pharyngitis, ulcerative intraoral lesions, bullous or vesicular rash, generalised adenopathy, or splenomegaly.
What is Incomplete Kawasaki Disease?
Scarily, this is so easily missed. They make up 15-20% of all cases!!
Consider KD if:
In addition, findings can provide support when considering Incomplete Kawasaki Disease – refer to the above algorithm.
What is the treatment?
Coronary artery abnormalities
What is the prognosis?