Clinicians Q & A

Undertake an echo at 6 weeks (following acute illness) and if coronaries are normal, aspirin can be stopped.

If coronary artery aneurysms persist beyond six weeks, even if they later remodel (resume normal size) aspirin should be continued (for life) as risk of major cardiac events in later life, including stenosis, are raised in this patient group.

Undertake an echo at 6 weeks (following acute illness) and if coronaries are normal, aspirin can be stopped. It’s good practice to see the patient again at 6 and 12 months – to answer questions and discuss concerns with parents. If there are no new issues, discharge to Primary care. An annual check-up for discussion of any new concerns, blood pressure check, dietary and lifestyle advice (including avoidance of cardiovascular risk factors) should be arranged. See Societi Long Term Issues leaflet for information on non cardiac issues which may arise.

Undertake an echo at 6 weeks (following acute illness) and if coronaries are normal, aspirin can be stopped. Care should be continued to 12 months (see above) if there are no ongoing cardiac issues. At 12 months, the patient should be discharged to Primary care.

Kawasaki Disease should be considered in ANY child with persistent fever for 5 days with no obvious cause. Around 25% of cases occur in children over the age of 5, 75% are under 5. Infants and young children are especially vulnerable to severe heart damage – possibly linked to delayed diagnosis and late treatment as the disease is often not considered soon enough. Older children also often experienced diagnosis delay and poorer outcomes as a result. Consider Kawasaki Disease in ANY child with persistent fever for 5 days.

Causes of fever in children are numerous and varied. Any of the following can be mistaken for Kawasaki disease or can occur prior to a case of Kawasaki Disease

Scarlet fever – remember you will NOT see red eyes in scarlet fever but you will in Kawasaki Disease.

Virus – runny nose typically associated with viral infection is not a feature of Kawasaki Disease. Remember Kawasaki can be present with a comorbid infection – do not rule out Kawasaki Disease simply based on the presence of another infection.

Meningitis – if this is suspected, treat but stay alert to the possibility of Kawasaki Disease which can present with fever and few other symptoms, especially in infants. If child is non responsive to antibiotics / treatment – maintain a high index of suspicion for Kawasaki Disease.

Persistent fever, disproportionate irritability and failure to respond to treatment for earlier diagnosed conditions should trigger continued suspicion. If Kawasaki Disease is suspected – DO NOT DELAY – treat.

Other important differential diagnoses, particularly when the illness persists beyond what might be expected for ‘typical ‘ Kawasaki Disease include systemic onset juvenile idiopathic arthritis; other chronic vasculitides such as polyarteritis nodosa or Takayasu arteritis; malignancy (we have seen lymphoma present initially like Kawasaki Disease; other connective tissue disease e.g. SLE.

IVIG and aspirin are the essential first line treatments for Kawasaki Disease. A rapid, systemic approach to the early reduction of fever and “switching off” of inflammatory processes is the aim. Corticosteroids have been shown to be very helpful as an additional therapy, in children who are in high risk groups or who fail to respond to IVIG. Children in Japan, where Kawasaki Disease is of increased frequency, have benefited from steroid use upfront.

To answer this question definitively, the KDCAAP trial – the single greatest opportunity for transformation in outcomes in Kawasaki Disease in a generation – will explore the use of oral prednisolone in addition to IVIG for unselected Kawasaki Disease cases in the UK and in Europe. We encourage recruitment to that trial which opened mid 2020. Other detailed guidance and recommendations in relation to this (in the interim) are provided in the recently published SHARE guidance which are evidence based standards of care for the management of Kawasaki Disease in Europe: https://doi.org/10.1093/rheumatology/key344

In Kawasaki Disease, a characteristic symptom is a persistent high fever which typically is unresponsive to antipyretics. Fevers may also spike and become very high or come and go. Continuous fever is typical but a child with a history of prolonged fever or 5 days with no obvious cause should raise suspicion of Kawasaki Disease.

Following Kawasaki Disease, those patients with coronary artery aneurysms which persist beyond the acute phase (even where they remodel later) need lifetime specialist care by a clinician with expertise in Kawasaki Disease.

However, there is no evidence to indicate that patients who have no lasting cardiac damage following the acute phase will experience subsequent cardiac complications linked to Kawasaki Disease, following resolution of their acute illness. Current guidance is that this low risk group with no coronary artery aneurysms persisting beyond the acute phase should be discharged at 12 months to Primary care for an annual check up for discussion of any new concerns, blood pressure check, dietary and lifestyle advise (including avoidance of cardiovascular risk factors) should be arranged. See Societi Long Term Issues leaflet for information on non-cardiac issues which may arise.

Yes. If Kawasaki Disease is suspected or confirmed based on clinical presentation, do not delay treatment – treat urgently as early treatment reduces the risk of heart damage. If treatment is started early, be prepared to give a second dose of IVIG since this is more likely.

Please refer to the flow diagram provided in recent European recommendations https://doi.org/10.1093/rheumatology/key344. Fever plus rash is a common presentation in infants. However, a persistent high fever with no obvious cause is not common and should always raise a suspicion of Kawasaki Disease. In Kawasaki Disease in infants, persistent fever may be accompanied only by a rash on presentation – but history is critical. Discuss the appearance (even if fleeting) of other symptoms with parents/carers and remain alert to the likelihood of Kawasaki Disease. 39% of infants (under 1 year) currently develop coronary artery aneurysms from Kawasaki Disease and will need lifetime specialist care. Giant coronary artery aneurysms are often seen in this patient group – this is a life changing and life threatening condition. Delay in diagnosis and treatment in infants is linked to these poor outcomes. Rapid treatment is key.

Key points:

**Continue to consider a potential Kawasaki Disease diagnosis even if commencing treatment for another diagnosis.

**If your patient does not respond as expected to treatment and maintains a high fever at 5 days – consider Kawasaki Disease and treat urgently.

**Remember that Kawasaki Disease can be present alongside other illnesses e.g Strep throat – do not discount because of presence of another illness

**Recent history is key – obtain a detailed history of symptoms, however fleeting, as these will inform you

**Although there is no diagnostic test for Kawasaki Disease, a C-reactive protein blood test can be incredibly useful for raising suspicions because the vast majority of viral infections are not associated with an elevated c-reactive protein, but in Kawasaki Disease it is high.

Kawasaki Disease with lasting cardiac damage is a life changing diagnosis. With increasing damage severity, the impact on the patient also increases. Care is needed when sharing insight about future care needs and risks ahead.

The patient group with giant aneurysms is at increased lifetime risk of major cardiac events, MI, stenosis and sudden death – with risk level increasing with severity of cardiac damage during the acute phase. Patients with persisting aneurysms and giant coronary artery aneurysms have highest levels of risk but those with small or moderate aneurysms also need to be followed up carefully.

Lifetime care must be undertaken by a clinician with active interest and expertise in Kawasaki Disease. Long term medication will be essential for these patients and a clinical regime for active review, annual tests (more frequent for the most severely affected) and regular imaging (at intervals determined by cardiac damage severity) will need to be put in place.

Patients with life changing and life threatening outcomes may require psychological support and counselling. This should be provided where needed and offered where considered helpful.

Long term cardiac management guidance for the U.K. has been developed and was published during 2019 which you can find here.  See also NHSI Patient Safety Alert (May 2016)

Societi have prepared a Long Term Issues leaflet for parents and carers of children which provides additional information and is helpful as patients adjust and resume pre-illness routines.

There are no data to guide you. Please refer to the range of dosing provided in a recent European guidance paper https://doi.org/10.1093/rheumatology/key344. The KDCAAP trial will use oral prednisolone at 2 mg per kilogram per day, tapering when the CRP is less than 10 and fever has settled. Some advise 3 days of 30mg per kilogram methylprednisolone intravenously (to a maximum of 1gm/day) once per day. Then a dose of 2mg/kg oral prednisolone per day until day 7 or until CRP normalizes; then wean over next 2-3 weeks. The key point is to make sure the CRP AND fever is settling: aim for “0 fever 0 CRP”.

Case reports exist (internationally) of infants as young as 12 days being diagnosed with Kawasaki Disease. See https://fn.bmj.com/content/86/2/f135

In the UK, infants as young as 6 weeks of age have been diagnosed and treated for Kawasaki Disease.

Research by the BPSU shows that babies under one year old tend to show the fewest symptoms but are more likely to develop coronary artery aneurysms – 39% of infants in the U.K. and Ireland who are affected by Kawasaki Disease develop coronary artery aneurysms.

Incidence is rising – because of increased disease NOT increased awareness. In Japan, for example, where Kawasaki Disease is very common and awareness is very high, there is a continued and rapid rate of increase in cases. In the UK, awareness is very low presently yet incidence is rising sharply. With increased awareness we’d expect to see subsequent increased correct diagnosis.  Currently diagnosis is often delayed, demonstrating poor awareness – Kawasaki Disease is arrived at as a diagnosis after on average 2 or 3 prior misdiagnoses (Societi Foundation diagnosis day research 2018). This does not correlate with increased awareness – but increased disease burden. Expect to see Kawasaki Disease. Be ready to treat it.

If there is suspicion of Kawasaki Disease – treat. There are risks associated with the administration of IVIG as a blood product and clinicians should always balance the risk of treatment versus non-treatment.

There are however very significant risks of delayed treatment – or non-treatment for a child with Kawasaki Disease. If Kawasaki Disease is suspected – treat.

Updated guidance published in November 2019 states:

Kawasaki disease

1.2.26 Be aware of the possibility of Kawasaki disease in children with fever that has lasted 5 days or longer. Additional features of Kawasaki disease may include:

1.2.27 Ask parents or carers about the presence of these features since the onset of fever, because they may have resolved by the time of assessment. [2019]

1.2.28 Be aware that children under 1 year may present with fewer clinical features of Kawasaki disease in addition to fever, but may be at higher risk of coronary artery abnormalities than older children. [2019]

https://www.nice.org.uk/guidance/ng143/chapter/Recommendations