Spotlight – Kawasaki Disease

Step 1: read A 3-month-old infant with atypical Kawasaki disease

It describes an interesting case report on atypical Kawasaki Disease (KD), which is a disease that can sometimes present a diagnostic challenge to medical professionals.

Thinking about KD in general, what would be the clinical findings you would see in a typical presentation?

You would need to consider KD in a child typically between 6 months of age and 5 years old, who presents with fever persisting for at least 5 days as well as 4 out of the 5 clinical criteria below:

Bilateral non-exudative conjunctivitis presents in 90% of patients with KD. This can be complicated by uveitis.
Mucositis: strawberry tongue and cracked red lips are typical findings as well as erythema of oropharynx. There are usually no vesicles or tonsillar exudate.
Polymorphous rash without vesicles, or crust. Usually starts with erythema and desquamation in perineal area, then macular/morbilliform or targetoid lesions spreading to trunk and extremities.
Extremity skin changes: oedema to dorsum of hands and feet, erythema of palms and soles progressing to desquamation
Cervical lymphadenopathy >1.5cm is the least consistent feature of KD, but if present, it usually involves the anterior cervical nodes. It tends to be unilateral and tender.

There are some other features that can be found on examination or history that are not part of the diagnostic criteria above, but can aid in the diagnosis. These include: arthritis, cardiac findings, sterile pyuria, dysuria, aseptic meningitis.

Once diagnosed, it is important to initiate prompt treatment, ideally within the first 10 days of illness. This is to prevent serious complications from occurring. What complications of KD are you aware of?

The main concern with KD is the potential for coronary involvement, which has a significant impact on morbidity and mortality. This includes coronary artery aneurysms, which can lead to cardiac ischaemia and coronary occlusion.

Other complications, due to systemic inflammation of medium-sized arteries, can include: hepatitis, pericarditis, pneumonitis.

There is also a 1:100 risk of recurrence of disease, according to the AHA.

What would be your management of a patient presenting with clinical signs of KD?

KD is mainly a clinical diagnosis. However, there are some laboratory findings that can support the diagnosis if unclear or atypical, such as our patient in the case report. These include:

CRP, ESR: elevated in setting of systemic inflammation
FBE: thrombocytosis, elevated WCC, anaemia
LFTs: elevated transaminases
Urinary microscopy: sterile pyuria

It is important to perform an echocardiogram on all patients with a suspected diagnosis of KD. This is both to establish baseline for follow up post treatment, as well as to assess for any coronary artery complications.

Once diagnosed, the treatment consists of:

Single dose of IVIG at 2g/kg on diagnosis, to prevent coronary artery complications. This dose can be repeated in case of failure to respond to the first dose.
Aspirin 3 to 5mg/kg daily for at least 6 weeks and continued until a normal follow-up echocardiogram.

Further immunosuppressants including glucocorticoids and cyclosporine have been used in some cases.

Every patient diagnosed with KD should have a follow-up echocardiogram at 6 weeks post treatment, as well as longer term follow up, especially in the event of cardiac complications from the disease.

Live vaccines needs to be postponed at least 11 months following treatment with IVIG.

As noted in the case report, 3 months of age is outside of the typical age rage for KD. What clinical features in an infant would make you consider a missed diagnosis of KD?

< 6 months of age with prolonged fevers and irritability without any other features.
Prolonged fever and unexplained aseptic meningitis.
Prolonged fever and cervical adenitis, not responding to antibiotics.

It is important to note that in relation to this case, there were skin changes at the inoculation site of her BCG vaccine (redness and crust). This is a finding that has been reported on multiple reviews and research, and could be an important sign to note if present in an infant younger than 6 months of age, to help in the diagnosis.

Prolonged/persistent fever is an important sign in the clinical diagnosis of KD. What differential diagnoses would you need to consider in a paediatric patient with prolonged fever?

There is a wide list of differential diagnoses in a child with prolonged fevers. It is important to take into consideration the environmental locale of the patient, including returned travellers, we would need to consider tropical diseases as part of our differential.

Generalised infection (EBV, CMV, Brucellosis, Typhoid fever, leptospirosis, toxoplasmosis, hepatitis, bacteraemia, sarcoidosis, tuberculosis, UTI, malaria, scarlet fever, Q fever, Ross River, other arboviral infections, …)
Localised infection (infective endocarditis, osteomyelitis, CNS infections, …)
Rheumatologic diseases such as Juvenile Idiopathic Arthritis, SLE
Neoplasms such as leukaemia and lymphoma
Others: HLH, immunodeficiency, hereditary periodic fever syndromes, …

Example where sterile pyuria is seen

Kawasaki disease
Urinary tract infection where urine sample taken after antibiotic treatment
Intra-abdominal infection – proximity of infection to bladder causing mucosal irritation
Genitourinary tuberculosis

A febrile neonate, aged 20 days, presents to your practice. Your examination reveals no clinical focus of infection. What investigations would you carry out?

Sepsis kills. Particularly in neonates with poor baseline reserves, it must be taken seriously.

Full blood count, CRP – monitor inflammatory markers
Blood culture
Blood glucose level – hypoglycaemia is a complication of sepsis, particularly in neonates who have low glycogen stores
Venous blood gas, including lactate
Urea, creatinine, electrolytes – monitor renal function
Urine microscopy, culture, sensitivities – gold standard remains to be a suprapubic aspirate; otherwise: in-out-catheter, clean-catch sample
Lumbar puncture – unless contraindicated (suspected raised intracranial pressure, coagulopathy, skin infection at site, acute spinal injury)
Coagulation studies – disseminated intravascular coagulopathy (DIC) is a complication of sepsis.
Chest x-ray can be considered if clinical concerns on history or examination

References

McCrindle, BW. et al, (2017), Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-e999. doi: 10.1161/CIR.0000000000000484. Epub 2017 Mar 29. https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000484

Saguil, A., Fargo, M. and Grogan, S. (2015), Diagnosis and management of kawasaki disease. Am Fam Physician, 15;91(6):365-71. https://www.aafp.org/afp/2015/0315/p365.html

Singh, S. , Jindal, A. K. and Pilania, R. K. (2018), Diagnosis of Kawasaki disease. Int J Rheum Dis, 21: 36-44. doi:10.1111/1756-185X.13224

Stasiak, A. & Smolewska, E. Rheumatol Int (2019) 39:1069. Retrospective study of the course, treatment and long-term follow-up of Kawasaki disease: a single-center experience from Poland. https://doi.org/10.1007/s00296-019-04286-9

UpToDate
The Royal Children’s Hospital Melbourne – Clinical Practice Guidelines
American Heart Association
Nelson Essentials of Paediatrics 8th edition