1st Revision: Nabil Jawlakh How has a disease discovered in just the last few decades become the leading cause of childhood heart disease? More importantly, can it be cured? This article will answer these questions and more, discussing the causes, treatments and symptoms of Kawasaki disease.
Kawasaki disease was discovered in the mid-late 20th century and is famous for causing children to develop a ‘strawberry tongue’. It is a type of vasculitis, affecting blood vessels within the body. Whilst rare, it is well-known across the world and is often curable within 48 hours when early treated.
Continue reading to learn the facts about Kawasaki disease including its symptoms, risk factors and specific treatment methods.
Overview
In January 1961, Tomisaku Kawasaki was working in the Japanese Red Cross Central Hospital when a four-year-old child was admitted with unexplained fever and abdominal pain. The Tokyo-based doctor noted the child’s red tongue, cracked lips, swollen extremities and whole-body rash, subsequently, he started treating the symptoms and battling the mystery disease for the next month.
He was successful, however, over the next five years Kawasaki would encounter fifty more cases of this unknown syndrome. After meticulously describing and outlining the symptoms of the disease, he eventually coined it mucocutaneous lymph node syndrome, or Kawasaki disease.1
Kawasaki disease is a syndrome predominantly found in children under the age of five years old. It has unknown origins and disease mechanisms, however, there are some known genetic risk factors.2
The disease is a form of vasculitis, where blood vessels within the body become inflamed. If this inflammation is affecting coronary arteries, surgery may be required to prevent coronary artery aneurysms. If left untreated, it is through this mechanism that Kawasaki disease can prove fatal.3
Children suffering from a confirmed case of Kawasaki Syndrome should be treated in a hospital. Typically, when caught early, Kawasaki’s is easily treatable and most patients can expect to make a full recovery.2,3
Since its first description in the 1960s,4 the prevalence of Kawasaki disease has been steadily increasing - particularly in East Asia. The reason behind this increase, and why the disease only appeared in the 1960s and 70s, is unclear. The prevailing theory is that before this period the disease was commonly misdiagnosed, mistaken for diseases such as scarlet fever or measles.1
Overall, Kawasaki disease is rare. Depending on the country, it affects between 2-53 children under five per 100’000. This excludes Japan, which experiences 134 cases per 100’000 children under five.5
Causes of kawasaki disease
The exact cause of Kawasaki disease is not known. Over the past two decades, scientists have made significant progress in isolating potential explanations for the disease mechanism.
The current leading theory is that the disease is caused by an abnormal immune response due to infection. The cause of the abnormal response is most likely genetic.6
Signs and symptoms of kawasaki disease
The disease is primarily characterised by a high-spiking fever which is not responsive to common treatments (paracetamol or ibuprofen).
Following the fever, children commonly present with at least four of the following symptoms:6
- Non-specific rash
- Conjunctivitis (inflammation of the eyes, causing a red colour)
- Red lips and mouth
- Red, rough tongue (strawberry tongue)
- Swollen, red hands and feet
- Swollen lymph glands in the neck
- Joint pain
The typical duration of the disease is 1-2 weeks with treatment. Without treatment, the expected duration is 3-4 weeks.6
The fever should subside over the course of the illness. If it does not, it is an indication of cardiac or coronary artery inflammation. This can lead to a coronary artery aneurysm.
If you suspect a child to be suffering from Kawasaki disease, see the child’s healthcare provider as soon as possible. If they suspect a confirmed case, the child will be hospitalised for treatment.2
Management and treatment for kawasaki disease
The majority of cases of Kawasaki disease will resolve themselves without intervention, however, it is best to follow up as a precautionary step and receive a full course of treatment to avoid complications and accelerate recovery time.
Kawasaki disease should be treated in a hospital. It is typically treated with high doses of intravenous immunoglobulin (IVIG) and aspirin. In the majority of cases, 1-2 doses of IVIG over the first ten days of the disease would be sufficient for each child.8
Within the first week of treatment, the fever should subside on its own and the risk of the child developing prolonging cardiac or coronary artery damage is drastically reduced.
What is intravenous immunoglobulin (IVIG)?
Intravenous immunoglobulin (IVIG), also known as gamma globulin, is essentially a mix of antibodies derived from thousands of health donors. This mix is used to help regulate and normalise a compromised or malfunctioning immune system.9
In the case of Kawasaki disease, the IVIG counters the abnormal immune response from the body, reducing the inflammation of the blood vessels.8 In turn, this drastically reduces the child’s chances of a coronary artery aneurysm.
What is aspirin used for?
Often IVIG will be coupled with aspirin in high doses when treating Kawasaki disease. Aspirin (or salicylate) is used in Kawasaki disease to help prevent coronary artery aneurysms and cardiac damage.10 It does this by reducing blood platelet counts to avoid blood clots forming.
The use of aspirin as a treatment for Kawasaki disease is controversial. Firstly, some studies show that aspirin has a limited effect on the probability of a coronary artery aneurysm.10 Secondly, aspirin is generally avoided in children outside of Kawasaki disease, as it is associated with the development of Reye syndrome and liver damage.3
Diagnosis of kawasaki disease
There is no reliable diagnostic test for Kawasaki disease and its similarity to other childhood illnesses leaves some patients vulnerable to a delayed diagnosis.
Most medical institutions will consider a confirmed case of Kawasaki disease if the patient displays five days of high fever and at least four other symptoms associated with the disease.2
This can lead to issues with diagnosis, where patients who do not present with the required number of symptoms remain undetected for over ten days, potentially leading to cardiac or coronary artery damage.
Furthermore, there are multiple serious paediatric illnesses which can be easily conflated with Kawasaki disease during a diagnosis. These include scarlet fever, measles, juvenile idiopathic arthritis and more.3
Making progress in the field of Kawasaki diagnoses is complicated and challenging. As this disease affects children below the age of five, there are significant ethical constraints to obtaining biopsies from arteries or lymph nodes. Access to the coronary artery is equally as challenging and is not possible to study whilst the patient is alive. The disease can also not be accurately replicated in any animal model, making the development of a diagnostic test a particularly difficult task.
Risk factors
Age
Kawasaki disease affects almost exclusively children below the age of five years old.
Sex
It appears to affect males more than females at a ratio of 1.5:1. Males may be more likely to be genetically predisposed to developing the disease.
Ethnicity
Kawasaki disease is most common in East Asia, specifically in Japan. The European, African and American continents still experience cases, but at a significantly lower rate.
Complications
Complications from Kawasaki disease arise from two main factors:
Firstly: the progression of the vasculitis to the coronary artery. This risks a coronary artery aneurysm, heart disease or, in rare cases, a heart attack. If untreated, the risk of a coronary artery aneurysm is 25-30% in patients who experience artery inflammation. With treatment, the risk of complications directly from the disease falls to less than 1%.3
Secondly: Reye’s syndrome (or other complications) due to aspirin treatment. This syndrome can arise due to the use of aspirin in minors, causing liver and brain damage. The exact cause is unknown; however, it typically follows a viral infection and has been consistently linked to aspirin use.11
FAQs
How can I prevent kawasaki disease
Kawasaki disease cannot be prevented.
When should I see a doctor
If you suspect a child has Kawasaki disease, it is important to see a doctor as soon as possible to confirm the case and begin treatment.
Summary
Kawasaki disease is a modern vasculitis disease which continues to be shrouded in a considerable amount of mystery. Overall, whilst the exact mechanisms remain unknown, the disease is overwhelmingly treatable and the majority of patients can expect to make a full recovery.
Whilst Kawasaki disease is rare, and concentrated mainly in Japan, increased awareness of the disease can help to reduce the time to diagnosis and treatment across the globe.
If you suspect your child of suffering from any of the symptoms associated with Kawasaki disease, speak to your doctor as soon as possible.
References
- Burns JC. History of the worldwide emergence of Kawasaki disease. Int J Rheum Dis [Internet]. 2018 Jan [cited 2023 Apr 21];21(1):13–5. Available from: https://onlinelibrary.wiley.com/doi/10.1111/1756-185X.13214
- Kawasaki disease [Internet]. nhs.uk. 2018 [cited 2023 Apr 21]. Available from: https://www.nhs.uk/conditions/kawasaki-disease/
- Pinna GS, Kafetzis DA, Tselkas OI, Skevaki CL. Kawasaki disease: an overview: Current Opinion in Infectious Diseases [Internet]. 2008 Jun [cited 2023 Apr 21];21(3):263–70. Available from: http://journals.lww.com/00001432-200806000-00009
- Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children]. Arerugi. 1967 Mar;16(3):178–222.
- Newburger JW, Taubert KA, Shulman ST, Rowley AH, Gewitz MH, Takahashi M, et al. Summary and abstracts of the seventh international kawasaki disease symposium: december 4–7, 2001, hakone, japan. Pediatr Res [Internet]. 2003 Jan [cited 2023 Apr 21];53(1):153–7. Available from: https://www.nature.com/articles/pr200326
- Rowley AH, Baker SC, Orenstein JM, Shulman ST. Searching for the cause of Kawasaki disease — cytoplasmic inclusion bodies provide new insight. Nat Rev Microbiol [Internet]. 2008 May [cited 2023 Apr 21];6(5):394–401. Available from: http://www.nature.com/articles/nrmicro1853
- Rowley AH, Shulman ST. The epidemiology and pathogenesis of kawasaki disease. Front Pediatr [Internet]. 2018 Dec 11 [cited 2023 Apr 21];6:374. Available from: https://www.frontiersin.org/article/10.3389/fped.2018.00374/full
- Oates-Whitehead RM, Baumer JH, Haines L, Love S, Maconochie IK, Gupta A, et al. Intravenous immunoglobulin for the treatment of Kawasaki disease in children. Cochrane Vascular Group, editor. Cochrane Database of Systematic Reviews [Internet]. 2003 Oct 20 [cited 2023 Apr 21];2021(12). Available from: http://doi.wiley.com/10.1002/14651858.CD004000
- Arumugham VB, Rayi A. Intravenous immunoglobulin(Ivig). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Apr 21]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK554446/
- Baumer JH, Love S, Gupta A, Haines L, Maconochie IK, Dua JS. Salicylate for the treatment of Kawasaki disease in children. Cochrane Vascular Group, editor. Cochrane Database of Systematic Reviews [Internet]. 2006 Oct 18 [cited 2023 Apr 21];2010(1). Available from: http://doi.wiley.com/10.1002/14651858.CD004175.pub2
- Sanati F, Bagheri M, Eslami S, Khalooei A. Evaluation of high-dose aspirin elimination in the treatment of Kawasaki disease in the incidence of coronary artery aneurysm. Ann Pediatr Card [Internet]. 2021 [cited 2023 Apr 21];14(2):146. Available from: https://journals.lww.com/10.4103/apc.APC_206_20
- Hurwitz ES. Reye’s syndrome. Epidemiologic Reviews [Internet]. 1989 [cited 2023 Apr 21];11(1):249–53. Available from: https://academic.oup.com/epirev/article-lookup/doi/10.1093/oxfordjournals.epirev.a036043
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