Kawasaki disease is a vasculopathy that mostly affects children in the vulnerable age group. The disease is also referred to as mucocutaneous lymph node syndrome due to the involvement of nodes and mucosal erythema. The vessels that are normally affected are small and medium-sized ones. The majority of the individuals affected by Kawasaki disease get better without treatment, but a small percentage require treatment to prevent complications (Ramphul & Mejias, 2018). It involves the coronary artery, which is an important vessel that supplies blood to the heart muscle, thus explains the pathologies that arise in the heart, such as an aneurysm. It is the commonest acquired heart disease of childhood. The incidence is higher at least ten times in children of Japan origin compared to those of other countries. The annual incidence of Kawasaki disease is at 19 per 100,000 children under five years. At least 80% of the reported cases occur under five years. There is almost no difference in the gender distribution cases.
History
It was discovered in the 1960s and named after Dr. Tomisaku Kawasaki. A 4-year-old child presented with fever, conjunctival injection, strawberry tongue, and extensive redness of the oral cavity that had been there for a fortnight. He also had the enlargement of the cervical nodes, which initially were on the left side, then later involved the right side. Two weeks later, the skin peeling off the extremities occurred. The case was perceived to be either atypical scarlet fever or Steven-Johnson syndrome (Ramphul & Mejias, 2018). The following year, six children under the age of five presented with similar symptoms. The number of cases rose over the years and this lead to the doctor publishing an article on the disease. A breakthrough occurred whereby funds were allocated for research, and coronary angiography was embraced to aid in diagnosis. The disease was initially discovered in Japan, but cases have been reported worldwide over the years.
Delegate your assignment to our experts and they will do the rest.
Immunological Impact
There are various theories that explain the pathophysiology of Kawasaki disease but are not understood well. There is a proposed theory whereby there is a hypersensitive reaction of T cells to an unrecognized antigen, which will trigger an immune response. The antigen is thought to be similar in structure to the vascular wall. The activation of B cells causes production of antibodies. The formation of autoantibodies to both the smooth muscle cells and the endothelial cells play a significant role in the development of vasculitis (Rowley & Shulman, 2018). The infiltration of the vascular wall with monocytes and neutrophils is responsible for arteritis. There is the production of cytokines and interleukins such as tumor necrosis factor α (TNF-α), interleukin-6, which propagate promote the cell interactions that cause endothelial injury. There is a genetic component that makes one susceptible to developing the disease and the extent of the disease. The genes involved are those that help to regulate the inflammatory cascade (Hara et al., 2016). During an acute illness, the patients have a higher number of toll-like receptor messenger RNA levels and activation of the genes in the IL-1 pathway. The innate immune system plays a great role in the pathogenesis of the disease. Kawasaki is a systemic vasculitis.
Signs and symptoms
Signs and symptoms play a significant role in the diagnosis of Kawasaki. The American Heart Association (AHA) published diagnostic criteria for classic (typical) and incomplete (atypical) Kawasaki disease. Incomplete or atypical patients are at risk of developing Kawasaki disease but do not meet all the criteria for diagnosis; laboratory testing and echocardiography are used to determine such types of patients (Ramphul & Mejias, 2018). There is a specific criterion for diagnosing someone with classic Kawasaki disease. Fever has to be present and has to be there for a minimum of five days with at least mucocutaneous changes involving the oral mucosa and presence of a strawberry tongue; a rash that is maculopapular sparing the face, conjunctival injection, generalized redness involving the extremities and enlargement of the cervical nodes. This is similar to the presentation with the first patient to present with Kawasaki disease in 1961.
Another criterion for diagnosis is a patient who has a fever with the involvement of the coronary arteries confirmed with echocardiography. There are some laboratory investigations done like full blood count, which is featured with anemia, leukocytosis, and thrombocytosis; deranged liver enzymes, elevated biomarkers of inflammation like high C-reactive protein level, low albumin levels. Some patients present with other symptoms like nausea, vomiting, and loose bowel movements that cause electrolyte abnormalities like low sodium, which warrants electrolyte replacement. The inflammation is generalized in the whole body, causing different organs to be inflamed. There is the involvement of both small and large joints in the body (McCrindle et al.,2017). Hepatitis and urethritis do occur but are rare. There is the involvement of the central nervous system where the infants present with meningism signs such as irritability, bulging fontanelles, photophobia, and increased tone. There may be nerve involvement, especially the seventh cranial nerve.
Cardiovascular abnormalities.
Cardiovascular findings occur due to the involvement of the valves, heart muscle, and the coronary artery, which have contributed greatly to claiming the lives of many children. On examination, the children may have raised heart rate and some murmurs during the acute phase (McCrindle et al., 2017). The mitral valve is the most common involved valve; thus, valvular dysfunction is a common complication in children. Some of the electrocardiograph changes noted include abnormal heart rhythms. The coronary arteries are involved and develop thrombosis and aneurysms.
Classic (typical) criteria
Fever is usually high-grade fever and persistent (>39°C to 40°C). The fever can continue for more than three weeks without appropriate treatment (Singh et al., 2018). The patients will present with the symptoms as explained above. Some of the differential diagnoses for Kawasaki include Stevens-Johnson syndrome, drug reaction, juvenile idiopathic arthritis, staphylococcal scalded skin syndrome, streptococcal scarlet fever, toxic shock syndrome, and viral infection.
Incomplete (atypical) criteria
Atypical Kawasaki disease is seen in 10% of the patients and mostly in infants and older children. The atypical disease is considered in patients with a fever for at least five days, with at least two of the main clinical features as stated above. Echocardiography is an essential diagnostic tool in infants under six months who have a fever of unknown origin for seven days and above with laboratory evidence of systemic inflammation (Zhu et al., 2016). Echocardiography helps to detect cardiac artery complications such as coronary aneurysms. Magnetic resonance coronary angiography is vital for evaluation of the extent of stenosis of the coronary artery after treatment and localize thrombi.
Treatment
Treatment should be initiated as soon as the diagnosis is made. Patients who meet the criteria should be treated with intravenous immunoglobulin at a dose of 2 g/kg given as a single intravenous infusion during the acute onset of the illness. The use of intravenous immunoglobulin helps reduce the occurrence of coronary artery abnormalities (McCrindle et al., 2017). The mode of action of intravenous immunoglobulin is not clearly understood. It is attributed to reducing cytokine production and antibody synthesis, enhancing T cell regulation activity, and neutralizing toxins. Inflammation is predominant during active disease.
There is a role of aspirin in preventing thrombi formation and reducing inflammation. The recommended dose is 25 mg per kg four times in a day until the patient is afebrile for 72 hours. The amount is then readjusted to 3 to 5 mg per kg daily for six to eight weeks after disease onset (McCrindle et al., 2017). For those with coronary complications, aspirin is prescribed for life. Therefore patients should be on intravenous immunoglobulin at 2 g/kg as a single infusion and aspirin. Coombs-positive hemolytic anemia and aseptic meningitis have been reported with the use of intravenous immunoglobulin. Aseptic meningitis resolves with minimal sequelae (McCrindle et al., 2017). Corticosteroids are used to treat patients who are refractory to the first dose of intravenous immunoglobulin. They have been shown to show marked improvement in symptoms and prevented the development of coronary artery abnormalities. Infliximab use was associated with a faster resolution of fever and fewer hospitalization days. Plasma exchange is meant for patients whom all appropriate medical therapies have failed. For those with cardiovascular collapse, hemodynamic stabilization is done with fluids, inotropic agents such as dopamine, and vasoactive agents to maintain the blood pressure (McCrindle et al., 2017).
Patients who fail to respond to a second dose or immunoglobulin or steroid or infliximab require other medication. Cyclosporine has been used in such kind of patients. Studies are being done to determine the efficacy of the use of cytotoxic drugs such as cyclophosphamide in combination with other drugs to treat refractory Kawasaki cases.
Outcomes
Despite being treated with the first dose of intravenous immunoglobulin, at least 20% of the children develop complications such as coronary artery dilation in the proximal left anterior descending coronary artery and the proximal right coronary artery (McCrindle et al., 2017). About 5% develop coronary artery aneurysms, and 1% will develop giant aneurysms. At least 10% of patients have not responded to intravenous immunoglobulin by day three and still have a fever. They benefit from a second dose of intravenous immunoglobulin at a similar amount as the initial one. Steroids are added, mostly methylprednisolone is administered at 30 mg/kg or three days. An oral dose of prednisolone is prescribed for two weeks, while the dose is reduced over the days slowly to avoid adrenal crisis due to the abrupt withdrawal of the steroids. Infliximab is administered if the patient is not responding to steroids. Then cycloserine and other medications are considered if the patient does not respond to the second dose of immunoglobulin plus steroids and infliximab.
It is important to watch out for some factors that determine whether is there is a high risk of developing coronary aneurysms. Some are adjustable others are not. These factors include male gender, delayed initiation of therapy, elevated inflammation biomarkers, age less than five years and under dosage (Ramphul & Mejias, 2018). Thus attention should be paid to the modifiable factors for better outcomes.
Conclusion
Kawasaki is a disease that causes mortality among a vulnerable group of children. Healthcare workers need to have a high index of suspicion and initiate therapy as soon as they diagnose them. The treatments have their side effects; thus, it is important to consider whether the benefits outweigh the risks. Some treatments have severe effects, so it is vital to begin with, intravenous immunoglobulin before initiating therapies like plasma exchange. Follow-up is recommended for all patients who had Kawasaki disease. Echocardiography should be done when the patient presents to the hospital in the acute phase. Another done at week 2, week 6, and week eight after that, frequent imaging is recommended if the patient still has the complications and risks of developing severe heart pathology.
References
Hara, T., Nakashima, Y., Sakai, Y., Nishio, H., Motomura, Y., & Yamasaki, S. (2016). Kawasaki disease: a matter of innate immunity. Clinical & Experimental Immunology, 186(2), 134-143.
McCrindle, B. W., Rowley, A. H., Newburger, J. W., Burns, J. C., Bolger, A. F., Gewitz, M., ... & Kobayashi, T. (2017). Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation, 135(17), e927-e999.
Singh, S., Jindal, A. K., & Pilania, R. K. (2018). Diagnosis of Kawasaki disease. International journal of rheumatic diseases, 21(1), 36-44.
Ramphul, K., & Mejias, S. G. (2018). Kawasaki disease: a comprehensive review. Archives of medical sciences. Atherosclerotic diseases, 3, e41.
Rowley, A. H., & Shulman, S. T. (2018). The epidemiology and pathogenesis of Kawasaki disease. Frontiers in pediatrics, 6, 374.
Zhu, F. H., & Ang, J. Y. (2016). The clinical diagnosis and management of Kawasaki disease: a review and update. Current infectious disease reports, 18(10), 32.
