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Kawasaki Disease: A Comprehensive Review of Clinical Aspects, Global Epidemiology, and Management Strategies
Authors & Affiliation
1.Bugubaeva Makhabat Mitalipovna.
2.Abhishek Singh
(1. Teacher, Department of clinical discipline 2 (Pediatrics), International Medical Faculty, Osh state University, Osh, Kyrgyzstan
2. Medical Student, International Medical Faculty, Osh State University, Osh, Kyrgyzstan)
Abstract
Kawasaki disease (KD) is one of the most common vasculitis of children with unknown etiology of coronary arteries. It is an acute, self-limiting medium vessel vasculitis. KD is characterized by fever, rash, conjunctival injection, oral mucositis, extremity changes, cervical lymphadenitis and, in a number of cases dilatation or aneurism of coronary and other arteries. In this we will learn about etiology by exploring a combination of genetic predisposition and environmental triggers in a susceptible host, leading to an exaggerated immune response and the characteristic vascular inflammation. With particular reference to its prevalence and features in nations like India and Kyrgyzstan.
1. Introduction: Unveiling the Enigma of Childhood Vasculitis
In pediatric medicine, Kawasaki Disease, commonly referred to as Mucocutaneous Lymph Node Syndrome, gives a serious diagnostic and treatment issue. Its idiopathic character, first marked by Dr. Tomisaku Kawasaki in 1961, despite the widespread hypothesis that it is caused by an infectious trigger in a genetically vulnerable host. It has the ability to cause serious cardiovascular problems, particularly CAA, which can result in myocardial infarction, sudden death, or persistent ischemic heart disease later in life, gives it great therapeutic relevance.
2. Historical Perspective and Etiological Hypotheses
2.1. Early Recognition
The first case of KD was diagnosed by Dr. Tomisaku Kawasaki in 1961 and a detailed description of this illness in 50 Japanese children was published in 1967 by him as an acute mucocutaneous lymph nodesyndrome.2.Since then the incidence of KD has been consistently increasing in Japan, Taiwan and Korea.
2.2. Etiology: The Lingering Mystery
The exact etiology of KD is still unknown after many investigations. According to the widely accepted theory, a bacterial or viral infectious agent acts as a trigger in those who are genetically susceptible. This is supported by the following evidence:
* Epidemic Patterns: Seasonal changes and outbreaks, which often occur in late winter or early spring, point to an infectious or environmental trigger;
* Age Distribution: Predominance in young children, because they have more frequent childhood diseases.
* Immunological Activation: During the acute phase, significant inflammation and immunological activation were seen.
A previously unidentified RNA virus which enters the body through mucosal surfaces as causative agents for KD. But no single pathogen is regularly identified, though Epstein- Barr virus, rotavirus, other viruses and some bacteria have been reported.
2.3. Pathophysiology: A Cascade of Inflammation
KD is characterized by a medium-sized muscular artery vasculitis that is systemic in nature.
* First Immune Activation: An unknown antigen provokes an innate and adaptive immune response.
* Endothelial Damage: T cells, B cells, macrophages, and inflammatory cytokines (e.g., TNF-α, IL-6) penetrate the vessel walls following activation.
* Vascular Remodeling: This results in degradation of the elastic laminae of the arterial wall and smooth muscle cells, which leads to dilation and potential aneurysm.
* Thrombosis risk: Endothelial damage predisposes platelet activation and hypercoagulability, increasing the risk of thrombus formation in aneurysms.
3. Clinical Presentation: The Diagnostic Challenge
The diagnosis of KD is based on clinical, depend on signs and symptoms. It basically has three phases: acute, subacute, and convalescent.
3.1. Acute Phase (Days 0-14)
The defining feature is a high, recurrent fever that lasts for at least five days and is frequently >39 Degrees
The diagnosis of classic KD is based on the presence of ≥5 days fever and the presence of e”4 of the 5 principal
clinical features. In the presence of e”4 principal clinical features, particularly when redness and swelling of the
hands and feet are present, the diagnosis of KD can be made with 4 days of fever, although experienced clinicians
who have treated many patients with KD may establish the diagnosis with 3 d of fever in rare cases.
1. Erythema and cracking of lips, strawberry tongue, and/or erythema of oral and phalangeal mucosa.
2. Bilateral bulbar conjunctival injection without exudates.
3. Rash: maculopapular, diffuse erythroderma, or erythema multiforme-like.
4. Erythema and edema of the hands and feet in acute phase and/or periungual desquamation in sub-acute phase.
5. Cervical lymphadenopathy (e” 1.5 cm diameter), usually unilateral
3.2. Subacute phase (Weeks 2-4)
Fever usually goes away at this stage, but youngsters are most vulnerable to developing CAA. The subacute phase, which lasts until about the 4th week, is characterized by gradual resolution of fever (if untreated) and other symptoms. Among the main features are:
* Desquamation: Skin peeling, particularly periungual (around the fingernails)
* Thrombocytosis: Platelet count can also rise significantly.
* Arthritis/Arthralgia: Joint pain or inflammation.
3.3. The Convalescent Phase (Weeks 6–8)
disappearance of every clinical symptom . Inflammatory markers and other laboratory parameters like ESR returns to normal. If no CAA appears, this period lasts for 6–8 weeks from the start of the fever. Beau lines of the fingernails may appear during this phase.
3.4. Atypical/Incomplete Kawasaki Disease
The diagnosis of incomplete (atypical) KD, which occurs more commonly in infants, is made when fever is present for at least 5 days, even if only two to three clinical criteria are present, particularly in the presence of CAA. The diagnosis of KD should be considered in infants less than 6 months of age with fever for at least 7 days even if no other criteria are present.
4. Workup for Diagnostics
As we know that there is no particular diagnostic test, clinical assessment is crucial. Imaging and laboratory tests can assure the diagnosis and can measure the severity of the illness.
4.1. Results from the Lab
* Raised Inflammatory Markers: C-Reactive Protein and ESR.
* Leukocytosis: high white blood cell count.
* Anemia: normochromic and normocytic.
* Thrombocytosis: A noticeably high subacute phase platelet count.
* Increased Liver Enzymes: There may be a little increase in AST and ALT.
* Sterile pyuria; WBC in urine without a bacterial infection.
4.2. Electrocardiography(ECG)
During acute phase, if there is a myocardial or pericardial involvement, ECG may show arrhythmia, including sinus node and atrio-ventricular node functional abnormalities with prolonged PR interval and nonspecific ST and T wave changes. If there is myocardial or pericardial involvement, there may be low voltage association. To check for CAA, it is done upon diagnosis, 1-2 weeks after treatment, and 6-8 weeks after the onset of the illness.
5. Epidemiology: A Global Perspective
5.1. Global Incidence * countries like Japan, south Korea, Taiwan shows high incidence per 100,000 children under 5years of age and other East Asian nations like Hong Kong, China, have the highest incidence rate.
* Western nations (Italy, Canada, Australia, USA, Europe) have a lower incidence rate, but now the cases are rising.
5.2. Indian Epidemiology
* Kawasaki disease is becoming more widely growing in India, although under diagnosis and treatment delays continue to be major problems, in part because of the high prevalence of other infectious diseases that appear similarly.
*Incidence data from different states like Chandigarh, Delhi, between 1994 to 2019 shows an increase of 0.002 cases/100,000 to 0.0165cases/100,000 of children under 5 years of age. suggest a sustainable rise of 0.0177 cases/100,000 children <15 years of age by the year 2020-2030.
*this can show a significant public health issue due to serious cardiovascular complications such as CAA, myocardial ischemia and sudden cardiac deaths due to KD.
* Many cases of KD in India are likely due to lack of awareness, delayed diagnosis, and more cost of treatment exacerbate the disease clinical and economic burden.
*Early diagnosis and appropriate management remain critical for reducing the long term morbidity.
5.3. Epidemiology in Kyrgyzstan
* Appearing Data: Compared to other areas , there is a lack of data on Kawasaki Disease from Central Asian nations like Kyrgyzstan. This suggests that how urgently we need stronger epidemiological research in central Asia.
* Problems with Diagnosis:
* The Lack of awareness between peoples may cause the diagnosis of KD to be delayed.
* The diagnostic instruments are barely allowed (e.g., advanced lab tests, echocardiography).
* There are too costly treatments like IVIG due to economic barrier.
* Implications for Public Health: The data is not enough to meet the necessity to improve the resources.
*the resources for diagnostic and treatment purpose needs to be improved;
* There should be a good training and learning of physician.
6. Management and Treatment Strategies
Prevent cardiac complication which requires action during the first ten days of fever development.
*The main treatment in the acute phase is IVIG. The incidence of CAA which is constantly decreasing from 25% to less than 5% with a single dosage of 2 g/kg given over 10–12 hours.
* Aspirin: * High-Dose (Anti-inflammatory): 30–50 mg/kg/day, split every 6 hours; started with IVIG and continued for 48–72 hours until the patient is afebrile.
* Low-Dose (Anti-platelet): 3-5 mg/kg/day once daily, initiated following the end of the fever and continued for 6-8 weeks after the onset (when there was no CAA) or indefinitely (when there was CAA).
6.2. Kawasaki Disease Refractory
10-20% of patients had chronic or recurrent fever 36 hours after IVIG, indicating that they did not react to the initial treatment. Refractory KD can be managed as follows:
* IVIG: we can repeat a second dose of 2 g/kg.
* Corticosteroids: methylprednisolone. It plays a role in acute phase and for children with persistent fever.
* Anakinra, an IL-1 receptor antagonist, or Infliximab, a TNF-alpha inhibitor which is given for severe or chronic inflammation.
7. Complications
The most serious result of cardiac disease is coronary artery aneurysms (CAA), Aneurysms can have different size it can be small, medium, or giant in size, and their clinical complication can also vary. The greatest risk of myocardial infarction and thrombosis is associated with giant aneurysms (with at least 8 mm in diameter or 10 mm in diameter).
* Inflammation of the heart muscle, sac, or valves is known as myocarditis, pericarditis, or valvulitis. Arrhythmias: Heartbeat irregularities.
*myocardial involvement is frequent in KD. It is reported that myocardial inflammation in KD occurs before coronary artery abnormalities.
*patients with serious condition including coronary artery may also form other medium sized arteries including axillary, subclavian, brachial, femoral, iliac, splanchnic, and mesenteric arteries.
Classification of CAA according to American heart association (AHA)guideline, it is always better to use z-scores for assessment of coronary arteries26.Z-Score Classification;
1. No involvement : always < 22.
2. Dilatation only: 2 to <2.5; or if initially <2, a decrease in Z score during follow up e”13.
3. Small aneurysm: e” from 2.5 to <54.
4. Medium aneurysm: e” 5 to more than 10, and absolute dimension <85.
5. Giant aneurysm: e”10 or absolute dimension e”
8. Conclusion
Kawasaki disease must be recognized and treated immediately because it can have very serious cardiac effects. clinical diagnosis, especially for incomplete forms, is still difficult and required a high level of suspicion between medical professionals worldwide. In countries like Kyrgyzstan, highlighting the need for the stronger management systems, better diagnostic tools and more awareness.
Diagnosing and managing Kawasaki disease is a challenge for all the paediatricians of developing countries including India and Kyrgyzstan and risk of developing coronary artery abnormality is about 25% if not diagnosed and treated timely. Missed KD in childhood can also result in coronary problems and present with Ischaemia, myocarditis, infarction or sudden death in young adults. Very high cost treatment (IVIG Therapy) is also a major challenge in countries like Kyrgyzstan. Therefore, KD needs to be considered as a disease of Public Health Importance. Governments should make policies to create awareness and the availability of IVIG at a low cost must be ensured.
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