Kawasaki Disease

Overview of Kawasaki Disease

More than 80% of cases are seen in children below the age of 5 yr. It is a common vasculitis disorder of childhood and has replaced acute rheumatic fever as the leading cause of acquired heart disease in children in many countries.

The condition has been reported from all parts of the world. In India this condition is now being increasingly recognized but the vast majority of patients still continue to remain undiagnosed probably because of lack of awareness amongst pediatricians.

It is important to remember that the diagnosis of KO is based entirely on the recognition of a temporal sequence of characteristic clinical findings and that there is no specific laboratory test.[1]

Kawasaki disease common in:

• Males than in female
• Children under 5 years of AGE.
• 95% of cases occur in children under the age of 10 years.
• It is also affected the people who are suffering from HIV.

Causes of Kawasaki Disease

• Etiology of Kawasaki disease is not known
• The certain genes are known to increase a child’s susceptibility towards the Kawasaki disease.
• The disease has a genetic tendency.
• Siblings of affected children have high risk of developing Kawasaki disease as compared to the general population.

Types

Kawasaki Disease (KD) is primarily classified into two types:

Complete Kawasaki Disease (Classic KD):

• This type presents with all the characteristic clinical features, including fever lasting for at least five days, bilateral conjunctival injection, polymorphous rash, changes in the extremities (edema, erythema, desquamation), oral mucosal changes (strawberry tongue, cracked lips), and cervical lymphadenopathy.

Incomplete Kawasaki Disease (Atypical KD):

• This type is characterized by the presence of fever and fewer than four of the principal clinical features. It is often more challenging to diagnose due to its variable presentation and can lead to delays in treatment [5]

Risk factor of Kawasaki Disease

• History of the patient
• Family history of the patient
• Boys are at more risk
• Children under 5 years of age are at more risk

Pathogenesis

The exact pathogenesis of Kawasaki Disease (KD) remains unknown, but it is believed to involve a complex interplay of genetic predisposition, immune dysregulation, and environmental triggers.

Current evidence suggests the following key elements in the pathogenesis:  

Genetic Predisposition:

• Certain genetic variations are associated with an increased susceptibility to KD, particularly in populations of Asian ancestry. These variations may influence immune responses and contribute to the development of vasculitis.

Infectious Trigger:

• While no specific pathogen has been identified, the seasonal pattern and clustering of cases suggest an infectious trigger, possibly a virus or bacterium.

Immune Dysregulation:

• KD is characterized by a heightened immune response, with the activation of various immune cells (T cells, B cells, macrophages) and the release of inflammatory cytokines. This dysregulated immune response leads to widespread inflammation, particularly affecting the medium-sized blood vessels.

Vasculitis:

• The hallmark of KD is vasculitis, an inflammation of the blood vessels. This inflammation primarily affects the coronary arteries, but other medium-sized arteries can also be involved. The vasculitis can lead to the formation of aneurysms, which can rupture or cause thrombosis, leading to serious cardiac complications. [6]

Pathophysiology

The exact pathophysiology of Kawasaki Disease (KD) remains elusive, but it is characterized by systemic vasculitis, predominantly affecting medium-sized arteries, with a predilection for the coronary arteries.

Acute Vasculitis:

• The hallmark of KD is acute vasculitis, involving inflammation of the blood vessel walls. This inflammation can lead to endothelial damage, fibrinoid necrosis, and infiltration of inflammatory cells, ultimately resulting in the weakening of the arterial wall and potential aneurysm formation.   

Immune Dysregulation:

• KD is associated with a dysregulated immune response, involving the activation of both innate and adaptive immunity. This dysregulation is characterized by increased levels of pro-inflammatory cytokines (e.g., TNF-α, IL-1, IL-6), T-cell activation, and autoantibody production, contributing to the ongoing inflammation and vascular damage.

Coronary Artery Involvement:

• The coronary arteries are particularly vulnerable to vasculitis in KD.
• The inflammation can lead to the formation of coronary artery aneurysms, which can subsequently thrombose or rupture, leading to myocardial infarction or sudden cardiac death. 

Systemic Inflammation:

• While vasculitis is the primary pathophysiological feature, KD is a systemic illness with widespread inflammation affecting multiple organ systems. This systemic inflammation can manifest as fever, rash, conjunctivitis, lymphadenopathy, and mucosal changes. [7]

Clinical Features:

Kawasaki Disease (KD) is a systemic vasculitis primarily affecting young children. It presents with a constellation of characteristic clinical features, often occurring in phases:

Acute Phase (Week 1-2):

• Fever: High-grade fever (>39°C or 102.2°F) lasting for at least five days, unresponsive to antipyretics
• Conjunctivitis: Bilateral, non-exudative conjunctivitis
• Mucosal Changes: Erythema and cracking of lips, strawberry tongue, erythema of oropharyngeal mucosa
• Rash: Polymorphous rash, often involving the trunk and extremities, may be macular, maculopapular, or scarlatiniform
• Extremity Changes: Erythema and edema of hands and feet, desquamation of fingertips and toes in the second week
• Cervical Lymphadenopathy: Unilateral, usually non-suppurative cervical lymphadenopathy

Subacute Phase (Week 2-4):

• Desquamation: Periungual desquamation of fingers and toes
• Thrombocytosis: Elevated platelet count
• Arthritis/Arthralgia: Transient joint pain and stiffness
• Cardiac Complications: Development of coronary artery aneurysms (most serious complication)

Convalescent Phase (Week 4-6):

• Resolution of Symptoms: Gradual resolution of fever, rash, and other clinical features
• Beau’s Lines: Transverse grooves on nails
• Continued Risk of Cardiac Complications: Monitoring for coronary artery aneurysms remains crucial [8]

Sign & Symptoms of Kawasaki Disease

Acute phase

• Fever more than 5 days
• Bilateral Conjunctivitis
• Red inflamed tongue called “Strawberry tongue”
• Gingivitis
• Dry, cracked lips
• Oropharyngeal edema
• Swollen lymph nodes in the neck
• Cough and runny nose
• Erythematous, edematous Rashes on the palms and soles
• Abdominal pain and vomiting due to biliary obstruction

Subacute phase

• Irritability
• Arthritis
• Myocarditis
• Arthralgias
• More prominent Desquamation

Convalescent phase

• Gradual resolution of symptoms

Clinical Examination

A comprehensive clinical examination is crucial for the diagnosis of Kawasaki Disease (KD), as it lacks specific laboratory tests. The examination should focus on the characteristic clinical features, which may vary depending on the stage of the illness:

General Examination:

• Assess the child’s overall appearance, noting irritability, lethargy, or signs of distress.
• Measure and record vital signs, including temperature, heart rate, respiratory rate, and blood pressure.
• Examine the skin for the presence of rash, focusing on its distribution, morphology, and evolution over time.
• Palpate for cervical lymphadenopathy, noting the size, location, and tenderness of lymph nodes.

Head and Neck Examination:

• Evaluate the eyes for bilateral conjunctival injection, noting the absence of exudate.
• Examine the oral cavity for erythema, cracking of lips, strawberry tongue, and other mucosal changes.

Extremity Examination:

• Assess the hands and feet for erythema, edema, and desquamation, particularly in the periungual region.
• Palpate for tenderness and warmth in the joints, indicating arthritis or arthralgia.

Cardiovascular Examination:

• Auscultate the heart for murmurs, gallops, or other abnormal sounds, which may suggest cardiac involvement.
• Palpate peripheral pulses to assess for any discrepancies or abnormalities.

Additional Examinations:

• Perform a thorough abdominal examination to rule out other potential causes of fever and lymphadenopathy.
• Conduct a neurological examination to assess for any signs of meningitis or other neurological complications. [9]

Diagnosis of Kawasaki Disease

1. Fever lasting for at least 5 days

2. Presence of any 4 of the following 5 conditions:

• Bilateral non-purulent conjunctiva! injection (no discharge)
• Changes of mucosae of oropharynx (e.g., injected pharynx, injected lips, strawberry tongue)
• Changes of peripheral extremities (acute stage: edema, erythema of hands or feet; convalescent [1] stage: desquamation, which usually begins periungual)
• Polymorphous rash (never vesicular)
• Cervical lymphadenopathy (at least 1 node -5 cm; usually unilateral)

3. Illness not explained by any other known disease process.

• It should be noted that the above clinical features evolve sequentially over a period of few days and all need not be present at one particular point of time.
• This partly explains the difficulty that the clinician experiences in arriving at a correct diagnosis. Most children have high grade fever and are extremely irritable.
• In fact, it is this irritability which often provides the first clinical clue to the diagnosis.[1]
• Kawasaki disease must be considered in the differential diagnosis of all children below 5 yrs. of age who have fever without apparent focus lasting more than 5 days. Beau lines may be seen during the convalescent phase.

Differential Diagnosis of Kawasaki Disease

• Juvenile Rheumatoid arthritis
• Lyme disease
• Rheumatic fever
• Rocky mountain spotted fever
• Infantile polyarteritis nodosa
• Measles
• Mercury Toxicity
• Staphylococcal Scalded skin syndrome

Complications of Kawasaki Disease

Heart attack at a younger age or later in life due to aneurysms and inflammation of vessels.

The basic lesion is a necrotizing vasculitis of medium-sized muscular arteries (especially coronaries), which may result in aneurysms, dilatations, and stenosis in untreated patients.[1]

Investigation of Kawasaki Disease

There is no diagnostic test for Kawasaki disease. Evaluation of symptoms and ruling other possible conditions (Scarlet fever, measles, Juvenile RA, allergic reaction, etc.) is necessary.

• ESR
• CBC to look for leukocytosis
• Serum Immunoglobulin levels to for elevated Ig.E level
• Chemistry panel to look for elevated bilirubin
• Blood also throat cultures to identify causative organisms.

Imaging study

• ECG To look for arrhythmias
• Chest radiography to look for cardiomegaly also infiltrates
• Echocardiogram to look for Valvular abnormalities also cardio myography.

Treatment of Kawasaki Disease

• The patient is hospitalized.
• High doses of aspirin reduce inflammation and it acts as a blood thinner.
• Administration of gamma- globulin through a vein.
• Anti-inflammatory drugs e.g., Ibuprofen or naproxen relives joint pains
• Plasmapheresis also help in giving relief to the patient.
• Single dose of intravenous immunoglobulin (2 g/kg) and
• Aspirin in anti-inflammatory doses (75-80 mg/kg) until the child becomes afebrile.
• Low dose aspirin (3-5 mg/kg/ day) is then continued for a few weeks for its antiplatelet activity.

In appropriately treated children, the long-term prognosis is excellent with less than 3% patients developing coronary artery abnormalities as compared to 15-25% in the untreated category.

Prevention

There is currently no known way to prevent Kawasaki Disease (KD), as its exact cause remains unknown. However, early diagnosis and prompt treatment are crucial to reduce the risk of complications, particularly coronary artery aneurysms.

While prevention is not possible, the following measures can help minimize the risk of complications:

Early Recognition and Diagnosis:

• Recognizing the characteristic clinical features of KD and seeking prompt medical attention is essential. Early diagnosis allows for timely initiation of treatment, reducing the risk of cardiac complications.

Prompt Treatment with Intravenous Immunoglobulin (IVIG):

• IVIG is the standard treatment for KD and is most effective when administered within the first 10 days of illness. IVIG can significantly reduce the risk of coronary artery aneurysms and other complications.

Regular Follow-up and Monitoring:

• Children diagnosed with KD require close follow-up and monitoring for cardiac complications, including echocardiograms to assess for coronary artery aneurysms.

Research and Surveillance:

• Continued research is necessary to understand the etiology and pathogenesis of KD, which could lead to the development of preventive strategies in the future. [10]

Homeopathic Treatment of Kawasaki Disease

Homeopathy treats the person as a whole. It means that homeopathic treatment focuses on the patient as a person, as well as his pathological condition. The homeopathic medicines selected after a full individualizing examination and case-analysis.

which includes

• The medical history of the patient,
• Physical and mental constitution,
• Family history,
• Presenting symptoms,
• Underlying pathology,
• Possible causative factors etc.

A miasmatic tendency (predisposition/susceptibility) also often taken into account for the treatment of chronic conditions.

What Homoeopathic doctors do?

A homeopathy doctor tries to treat more than just the presenting symptoms. The focus is usually on what caused the disease condition? Why ‘this patient’ is sick ‘this way’?.

The disease diagnosis is important but in homeopathy, the cause of disease not just probed to the level of bacteria and viruses. Other factors like mental, emotional and physical stress that could predispose a person to illness also looked for. No a days, even modern medicine also considers a large number of diseases as psychosomatic. The correct homeopathy remedy tries to correct this disease predisposition.

The focus is not on curing the disease but to cure the person who is sick, to restore the health. If a disease pathology not very advanced, homeopathy remedies do give a hope for cure but even in incurable cases, the quality of life can greatly improved with homeopathic medicines.

Homeopathic Medicines for Kawasaki Disease:

The homeopathic remedies (medicines) given below indicate the therapeutic affinity but this is not a complete and definite guide to the homeopathy treatment of this condition. The symptoms listed against each homeopathic remedy may not be directly related to this disease because in homeopathy general symptoms and constitutional indications also taken into account for selecting a remedy.

Medicines:

Aconite [Acon]

• This remedy typifies a synochal asthenic fever, also corresponds to hyperemia congestion and chill preceding inflammatory fever. Frequent chilliness is common in fevers calling for Aconite.
• There is redness of the face, great heat also oftentimes an outward pressing headache. A slight degree of delirium does not contra-indicate Aconite.
• The mental symptoms are all important; there is anxiety, and restlessness from the violent circulatory storm; there is dry skin, violent thirst, full bounding frequent pulse also sweating relieves.
• If it is brought on by exposure to dry cold winds or chilling of the body after overheat, especially when warm also sweaty it is well indicated.
• It suits the young and robust and has no relation to the weak also sickly. The never-failing characteristics of mental anguish must be present.
• The attack of fever often terminates with a critical sweat. Veratrum viride. This remedy suits cases similar to Aconite, but it has more arterial excitement also no anxiety.[2]

Belladonna [Bell]

• This remedy is marked by erethism, violent delirium, headache, throbbing carotids and cerebral symptoms.
• Eyes red and glistering; the skin is hot and burning; the heat seems to steam out from the body; it may be followed by a profuse sweat which brings no relief.
• The characteristics are briefly: General dry heat with chills, little or no thirst, in fact, the patient may have a dread of water, cool extremities also throbbing headache.
• The fever is worse at night. patient feels chilly when uncovering.

Bryonia [Bry]

• Suits especially a quite form of fever; true, the patient may restless also toss about, but always made worse thereby.
• There is intense headache, dull, stupefying with a sensation as if the head would burst at the temples; sharp pains over the eyes, faintness on rising up, dry mouth also a tongue coated white in the middle.
• Cold, chilly sensations predominate in fevers calling for Bryonia, and there is much thirst for large drinks of water at rather infrequent intervals.
• The fever of Bryonia is unmarked by the violence, acuteness also general storm of Aconite or the decomposition also great debility of the acids.
• It is neither synochal nor so markedly asthenic in character, it is between the two and is dependent upon local affections, state of stomach, liver, chest, etc. [2]

Chamomilla

• Ugly in behavior, Cross also uncivil, quarrelsome, Vexed at every trifle. Abrupt.
• Averse to being spoken to or touched; or being looked at. Children want to be carries also petted. Want many things, but refuse them when given. Piteous moaning because he cannot have what he wants.
• Aversion to talking. Omits words while writing also speaking. Women become suddenly capricious, quarrelsome, obstinate, before menses.
• Hasty, hurried. Cannot bear anyone near him. Chilly yet easily overheated; hence takes cold.
• Coldness of one part, with heat of another worse uncovering. Alternate chill also heat.
• Feverish from suppressed discharges. Sweat on head. Thirst during fever yellow conjunctiva.
• Spasmodic closing of lids. Bloody water from the eyes of new born babies. 

Gelsemium [Gels]

• This remedy suits dull, foolish, apathetic conditions. The patient is dizzy and drowsy, the chill is partial; there is a full flowing pulse with an element of weakness in it.
• It corresponds especially to remittent types of fever also to fevers brought on by warm, relaxing weather.
• The fever is accompanied by languor, muscular weakness also a desire for absolute rest and is unaccompanied by thirst.
• This remedy stands midway between Aconite also Gelsemium in febrile conditions, and it may be differentiated from its neighbors by the pulse, which, under Aconite, is full and bounding also under Gelsemium soft and flowing, and by the mental symptoms, Aconite being marked by anxiety and Gelsemium by drowsiness and dullness.
• Hughes praises this remedy in simple continued fevers, where he believes it is specific. Gastric fever, he claims, will never run into typhoid if treated with this remedy. [2]

Pulsatilla

• Mild, timid, emotional, tearful, very irritable, touchy Conjunctivitis from colds. Thirst less ness; with nearly all complaints. Vomiting of food eaten long before.
• Chilly, yet averse to heat; in warm room with pain; on lying down at night. One sided coldness with numbness.
• Pains during sweat. One hand cold. Partial sweat. Feverish, hot, body temperature normal. Erratic temperature in fevers.
• Breath offensive. Dry or slimy; without thirst Hard painful lumps in both groins Diminished taste to all food Itching, burning in eyes, causing rubbing. Weeping eyes.

Rhus Toxicodendron [Rhus-t]

• A form of catarrhal fever, so-called, which is met with frequently calls for Rhus more than for any other remedy.
• It commences with weakness of the whole body with desire to lie down, soreness or bruised sensations in the limbs, aching of limbs and bones, great pain in back, restlessness, worse while lying still, sickness at the stomach, loss of appetite, repugnance for food, great thirst, dry tongue and mouth.
• It is useful on that borderland where febrile cases merge into a typhoid condition.
• Here the fever is characterized by weariness, prostration also trembling. It is slow, lingering fever, generally a gastric or a bilious, remittent fever.
• It is characterized by the following combination of symptoms which no other drug has: Profuse salivation, dry throat and great thirst for cold water.

Sulphur [Sulph]

• An excellent fever remedy, it comes in after Aconite when the skin is dry and hot and there is no sweat; the fever seems to burn the patient up, the tongue is dry and red and the patient at first is sleepless and restless, but soon becomes drowsy.
• There are no blood changes; additionally it is a chronic Aconite or a passive Aconite does to the arteries.[2]

Terminology

References use for Article Kawasaki Disease

1. Paediatrics (8th Edition) -O.P. Ghai- -Reduced
2. Therapeutics from Zomeo ultimate LAN
3. https://hpathy.com/cause-symptoms-treatment/kawasaki-disease/
4. A study published in the Indian Pediatrics journal in 2009, titled "Kawasaki disease – an Indian perspective

5. Book Nelson Textbook of Pediatrics, 21st Edition, Authors: Robert M. Kliegman, Bonita M.D. Stanton, Joseph St. Geme, Nina Felice Schor, Richard E. Behrman
   Year of Publication: 2020, Publisher: Elsevier

6. Book Rudolph’s Pediatrics, 23rd Edition, Authors: Abraham Rudolph, Colin D. Rudolph, Lewis R. First, Anne A. Gershon, Year of, Publication: 2021, Publisher: McGraw-Hill Education

7. Book Harrison’s Principles of Internal Medicine, 21st Edition
   Authors: Dennis L. Kasper, Anthony S. Fauci, Stephen L. Hauser, Dan L. Longo, J. Larry Jameson, Joseph Loscalzo Year of Publication: 2022
   Publisher: McGraw-Hill Education

8. Book Nelson Essentials of Pediatrics, 8th Edition, Authors: Karen Marcdante, Robert M. Kliegman, Year of Publication: 2021
   Publisher: Elsevier

9. Book Pediatric Physical, Examination, 5th Edition, Authors: Karen Duderstadt, Lucy Rorke-Adams, Year of Publication: 2018
   Publisher: Elsevier

10. Book Red Book: 2021-2024 Report of the Committee on Infectious, Diseases, 32nd Edition, Editor: Sarah S. Long, Year of Publication: 2021, Publisher: American Academy of Pediatrics