Kawasaki disease
Encyclopedia
Kawasaki disease also known as Kawasaki syndrome, lymph node syndrome and mucocutaneous lymph node syndrome, is an autoimmune
disease in which the medium-sized blood vessels throughout the body become inflamed. It is largely seen in children under five years of age. It affects many organ systems, mainly those including the blood vessel
s, skin
, mucous membrane
s and lymph node
s; however, its rare but most serious effect is on the heart
where it can cause fatal coronary artery aneurysm
s in untreated children. Without treatment, mortality may approach 1%, usually within six weeks of onset. With treatment, the mortality rate is less than 0.01% in the U.S.
There is often a pre-existing viral infection that may play a role in its pathogenesis
. The conjunctiva
e and oral mucosa
, along with the epidermis (skin), become erythematous (red and inflamed). Edema
is often seen in the hands and feet and one or both of the cervical lymph nodes
are often enlarged. Also, a remittent fever, often 40°C (104°F) or higher, is characteristic of the acute phase of the disease. In untreated children, the febrile period lasts on average approximately 10 days, but may range from five to 25 days. The disorder was first described in 1967 by Dr. Tomisaku Kawasaki
in Japan.
is an inflammatory condition affecting both vein
s and arteries
throughout the body, and is usually caused by a proliferation of cells associated with an immune
response to a pathogen
, or autoimmunity. Systemic vasculitides may be classified according to the type of cells involved in the proliferation, as well as the specific type of tissue damage occurring within the vein or arterial walls. Under this classification scheme for systemic vasculitis, Kawasaki disease is considered to be a necrotizing
vasculitis (also called necrotizing angeititis), which may be identified histologically
by the occurrence of necrosis
(tissue
death), fibrosis
, and proliferation of cells associated with inflammation in the inner layer of the vascular wall. Other diseases featuring necrotizing vasculitis include Polyarteritis nodosa
, Wegener's granulomatosis
, Henoch-Schönlein purpura
and Churg-Strauss syndrome
. Kawasaki disease may be further classified as a medium-sized-vessel vasculitis, affecting medium and small sized blood vessels, such as the smaller cutaneous vasculature (veins and arteries in the skin) that range from 50 to 100µm
in diameter. KD is also considered to be a primary childhood vasculitis, a disorder associated with vasculitis that mainly affects children under the age of 18. A recent, consensus-based evaluation of vasculitides occurring primarily in children resulted in a classification scheme for these disorders, to both distinguish them and suggest a more concrete set of diagnostic criteria for each. Within this classification of childhood vasculitides, Kawasaki disease is, again, a predominantly medium-sized vessel vasculitis.
It is also an autoimmune form of vasculitis, and is not associated with ANCA
antibodies, unlike other vasculitic disorders associated with them, such as wegener's granulomatosis
, microscopic polyangiitis
, and Churg-Strauss syndrome
. This categorization is considered essential for appropriate treatment.
that is not very responsive to normal treatment with paracetamol
(acetaminophen) or ibuprofen
. it is the most prominent symptom in Kawasaki disease, which is a characteristic sign of the acute phase of the disease, is normally high (above 39-40º C), remittent
and followed by extreme irritability
. recent reports says it is even present in patients with atypical or incomplete KD,nevertheless recent reports says it is not present on 100% of cases. The first day of fever is considered the first day of illness, and the duration of fever is on average one to two weeks; in the absence of treatment, it may extend for three to four weeks, Prolonged fever is associated with higher incidence of cardiac involvement. It responds partially to antipyretic drugs and does not cease with the introduction of antibiotics. However, when appropriate therapy is started – intravenous immunoglobulin
(IVIG
) and aspirin
– the fever is gone after two days.
Bilateral conjunctival injection
was reported by many publications to be the most common symptom after fever, it typically involves the bulbar conjunctivae, is not accompanied by suppuration, it is not painful. It usually begins shortly after the onset of fever during the acute stage of the disease. Anterior uveitis may be present on slit-lamp examination. iritis
can occur too. Keratic precipitate
s is another eye manifestation (detectable by a slit lamp
but usually too small to be seen by the unaided eye.
Kawasaki disease presents with set of oral
manifestations, the most characteristic changes are the bright red (erythema
), swollen lips (edema
) with vertical cracking (fissures) and bleeding
. The mucosa of the oropharynx
may be bright red, and the tongue
may have a typical "strawberry tongue
" appearance (marked erythema with prominent gustative papillae). These oral manifestations are caused by the typical necrotizing
microvasculitis
with fibrinoid necrosis
.
Cervical lymphadenopathy
, is seen in approximately 50 to 75% of patients, whereas the other features are estimated to occur in 90% of patients. But sometimes it can be the dominant presenting symptom. According to the definition of the diagnostic criteria, there should be more than one impaired lymph node
and > 1.5 cm in diameter. Affected lymph nodes are not painful or little painful, not-fluctuating and non-suppurative; erythema of the neighboring skin may occur. We should be attentive to those children with fever and neck adenitis
that do not respond to antibiotics, because Kawasaki disease should be part of the differential diagnoses.
In the acute phase of the disease changes in the peripheral extremities can include erythema
of the palms and soles, which is often striking with sharp demarcation, and often accompanied by painful, brawny edema
of the dorsa of the hands or feet in the acute phase of the disease, and it is why affected children frequently refuse to hold objects in their hands or to bear weight on their feet. Later during the convalescent or the subacute phase desquamation
of the fingers and toes usually begins in the periungual region within two to three weeks after the onset of fever and may extend to include the palms and soles, and around 11% of children affected by the disease may continue skin peeling for many years. 1 to 2 months after the onset of fever deep transverse grooves
across the nails may develop (Beau’s lines), And occasionally nail are shed.
The most common cutaneous manifestation is a diffuse macular
-papular erythematous rash, which is quite nonspecific. The rash varies over time and is characteristically located on the trunk and may further spread to involve the face, extremities, and perineum. many other forms of cutaneous lesions have been reported also, they may include Scarlatiniform, popular
, urticariform
, multiform-like erythema
, and purpuric lesions, even micropustules were reported, it can be polymorphic, non-itchy
and normally observed up to the fifth day of fever. however it is never bullous or vesicular
The syndrome affecting multiple organ systems, and in the acute stage of KD, systemic inflammatory changes are evident in many organs. Joint pain (arthralgia
) and swelling, frequently symmetrical, Also arthritis
can occur. Myocarditis
, diarrhea
, pericarditis
, valvulitis, aseptic meningitis
, pneumonitis
, lymphadenitis, and hepatitis
may be present and are manifested by the presence of inflammatory cells in the affected tissues. If left untreated, some symptoms will eventually relent, but coronary artery aneurysms will not improve, resulting in a significant risk of death or disability due to myocardial infarction
(heart attack). If treated in a timely fashion, this risk can be mostly avoided and the course of illness cut short.
Other reported non-specific symptoms include cough
, rhinorrhea
, sputum
, vomiting
, headache
, and seizure
.
The course of the disease can be divided into three clinical phases. The acute
febrile phase, which usually lasts for 1 to 2 weeks, is characterized by fever, conjunctival injection, erythema of the oral mucosa, erythema and swelling of the hands and feet, rash, cervical adenopathy, aseptic meningitis
, diarrhea, and hepatic dysfunction. Myocarditis is common during this time, and a pericardial effusion may be present. Coronary arteritis
may be present, but aneurysms are generally not yet visible by echocardiography
. The subacute phase begins when fever, rash, and lymphadenopathy
resolve at about 1 to 2 weeks after the onset of fever, but irritability, anorexia, and conjunctival injection persist. Desquamation
of the fingers and toes and thrombocytosis
are seen during this stage, which generally lasts until about 4 weeks after the onset of fever. Coronary artery aneurysms usually develop during this time, and the risk for sudden death
is highest during this stage. The convalescent stage begins when all clinical signs of illness have disappeared and continues until the sedimentation rate
returns to normal, usually at 6 to 8 weeks after the onset of illness.
There is differences in clinical presentation between adults and children, as adults have more affection of neck lymph nodes (93% of adults versus 15% of children); hepatitis
(65% versus 10%), and arthralgia
(61% versus 24-38%). Some patients have atypical presentations and may not have the classical symptoms and this occurs in particular in young infants, and those patients are especially at higher risk for cardiac artery aneurysms.
s. These aneurysms can lead to myocardial infarction
(heart attack) even in young children. Overall, about 10–18% of children with Kawasaki disease develop coronary artery aneurysms with much higher prevalence among patients who are not treated early in the course of illness. Kawasaki disease and rheumatic fever
are the most common causes of acquired heart disease among children in the United States. Other Kawasaki disease complications have been described, such as aneurysm
of other arteries: aortic aneurysm, with a higher number of reported cases involving the abdominal aorta
, axillary artery
aneurysm, brachiocephalic artery
aneurysm, aneurysm of iliac and femoral arteries, and renal artery
aneurysm.
Gastrointestinal complications in Kawasaki disease are similar to those observed in Henoch-Schönlein purpura
, such as: intestinal obstruction, colon
swelling, intestinal ischemia, intestinal pseudo-obstruction, and acute abdomen
.
Ophthalmologic changes associated with the disease have been described since the 1980's, being found as uveitis
, iridocyclitis
, conjunctival hemorrhage, optic neuritis
, amaurosis
and ocular artery obstruction. It can also be found as necrotizing vasculitis, progressing into peripheral gangrene.
The neurological complications per central nervous system
(CNS) lesion are increasingly reported. The neurological complications found are meningoencephalitis
, subdural effusion
, cerebral hypoperfusion, cerebral ischemia
and infarct, cerebelar infarction
, manifesting with seizures, chorea, hemiplegia
, mental confusion
, lethargy and coma
, or even a cerebral infarction with no neurological manifestations. Other neurological complications from cranial nerve involvement are reported as ataxia
, facial palsy, and sensorineural auditory loss.
center primarily on immunological
causes for the disease. Evidence increasingly points to an infectious etiology
, but debate continues on whether the cause is a conventional antigen
ic substance or a superantigen
. Children's Hospital Boston
reported that "some studies have found associations between the occurrence of Kawasaki disease and recent exposure to carpet cleaning or residence near a body of stagnant water; however, cause and effect have not been established." Other data suggests possible correlation of KD with tropospheric wind patterns
An association has been identified with a SNP in the ITPKC
gene, which codes an enzyme
that negatively regulates T-cell activation. An additional factor that suggests genetic susceptibility is the fact that regardless of where they are living, Japanese children are more likely than other children to contract the disease. The HLA-B51
serotype has been found to be associated with endemic
instances of the disease.
Kawasaki disease can only be diagnosed clinically (i.e. by medical sign
s and symptom
s). There exists no specific laboratory test for this condition. It is difficult to establish the diagnosis, especially early in the course of the illness, and frequently children are not diagnosed until they have seen several health care providers. Many other serious illnesses can cause similar symptoms, and must be considered in the differential diagnosis
, including scarlet fever
, toxic shock syndrome, juvenile idiopathic arthritis
, and childhood mercury poisoning (infantile acrodynia).
Classically, five days of fever plus four of five diagnostic
criteria must be met in order to establish the diagnosis. The criteria are: (1) erythema
of the lips or oral cavity or cracking of the lips; (2) rash on the trunk; (3) swelling or erythema of the hands or feet; (4) red eyes (conjunctival injection) (5) swollen lymph node in the neck of at least 15 millimeters.
Many children, especially infants, eventually diagnosed with Kawasaki disease do not exhibit all of the above criteria. In fact, many experts now recommend treating for Kawasaki disease even if only three days of fever have passed and at least three diagnostic criteria are present, especially if other tests reveal abnormalities consistent with Kawasaki disease. In addition, the diagnosis can be made purely by the detection of coronary artery aneurysms in the proper clinical setting.
Blood tests
Other optional tests
and pediatric infectious disease
specialists (although no specific infectious agent has been identified as yet). It is imperative that treatment be started as soon as the diagnosis is made to prevent damage to the coronary arteries.
Intravenous immunoglobulin
(IVIG) is the standard treatment for Kawasaki disease and is administered in high doses with marked improvement usually noted within 24 hours. If the fever does not respond, an additional dose may have to be considered. In rare cases, a third dose may be given to the child. IVIG by itself is most useful within the first seven days of onset of fever, in terms of preventing coronary artery aneurysm.
Salicylate therapy, particularly aspirin
, remains an important part of the treatment (though questioned by some) but salicylates alone are not as effective as IVIG. Aspirin therapy is started at high doses until the fever subsides, and then is continued at a low dose when the patient returns home, usually for two months to prevent blood clots from forming. Except for Kawasaki disease and a few other indications, aspirin is otherwise normally not recommended for children due to its association with Reye's syndrome
. Because children with Kawasaki disease will be taking aspirin for up to several months, vaccination against varicella and influenza
is required, as these infections are most likely to cause Reye's syndrome.
Corticosteroids have also been used, especially when other treatments fail or symptoms recur, but in a randomized controlled trial, the addition of corticosteroid to immune globulin and aspirin did not improve outcome. Additionally, corticosteroid use in the setting of Kawasaki disease is associated with increased risk of coronary artery aneurysm, and so its use is generally contraindicated in this setting. In cases of kawasaki disease refractory to IVIG, cyclophosphamide and plasma exchange have been investigated as possible treatments, with variable outcomes.
There are also treatments for iritis and other eye symptoms.
Another treatment may include the use of Infliximab (Remicade). Infliximab works by binding tumour necrosis factor alpha.
It is also not uncommon that a relapse
of symptoms may occur soon after initial treatment with IVIG. This usually requires re-hospitalization and re-treatment. Treatment with IVIG can cause allergic and non-allergic acute reactions, aseptic meningitis, fluid overload and, rarely, other serious reactions. Overall, life-threatening complications resulting from therapy for Kawasaki disease are exceedingly rare, especially compared with the risk of non-treatment. There is also evidence that Kawasaki disease produces altered lipid metabolism
that persists beyond clinical resolution of the disease.
Currently, Kawasaki disease is the most commonly diagnosed pediatric vasculitis in the world. By far the highest incidence of Kawasaki disease occurs in Japan
, with the most recent study placing the attack rate at 218.6 per 100,000 children <5 years of age (~1 in 450 children). At this present attack rate, more than 1 in 150 children in Japan will develop Kawasaki disease during their lifetime.
However, its incidence in the United States
is increasing. Kawasaki disease is predominantly a disease of young children, with 80% of patients younger than five years of age. Approximately 2,000-4,000 cases are identified in the United States each year.
In the United Kingdom
, estimates of incidence rate vary because of the rarity of Kawasaki disease. However, Kawasaki disease is believed to affect fewer than 1 in every 25,000 people. Incidence of the disease doubled from 1991 to 2000 however, with 4 cases in per 100,000 children in 1991 compared with a rise of 8 cases per 100,000 in 2000.
, Japan
in January of 1961, and later published a report on 50 similar cases.Later Yamamoto and colleagues were persuade that there is definite cardiac involvement when they studied and reported 23 cases, of which 11(48%) patients had abnormalities detected by an electrocardiogram
. It was not until 1974 that the first description of this disorder was published in the English language literature.in the year 1976 Melish et al., described the same illness in 16 children in Hawaii.Melish and Kawasaki had independently developed the same diagnostic criteria for the disorder, which are still used today to make the diagnosis of classic KS.
A question was raised whether the disease only started during the period between 1960 and 1970, but later a preserved heart of a 7 year old boy died in 1870 was examined and showed three aneurysms of the coronary arteries with clots, as well as pathologic changes consistent with KS. KS is now recognized worldwide. In the United States and other developed nations, it appears to have replaced acute rheumatic fever as the most common cause of acquired heart disease in children.
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
disease in which the medium-sized blood vessels throughout the body become inflamed. It is largely seen in children under five years of age. It affects many organ systems, mainly those including the blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, mucous membrane
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
s and lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s; however, its rare but most serious effect is on the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
where it can cause fatal coronary artery aneurysm
Coronary artery aneurysm
Coronary artery aneurysm is an abnormal dilatation of part of the coronary artery.-Causes:Acquired causes include atherosclerosis, Kawasaki disease and coronary catheterization.It can also be congenital....
s in untreated children. Without treatment, mortality may approach 1%, usually within six weeks of onset. With treatment, the mortality rate is less than 0.01% in the U.S.
There is often a pre-existing viral infection that may play a role in its pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
. The conjunctiva
Conjunctiva
The conjunctiva covers the sclera and lines the inside of the eyelids. It is composed of rare stratified columnar epithelium.-Function:...
e and oral mucosa
Oral mucosa
The oral mucosa is the mucous membrane epithelium of the mouth. It can be divided into three categories.*Masticatory mucosa, para-keratinized stratified squamous epithelium, found on the dorsum of the tongue, hard palate and attached gingiva....
, along with the epidermis (skin), become erythematous (red and inflamed). Edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
is often seen in the hands and feet and one or both of the cervical lymph nodes
Cervical lymph nodes
Cervical lymph nodes are lymph nodes found in the neck.-Classification:There are approximately 300 lymph nodes in the neck, and they can be classified in many different ways.Henri Rouvière produced an influential classification in 1938...
are often enlarged. Also, a remittent fever, often 40°C (104°F) or higher, is characteristic of the acute phase of the disease. In untreated children, the febrile period lasts on average approximately 10 days, but may range from five to 25 days. The disorder was first described in 1967 by Dr. Tomisaku Kawasaki
Tomisaku Kawasaki
is a Japanese pediatrician.Kawasaki disease is named for him. He published a description in Japanese in 1967, and a description in English in 1974.He first observed the condition in 1961....
in Japan.
Classification
Systemic vasculitisVasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
is an inflammatory condition affecting both vein
Vein
In the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...
s and arteries
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
throughout the body, and is usually caused by a proliferation of cells associated with an immune
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
response to a pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
, or autoimmunity. Systemic vasculitides may be classified according to the type of cells involved in the proliferation, as well as the specific type of tissue damage occurring within the vein or arterial walls. Under this classification scheme for systemic vasculitis, Kawasaki disease is considered to be a necrotizing
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
vasculitis (also called necrotizing angeititis), which may be identified histologically
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
by the occurrence of necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
(tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
death), fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
, and proliferation of cells associated with inflammation in the inner layer of the vascular wall. Other diseases featuring necrotizing vasculitis include Polyarteritis nodosa
Polyarteritis nodosa
Polyarteritis nodosa is a vasculitis of medium & small-sized arteries, which become swollen and damaged from attack by rogue immune cells. Polyarteritis nodosa is also called Kussmaul disease or Kussmaul-Maier disease...
, Wegener's granulomatosis
Wegener's granulomatosis
Wegener's granulomatosis , more recently granulomatosis with polyangiitis , is an incurable form of vasculitis that affects the nose, lungs, kidneys and other organs. Due to its end-organ damage, it is life-threatening and requires long-term immunosuppression...
, Henoch-Schönlein purpura
Henoch-Schönlein purpura
Henoch–Schönlein purpura is a disease of the skin and other organs that most commonly affects children. In the skin, the disease causes palpable purpura ; often with joint and abdominal pain...
and Churg-Strauss syndrome
Churg-Strauss syndrome
Churg–Strauss syndrome is a medium and small vessel autoimmune vasculitis, leading to necrosis. It involves mainly the blood vessels of the lungs , gastrointestinal system, and peripheral nerves, but also affects the heart, skin and kidneys. It is a rare disease that is non-inheritable and...
. Kawasaki disease may be further classified as a medium-sized-vessel vasculitis, affecting medium and small sized blood vessels, such as the smaller cutaneous vasculature (veins and arteries in the skin) that range from 50 to 100µm
Micrometer
A micrometer , sometimes known as a micrometer screw gauge, is a device incorporating a calibrated screw used widely for precise measurement of small distances in mechanical engineering and machining as well as most mechanical trades, along with other metrological instruments such as dial, vernier,...
in diameter. KD is also considered to be a primary childhood vasculitis, a disorder associated with vasculitis that mainly affects children under the age of 18. A recent, consensus-based evaluation of vasculitides occurring primarily in children resulted in a classification scheme for these disorders, to both distinguish them and suggest a more concrete set of diagnostic criteria for each. Within this classification of childhood vasculitides, Kawasaki disease is, again, a predominantly medium-sized vessel vasculitis.
It is also an autoimmune form of vasculitis, and is not associated with ANCA
ANCA
ANCA Pty Ltd is an Australia company which designs and manufactures CNC grinding machines. The company was founded in 1974 by Pat Boland and Pat McCluskey in Melbourne, Australia....
antibodies, unlike other vasculitic disorders associated with them, such as wegener's granulomatosis
Wegener's granulomatosis
Wegener's granulomatosis , more recently granulomatosis with polyangiitis , is an incurable form of vasculitis that affects the nose, lungs, kidneys and other organs. Due to its end-organ damage, it is life-threatening and requires long-term immunosuppression...
, microscopic polyangiitis
Microscopic polyangiitis
Microscopic polyangiitis is an ill-defined autoimmune disease characterized by pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of necrotizing granulomatous inflammation.-Presentation:Because many different organ systems may be involved, a wide range of...
, and Churg-Strauss syndrome
Churg-Strauss syndrome
Churg–Strauss syndrome is a medium and small vessel autoimmune vasculitis, leading to necrosis. It involves mainly the blood vessels of the lungs , gastrointestinal system, and peripheral nerves, but also affects the heart, skin and kidneys. It is a rare disease that is non-inheritable and...
. This categorization is considered essential for appropriate treatment.
Signs and symptoms
Kawasaki disease often begins with a high and persistent feverFever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
that is not very responsive to normal treatment with paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
(acetaminophen) or ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
. it is the most prominent symptom in Kawasaki disease, which is a characteristic sign of the acute phase of the disease, is normally high (above 39-40º C), remittent
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
and followed by extreme irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
. recent reports says it is even present in patients with atypical or incomplete KD,nevertheless recent reports says it is not present on 100% of cases. The first day of fever is considered the first day of illness, and the duration of fever is on average one to two weeks; in the absence of treatment, it may extend for three to four weeks, Prolonged fever is associated with higher incidence of cardiac involvement. It responds partially to antipyretic drugs and does not cease with the introduction of antibiotics. However, when appropriate therapy is started – intravenous immunoglobulin
Intravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
(IVIG
Intravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
) and aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
– the fever is gone after two days.
Bilateral conjunctival injection
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...
was reported by many publications to be the most common symptom after fever, it typically involves the bulbar conjunctivae, is not accompanied by suppuration, it is not painful. It usually begins shortly after the onset of fever during the acute stage of the disease. Anterior uveitis may be present on slit-lamp examination. iritis
Iritis
Iritis is a form of anterior uveitis and refers to the inflammation of the iris of the eye.-Types:There are two main types of iritis: acute and chronic. They differ in numerous ways....
can occur too. Keratic precipitate
Keratic precipitate
Keratic precipitate is inflammatory cellular deposit seen on corneal endothelium. Acute KPs is white and round in shape whereas old KPs r faded and irregular in shape. Mutton-fat KPs are large in shape and is greasy-white in color and is formed from macrophages and epithelioid cells....
s is another eye manifestation (detectable by a slit lamp
Slit lamp
The slit lamp is an instrument consisting of a high-intensity light source that can be focused to shine a thin sheet of light into the eye. It is used in conjunction with a biomicroscope...
but usually too small to be seen by the unaided eye.
Kawasaki disease presents with set of oral
Oral
The word oral may refer to:As an adjective:* the mouth, the first portion of the alimentary canal that receives food and saliva* speech communication as opposed to writing* oral administration of medicines...
manifestations, the most characteristic changes are the bright red (erythema
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
), swollen lips (edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
) with vertical cracking (fissures) and bleeding
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
. The mucosa of the oropharynx
Oropharynx
The Oropharynx reaches from the Uvula to the level of the hyoid bone.It opens anteriorly, through the isthmus faucium, into the mouth, while in its lateral wall, between the two palatine arches, is the palatine tonsil....
may be bright red, and the tongue
Tongue
The tongue is a muscular hydrostat on the floors of the mouths of most vertebrates which manipulates food for mastication. It is the primary organ of taste , as much of the upper surface of the tongue is covered in papillae and taste buds. It is sensitive and kept moist by saliva, and is richly...
may have a typical "strawberry tongue
Strawberry tongue
Strawberry tongue is the appearance of tongue with inflamed red papillae, giving an appearance suggestive to a red strawberry.-Associated conditions:It is seen in Kawasaki disease, toxic shock syndrome, and scarlet fever....
" appearance (marked erythema with prominent gustative papillae). These oral manifestations are caused by the typical necrotizing
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
microvasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
with fibrinoid necrosis
Fibrinoid necrosis
Fibrinoid necrosis is a form of necrosis, or tissue death, in which there is accumulation of amorphous, basic, proteinaceous material in the tissue matrix with a staining pattern reminiscent of fibrin. It is associated with conditions such as immune vasculitis Fibrinoid necrosis is a form of...
.
Cervical lymphadenopathy
Cervical lymphadenopathy
-Causes:*Rubella*Cat scratch fever*Leukemia*Infectious mononucleosis*Lymphoma*Streptococcal pharyngitis*Viral respiratory infection*Toxoplasmosis*Tuberculosis*Rhabdomyosarcoma*Neuroblastoma*Lymphadenitis*Kawasaki disease*Kikuchi-Fujimoto disease...
, is seen in approximately 50 to 75% of patients, whereas the other features are estimated to occur in 90% of patients. But sometimes it can be the dominant presenting symptom. According to the definition of the diagnostic criteria, there should be more than one impaired lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
and > 1.5 cm in diameter. Affected lymph nodes are not painful or little painful, not-fluctuating and non-suppurative; erythema of the neighboring skin may occur. We should be attentive to those children with fever and neck adenitis
Adenitis
Adenitis is a general term for an inflammation of a gland or lymph node.-Lymph node adenitis:"Lymph adenitis" or "lymph node adenitis" is caused by bacterial infection in lymph nodes. The infected lymph nodes typically become enlarged, warm and tender. A swelling of lymph nodes due to growth of...
that do not respond to antibiotics, because Kawasaki disease should be part of the differential diagnoses.
| Less common manifestations | |
|---|---|
| System | Manifestations |
| GIT | Diarrhea Diarrhea Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and... , abdominal pain Abdominal pain Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem... , vomiting Vomiting Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose... , liver dysfunction, pancreatitis Pancreatitis Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years... , Hydrops gallbladder, parotitis Parotitis Parotitis is an inflammation of one or both parotid glands, the major salivary glands located on either side of the face, in humans. The parotid gland is the salivary gland most commonly affected by inflammation.-Infectious parotitis:... , cholangitis, intussusception Intussusception (medical disorder) An intussusception is a medical condition in which a part of the intestine has invaginated into another section of intestine, similar to the way in which the parts of a collapsible telescope slide into one another. This can often result in an obstruction... , intestinal pseudo-obstruction, ascites Ascites Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver... , splenic infarction Splenic infarction In medicine, splenic infarction is a condition in which oxygen supply to the spleen is interrupted, leading to partial or complete infarction in the organ.... . |
| MSS Musculoskeletal system A musculoskeletal system is an organ system that gives animals the ability to move using the muscular and skeletal systems... |
Polyarthritis Polyarthritis Polyarthritis is any type of arthritis which involves 5 or more joints simultaneously. It is usually associated with autoimmune conditions.Polyarthritis may be experienced at any age and is not gender specific.-Causes:... and arthralgia Arthralgia Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication.... . |
| CVS Circulatory system The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc... |
Myocarditis Myocarditis Myocarditis is inflammation of heart muscle . It resembles a heart attack but coronary arteries are not blocked.Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi or Trypanosoma cruzi, or as a... , pericarditis Pericarditis Pericarditis is an inflammation of the pericardium . A characteristic chest pain is often present.The causes of pericarditis are varied, including viral infections of the pericardium, idiopathic causes, uremic pericarditis, bacterial infections of the precardium Pericarditis is an inflammation of... , Tachycardia Tachycardia Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate... , valvular heart disease Valvular heart disease Valvular heart disease is any disease process involving one or more of the valves of the heart . Valve problems may be congenital or acquired... . |
| GU Genitourinary system In anatomy, the genitourinary system or urogenital system is the organ system of the reproductive organs and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathways, like the male urethra... |
Urethritis Urethritis Urethritis is inflammation of the urethra. The most common symptom is painful or difficult urination.-Causes:The disease is classified as either gonococcal urethritis, caused by Neisseria gonorrhoeae, or non-gonococcal urethritis , most commonly caused by Chlamydia trachomatis... , prostatitis Prostatitis Prostatitis is an inflammation of the prostate gland, in men. A prostatitis diagnosis is assigned at 8% of all urologist and 1% of all primary care physician visits in the United States.-Classification:... , cystitis Cystitis Cystitis is a term that refers to urinary bladder inflammation that results from any one of a number of distinct syndromes. It is most commonly caused by a bacterial infection in which case it is referred to as a urinary tract infection.-Signs and symptoms:... , priapism Priapism Priapism is a potentially harmful and painful medical condition in which the erect penis or clitoris does not return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours. There are two types of priapism: low-flow and high-flow. Low-flow... , Interstitial nephritis Interstitial nephritis Interstitial nephritis is a form of nephritis affecting the interstitium of the kidneys surrounding the tubules... , orchitis Orchitis Orchitis or orchiditis is a condition of the testes involving inflammation. It can also involve swelling and frequent infection.-Symptoms:Symptoms of orchitis are similar to those of testicular torsion... , nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine.... . |
| CNS Central nervous system The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish... |
Lethargy, semicoma, Aseptic meningitis Aseptic meningitis Aseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings... , and sensorineural deafness. |
| RS Respiratory system The respiratory system is the anatomical system of an organism that introduces respiratory gases to the interior and performs gas exchange. In humans and other mammals, the anatomical features of the respiratory system include airways, lungs, and the respiratory muscles... |
Shortness of breath, Influenza-like illness Influenza-like illness Influenza-like illness , also known as acute respiratory infection and flu-like syndrome, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms, with SARI referring to Severe Acute Respiratory Infection.Symptoms commonly include fever, shivering, chills,... , plural effusion, Atelectasis Atelectasis Atelectasis is defined as the collapse or closure of alveoli resulting in reduced or absent gas exchange. It may affect part or all of one lung. It is a condition where the alveoli are deflated, as distinct from pulmonary consolidation.It is a very common finding in chest x-rays and other... . |
| Skin Skin -Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat... |
Erythema Erythema Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation... and induration at BCG Bacillus Calmette-Guérin Bacillus Calmette-Guérin is a vaccine against tuberculosis that is prepared from a strain of the attenuated live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially subcultured in an artificial medium for 13 years, and also prepared from... vaccine site, Beau's lines Beau's lines Beau's lines are deep grooved lines that run from side to side on the fingernail. They may look like indentations or ridges in the nail plate. This condition of the nail was named by a French physician, Joseph Honoré Simon Beau , who first described it in 1846.Beau's lines are horizontal, going... , and finger Finger A finger is a limb of the human body and a type of digit, an organ of manipulation and sensation found in the hands of humans and other primates.... gangrene Gangrene Gangrene is a serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies . This may occur after an injury or infection, or in people suffering from any chronic health problem affecting blood circulation. The primary cause of gangrene is reduced blood... . |
| Source: review, table. | |
In the acute phase of the disease changes in the peripheral extremities can include erythema
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
of the palms and soles, which is often striking with sharp demarcation, and often accompanied by painful, brawny edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
of the dorsa of the hands or feet in the acute phase of the disease, and it is why affected children frequently refuse to hold objects in their hands or to bear weight on their feet. Later during the convalescent or the subacute phase desquamation
Desquamation
Desquamation , also called skin peeling, is the shedding of the outermost membrane or layer of a tissue, such as the skin.-Skin:Normal, nonpathologic desquamation of the skin occurs when keratinocytes, after moving apically over about 14 days, are individually shed unnoticeably...
of the fingers and toes usually begins in the periungual region within two to three weeks after the onset of fever and may extend to include the palms and soles, and around 11% of children affected by the disease may continue skin peeling for many years. 1 to 2 months after the onset of fever deep transverse grooves
Beau's lines
Beau's lines are deep grooved lines that run from side to side on the fingernail. They may look like indentations or ridges in the nail plate. This condition of the nail was named by a French physician, Joseph Honoré Simon Beau , who first described it in 1846.Beau's lines are horizontal, going...
across the nails may develop (Beau’s lines), And occasionally nail are shed.
The most common cutaneous manifestation is a diffuse macular
Cutaneous conditions
There are many conditions of or affecting the human integumentary system—the organ system that comprises the entire surface of the body and includes skin, hair, nails, and related muscle and glands.- Diseases :...
-papular erythematous rash, which is quite nonspecific. The rash varies over time and is characteristically located on the trunk and may further spread to involve the face, extremities, and perineum. many other forms of cutaneous lesions have been reported also, they may include Scarlatiniform, popular
Popular
Popular may in various ways refer to:*an adjective referring to any people or population*Social status, the quality of being well-liked or well-known*Popularity, the quality of being well-liked...
, urticariform
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
, multiform-like erythema
Erythema multiforme
Erythema multiforme is a skin condition of unknown cause, possibly mediated by deposition of immune complex in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure...
, and purpuric lesions, even micropustules were reported, it can be polymorphic, non-itchy
Itch
Itch is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to classify it as any one type of sensory experience. Modern science has shown that itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response...
and normally observed up to the fifth day of fever. however it is never bullous or vesicular
The syndrome affecting multiple organ systems, and in the acute stage of KD, systemic inflammatory changes are evident in many organs. Joint pain (arthralgia
Arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
) and swelling, frequently symmetrical, Also arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
can occur. Myocarditis
Myocarditis
Myocarditis is inflammation of heart muscle . It resembles a heart attack but coronary arteries are not blocked.Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi or Trypanosoma cruzi, or as a...
, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, pericarditis
Pericarditis
Pericarditis is an inflammation of the pericardium . A characteristic chest pain is often present.The causes of pericarditis are varied, including viral infections of the pericardium, idiopathic causes, uremic pericarditis, bacterial infections of the precardium Pericarditis is an inflammation of...
, valvulitis, aseptic meningitis
Aseptic meningitis
Aseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings...
, pneumonitis
Pneumonitis
Pneumonitis or pulmonitis is a general term that refers to inflammation of lung tissue.Pneumonia is pneumonitis combined with consolidation and exudation...
, lymphadenitis, and hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
may be present and are manifested by the presence of inflammatory cells in the affected tissues. If left untreated, some symptoms will eventually relent, but coronary artery aneurysms will not improve, resulting in a significant risk of death or disability due to myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
(heart attack). If treated in a timely fashion, this risk can be mostly avoided and the course of illness cut short.
Other reported non-specific symptoms include cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, rhinorrhea
Rhinorrhea
Rhinorrhea or rhinorrhoea is a condition where the nasal cavity is filled with a significant amount of mucous fluid. The condition, commonly known as "runny nose", occurs relatively frequently and is not usually considered dangerous. Rhinorrhea is a common symptom of allergies or certain diseases,...
, sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....
, vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, and seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
.
The course of the disease can be divided into three clinical phases. The acute
Acute
Acute may refer to:* Acute accent* Acute angle* Acute * Acute * Acute toxicity...
febrile phase, which usually lasts for 1 to 2 weeks, is characterized by fever, conjunctival injection, erythema of the oral mucosa, erythema and swelling of the hands and feet, rash, cervical adenopathy, aseptic meningitis
Aseptic meningitis
Aseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings...
, diarrhea, and hepatic dysfunction. Myocarditis is common during this time, and a pericardial effusion may be present. Coronary arteritis
Arteritis
Arteritis is inflammation of the walls of arteries, usually as a result of infection or auto-immune response.-Types:Some disorders have arteritis as their main feature...
may be present, but aneurysms are generally not yet visible by echocardiography
Echocardiography
An echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart . Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart...
. The subacute phase begins when fever, rash, and lymphadenopathy
Lymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
resolve at about 1 to 2 weeks after the onset of fever, but irritability, anorexia, and conjunctival injection persist. Desquamation
Desquamation
Desquamation , also called skin peeling, is the shedding of the outermost membrane or layer of a tissue, such as the skin.-Skin:Normal, nonpathologic desquamation of the skin occurs when keratinocytes, after moving apically over about 14 days, are individually shed unnoticeably...
of the fingers and toes and thrombocytosis
Thrombocytosis
Thrombocytosis is the presence of high platelet counts in the blood, and can be either primary or reactive...
are seen during this stage, which generally lasts until about 4 weeks after the onset of fever. Coronary artery aneurysms usually develop during this time, and the risk for sudden death
Sudden death
In a sport or game, sudden death is a form of competition where play ends as soon as one competitor is ahead of the others, with that competitor becoming the winner. Sudden death is typically used as a tiebreaker when a contest is tied at the end of the normal playing time or the completion of...
is highest during this stage. The convalescent stage begins when all clinical signs of illness have disappeared and continues until the sedimentation rate
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
returns to normal, usually at 6 to 8 weeks after the onset of illness.
There is differences in clinical presentation between adults and children, as adults have more affection of neck lymph nodes (93% of adults versus 15% of children); hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
(65% versus 10%), and arthralgia
Arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
(61% versus 24-38%). Some patients have atypical presentations and may not have the classical symptoms and this occurs in particular in young infants, and those patients are especially at higher risk for cardiac artery aneurysms.
Complications
The cardiac complications are the most important aspect of the disease. Kawasaki disease can cause vasculitic changes (inflammation of blood vessels) in the coronary arteries and subsequent coronary artery aneurysmCoronary artery aneurysm
Coronary artery aneurysm is an abnormal dilatation of part of the coronary artery.-Causes:Acquired causes include atherosclerosis, Kawasaki disease and coronary catheterization.It can also be congenital....
s. These aneurysms can lead to myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
(heart attack) even in young children. Overall, about 10–18% of children with Kawasaki disease develop coronary artery aneurysms with much higher prevalence among patients who are not treated early in the course of illness. Kawasaki disease and rheumatic fever
Rheumatic fever
Rheumatic fever is an inflammatory disease that occurs following a Streptococcus pyogenes infection, such as strep throat or scarlet fever. Believed to be caused by antibody cross-reactivity that can involve the heart, joints, skin, and brain, the illness typically develops two to three weeks after...
are the most common causes of acquired heart disease among children in the United States. Other Kawasaki disease complications have been described, such as aneurysm
Aneurysm
An aneurysm or aneurism is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart...
of other arteries: aortic aneurysm, with a higher number of reported cases involving the abdominal aorta
Abdominal aorta
The abdominal aorta is the largest artery in the abdominal cavity. As part of the aorta, it is a direct continuation of the descending aorta .-Path:...
, axillary artery
Axillary artery
In human anatomy, the axillary artery is a large blood vessel that conveys oxygenated blood to the lateral aspect of the thorax, the axilla and the upper limb...
aneurysm, brachiocephalic artery
Brachiocephalic artery
The brachiocephalic artery is an artery of the mediastinum that supplies blood to the right arm and the head and neck....
aneurysm, aneurysm of iliac and femoral arteries, and renal artery
Renal artery
The renal arteries normally arise off the side of the abdominal aorta, immediately below the superior mesenteric artery, and supply the kidneys with blood. Each is directed across the crus of the diaphragm, so as to form nearly a right angle with the aorta....
aneurysm.
Gastrointestinal complications in Kawasaki disease are similar to those observed in Henoch-Schönlein purpura
Henoch-Schönlein purpura
Henoch–Schönlein purpura is a disease of the skin and other organs that most commonly affects children. In the skin, the disease causes palpable purpura ; often with joint and abdominal pain...
, such as: intestinal obstruction, colon
Colón
Colón is a Spanish and Portuguese surname, comparable to the Italian and Portuguese Colombo . It may refer to:People:* Cristóbal Colón, the Spanish language name for the explorer Christopher Columbus...
swelling, intestinal ischemia, intestinal pseudo-obstruction, and acute abdomen
Acute abdomen
The term acute abdomen refers to a sudden, severe abdominal pain of unclear etiology that is less than 24 hours in duration. It is in many cases a medical emergency, requiring urgent and specific diagnosis...
.
Ophthalmologic changes associated with the disease have been described since the 1980's, being found as uveitis
Uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, iridocyclitis
Iridocyclitis
Iridocyclitis, a type of anterior uveitis, is a condition in which the uvea of the eye is inflamed.Iridocyclitis isInflammation of the iris and the ciliary body.- Symptoms :Symptoms include:* Photophobia* Redness* Watering of the eyes* Lacrimation...
, conjunctival hemorrhage, optic neuritis
Optic neuritis
Optic neuritis is the inflammation of the optic nerve that may cause a complete or partial loss of vision.-Causes:The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the...
, amaurosis
Amaurosis
Amaurosis is vision loss or weakness that occurs without an apparent lesion affecting the eye. It may result from either a medical condition or from excess acceleration, as in flight...
and ocular artery obstruction. It can also be found as necrotizing vasculitis, progressing into peripheral gangrene.
The neurological complications per central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS) lesion are increasingly reported. The neurological complications found are meningoencephalitis
Meningoencephalitis
Meningoencephalitis is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain.-Causes:...
, subdural effusion
Subdural effusion
Subdural effusion refers to an effusion in the subdural space, usually of cerebrospinal fluid.It is sometimes treated with surgery....
, cerebral hypoperfusion, cerebral ischemia
Cerebral ischemia
Brain ischemia, also known as cerebral ischemia, is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus to the death of brain tissue or cerebral infarction / ischemic stroke...
and infarct, cerebelar infarction
Infarction
In medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:...
, manifesting with seizures, chorea, hemiplegia
Hemiplegia
Hemiplegia /he.mə.pliː.dʒiə/ is total paralysis of the arm, leg, and trunk on the same side of the body. Hemiplegia is more severe than hemiparesis, wherein one half of the body has less marked weakness....
, mental confusion
Mental confusion
Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...
, lethargy and coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
, or even a cerebral infarction with no neurological manifestations. Other neurological complications from cranial nerve involvement are reported as ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, facial palsy, and sensorineural auditory loss.
Causes
Like all autoimmune diseases, the cause of Kawasaki disease is presumably the interaction of genetic and environmental factors, possibly including an infection. The specific cause is unknown, but current theoriesTheory
The English word theory was derived from a technical term in Ancient Greek philosophy. The word theoria, , meant "a looking at, viewing, beholding", and referring to contemplation or speculation, as opposed to action...
center primarily on immunological
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
causes for the disease. Evidence increasingly points to an infectious etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
, but debate continues on whether the cause is a conventional antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
ic substance or a superantigen
Superantigen
Superantigens are a class of antigens which cause non-specific activation of T-cells resulting in oligoclonal T cell activation and massive cytokine release...
. Children's Hospital Boston
Children's Hospital Boston
Children's Hospital Boston is a 396-licensed bed children's hospital in the Longwood Medical and Academic Area of Boston, Massachusetts.At 300 Longwood Avenue, Children's is adjacent both to its teaching affiliate, Harvard Medical School, and to Dana-Farber Cancer Institute...
reported that "some studies have found associations between the occurrence of Kawasaki disease and recent exposure to carpet cleaning or residence near a body of stagnant water; however, cause and effect have not been established." Other data suggests possible correlation of KD with tropospheric wind patterns
An association has been identified with a SNP in the ITPKC
ITPKC
ITPKC is a gene that has been associated with Kawasaki disease.It codes an enzyme that negatively regulates T-cell activation....
gene, which codes an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that negatively regulates T-cell activation. An additional factor that suggests genetic susceptibility is the fact that regardless of where they are living, Japanese children are more likely than other children to contract the disease. The HLA-B51
HLA-B51
HLA-B51 is an HLA-B serotype. The serotype identifies the more common HLA-B*51 gene products.B51 is a split antigen of the broad antigen B5, and is a sister serotype of B52. There are a large number of alleles within the B*51 allele group...
serotype has been found to be associated with endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
instances of the disease.
Diagnosis
| Criteria for Diagnosis of Kawasaki Disease |
|---|
| Fever of ≥5 days' duration associated with at least 4† of the following 5 changes |
| Bilateral nonsuppurative conjunctivitis Conjunctivitis Conjunctivitis refers to inflammation of the conjunctiva... |
| One of more changes of the mucous membranes of the upper respiratory tract Upper respiratory tract The upper respiratory tract or upper airway primarily refers to the parts of the respiratory system lying outside of the thorax or above the sternal angle. Another definition commomly used in medicine is the airway above the glottis or vocal cords... , including pharyngeal Human pharynx The human pharynx is the part of the throat situated immediately posterior to the mouth and nasal cavity, and anterior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx , the oropharynx , and the laryngopharynx... injection, dry fissured lips, injected lips, and "strawberry" tongue Strawberry tongue Strawberry tongue is the appearance of tongue with inflamed red papillae, giving an appearance suggestive to a red strawberry.-Associated conditions:It is seen in Kawasaki disease, toxic shock syndrome, and scarlet fever.... |
| One or more changes of the extremities, including peripheral erythema Erythema Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation... , peripheral edema Edema Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling... , periungual desquamation Desquamation Desquamation , also called skin peeling, is the shedding of the outermost membrane or layer of a tissue, such as the skin.-Skin:Normal, nonpathologic desquamation of the skin occurs when keratinocytes, after moving apically over about 14 days, are individually shed unnoticeably... , and generalized desquamation |
| Polymorphous rash Rash A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and... , primarily truncal |
| Cervical lymphadenopathy Lymphadenopathy Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy.... >1.5 cm in diameter |
| Disease cannot be explained by some other known disease process |
| †A diagnosis of Kawasaki disease can be made if fever and only 3 changes are present in conjunction with coronary artery disease documented by two-dimensional echocardiography Echocardiography An echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart . Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart... or coronary angiography. |
| Source: Nelson's essentials of pediatrics, Review |
Kawasaki disease can only be diagnosed clinically (i.e. by medical sign
Medical sign
A medical sign is an objective indication of some medical fact or characteristic that may be detected by a physician during a physical examination of a patient....
s and symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s). There exists no specific laboratory test for this condition. It is difficult to establish the diagnosis, especially early in the course of the illness, and frequently children are not diagnosed until they have seen several health care providers. Many other serious illnesses can cause similar symptoms, and must be considered in the differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...
, including scarlet fever
Scarlet fever
Scarlet fever is a disease caused by exotoxin released by Streptococcus pyogenes. Once a major cause of death, it is now effectively treated with antibiotics...
, toxic shock syndrome, juvenile idiopathic arthritis
Juvenile idiopathic arthritis
Juvenile idiopathic arthritis is the most common form of persistent arthritis in children. JIA is a subset of arthritis seen in childhood, which may be transient and...
, and childhood mercury poisoning (infantile acrodynia).
Classically, five days of fever plus four of five diagnostic
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
criteria must be met in order to establish the diagnosis. The criteria are: (1) erythema
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
of the lips or oral cavity or cracking of the lips; (2) rash on the trunk; (3) swelling or erythema of the hands or feet; (4) red eyes (conjunctival injection) (5) swollen lymph node in the neck of at least 15 millimeters.
Many children, especially infants, eventually diagnosed with Kawasaki disease do not exhibit all of the above criteria. In fact, many experts now recommend treating for Kawasaki disease even if only three days of fever have passed and at least three diagnostic criteria are present, especially if other tests reveal abnormalities consistent with Kawasaki disease. In addition, the diagnosis can be made purely by the detection of coronary artery aneurysms in the proper clinical setting.
Investigations
A physical examination will demonstrate many of the features listed above.Blood tests
- Complete blood countComplete blood countA complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
(CBC) may reveal normocytic anemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
and eventually thrombocytosisThrombocytosisThrombocytosis is the presence of high platelet counts in the blood, and can be either primary or reactive... - Erythrocyte sedimentation rateErythrocyte sedimentation rateThe erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
(ESR) will be elevated - C-reactive proteinC-reactive proteinC-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
(CRP) will be elevated - Liver function testsLiver function testsLiver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...
may show evidence of hepatic inflammation and low serum albuminSerum albuminSerum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
Other optional tests
- ElectrocardiogramElectrocardiogramElectrocardiography is a transthoracic interpretation of the electrical activity of the heart over a period of time, as detected by electrodes attached to the outer surface of the skin and recorded by a device external to the body...
may show evidence of ventricularVentricle (heart)In the heart, a ventricle is one of two large chambers that collect and expel blood received from an atrium towards the peripheral beds within the body and lungs. The Atria primes the Pump...
dysfunction or, occasionally, arrhythmia due to myocarditisMyocarditisMyocarditis is inflammation of heart muscle . It resembles a heart attack but coronary arteries are not blocked.Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi or Trypanosoma cruzi, or as a... - Echocardiogram may show subtle coronary artery changes or, later, true aneurysms.
- UltrasoundUltrasoundUltrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
or computerized tomography may show hydrops (enlargement) of the gallbladderGallbladderIn vertebrates the gallbladder is a small organ that aids mainly in fat digestion and concentrates bile produced by the liver. In humans the loss of the gallbladder is usually easily tolerated.... - UrinalysisUrinalysisA urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
may show white blood cells and protein in the urine (pyuriaPyuriaIn medicine, Pyuria refers to urine which contains pus. Defined as the presence of 4 or more neutrophils per high power field of unspun, voided mid-stream urine. It can be sign of a bacterial urinary tract infection...
and proteinuriaProteinuriaProteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
) without evidence of bacterial growth - Lumbar punctureLumbar punctureA lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
may show evidence of aseptic meningitisAseptic meningitisAseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings... - Angiography was historically used to detect coronary artery aneurysms and remains the gold standard for their detection, but is rarely used today unless coronary artery aneurysms have already been detected by echocardiography.
- Temporal artery biopsy
Treatment
Children with Kawasaki disease should be hospitalized and cared for by a physician who has experience with this disease. When in an academic medical center, care is often shared between pediatric cardiologyCardiology
Cardiology is a medical specialty dealing with disorders of the heart . The field includes diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular heart disease and electrophysiology...
and pediatric infectious disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
specialists (although no specific infectious agent has been identified as yet). It is imperative that treatment be started as soon as the diagnosis is made to prevent damage to the coronary arteries.
Intravenous immunoglobulin
Intravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
(IVIG) is the standard treatment for Kawasaki disease and is administered in high doses with marked improvement usually noted within 24 hours. If the fever does not respond, an additional dose may have to be considered. In rare cases, a third dose may be given to the child. IVIG by itself is most useful within the first seven days of onset of fever, in terms of preventing coronary artery aneurysm.
Salicylate therapy, particularly aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
, remains an important part of the treatment (though questioned by some) but salicylates alone are not as effective as IVIG. Aspirin therapy is started at high doses until the fever subsides, and then is continued at a low dose when the patient returns home, usually for two months to prevent blood clots from forming. Except for Kawasaki disease and a few other indications, aspirin is otherwise normally not recommended for children due to its association with Reye's syndrome
Reye's syndrome
Reye's syndrome is a potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver, as well as causing a lower than usual level of blood sugar . The classic features are liver damage, aspirin use and a viral infection...
. Because children with Kawasaki disease will be taking aspirin for up to several months, vaccination against varicella and influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
is required, as these infections are most likely to cause Reye's syndrome.
Corticosteroids have also been used, especially when other treatments fail or symptoms recur, but in a randomized controlled trial, the addition of corticosteroid to immune globulin and aspirin did not improve outcome. Additionally, corticosteroid use in the setting of Kawasaki disease is associated with increased risk of coronary artery aneurysm, and so its use is generally contraindicated in this setting. In cases of kawasaki disease refractory to IVIG, cyclophosphamide and plasma exchange have been investigated as possible treatments, with variable outcomes.
There are also treatments for iritis and other eye symptoms.
Another treatment may include the use of Infliximab (Remicade). Infliximab works by binding tumour necrosis factor alpha.
Prognosis
With early treatment, rapid recovery from the acute symptoms can be expected and the risk of coronary artery aneurysms greatly reduced. Untreated, the acute symptoms of Kawasaki disease are self-limited (i.e. the patient will recover eventually), but the risk of coronary artery involvement is much greater. Overall, about 2% of patients die from complications of coronary vasculitis. Patients who have had Kawasaki disease should have an echocardiogram initially every few weeks, and then every one or two years to screen for progression of cardiac involvement.It is also not uncommon that a relapse
Relapse
Relapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...
of symptoms may occur soon after initial treatment with IVIG. This usually requires re-hospitalization and re-treatment. Treatment with IVIG can cause allergic and non-allergic acute reactions, aseptic meningitis, fluid overload and, rarely, other serious reactions. Overall, life-threatening complications resulting from therapy for Kawasaki disease are exceedingly rare, especially compared with the risk of non-treatment. There is also evidence that Kawasaki disease produces altered lipid metabolism
Lipid metabolism
Lipid metabolism refers to the processes that involve the intercourse and degradation of lipids.The types of lipids involved include:* Bile salts* Cholesterols* Eicosanoids* Glycolipids* Ketone bodies* Fatty acids - see also fatty acid metabolism...
that persists beyond clinical resolution of the disease.
Epidemiology
Kawasaki disease affects boys more than girls with people of Asian ethnicity, particularly Japanese and Korean people are most susceptible as well as people of Afro-Caribbean ethnicity. The disease was rare in Caucasians until the last few decades and incidence rate fluctuates from country to country.Currently, Kawasaki disease is the most commonly diagnosed pediatric vasculitis in the world. By far the highest incidence of Kawasaki disease occurs in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, with the most recent study placing the attack rate at 218.6 per 100,000 children <5 years of age (~1 in 450 children). At this present attack rate, more than 1 in 150 children in Japan will develop Kawasaki disease during their lifetime.
However, its incidence in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
is increasing. Kawasaki disease is predominantly a disease of young children, with 80% of patients younger than five years of age. Approximately 2,000-4,000 cases are identified in the United States each year.
In the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, estimates of incidence rate vary because of the rarity of Kawasaki disease. However, Kawasaki disease is believed to affect fewer than 1 in every 25,000 people. Incidence of the disease doubled from 1991 to 2000 however, with 4 cases in per 100,000 children in 1991 compared with a rise of 8 cases per 100,000 in 2000.
History
The disease was first reported by Dr. Tomisaku Kawasaki in a four-year-old child with a rash and fever at the Red Cross Hospital in TokyoTokyo
, ; officially , is one of the 47 prefectures of Japan. Tokyo is the capital of Japan, the center of the Greater Tokyo Area, and the largest metropolitan area of Japan. It is the seat of the Japanese government and the Imperial Palace, and the home of the Japanese Imperial Family...
, Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
in January of 1961, and later published a report on 50 similar cases.Later Yamamoto and colleagues were persuade that there is definite cardiac involvement when they studied and reported 23 cases, of which 11(48%) patients had abnormalities detected by an electrocardiogram
Electrocardiogram
Electrocardiography is a transthoracic interpretation of the electrical activity of the heart over a period of time, as detected by electrodes attached to the outer surface of the skin and recorded by a device external to the body...
. It was not until 1974 that the first description of this disorder was published in the English language literature.in the year 1976 Melish et al., described the same illness in 16 children in Hawaii.Melish and Kawasaki had independently developed the same diagnostic criteria for the disorder, which are still used today to make the diagnosis of classic KS.
A question was raised whether the disease only started during the period between 1960 and 1970, but later a preserved heart of a 7 year old boy died in 1870 was examined and showed three aneurysms of the coronary arteries with clots, as well as pathologic changes consistent with KS. KS is now recognized worldwide. In the United States and other developed nations, it appears to have replaced acute rheumatic fever as the most common cause of acquired heart disease in children.
External links
- Kawasaki Disease Research Program
- Kawasaki Disease information from Seattle Children's Hospital Heart Center