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{{Kawasaki disease}}
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   Name          = Kawasaki disease |
   Name          = Kawasaki disease |
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   eMedicineTopic = 1236 |
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'''For patient information, click [[Kawasaki disease (patient information)|here]]'''


{{CMG}}; {{AE}} {{CZ}}
{{CMG}}; {{AE}} {{SH}}, {{AKK}}


{{SK}} Mucocutaneous lymph node syndrome; Lymph node syndrome; Acute febrile vasculitic syndrome
===[[The Heart in Kawasaki Disease | For the heart in Kawasaki disease click here]]===
===[[The Heart in Kawasaki Disease | For the heart in Kawasaki disease click here]]===


'''Kawasaki disease''', also known as '''lymph node syndrome''', '''mucocutaneous node disease''', '''infantile polyarteritis''' and '''Kawasaki syndrome''', is a poorly understood self-limited [[vasculitis]] that affects many organs, including the [[skin]] and [[mucous membrane]]s, [[lymph node]]s, [[blood vessel]] walls, and the [[heart]]. It does not seem to be contagious. It was first described in 1967 by Dr. Tomisaku Kawasaki in Japan.<ref>{{cite journal | author = Kawasaki T | title = [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children] | format=in Japanese | journal = Arerugi | volume = 16 | issue = 3 | pages = 178-222 | year = 1967 | id = PMID 6062087}}</ref>
==[[Kawasaki disease overview|Overview]]==


== Epidemiology and Demographics ==
==[[Kawasaki disease historical perspective|Historical Perspective]]==
KS occurs worldwide, with the highest incidence in Japan, and it most often affects boys and younger children. KS may have a winter-spring seasonality, and community-wide outbreaks have been reported occasionally. In the continental United States, population-based and hospitalization studies have estimated an incidence of KS ranging from 9 to 19 per 100,000 children younger than 5 years of age. Approximately 4248 hospitalizations for KS, of which 3277 (77%) were for children under 5 years of age, were estimated among children younger than 18 years of age in the United States in the year 2000.


CDC uses hospital discharge data, a passive KS surveillance system, and special studies to describe the incidence and epidemiology of KS in the United States. The KS surveillance system has been maintained by CDC since 1976 and is based on voluntary reporting of KS cases by health care providers and local and state health authorities. A standardized case report form is used to collect information on patients.
==[[Kawasaki disease classification|Classification]]==


For epidemiologic surveillance, CDC defines a case of KS as illness in a patient with fever of 5 or more days duration (or fever until the date of administration of intravenous immunoglobulin if it is given before the fifth day of fever), and the presence of at least 4 of the following 5 clinical signs:
==[[Kawasaki disease pathophysiology|Pathophysiology]]==


*Rash
==[[Kawasaki disease causes|Causes]]==
*Cervical lymphadenopathy (at least 1.5 cm in diameter)
*Bilateral conjuctival injection
*Oral mucosal changes
*Peripheral extremity changes.


Patients whose illness does not meet the above KS case definition but who have fever and coronary artery abnormalities are classified as having atypical or incomplete KS.
==[[Kawasaki disease differential diagnosis|Differentiating Kawasaki disease from other Diseases]]==


==Incidence, causes, and risk factors==
==[[Kawasaki disease epidemiology and demographics|Epidemiology and Demographics]]==
By far, the highest incidence of Kawasaki disease occurs in Japan (175 per 100,000), though its incidence in the United States is increasing. Kawasaki disease is predominantly a disease of young children, with 80% of patients younger than 5 years of age. Additional risk factors in the United States include Asian race and male sex.


The causative agent of Kawasaki disease is still unknown. However, current [[etiology|etiological]] theories center primarily on [[immune system|immunological]] causes for the disease. Much research is being performed to discover a definitive [[toxin]] or [[antigen]]ic substance, possibly a [[superantigen]], that is the specific cause of the disease. An unknown virus may play a role as an inciting factor as well.
==[[Kawasaki disease risk factors|Risk Factors]]==


The [[cardiac]] complications are, by far, 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 [[aneurysm]]s'''. These aneurysms can lead to [[myocardial infarction]] ([[myocardial infarction|heart attack]]) even in young children. Overall, about 10&ndash;18% of children with Kawasaki disease develop coronary artery aneurysms<ref>{{cite journal | author = Belay E, Maddox R, Holman R, Curns A, Ballah K, Schonberger L | title = Kawasaki syndrome and risk factors for coronary artery abnormalities: United States, 1994-2003. | journal = Pediatr Infect Dis J | volume = 25 | issue = 3 | pages = 245-9 | year = 2006 | id = PMID 16511388}}</ref>, with much higher prevalence among patients who are not treated early in the course of illness.  Kawasaki disease is the most common cause of acquired heart disease among children in the United States.
==[[Kawasaki disease screening|Screening]]==


==Symptoms==
==[[Kawasaki disease natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
Kawasaki disease often begins with a high and persistent [[fever]] that is not very responsive to normal doses of [[acetaminophen]] or [[ibuprofen]]. The fever may persist steadily for up to two weeks and is normally accompanied by irritability. Affected children develop red eyes, red [[mucous membrane]]s in the mouth, red cracked lips, a "[[strawberry tongue]]", iritis, keratic precipitates (detectable by an ophthalmologist but usually too small to be seen by the unaided eye), and swollen [[lymph node]]s. [[Skin rash]]es occur early in the disease, and peeling of the skin in the [[genital area]], hands, and feet (especially around the nails and on the palms and soles) may occur in later phases. Some of these symptoms may come and go during the course of the illness. If left untreated, the 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.
 
* High-grade fever (greater than 39&nbsp;°C or 102&nbsp;°F; often as high as 40&nbsp;°C  or 104&nbsp;°F) that normally lasts for more than a week if left untreated.
* Red eyes ([[conjunctivitis]]) without pus or drainage, also known as "conjunctival injection"
* Bright red, chapped, or cracked lips
* Red [[mucous membrane]]s in the mouth
* Strawberry tongue, white coating on the tongue or prominent red bumps ([[papillae]]) on the back of the tongue
* Red palms of the hands and the soles of the feet
* Swollen hands and feet
* Rash which may take many forms, but not vesicular (blister-like), on the trunk
* Swollen [[lymph node]]s (frequently only one lymph node is swollen), particularly in the neck area
* Joint pain ([[arthralgia]]) and swelling, frequently symmetrical
* Irritability
* [[Tachycardia]] (rapid heart beat)
* Peeling (desquamation) palms and soles (later in the illness); peeling may begin around the nails
 
==Signs and tests==
A physical examination will demonstrate many of the features listed above.
 
Blood tests
* [[Complete blood count]] (CBC) may reveal normocytic [[anemia]] and eventually [[thrombocytosis]]
* [[Erythrocyte sedimentation rate]] (ESR) will be elevated
* [[C-reactive protein]] (CRP) will be elevated
* [[Liver function tests]] may show evidence of hepatic inflammation and low [[serum albumin]]
 
Other tests (may or may not be performed)
* [[Electrocardiogram]] may show evidence of [[ventricular]] dysfunction or, occasionally, [[arrhythmia]] due to [[myocarditis]]
* [[Echocardiogram]] may show subtle coronary artery changes or, later, true aneurysms.
* [[Ultrasound]] or [[computerized tomography]] may show hydrops (enlargement) of the [[gallbladder]]
* [[Urinalysis]] may show white blood cells and protein in the urine ([[pyuria]] and [[proteinuria]]) without evidence of bacterial growth
* [[Lumbar puncture]] may show evidence of [[aseptic meningitis]]
* [[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.


==Diagnosis==
==Diagnosis==
Kawasaki disease is diagnosed clinically (by [[medical sign]]s and [[symptom]]s), and there exists no specific laboratory test that can tell if someone has it. It is normally difficult to establish the diagnosis, especially early in the course of illness, and frequently children are not diagnosed until they have seen their doctor several times, or visited a number of different 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, and [[juvenile idiopathic arthritis]].
[[Kawasaki disease diagnostic criteria|Diagnostic criteria]] | [[Kawasaki disease history and symptoms|History and Symptoms]] | [[Kawasaki disease physical examination|Physical Examination]] | [[Kawasaki disease laboratory findings|Laboratory Findings]] | [[Kawasaki disease electrocardiogram|Electrocardiogram]] | [[Kawasaki disease x ray|X-Ray Findings]] | [[Kawasaki disease echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Kawasaki disease CT scan|CT-Scan Findings]] | [[Kawasaki disease MRI|MRI Findings]] | [[Kawasaki disease other imaging findings|Other Imaging Findings]] | [[Kawasaki disease other diagnostic studies|Other Diagnostic Studies]]
 
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.
 
==Differentiating Kawasaki disease from other diseases==
Different [[rash]]-like conditions may be misdiagnosed with [[Kawasaki disease]], including:<ref name="MooreSeward2006">{{cite journal|last1=Moore|first1=Zack S|last2=Seward|first2=Jane F|last3=Lane|first3=J Michael|title=Smallpox|journal=The Lancet|volume=367|issue=9508|year=2006|pages=425–435|issn=01406736|doi=10.1016/S0140-6736(06)68143-9}}</ref>
*[[Insect bite]]s - In an [[insect bite]], the insect injects [[formic acid]], which can cause an immediate [[skin]] reaction often resulting in a [[rash]] and swelling in the injured area, often with formation of [[vesicles]].
 
*[[Measles]] - commonly presents with high [[fever]], [[coryza]] and [[conjunctivitis]], with observation of [[oral mucosa|oral mucosal]] lesions ([[Koplik's spots]]), followed by widespread [[skin rash]].
 
*[[Monkeypox]] - presentation is similar to [[smallpox]], although it is often a milder form, with [[fever]], [[headache]], [[myalgia]], [[back pain]], [[swollen lymph nodes]], a general feeling of discomfort, and exhaustion. Within 1 to 3 days (sometimes longer) after the appearance of [[fever]], the patient develops a papular [[rash]], often first on the face. The lesions usually develop through several stages before crusting and falling off.
 
*[[Rubella]] - commonly presents with a facial [[rash]] which then spreads to the [[trunk]] and [[limbs]], fading after 3 days, low grade [[fever]], swollen [[glands]], [[joint pain]]s, [[headache]] and [[conjunctivitis]]. The [[rash]] disappears after a few days with no staining or peeling of the [[skin]]. ''[[Forchheimer's sign]]'' occurs in 20% of cases, and is characterized by small, red [[papules]] on the area of the [[soft palate]].
 
*Atypical [[measles]] - symptoms commonly begin about 7-14 days after infection and present as [[fever]], [[cough]], [[coryza]] and [[conjunctivitis]]. Observation of [[Koplik's spots]] is also a characteristic finding in measles.
 
*[[Coxsackievirus]] - the most commonly caused disease is the [[Coxsackie A]] disease, presenting as ''hand, foot and mouth disease''. It may be [[asymptomatic]] or cause mild [[symptoms]], or it may produce [[fever]] and painful [[blisters]] in the mouth ([[herpangina]]), on the palms and fingers of the hand, or on the soles of the feet. There can also be [[blisters]] in the [[throat]]  or above the [[tonsils]]. Adults can also be affected. The [[rash]], which can appear several days after high temperature and painful sore throat, can be itchy and painful, especially on the hands/fingers and bottom of feet.
 
*[[Acne]] - typical of teenagers, usually appears on the [[face]] and upper neck, but the [[chest]], [[human back|back]] and [[shoulder]]s may have [[acne]] as well. The upper [[arm]]s can also have [[acne]], but lesions found there are often [[keratosis pilaris]], not [[acne]]. The typical [[acne]] lesions are [[comedones]] and [[inflammatory]] [[papules]], [[pustules]], and [[nodules]]. Some of the large [[nodules]] were previously called "[[cyst]]s"
 
*[[Syphilis]] - commonly presents with gneralized systemic [[symptoms]] such as [[malaise]], [[fatigue]], [[headache]] and [[fever]]. [[Skin]] eruptions may be subtle and [[asymptomatic]] Classically described as 1) non-pruritic bilateral symmetrical mucocutaneous [[rash]]; 2) non-tender regional [[lymphadenopathy]]; 3) condylomata lata; and 4) patchy [[alopecia]].
 
*[[Molluscum contagiosum]] -  lesions are commonly flesh-colored, dome-shaped, and pearly in appearance. They are often 1-5 millimeters in diameter, with a dimpled center. Generally not painful, but they may itch or become irritated. Picking or scratching the lesions may lead to further [[infection]] or scarring. In about 10% of the cases, [[eczema]] develops around the lesions. They may occasionally be complicated by secondary [[bacterial infections]].
 
*[[Mononucleosis]] - Common [[symptoms]] include low-grade [[fever]] without [[chills]], [[sore throat]], white patches on [[tonsils]] and back of the throat, [[muscle weakness]] and sometime extreme [[fatigue]], tender [[lymphadenopathy]], [[petechial hemorrhage]] and [[skin rash]].
 
*Toxic [[erythema]] - common [[rash]] in infants, with clustered and [[vesicular]] appearance.
 
*[[Rat-bite fever]] - commonly presents with [[fever]], [[chills]], open sore at the site of the bite and [[rash]], which may show red or purple plaques.
 
*[[Parvovirus B19]] - the [[rash]] of fifth disease is typically described as "slapped cheeks," with [[erythema]] across the cheeks and sparing the nasolabial folds, forehead, and mouth.
 
*[[Cytomegalovirus]] - common [[symptoms]] include [[sore throat]], swollen [[lymph nodes]], [[fever]], [[headache]], [[fatigue]], [[weakness]], [[muscle pain]]  and [[loss of appetite]].
 
*[[Scarlet fever]] - commonly includes [[fever]], punctate red [[macules]] on the hard and soft [[palate]] and [[uvula]] ([[Forchheimer's spots]]), bright red [[tongue]] with a "strawberry" appearance, [[sore throat]] and [[headache]] and [[lymphadenopathy]].
 
*[[Rocky Mountain spotted fever]] - [[symptoms]] may include [[maculopapular rash]], [[petechial rash]], [[abdominal pain]] and [[joint pain]].
 
*[[Stevens-Johnson syndrome]] - [[symptoms]] may include [[fever]], [[sore throat]]  and [[fatigue]]. Commonly presents [[ulcers]] and other lesions in the [[mucous membranes]], almost always in the [[mouth]] and lips but also in the genital and anal regions. Those in the mouth are usually extremely painful and reduce the patient's ability to eat or drink. [[Conjunctivitis]] of the eyes occurs in about 30% of children. A [[rash]] of round lesions about an inch across, may arise on the face, trunk, arms and legs, and soles of the feet, but usually not on the scalp.
 
*[[Varicella-zoster virus]] - commonly starts as a painful [[rash]] on one side of the face or body. The [[rash]] forms blisters that typically scab over in 7-10 days and clears up within 2-4 weeks.
 
*[[Chickenpox]] - commonly starts with [[conjunctival]] and catarrhal [[symptoms]] and then characteristic spots appearing in two or three waves, mainly on the body and head, rather than the hands, becoming itchy raw pox (small open sores which heal mostly without scarring). Touching the fluid from a [[chickenpox]] blister can also spread the disease.
 
*[[Meningococcemia]] - commonly presents with [[rash]], [[petechiae]], [[headache]], [[confusion]], and [[stiff neck]], high [[fever]], mental status changes, [[nausea]] and [[vomiting]].
 
*[[Rickettsialpox]] - first [[symptom]] is commonly a bump formed by a mite-bite, eventually resulting in a black, crusty scab. Many of the [[symptoms]] are [[flu]]-like including [[fever]], [[chills]], [[weakness]] and [[muscle pain]] but the most distinctive [[symptom]] is the [[rash]] that breaks out, spanning the person's entire body.
 
*[[Meningitis]] - commonly presents with [[headache]], [[nuchal rigidity]], [[fever]], [[petechiae]] and [[altered mental status]].
 
*[[Impetigo]] - commonly presents with pimple-like lesions surrounded by [[erythematous]] [[skin]]. Lesions are [[pustules]], filled with [[pus]], which then break down over 4-6 days and form a thick crust. It's often associated with insect bites, cuts, and other forms of [[trauma]] to the [[skin]].


==Treatment==
==Treatment==
The mainstay of therapy for Kawasaki disease is [[Intravenous Immunoglobulin]] ([[IVIG]]) and [[salicyclate]] therapy, particularly [[aspirin]].  It is imperative that treatment be started as soon as the diagnosis is made to prevent damage to the [[coronary arteries]].  Except for Kawasaki disease and a couple of other indications, aspirin is otherwise normally not recommended for children due to its association with [[Reye's syndrome]].  Children with Kawasaki disease should be hospitalized. [[Corticosteroids]] have also been used, especially when other treatments fail or symptoms recur. <ref>Newburger JW et al, Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease, N Engl J Med. 2007 Feb 25;356(7):663-75</ref>
[[Kawasaki disease medical therapy|Medical Therapy]] | [[Kawasaki disease surgery|Surgery]] | [[Kawasaki disease primary prevention|Primary Prevention]] | [[Kawasaki disease cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Kawasaki disease future or investigational therapies|Future or Investigational Therapies]]
 
 
*1. '''Initial treatment''' <ref>{{cite web | title = Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease
| url =http://circ.ahajournals.org/content/110/17/2747.full }}</ref>
:* Preferred regimen: [[IVIG]] 2 g/kg single infusion within the first 7-10 days of illness {{and}} [[Aspirin]] 80-100 mg/kg/day qid , reduce the aspirin dose after the child has been afebrile for 48 to 72 hours, then begin low-dose aspirin (3 to 5 mg/kg/day) and maintain it until the patient shows no evidence of coronary changes by 6 to 8 weeks after the onset of illness
:* Note (1): Other clinicians continue highdose aspirin until day 14 of illness and 48 to 72 hours after fever cessation
:* Note (2): For children who develop coronary abnormalities, aspirin may be continued indefinitely
 
*2. '''Treatment of Patients Who Failed to Respond to Initial Therapy (persistent or recrudescent fever ≥ 36 hours after completion of the initial IVIG infusion)'''
:* Preferred regimen: [[IVIG]] 2 g/kg q24h for 1-3 days {{or}} [[Methylprednisolone]] 30 mg/kg IV for 2-3 hours q24h for 1-3 days


==Prognosis==
==Case Studies==
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 1&ndash;2 years to screen for progression of cardiac involvement.
[[Kawasaki disease case study one|Case #1]]
 
It is also not uncommon that a [[relapse]] of symptoms may occur soon after initial treatment with [[IVIG]]. This usually requires re-hospitalization and retreatment. Treatment with [[IVIG]] can cause allergic and non-allergic acute reactions, aseptic meningitis, [[fluid overload]] and, rarely, other serious reactions. Aspirin may increase the risk of bleeding from other causes and may be associated with Reye's syndrome. Overall, life-threatening complications resulting from therapy for Kawasaki disease are exceedingly rare, especially compared with the risk of non-treatment.
 
==Media==
Kawasaki disease was mentioned in the television programs Nip/Tuck and Without a Trace <ref>Episode 86 (4x16) - The Little Things (2 March, 2006)</ref>.  In the episode All In of the TV series House, it was inexplicably mentioned as a possible diagnosis for a 6 year old boy that was admitted with bloody diarrhea and coordination problems, as well as an elderly woman with unexplained respiratory, cardiovascular and neural deficiencies. Maxie Jones, a fictional character on General Hospital suffers from it. According to John Travolta and Kelly Preston, their son Jett Travolta also suffers from the disease.
 
==References==
{{Reflist|2}}


[[Category: (name of the system)]]
==External links==
==External links==
*[http://www.kdfoundation.org/ Kawasaki Disease Foundation]
*[http://www.kdfoundation.org/ Kawasaki Disease Foundation]
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Latest revision as of 14:35, 24 April 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2], Arzu Kalayci, M.D. [3]

Synonyms and keywords: Mucocutaneous lymph node syndrome; Lymph node syndrome; Acute febrile vasculitic syndrome

For the heart in Kawasaki disease click here

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