Kawasaki disease

Kawasaki disease
Classification and external resources
Verkalkte aneurysmatische Coronarien.jpg
Kawasaki syndrome
ICD-10 M30.3
ICD-9 446.1
OMIM 611775
DiseasesDB 7121
MedlinePlus 000989
eMedicine ped/1236 
MeSH D009080

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 membranes, lymph nodes, 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.[1]

Contents

Incidence and risk factors

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.

The disease affects boys more than girls. Approximately 2000-4000 cases are identified in the United States each year.[2][3]

Causes

The causative agent of Kawasaki disease is still unknown,[4] but current theories 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 antigenic substance or a superantigen.[5] Per a Children's Hospital Boston / Harvard Medical school information page on the disease, "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."[3]

An association has been identified with an SNP in the ITPKC gene, which codes an enzyme that negatively regulates T-cell activation.[6] 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.[3] The HLA-B51 serotype has been found to be associated with endemic instances of the disease.[7]

Presentation

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 aneurysms. 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 Kawasaki syndrome and risk factors for coronary artery abnormalities: United States, 1994-2003. with much higher prevalence among patients who are not treated early in the course of illness. Kawasaki disease and rheumatic fever are most common causes of acquired heart disease among children in the United States.

Symptoms

Kawasaki disease often begins with a high and persistent fever that is not very responsive to normal doses of paracetamol (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 membranes 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 nodes. Skin rashes 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.

Signs and tests

A physical examination will demonstrate many of the features listed above.

Blood tests

Other tests (may or may not be performed)

Diagnosis

Kawasaki disease can only be diagnosed clinically (by medical signs and symptoms), as 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.

Classically, five days of fever[8] 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.

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 cardiology and pediatric infectious disease specialists (although no specific infectious agent has been identified yet[3]). 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[9] 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. IVIG by itself is most useful within the first 7 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)[10] but salicylates alone are not as effective as Intravenous immunoglobulin. 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 2 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.

Corticosteroids have also been used,[11] 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. [12]

There are also treatments for iritis and other eye symptoms.

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 1–2 years to screen for progression of cardiac involvement.

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.

References

  1. ↑ Kawasaki T (1967). "[Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children]" (in Japanese). Arerugi 16 (3): 178–222. PMID 6062087. 
  2. ↑ "Kawasaki Disease - Signs and Symptoms".
  3. ↑ 3.0 3.1 3.2 3.3 http://www.childrenshospital.org/clinicalservices/Site468/mainpageS468P5.html
  4. ↑ Rowley AH, Baker SC, Orenstein JM, Shulman ST (May 2008). "Searching for the cause of Kawasaki disease--cytoplasmic inclusion bodies provide new insight". Nat. Rev. Microbiol. 6 (5): 394–401. doi:10.1038/nrmicro1853. PMID 18364728. 
  5. ↑ Freeman AF, Shulman ST (June 2001). "Recent developments in Kawasaki disease". Curr Opin Infect Dis 14 (3): 357-61. PMID 11964855. 
  6. ↑ Onouchi Y, Gunji T, Burns JC, et al (January 2008). "ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms". Nat. Genet. 40 (1): 35–42. doi:10.1038/ng.2007.59. PMID 18084290. 
  7. ↑ Keren G, Danon YL, Orgad S, Kalt R, Gazit E (August 1982). "HLA Bw51 is increased in mucocutaneous lymph node syndrome in Israeli patients". Tissue Antigens 20 (2): 144–6. PMID 6958087. 
  8. ↑ "Kawasaki Disease - June 1999 - American Academy of Family Physicians".
  9. ↑ Oates-Whitehead RM, Baumer JH, Haines L, et al (2003). "Intravenous immunoglobulin for the treatment of Kawasaki disease in children". Cochrane Database Syst Rev (4): CD004000. doi:10.1002/14651858.CD004000. PMID 14584002. 
  10. ↑ Hsieh KS, Weng KP, Lin CC, Huang TC, Lee CL, Huang SM (December 2004). "Treatment of acute Kawasaki disease: aspirin's role in the febrile stage revisited". Pediatrics 114 (6): e689–93. doi:10.1542/peds.2004-1037. PMID 15545617. http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&pmid=15545617. 
  11. ↑ Sundel RP, Baker AL, Fulton DR, Newburger JW (June 2003). "Corticosteroids in the initial treatment of Kawasaki disease: report of a randomized trial". J. Pediatr. 142 (6): 611–6. PMID 12838187. http://linkinghub.elsevier.com/retrieve/pii/S0022347603001173. 
  12. ↑ 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

External links

Systemic CT disorders (M30-M36, 710, 440-448)
Vasculitis/arteritis
(including ANCA-associated vasculitides)
Takayasu's arteritis · Temporal arteritis
Polyarteritis nodosa · Wegener's granulomatosis · Kawasaki disease
Churg-Strauss syndrome · Microscopic polyangiitis · Hypersensitivity vasculitis
Mixed connective tissue disease
Systemic lupus erythematosus (Drug-induced) - Dermatomyositis (Juvenile dermatomyositis) · Polymyositis · Scleroderma (Systemic sclerosis)
Other hypersensitivity/autoimmune
Goodpasture's syndrome · Sjögren's syndrome
Other
Behçet's disease · Polymyalgia rheumatica · Eosinophilic fasciitis · Marfan syndrome
see also soft tissue disorders