- •
Many of the differences between adult and pediatric vasculitis are highlighted in Kawasaki disease, a relatively common condition in children yet essentially unknown in adults.
- •
Kawasaki disease is an acute, self-limited vasculitis that affects 0.01% of children during or shortly after one of many common viral and bacterial infections.
- •
Therapy with IVIG within 10 days of onset effectively controls the signs and symptoms of mucocutaneous inflammation and cervical lymphadenopathy characteristic of
Kawasaki Disease
Section snippets
Key points
Epidemiology
Vasculitis is rare in children. Its incidence is between 10 and 50/100,000 in various studies and populations, although all such estimates are affected by referral patterns and selection bias.1, 2 Vasculitis generally makes up less than 5% of referrals to pediatric rheumatologists, whereas if the 2 most common types, KD and HSP, are removed, they represent less than 1% of chronic inflammatory disorders of childhood.
The epidemiology of vasculitis in children sheds some light on their possible
Risk factors
Because the causes of most types of vasculitis are not known, it is not surprising that risk factors for their development are equally hidden. As noted earlier, a sizable number of cases of pediatric vasculitis follow infections or immunizations, but the overall percentage of children who develop vasculitis after exposure to these agents is vanishingly small. Genetic factors offer an attractive explanation for individual susceptibility, but even the many immunomodulatory, haplotypic, and
Pathophysiology
Despite extensive research, mechanisms underlying the onset and perpetuation of vascular inflammation are poorly understood. Some aspects of the development of KD are apparently unique, whereas others likely represent stereotypical expressions of disease limited by the anatomic, physiologic, and genetic characteristics of human beings. Epidemiologic and basic studies, animal models, and response to specific biological response modifiers are shedding light on the processes involved, in
Clinical features
The clinical evolution of KD differs from that of other, more chronic vasculitides. Characteristic of any type of vasculitis, early findings are nonspecific, primarily reflecting systemic inflammation (fever, malaise, fatigue, failure to thrive, increased levels of acute-phase reactants). However, unique to KD, progression mimics an infectious disease, with development of a rash, mucosal inflammation and extremity changes. In the early 1960s, when Tomasaku Kawasaki attempted to convince his
Laboratory findings
Although no laboratory studies are included among the diagnostic criteria for KD, certain findings may help distinguish KD from mimics in ambiguous cases20:
- •
Systemic inflammation is most characteristic, manifested by increase of acute-phase reactants (eg, C-reactive protein, erythrocyte sedimentation rate, and α1 antitrypsin), leukocytosis, and a left shift in the white blood cell count. By the second week of illness, platelet counts generally increase and may reach 1,000,000/mm3 in the most
Differential diagnosis
KD is most commonly confused with infectious exanthema of childhood,32 although other vasculitides and chronic inflammatory disorders as well as immunologic reactions may mimic KD as well:
- •
Measles, echovirus, and adenovirus may share many of the signs of mucocutaneous inflammation, but they typically have less evidence of systemic inflammation and generally lack the extremity changes seen in KD.
- •
Toxin-mediated illnesses, especially β-hemolytic streptococcal infection and toxic shock syndrome,
Management
Patients who fulfill the criteria for KD are hospitalized and treated with IVIG and aspirin. The AHA algorithm should be used to determine management of children with suspected KD who do not meet diagnostic criteria.22 In such cases, based on the child’s estimated risk of developing coronary artery aneurysms, the duration of fever, and supportive data including results of laboratory tests, slit-lamp examinations, and echocardiograms, treatment may be indicated, even when the diagnosis is
Prognosis
The most characteristic and specific manifestation of KD is cardiac involvement, and this factor drives all diagnostic and therapeutic decision making. KD is the leading cause of acquired heart disease in developed countries, with coronary artery aneurysms developing in almost one-quarter of untreated children and accounting for a mortality of more than 1% in the pre-IVIG era. As with acute rheumatic fever, tachycardia caused by myocarditis is nearly universal in children who develop
Current controversies
As with many areas of medicine, increasingly daunting controversies in the realm of KD are shown as layers of supposed knowledge are peeled away. Most simply, all clinicians would greatly appreciate biomarkers or other tools that would objectify a diagnostic process that is often frustratingly subjective and inexact. Each generation of analytical tools provides candidate tests, most recently urinary proteomic measures that seem to identify children with KD early and reliably.44 However, more
References (45)
- et al.
Incidence of Henoch-Schönlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins
Lancet
(2002) - et al.
Post-varicella angiopathy: report of a case with pathologic correlation
Pediatr Neurol
(2001) - et al.
Kawasaki syndrome
Lancet
(2004) - et al.
The role of infection in Kawasaki syndrome
J Infect
(2013) - et al.
Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease. United States Multicenter Kawasaki Disease Study Group
J Pediatr
(1991) - et al.
Arthritis presenting during the acute phase of Kawasaki disease
J Pediatr
(2006) - et al.
High-dose intravenous gammaglobulin for Kawasaki disease
Lancet
(1984) - et al.
A predictive instrument for coronary artery aneurysms in Kawasaki disease. US Multicenter Kawasaki Disease Study Group
Am J Cardiol
(1998) - et al.
Economic evaluation of intravenous immune globulin therapy for Kawasaki syndrome
J Pediatr
(1993) - et al.
Incidence of vasculitis in children in the Czech Republic: 2-year prospective epidemiology survey
J Rheumatol
(2004)
Infections and Kawasaki disease: implications for coronary artery outcome
Pediatrics
Why are women predisposed to autoimmune rheumatic diseases?
Arthritis Res Ther
Nationwide surveillance of Kawasaki disease in Japan, 1984 to 1993
Pediatr Infect Dis J
Update on etio and immunopathogenesis of Kawasaki disease
Curr Opin Rheumatol
Genetics of Kawasaki disease: what we know and don't know
Circ J
Kawasaki disease. With particular emphasis on arterial lesions
Acta Pathol Jpn
CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease
J Infect Dis
Gene-expression patterns reveal underlying biological processes in Kawasaki disease
Genome Biol
The role of pathology in the diagnosis of systemic vasculitis
Clin Exp Rheumatol
Genetic analysis of Kawasaki syndrome
Am J Hum Genet
Kawasaki disease in parents and children
Acta Paediatr
Vasculitis: determinants of disease patterns
Nat Rev Rheumatol
Cited by (68)
IgG4-related disease as a variable-vessel vasculitis: A case series of 13 patients with medium-sized coronary artery involvement
2023, Seminars in Arthritis and RheumatismEnvironmental Triggers for Vasculitis
2022, Rheumatic Disease Clinics of North AmericaCitation Excerpt :Unlike most other systemic vasculitides, which typically present as chronic inflammatory syndromes, KD is usually a monophasic, acute, febrile illness.49 Also, unlike most other primary systemic vasculitides, it affects almost exclusively young children.49 These features, as well as the overwhelming overlap in clinical manifestations between KD and certain pediatric infections, has led to a long-standing hypothesis that infection is an important trigger.
Recent Advances in Pediatric Vasculitis
2021, Rheumatic Disease Clinics of North AmericaCitation Excerpt :Intravenous immunoglobulin (IVIG), 2 g/kg, and aspirin are first-line therapies for KD. CAAs are a major morbidity of KD and are the leading cause of pediatric acquired heart disease in western countries.20 IVIG treatment reduces CAA development by 5-fold and ideally should be administered within 10 days of fever onset.21
Extrapulmonary manifestations of COVID-19 in children: a comprehensive review and pathophysiological considerations
2021, Jornal de PediatriaCitation Excerpt :Furthermore, MIS-C laboratory findings include leukopenia and extremely elevated levels of ventricular natriuretic peptide, while these alterations are not found in KD’s patients.74 Coronary aneurysms are a typical finding of KD, while reports of this presentation are rare in MIS-C.69,74 Previousl epidemiological reports suggest that the mean age of children with KD is 2 years, with few reports beyond late childhood, while MIS-C can affect older children and adolescents.69 Data implies that Asian children are more prone to have KD, and African children are more susceptible to MIS-C.62,63,74
Multisystemic Inflammatory Syndrome in Children and Kawasaki Disease: Parallels in Pathogenesis and Treatment
2023, Current Allergy and Asthma Reports
Disclosure: nothing to disclose.