Ultrastructural, Immunofluorescence, and RNA Evidence Support the Hypothesis of a “New” Virus Associated With Kawasaki Disease

Rowley, Anne H.; Baker, Susan C.; Shulman, Stanford T.; Rand, Kenneth H.; Tretiakova, Maria; Perlman, Elizabeth J.; Garcia, Francesca L.; Tajuddin, Nuzhath F.; Fox, Linda M.; Huang, Julia; Ralphe, J. Carter; Takahashi, Kei; Flatow, Jared; Lin, S. C.; Kalelkar, Mitra B.; Soriano, Benjamin J.; Orenstein, Jan M.

doi:10.1093/infdis/jiq136

Cited by 119 publications

(89 citation statements)

References 24 publications

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“…One line of investigation suggests infection with a novel RNA virus that enters through the upper respiratory tract. 67,68 Intracytoplasmic inclusion bodies in bronchial epithelial cells and multiple other cell types throughout the body appear to contain RNA and could be linked to the KD agent. Efforts to characterize the molecular details of these inclusion bodies have been hampered by the paucity of autopsy tissues available for study.…”

Section: Causes and Pathogenesismentioning

confidence: 99%

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Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

McCrindle¹,

Rowley²,

Newburger³

et al. 2017

Circulation

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2,870

4,124

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BACKGROUND:Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries. METHODS AND RESULTS:To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and longterm outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up. CONCLUSIONS:These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances. K awasaki disease (KD) is an acute, self-limited febrile illness of unknown cause that predominantly affects children <5 years of age. When initially described, the potential for coronary artery complications was not appreciated. KD is now the most common cause of acquired heart disease in children in developed countries. In the absence of pathognomonic tests, the diagnosis continues to rest on the identification of principal clinical findings and the exclusion of other clinically similar entities with known causes. Timely initiation of treatment with intravenous immunoglobulin (IVIG) has reduced the incidence of coronary artery aneurysms defined from absolute luminal dimensions from 25% to ≈4%. Ongoing studies with additional therapies have not substantially reduced this residual risk. The long-term prognosis is determined by the initial and current level of coronary artery involvement. Certain subsets of patients are at risk for myocardial ischemia from coronary artery thrombosis and stenoses. Medical management of such patients hinges on judicious use of thromboprophylaxis and vigilance to identify evolving stenoses. Invasive revascul...

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Section: Causes and Pathogenesismentioning

confidence: 99%

“…Intracytoplasmic inclusion bodies are commonly observed in ciliated bronchial epithelial cells in autopsied cases. 67,68,72 A recently proposed model of KD arteriopathy identified 3 pathological processes. The first is a necrotizing arteritis that consists of a synchronized neutrophilic process complete within 2 weeks after fever onset.…”

Section: Pathologymentioning

confidence: 99%

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

McCrindle¹,

Rowley²,

Newburger³

et al. 2017

Circulation

Self Cite

2,870

4,124

View full text Add to dashboard Cite

show abstract

“…Application of reverse genetics to engineer synthetic antibodies to track down a putative new virus has shown some promise, but the agent remains elusive. 2 …”

mentioning

confidence: 99%

Of Mice and Children

Burns

2012

Circulation

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“…Because clinical picture of Kawasaki disease, including hematological and blood chemistry data, is not compatible with these known viral infections, these viruses should not take etiological role. However, it may be possible that unknown virus infection [29] may induce an initial process and decrease circulating DCs.…”

Section: Discussionmentioning

confidence: 99%

Circulating Myeloid Dendritic Cells is Decreased in the Acute Phase of Kawasaki Disease

Takahashi¹

2013

J Clin Exp Cardiolog

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Ultrastructural, Immunofluorescence, and RNA Evidence Support the Hypothesis of a “New” Virus Associated With Kawasaki Disease

Cited by 119 publications

References 24 publications

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

Of Mice and Children

Circulating Myeloid Dendritic Cells is Decreased in the Acute Phase of Kawasaki Disease

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