# pos

id: cord-270035-1e1wzdri
pos: NNP
token:
  https://mailchi.mp/05cc3497cda5/alert-possiblesars-cov-2-related-inflammatory-syndrome-in-children?e=

lemma:
  https://mailchi.mp/05cc3497cda5/alert-possiblesars-cov-2-related-inflammatory-syndrome-in-children?e=


# ent

id: cord-259996-uhrhsrky
type: PROTEIN
entity:
  alanine aminotransferase ALT aspartate aminotransferase AST serum total protein albumin C reactive protein CRP N terminal pro


id: cord-280280-9jr7ekbu
type: GGP
entity:
  angiotensin II inhibitor 61 62 It remains controversial whether patients with COVID 19 under treatment with an ACE inhibitor


id: cord-280280-9jr7ekbu
type: ORG
entity:
  Children Korean Society of Pediatric Infectious Diseases Korean Society of Epidemiology Korean Society for Antimicrobial Therapy Korean Society for Healthcare associated Infection Control and Prevention Report


id: cord-280280-9jr7ekbu
type: ORG
entity:
  Acute Myocarditis and Pericarditis in Children Disease A Scientific Statement for Health Professionals


id: cord-280280-9jr7ekbu
type: DISEASE
entity:
  ventricular septal defect atrioventricular septal defect tetralogy of Fallot total anomalous pulmonary venous


id: cord-353229-k3zerr83
type: GGP
entity:
  SARS CoV 2 Toxic shock like syndrome and COVID 19 a case report of multisystem inflammatory syndrome in children MIS C Patterns of myocardial


id: cord-030192-ebsh62ll
type: DISEASE
entity:
  multisystem 2 organ involvement cardiac renal respiratory hematologic gastrointestinal dermatologic or neurologic 2


id: cord-292719-n5lg43tr
type: CELL_LINE
entity:
  MagNA Pure LC 2 0 System and MagNA Pure LC Total Nucleic Acid Isolation Kit Roche Applied Science Roche Diagnostics Indianapolis IN


id: cord-292719-n5lg43tr
type: PRODUCT
entity:
  MagNA Pure LC 2 0 System and MagNA Pure LC Total Nucleic Acid Isolation Kit Roche Applied Science Roche Diagnostics


id: cord-292719-n5lg43tr
type: DISEASE
entity:
  influenza B virus 50 for rhinovirus 50 for metapneumovirus and 10 000 for coronavirus If the samples


id: cord-018638-4pyjhpbk
type: DISEASE
entity:
  infection Adenovirus coronavirus dengue virus enteroviruses measles virus respiratory syncytial virus


id: cord-017161-lcqrd4v0
type: DISEASE
entity:
  pericardial effusion electrocardiographic abnormalities pericarditis myocarditis valvular incompetence cardiac failure


id: cord-286607-5i406twr
type: GGP
entity:
  Staphylococcus Streptococcus Enterococcus Enterobacteriaceae Bifidobacterium Clostridium Veillonella


id: cord-314662-nem6dw34
type: PROTEIN
entity:
  alanine transaminase AST aspartate transaminase pro BNP pro B type natriuretic peptide BUN blood urea nitrogen CRP C reactive protein CT


id: cord-314662-nem6dw34
type: ORG
entity:
  SARS CoV 2 Infection Review of Clinical Presentation Hypothetical Pathogenesis and Proposed Management


id: cord-300216-3mvfiuwc
type: GGP
entity:
  Cureus DOI 10 7759 cureus 10212 sha 4e08968e1158d8fcb4390d1e682f8ec2d72aef2f doc_id 300216 cord_uid 3mvfiuwc Kawasaki disease


id: cord-342372-2g9sq36w
type: DNA
entity:
  Staphylococcus aureus Streptococcus pyogenes adenovirus parvovirus B19 human herpes virus 6 rotavirus human coronavirus bocavirus parainfluenza Epstein Barr dengue varicella zoster measles


id: cord-342372-2g9sq36w
type: CL
entity:
  pyogenes adenovirus parvovirus B19 human herpes virus 6 rotavirus human coronavirus bocavirus parainfluenza Epstein Barr dengue varicella zoster measles and influenza viruses


id: cord-261058-yu2qw02l
type: DNA
entity:
  Bacillus Calmette Guerin and purified protein derivative inoculation sites Kawasaki disease Kawasaki


id: cord-331249-jrzgqq8q
type: CHEBI
entity:
  pancreáticas mesentéricas espermáticas y testiculares ováricas y uterinas musculoesqueléticas y otras así


id: cord-331249-jrzgqq8q
type: FAC
entity:
  ser excluida dado el reciente hallazgo de una expansión natural de linfocitos T con expresión del receptor


id: cord-331249-jrzgqq8q
type: PRODUCT
entity:
  diferencias significativas de las cifras de colesterol total colesterol de las lipoproteínas de baja y alta


id: cord-024189-t7mbsr25
type: DISEASE
entity:
  ischemic attacks TIAs cerebral infarction paraparesis quadriparesis hemiparesis ataxia seizures aphasia


id: cord-333145-a20dlaxn
type: DNA
entity:
  paired human immunoglobulin heavy and light chain repertoire 23 Taesung Park 24 Korean Kawasaki Disease Genetics Consortium Taiwan Kawasaki Disease Genetics Consortium Acknowledgements


id: cord-333145-a20dlaxn
type: GGP
entity:
  NC_000006 11 25 5 32 78 Mb and one in the immunoglobulin heavy variable gene IGHV region on chromosome 14q32


# url

id: cord-270035-1e1wzdri
domain: mailchi.mp
url:
  http://mailchi.mp/05cc3497cda5/alert-possiblesars-cov-2-related-inflammatory-syndrome-in-children?e=


# bib

id: cord-000627-gvzs9vxr
author: Yang, Ya-Ling
date: 2011-12-22
txt: ./txt/cord-000627-gvzs9vxr.txt
cache: ./cache/cord-000627-gvzs9vxr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318896/
doi: 10.1155/2012/398628
summary:
  In the patients, polymorphisms of CLEC5A showed no significant association with coronary artery lesion formation and intravenous immunoglobulin treatment response. This study showed for the first time that polymorphisms of CLEC5A are not associated with susceptibility to KD, coronary artery lesion formation, and intravenous immunoglobulin treatment response in a Taiwanese population. To gain further understanding of the genetic role of CLEC5A in the pathogenesis of KD, the aim of our study was to determine if any CLEC5A SNPs are associated with susceptibility to KD, CAL formation, or IVIG treatment response in Taiwanese children. Additionally, the CLEC5A polymorphisms tested in this study failed to show any significant associations with genotype or allele frequency in the KD patients who showed a response to IVIG treatment (Table 4 ). In conclusion, this study showed for the first time that tSNPs of CLEC5A are not associated with susceptibility to KD, CAL formation, and IVIG treatment response in a Taiwanese population.

title:
  Lack of Association between CLEC5A Gene Single-Nucleotide Polymorphisms and Kawasaki Disease in Taiwanese Children

abstract:
  Background. Kawasaki disease is characterized by systemic vasculitis of unknown etiology. Previous genetic studies have identified certain candidate genes associated with susceptibility to KD and coronary artery lesions. Host innate immune response factors are involved in modulating the disease outcome. The aim of this study was to investigate CLEC5A (C-type lectin domain family 5) genetic polymorphisms with regards to the susceptibility and outcome of KD. Methods. A total of 1045 subjects (381 KD patients and 664 controls) were enrolled to identify 4 tagging single-nucleotide polymorphisms (tSNPs) of CLEC5A (rs1285968, rs11770855, rs1285935, rs1285933) by using the TaqMan Allelic Discrimination Assay. The Hardy-Weinberg equilibrium was assessed in cases and controls, and genetic effects were evaluated by the chi-square test. Results. No significant associations were noted between the genotypes and allele frequency of the 4 CLEC5A tSNPs between controls and patients. In the patients, polymorphisms of CLEC5A showed no significant association with coronary artery lesion formation and intravenous immunoglobulin treatment response. Conclusions. This study showed for the first time that polymorphisms of CLEC5A are not associated with susceptibility to KD, coronary artery lesion formation, and intravenous immunoglobulin treatment response in a Taiwanese population.


id: cord-003713-n3o8lwu4
author: Min, Dong Eun
date: 2018-11-07
txt: ./txt/cord-003713-n3o8lwu4.txt
cache: ./cache/cord-003713-n3o8lwu4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584233/
doi: 10.3345/kjp.2018.06989
summary:
  title: High antistreptolysin O titer is associated with coronary artery lesions in patients with Kawasaki disease PURPOSE: In Kawasaki disease (KD) patients, coronary artery complications, incomplete and refractory types occur more frequently in patients with streptococcal or other bacterial/viral infections. Therefore, we hypothesized that KD patients diagnosed with concurrent streptococcal infection have poor prognoses, with respect to treatment response and development of coronary artery lesions. CONCLUSION: It is not certain whether acute streptococcal infection may cause KD, but this study revealed that KD with high ASO titers showed higher rates of severe clinical course. A good clinical course group is defined as fever subsiding within 36 hours after the end of first IVIG treatment without any coronary artery abnormalities. All patients in the good clinical course group had complete KD, fevers that subsided within 36 hours after the first IVIG treatment, and normal coronary arteries.

title:
  High antistreptolysin O titer is associated with coronary artery lesions in patients with Kawasaki disease

abstract:
  PURPOSE: In Kawasaki disease (KD) patients, coronary artery complications, incomplete and refractory types occur more frequently in patients with streptococcal or other bacterial/viral infections. Recently, we observed a higher incidence of coronary lesions in KD patients with high anti-streptolysin O (ASO) titer. Therefore, we hypothesized that KD patients diagnosed with concurrent streptococcal infection have poor prognoses, with respect to treatment response and development of coronary artery lesions. METHODS: A retrospective review was performed in 723 patients with KD who were admitted to 2 major hospitals between June 2010 and September 2017. RESULTS: Among 723 patients with KD, 11 initially showed an elevated ASO titer (>320 IU/mL) or elevated follow-up ASO titer after treatment. Of these patients, 5 showed no response to the first intravenous immunoglobulin treatment, 3 had abnormalities of the coronary arteries. This is a significantly higher proportion of patients with a high ASO titer (n=3, 27.3%) than those with a normal ASO titer (n=53 [7.4%], P=0.047). A severe clinical course was seen in 81.8% of patients in the high ASO group versus 14.5% of patients in the normal ASO group. CONCLUSION: It is not certain whether acute streptococcal infection may cause KD, but this study revealed that KD with high ASO titers showed higher rates of severe clinical course. It may be helpful to analyze concurrent streptococcal infection in patients with a severe clinical course.


id: cord-007277-86lynlxn
title: Coronaviruses in the Limelight
author: Kenneth, McIntosh
date: 2005-02-15
txt: ./txt/cord-007277-86lynlxn.txt
cache: ./cache/cord-007277-86lynlxn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110118/
doi: 10.1086/428510
abstract: nan
summary:
  started their work), but rather that, in some of the earliest work on CoVs during the 1960s, viruses were reported that were then forgotten-viruses that came from adults with respiratory illness, that grew only in human embryonic tracheal organ culture, that caused illness in volunteers, and that were not, or were only distantly, antigenically related to the 2 HCoV species that were subsequently the best studied, HCoV-229E and HCoV-OC43. However, the details from Esper et al.''s study-the seasonal distribution, the percentage of positive samples, the associated respiratory syndromes, and the numbers of infected children at various ages, for example-were heavily influenced by both the particular population that was investigated and the clinical setting, so it is essentially impossible to draw conclusions on the epidemiology, pathogenicity, and relative importance of HCoV-NH in relation to other respiratory viruses. Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children


id: cord-017161-lcqrd4v0
title: The Molecular Biology and Treatment of Systemic Vasculitis in Children
author: Eleftheriou, Despina
date: 2012-02-23
txt: ./txt/cord-017161-lcqrd4v0.txt
cache: ./cache/cord-017161-lcqrd4v0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121654/
doi: 10.1007/978-1-61779-906-8_2
summary:
  Apart from relatively common vasculitides such as Henoch-Schönlein Purpura (HSP) and Kawasaki disease (KD), most of the primary vasculitic syndromes are rare in childhood, but when present are associated with signi fi cant morbidity and mortality [ 2, 3 ] . This chapter summarizes the fi ndings of recent studies relating to the pathogenesis of systemic vasculitis, and considers HSP, KD, antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis, polyarteritis nodosa and Takayasu arteritis (TA). The common features between this murine model and the human disease include an infectious trigger leading to immune activation; disease susceptibility in the young; a time course similar to that seen clinically in KD; similar pathology of coronary arteritis; and response to intravenous immunoglobulin (IVIG) treatment [ 55 ] . Additional data TNF-a -308A associated with increased intravenous immune globulin (IVIG) resistance [ 82 ] Interleukin-10 (IL10) IL-10 gene promoter polymorphisms in fl uence risk of CAA [ 82 ] Vascular endothelial growth factor (VEGF) and its receptor (KDR)

abstract:
  Primary systemic vasculitides are rare in childhood but are associated with significant morbidity and mortality. The cause of the majority of vasculitides is unknown, although it is likely that a complex interaction between environmental factors, such as infections and inherited host responses, triggers the disease and determines the vasculitis phenotype. Several genetic polymorphisms in vasculitides have now been described, which may be relevant in terms of disease predisposition or development of disease complications. Treatment regimens continue to improve with the use of different immunosuppressive medications and newer therapeutic approaches such as biologic agents. This chapter reviews recent studies shedding light on the pathogenesis of vasculitis with emphasis on molecular biology where known, and summarizes current treatment strategies. We discuss new emerging challenges particularly with respect to the long-term cardiovascular morbidity for children with systemic vasculitis and emphasize the importance of future international multicenter collaborative studies to further increase and standardize the scientific base investigating and treating childhood vasculitis.


id: cord-017245-kxqh32ip
title: Kawasaki Disease
author: Sharma, Avinash
date: 2016-06-02
txt: ./txt/cord-017245-kxqh32ip.txt
cache: ./cache/cord-017245-kxqh32ip.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121756/
doi: 10.1007/978-981-10-1750-6_35
summary:
  Initially described in 1967 by Dr. Tomisaku Kawasaki in Japanese children as an acute mucocutaneous lymph node syndrome [ 1 -3 ] , KD may lead to coronary artery abnormalities (CAAs) in up to 25 % of patients if left untreated. Japan reports the highest incidence of KD in the world -the present fi gure being 265/100,000 children below the age of 5 years. In the years to come, KD may soon replace rheumatic fever to become the leading cause of acquired heart disease in children in India, just as in Japan, Europe and North America. If a child has fever for less than 5 days or has less than four criteria, the presence of coronary artery abnormalities (CAAs) detected on 2D echocardiography would also suggest a diagnosis of KD [ 17 ] . A replication study for association of ITPKC and CASP3 two-locus analysis in IVIG unresponsiveness and coronary artery lesion in Kawasaki disease

abstract:
  To learn about the epidemiology, aetiopathogenesis, clinical features and differential diagnosis of Kawasaki disease (KD)


id: cord-018638-4pyjhpbk
title: Kawasaki Disease
author: Pilania, Rakesh Kumar
date: 2019-10-30
txt: ./txt/cord-018638-4pyjhpbk.txt
cache: ./cache/cord-018638-4pyjhpbk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123566/
doi: 10.1007/978-3-030-19055-2_4
summary:
  Acute non-purulent cervical lymphadenopathy Table 4 .2 AHA 2017 diagnostic criteria for KD [28] Diagnosis of classic KD can be proffered in the presence of fever for at least 5 days associated with at least 4 of the 5 following principal clinical features. Cervical lymphadenopathy (>1.5 cm diameter), usually unilateral A careful history may reveal that ≥1 principal clinical features were present during the illness but resolved by the time of presentation Exclusion of other diseases with similar findings (e.g., scarlet fever, viral infections like measles, adenovirus, enterovirus, Stevens-Johnson syndrome, toxic shock syndrome, drug hypersensitivity reactions, systemic juvenile idiopathic arthritis) unusual for KD. Perianal desquamation is virtually pathognomonic of KD and is a useful clinical sign for diagnosis of the disease during the acute phase ( Fig. 4 .3c). Epidemiological and clinical characteristics of Kawasaki disease and factors associated with coronary artery abnormalities in East China: nine years experience

abstract:
  Kawasaki disease (KD) is the commonest cause of acquired heart disease in children in the developed world and is increasingly being reported from developing countries. KD has a predilection for the coronary arteries. Etiology of this disorder is remains an enigma. Diagnosis of KD is essentially clinical with the help of set of clinical criteria. Incomplete KD is said to occur when these criteria are not fulfilled. However, incomplete KD should not be considered as a milder form of the disease. 2D-echocardiography remains the imaging modality of choice for evaluation and monitoring of cardiac complications but often needs to be supplemented by CT coronary angiography. Intravenous immunoglobulin along with aspirin is the gold standard therapy of treatment for KD. However, there is no consensus on treatment of resistant forms of KD. Patients with KD should be on long-term follow-up especially if they have developed coronary artery abnormalities during the acute stage.


id: cord-024189-t7mbsr25
title: Vasculitides
author: Weyand, Cornelia M.
date: 2008
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193731/
doi: 10.1007/978-0-387-68566-3_21
abstract:
  Despite the spatial closeness of blood vessels and inflammatory cells, blood vessel walls are infrequently targeted by inflammation. Giant cell arteritis (GCA) and Takayasu’s arteritis (TA) are characterized by inflammation directed against the vessel wall. GCA and TA display stringent tissue tropism and affect defined vascular territories in a preferential manner. GCA predominantly affects the second- to fifth-order aortic branches, often in the extracranial arteries of the head. The aorta itself may also be affected in GCA, albeit less often than other regions. In contrast, in TA, the aorta and its major branches are the prime disease targets.


id: cord-027870-cuvfy4pj
title: Inflammatory and Purpuric Eruptions
author: Baselga, Eulalia
date: 2020-06-22
txt: ./txt/cord-027870-cuvfy4pj.txt
cache: ./cache/cord-027870-cuvfy4pj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315339/
doi: 10.1016/b978-1-4160-3432-2.50022-4
abstract: nan
summary:
  Other annular erythemas known to be a manifestation of well-defi ned diseases (e.g. neonatal lupus) or with distinctive clinical or histologic features (e.g. erythema multiforme, erythema chronicum migrans, erythema marginatum rheumaticum, and erythema gyratum repens) are not considered under this heading. Differential diagnosis includes other eruptions with ringlike lesions, such as neonatal lupus, erythema multiforme, urticaria, urticarial lesions of pemphigoid, fungal infections, erythema chronicum migrans, and congenital Lyme disease. [98] [99] [100] This type of reaction may be seen in infants with an unknown or presumably viral etiology ( Fig. 19-9) Hypersensitivity syndrome reaction is a serious drug reaction characterized by fever, skin rash, lymphadenopathy, and internal organ involvement, especially of the liver. Sweet syndrome, or acute febrile neutrophilic dermatosis, is a benign disease characterized by tender, raised erythematous plaques, fever, peripheral leukocytosis, histologic fi ndings of a dense dermal infi ltrate of polymorphonuclear leukocytes, and a rapid response to systemic corticosteroids. 412 Congenital erythropoietic porphyria and transient elevated porphyrin levels in neonates with hemolytic disease may also cause photosensitivity.


id: cord-030192-ebsh62ll
author: Winant, Abbey J.
date: 2020-07-30
txt: ./txt/cord-030192-ebsh62ll.txt
cache: ./cache/cord-030192-ebsh62ll.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397565/
doi: 10.1148/ryct.2020200346
summary:
  12 Furthermore, emerging new evidence suggests that COVID-19 infection in children and adolescents is associated with a multisystem inflammatory syndrome (MIS-C), with features similar to Kawasaki disease and toxic shock syndrome, frequently requiring intensive care unit (ICU) admissions. The United States CDC has presented the following case definition for a diagnosis of MIS-C associated with COVID-19, with pediatric patients required to meet all three of the following criteria: (1.) Individual under 21 years of age presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurologic); (2.) No alternative plausible diagnosis; (3.) Positive current or recent SARS-CoV-2 infection by RT-PCR, serology, or I n p r e s s antigen test; or COVID-19 exposure within four weeks prior to symptom onset.

title:
  Thoracic Imaging Findings of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: What Radiologists Need to Know Now

abstract:
  The COVID-19 global pandemic is an ongoing public health emergency, with over 4 million confirmed cases worldwide. Due to the novel nature of this coronavirus and our evolving understanding of its pathophysiology, there is continued uncertainty surrounding diagnosis and management of COVID-19, especially in pediatric patients. In addition, a new febrile hyperinflammatory Kawasaki-like syndrome (also known as multisystem inflammatory syndrome in children, or MIS-C) has emerged in pediatric patients with temporal association to COVID-19 infection. This review article aims to provide an up-to-date review of the clinical and imaging findings of pediatric MIS-C associated with COVID-19, compared with typical acute pediatric COVID-19 infection, with an emphasis on thoracic imaging findings.


id: cord-253056-765rs3e7
title: Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection
author: Dionne, Audrey
date: 2018-10-17
txt: ./txt/cord-253056-765rs3e7.txt
cache: ./cache/cord-253056-765rs3e7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30332473/
doi: 10.1371/journal.pone.0206001
summary:
  title: Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. RESULTS: Children with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with concurrent infection had higher rates of IVIG resistance (19 (33%) versus 17 (18%) patients, p = 0.04), and higher temperature at 48 hours (Fig 1) . In this retrospective series, the presence of a concomitant infection was associated with a higher rate of resistance to IVIG treatment. In this study, patients with concomitant infection had a higher rate of resistance to IVIG treatment.

abstract:
  INTRODUCTION: Kawasaki disease (KD) can be associated with concomitant viral or bacterial infections. Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. Although concomitant infection does not affect coronary outcome, it is unknown how it influences the response to IVIG treatment. METHODOLOGY: Retrospective cohort study between 2008 and 2016 in a tertiary pediatric university hospital, including 154 children, of which 59 (38%) had concomitant infection. RESULTS: Children with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with infection had higher C-reactive protein at the time of diagnosis (148 vs 112 mg/L, p = 0.04), and 48 hours after IVIG administration (111 vs 59 mg/L, p = 0.003). Nevertheless, there was no statistically significant difference in the prevalence of coronary complications (Z-score > 2.5) between children with and without concomitant infection (36% vs 39%, p = 0.68). CONCLUSION: Children with KD and concomitant infection are more likely to have persistent fever and elevated inflammatory markers after treatment. This association increases the likelihood of receiving a second dose of IVIG but not the risk of coronary complication. Accordingly, prospective studies to distinguish true IVIG resistance from infection induced persistent fever is warranted.


id: cord-256642-payjduek
title: Measles infection causing Bacillus Calmette-Guérin reactivation: a case report
author: Muthuvelu, Sobana
date: 2019-07-24
txt: ./txt/cord-256642-payjduek.txt
cache: ./cache/cord-256642-payjduek.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31340782/
doi: 10.1186/s12887-019-1635-z
summary:
  BACKGROUND: Reactivation of the Bacillus Calmette-Guérin (BCG), manifesting as erythema, induration, ulceration or crust formation at a previous BCG inoculation site, is a common and highly specific feature of Kawasaki disease (KD). CONCLUSIONS: This case report highlights the rare finding of BCG reactivation in a child with confirmed measles infection, and suggests that this clinical manifestation may occasionally occur in children with infections or conditions other than KD. Reactivation of the BCG, manifesting as erythema, induration, ulceration or crust formation at the BCG site months or years after inoculation, has been described as an important feature of Kawasaki disease (KD) [5, 6] . Here, we present a case report of a 7-month old infant with laboratory-confirmed measles who presented with erythema and induration at the BCG inoculation site. Apart from those to confirm the measles infection, no laboratory investigations were undertaken to determine if additional viral pathogens were present in the patient and contributed to the development of the BCG reactivation.

abstract:
  BACKGROUND: Reactivation of the Bacillus Calmette-Guérin (BCG), manifesting as erythema, induration, ulceration or crust formation at a previous BCG inoculation site, is a common and highly specific feature of Kawasaki disease (KD). We report the unusual finding of BCG reactivation in an infant with laboratory-confirmed measles. CASE PRESENTATION: A previously healthy 7-month old infant presented initially with fever, cough and coryza, and subsequently developed Koplik’s spots followed by a typical morbilliform skin rash. There was significant contact history with a household relative who had recently been diagnosed with measles. On examination, a 2.5 cm area of erythema and induration was seen at the previous BCG inoculation site, in addition to the widespread maculopapular rash. No other clinical features of KD were present. Measles virus was isolated from the throat swab and measles antibodies (IgM) were present in the serum. The patient recovered completely with oral vitamin A and supportive therapy, and had normal echocardiography examination on follow up. CONCLUSIONS: This case report highlights the rare finding of BCG reactivation in a child with confirmed measles infection, and suggests that this clinical manifestation may occasionally occur in children with infections or conditions other than KD.


id: cord-259996-uhrhsrky
title: Cardiac Function in Kawasaki Disease Patients with Respiratory Symptoms
author: Lee, Seul Bee
date: 2015-07-16
txt: ./txt/cord-259996-uhrhsrky.txt
cache: ./cache/cord-259996-uhrhsrky.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26240586/
doi: 10.4070/kcj.2015.45.4.317
summary:
  Coronary artery diameter, C-reactive protein levels, platelet count, alanine aminotransferase levels, and NT-pro BNP levels were significantly higher and albumin levels lower in group 2 compared with group 3. Laboratory data obtained from each patient included complete blood count, erythrocyte sedimentation rate (ESR), and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total protein, albumin, C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP). The KD patients in their studies had significantly higher positive rates for virus isolation and PCR for those viruses compared with the control group (50.4% vs. 12) found that children with KD who had respiratory virus infections had a higher incidence of coronary artery dilatation than KD patients without viral infections, and the former group were more often diagnosed with incomplete KD. Detection rate and clinical impact of respiratory viruses in children with Kawasaki disease

abstract:
  BACKGROUND AND OBJECTIVES: Respiratory symptoms are often observed in children with Kawasaki disease (KD) during the acute phase. The association of respiratory viruses in children with KD was investigated using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) and tissue Doppler echocardiography. SUBJECTS AND METHODS: 138 KD patients were included from January 2010 to June 2013. We compared 3 groups (group 1: n=94, KD without respiratory symptoms; group 2: n=44, KD with respiratory symptoms; and group 3: n=50, febrile patients with respiratory symptoms). Laboratory data were obtained from each patient including N-terminal pro-brain natriuretic peptide (NT-proBNP). Echocardiographic measurements were compared between group 1 and group 2. RT-PCR was performed using nasopharyngeal secretion to screen for the presence of 14 viruses in groups 2 and 3. RESULTS: The incidence of KD with respiratory symptoms was 31.8%. The duration of fever was significantly longer, and coronary artery diameter was larger in group 2 than in group 1. Tei index was significantly higher and coronary artery diameter larger in group 2 than group 1. Coronary artery diameter, C-reactive protein levels, platelet count, alanine aminotransferase levels, and NT-pro BNP levels were significantly higher and albumin levels lower in group 2 compared with group 3. CONCLUSION: NT-pro BNP was a valuable diagnostic tool in differentiating KD from other febrile viral respiratory infections. Some viruses were more frequently observed in KD patients than in febrile controls. Tei index using tissue Doppler imaging was increased in KD patients with respiratory symptoms.


id: cord-261058-yu2qw02l
title: Kawasaki disease: What is the epidemiology telling us about the etiology?
author: Burgner, David
date: 2005-06-03
txt: ./txt/cord-261058-yu2qw02l.txt
cache: ./cache/cord-261058-yu2qw02l.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15936970/
doi: 10.1016/j.ijid.2005.03.002
summary:
  Thus in genetically susceptible children, acute infections such as those causing fever and rash, may result in unrecognised damage to the cardiovascular system that later manifests itself as adult cardiovascular disease. 3 The consensus view is that KD results from a widely distributed infectious agent (or possibly agents) that causes the clinical syndrome in genetically susceptible children. Kawasaki disease is more common in boys (male:female ratio 1.6:1) 1 a feature observed in many infectious diseases 30, 31 and also in coronary atherosclerosis, where sex differences in immune responses are suggested to mediate susceptibility. A recent report of an association between the presence of genetic material from a novel coronavirus and Kawasaki disease in a handful of cases 48 remains unproven and may reflect an epiphenomenon; the putative etiological agent is a relatively common viral pathogen in young children and it is unclear how long the DNA persists.

abstract:
  Kawasaki disease (KD) is an important and common inflammatory vasculitis of early childhood with a striking predilection for the coronary arteries. It is the predominant cause of paediatric acquired heart disease in developed countries. Despite 40 years of research, the aetiology of KD remains unknown and consequently there is no diagnostic test and treatment is non-specific and sub-optimal. The consensus is that KD is due to one or more widely distributed infectious agent(s), which evoke an abnormal immunological response in genetically susceptible individuals. The epidemiology of KD has been extensively investigated in many populations and provides much of the supporting evidence for the consensus regarding etiology. These epidemiological data are reviewed here, in the context of the etiopathogenesis. It is suggested that these data provide additional clues regarding the cause of KD and may account for some of the continuing controversies in the field.


id: cord-269170-9f460xbq
title: Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota
author: Kaneko, Kazunari
date: 2020-07-24
txt: ./txt/cord-269170-9f460xbq.txt
cache: ./cache/cord-269170-9f460xbq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32793240/
doi: 10.3389/fimmu.2020.01616
summary:
  The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Recent advances in culture-independent techniques for detection and identification of intestinal commensal bacteria enabled the discovery that Th17 and Treg differentiation are regulated by short chain fatty acids (SCFAs), in particular butyrate, produced by the gut microbiota. This perspective is illustrated in Figure 1 and can be explained as follows: [1] various factors during the in utero and postnatal period drive dysbiosis in young children; [2] dysbiosis results in reduced intestinal production of SCFAs including butyrate; [3] reduced levels of SCFAs in the gut cause an imbalance of Th17s/Tregs; and [4] individuals with Th17/Treg imbalances develop hypercytokinemia triggered by ubiquitous infectious agents(s), followed by KD (Figure 1) .

abstract:
  Kawasaki disease (KD) was first described by Dr. Tomisaku Kawasaki in 1967. The etiology of KD has been studied comprehensively but remains largely unknown. The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Evidence has mounted to suggest that an imbalance between T helper 17 cells (Th17s) and regulatory T cells (Tregs) is associated with aberrant immune responses in KD. Recent advances in culture-independent techniques for detection and identification of intestinal commensal bacteria enabled the discovery that Th17 and Treg differentiation are regulated by short chain fatty acids (SCFAs), in particular butyrate, produced by the gut microbiota. This finding provided a mechanistic link between dysbiosis, defined as changes in the composition of the gut microbiota, and various inflammatory diseases. On this basis, we propose that dysbiosis, with reduced production of SCFAs leading to imbalances of Th17s/Tregs, could be involved in the etiology of KD. A pilot study supported this hypothesis, as only fecal concentrations of butyrate were significantly reduced in KD patients among SCFAs. This evolving perspective prompted us to undertake metagenomic analyses of bacterial DNA from the feces of KD patients who were antibiotic-naïve at diagnosis. Simultaneous measurements of Th17s/Tregs in peripheral blood and SCFA concentrations in feces would provide valuable information regarding the association between dysbiosis and dysregulated immune responses in KD.


id: cord-270035-1e1wzdri
title: SARS-COV-2 Infection and Kawasaki Disease: Case Report of a Hitherto Unrecognized Association
author: Cazzaniga, Marco
date: 2020-07-03
txt: ./txt/cord-270035-1e1wzdri.txt
cache: ./cache/cord-270035-1e1wzdri.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32719757/
doi: 10.3389/fped.2020.00398
summary:
  The association of Kawasaki disease and COVID-19 infection has to our knowledge been reported only once (5), we report a second case from Italy, currently the third most affected country in the world with regard to number of proven SARS-COV-2 infections. We were then contacted as reference Center for Kawasaki Disease (KD) in our Pediatric Immunology Unit: considering the clinical history (fever lasting more than 5 days, erythematous rash, labial, and conjunctival hyperemia) and the result of laboratory tests we confirmed the diagnostic suspicion of atypical/incomplete KD without coronary involvement, and started treatment with high dose intravenous immunoglobulins (IVIG) 2 g/kg and high dose acetylsalicylic acid (ASA 50 mg/kg/day). In the setting of COVID-19 there are several reports of using corticosteroids for Acute Respiratory Disease Syndrome (ARDS), but considering the not severe clinical course and presentation in our patient we did not start steroid therapy.

abstract:
  Coronavirus-associated disease (COVID-19) was firstly reported at the end of 2019. Generally, COVID-19 seems to be a less severe disease in children than in adults. According to the current literature, children account approximately for 2% of diagnosed COVID-19 cases. Northern Italy is one of the geographical areas mainly affected by the ongoing COVID-19 pandemic. We describe a pediatric patient diagnosed and treated for atypical/incomplete Kawasaki Disease (KD) complicated with paralytic ileus, who also resulted positive for SARS-COV-2.


id: cord-277908-d26xzean
title: Kawasaki-like disease among Italian children in the COVID-19 era
author: Kuo, Ho-Chang
date: 2020-08-18
txt: ./txt/cord-277908-d26xzean.txt
cache: ./cache/cord-277908-d26xzean.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0022347620308659
doi: 10.1016/j.jpeds.2020.07.022
abstract: nan
summary:
  Early-childhood prescribed antibiotics associated with type 1 Diabetes Main Results 1,297 children (0.2%) developed DM1 (median age 4.0 years, range 0-8.3). Conclusions Early-life prescribed antibiotics for otitis media and respiratory infections, are associated with DM1 development, with a higher risk in cesarean delivery birth. Those diagnosed in the COVID-19 era demonstrated a higher incidence: 10 vs 0.3 per month, mean age: 7.5 vs 3.0 years, Kawasaki disease shock syndrome: 50% vs 0%, MAS: 50% vs 0%, and steroid requirement: 80% vs 15%, all P < .01. Emphasizing, at health supervision visits, the American Academy of Pediatrics recommendations regarding appropriate media use with children, 3 parents should also be apprised of the association between earlier screen exposure and the risk of developing ASD-like symptoms, although currently, a causal relationship cannot be inferred. 1 US studies based on vital statistics data, found a higher risk of neonatal death in home compared with hospital births.


id: cord-278761-cqrggpmj
title: Sars-CoV-2 et Kawasaki, rapprochement à risque
author: Manus, Jean-Marie
date: 2020-07-01
txt: ./txt/cord-278761-cqrggpmj.txt
cache: ./cache/cord-278761-cqrggpmj.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1773035X2030215X
doi: 10.1016/s1773-035x(20)30215-x
abstract: nan
summary:
  title: Sars-CoV-2 et Kawasaki, rapprochement à risque Focus © zilvergolf/stock.adobe.com Le Lancet a publié une observation, d''une équipe de pédiatrie de l''hôpital Pape-Jean-XXIII de Bergame [1] , évoquant ce Kawasaki-like sévère avec l''épidémie de Covid-19. Les médecins ont évalué les caractéristiques cliniques d e s p a t i e n t s K a w a s a k i -l i k e lors de l''épidémie, ilsont repris les obser vations de maladie de Kawasaki des cinq dernières années au service de pédiatrie, selon un groupe 1 (avant le Covid-19) et un groupe 2 (après le début du Covid-19). La présentation de Kawasaki-like a été comparée à la maladie de Kawasaki selon les critères de l''American Heart Des cliniciens français ont récemment établi un rapprochement entre le Covid-19 et la maladie de Kawasaki chez l''enfant très symptomatique porteur du Sars-CoV-2, à type de Kawasaki-like. Sars-CoV-2 et Kawasaki, rapprochement à risque .


id: cord-280280-9jr7ekbu
title: COVID19: potential cardiovascular issues in pediatric patients
author: Bertoncelli, Deborah
date: 2020-05-11
txt: ./txt/cord-280280-9jr7ekbu.txt
cache: ./cache/cord-280280-9jr7ekbu.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.23750/abm.v91i2.9655
doi: 10.23750/abm.v91i2.9655
summary:
  Ongoing studies and accumulated data are detailing the features and the effects of the new coronavirus disease 19 (COVID 19) in the adult population, and cardiovascular involvement is emerging as the most significant and life-threatening complication, with an increased risk of morbidity and mortality in patients with underlying cardiovascular disease. At present, though the limited data on the effects of COVID 19 in pediatric patients, children seem to count for a little proportion of SARS-COV 2 infection, and present with less severe disease and effects However infants and toddlers are at risk of developing critical course. Coronavirus disease 19 (COVID-19) is a severe acute respiratory syndrome for which the etiologic agent is the novel beta coronavirus SARS-CoV-2, first described in December 2019 in China in a cluster of patients presenting with pneumonia. The main presenting clinical feature of the disease is pneumonia, ranging from asymptomatic or mildly symptomatic to severe acute respiratory distress syndrome, but cardiovascular involvement is emerging as one of the most significant and life-threatening complications of SARS-CoV-2 infection (1, 2) .

abstract:
  The novel severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) has rapidly spread worldwide with increasing hospitalization and mortality rate. Ongoing studies and accumulated data are detailing the features and the effects of the new coronavirus disease 19 (COVID 19) in the adult population, and cardiovascular involvement is emerging as the most significant and life-threatening complication, with an increased risk of morbidity and mortality in patients with underlying cardiovascular disease. At present, though the limited data on the effects of COVID 19 in pediatric patients, children seem to count for a little proportion of SARS-COV 2 infection, and present with less severe disease and effects However infants and toddlers are at risk of developing critical course. The disease has a range of clinical presentations in children, for which the potential need for further investigation of myocardial injury and cardiovascular issues should be kept in mind to avoid misdiagnosing severe clinical entities. Overlapping with Kawasaki disease is a concern, particularly the incomplete and atypical form. We aim to summarize the initial considerations and potential cardiovascular implications of COVID-19 for children and patients with congenital heart disease. (www.actabiomedica.it)


id: cord-283349-9x2d1qip
author: Paolino, Jonathan
date: 2020-07-24
txt: ./txt/cord-283349-9x2d1qip.txt
cache: ./cache/cord-283349-9x2d1qip.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32706422/
doi: 10.1002/pbc.28551
abstract: nan
summary:
  title: Peripheral blood smears of children with multisystem inflammatory syndrome demonstrate prominence of early myeloid forms with morphologic evidence of toxic change There is a growing body of evidence that suggests that children have largely been spared of much of the morbidity associated with the ongoing SARS-CoV-2 pandemic 1,2 Over the last several weeks, however, there has been an increasing awareness and understanding of a hyperinflammatory shock syndrome that appears to mimic some aspects of Kawasaki disease in some pediatric patients. While the role that neutrophils play in the development of Kawasaki disease continues to be clarified, it is described in the literature that higher neutrophil to lymphocyte ratios (NLRs) may portend an increased risk of resistance to treatment with intravenous immunoglobulin as well as development of coronary aneurysms 6, 7 Indeed, there is also evidence that suggests that higher NLRs in patients with COVID-19 are associated with increased levels of inflammation and clinical severity.

title:
  Peripheral blood smears of children with multisystem inflammatory syndrome demonstrate prominence of early myeloid forms with morphologic evidence of toxic change


id: cord-286607-5i406twr
title: The Gut Microbiota-Host Partnership as a Potential Driver of Kawasaki Syndrome
author: Esposito, Susanna
date: 2019-04-05
txt: ./txt/cord-286607-5i406twr.txt
cache: ./cache/cord-286607-5i406twr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31024869/
doi: 10.3389/fped.2019.00124
summary:
  Kawasaki syndrome (KS) is a necrotizing vasculitis of smalland medium-sized vessels mostly affecting children under 5 years of age; a host of clinical and epidemiological data supports the notion that KS might result from an infectious disease. All studies available to date have confirmed that an imbalance in the gut microbiota might indirectly interfere with the normal function of innate and adaptive immunity, and that variable microbiota interactions with environmental factors, mainly infectious agents, might selectively drive the development of KS in genetically susceptible children. The microbiota, a microbial community of trillions of microorganisms and at least 1,000 different bacterial species, some eukaryotic fungi and viruses, and which covers every surface of the human body, plays a contributory role in many infections, immune-mediated disorders, rheumatologic diseases, and disorders of the nervous system.

abstract:
  Kawasaki syndrome (KS) is a necrotizing vasculitis of small- and medium-sized vessels mostly affecting children under 5 years of age; a host of clinical and epidemiological data supports the notion that KS might result from an infectious disease. However, many efforts have failed to identify a potentially universal trigger of KS. The contribution of the intestinal microbial community—called the “microbiota”—to KS has been evaluated by an increasing number of studies, though limited to small cohorts of patients. Differences in the microbiota composition were found in children with KS, both its acute and non-acute phase, with abnormal colonization by Streptococcus species in the intestinal tract and a wider presence of Gram-positive cocci in jejunal biopsies. In particular, a higher number of Gram-positive cocci (of the genera Streptococcus and Staphylococcus), Eubacterium, Peptostreptococcus, and HSP60-producing Gram-negative microbes have been found in the stools of KS children, and their effects on the antigenic repertoire of specific T cells and Vβ2 T cell expansion have been assessed. Conversely, Lactobacilli were lacking in most children with KS compared with other febrile illnesses and healthy controls. All studies available to date have confirmed that an imbalance in the gut microbiota might indirectly interfere with the normal function of innate and adaptive immunity, and that variable microbiota interactions with environmental factors, mainly infectious agents, might selectively drive the development of KS in genetically susceptible children. Further investigations of the intestinal microflora in larger cohorts of KS patients will provide clues to disentangle the pathogenesis of this disease and probably indicate disease-modifying agents or more rational KS-specific therapies.


id: cord-292719-n5lg43tr
title: Viral infections associated with Kawasaki disease
author: Chang, Luan-Yin
date: 2014-02-01
txt: ./txt/cord-292719-n5lg43tr.txt
cache: ./cache/cord-292719-n5lg43tr.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jfma.2013.12.008
doi: 10.1016/j.jfma.2013.12.008
summary:
  To investigate the infectious etiology of Kawasaki disease, we initiated a prospective case-control study to investigate possible links between common viral infections and Kawasaki disease. The infectious evidence of Kawasaki disease includes temporal clustering and marked seasonality, geographic clustering, family clustering, a high association between Kawasaki disease and infectious disease surveillance, and age distribution, for which the highest incidence rates are seen among 6 monthe2-year-old children who have low maternal antibodies and are most susceptible to infections in general. We thus carried out a prospective case-control study to investigate the association of common viral infections with Kawasaki disease to test the above hypothesis. We enrolled Kawasaki disease cases that had fever for over 5 days and at least four of the following five manifestations: neck lymphadenopathy, lip fissure and/or strawberry tongue, skin rash, nonpurulent bulbar conjunctivitis, palm/sole erythema, and induration followed by periungual desquamation. The c 2 test was used to compare the rates of viral isolation and PCR of various viruses between KD cases and the control children.

abstract:
  BACKGROUND/PURPOSE: Kawasaki disease (KD) is a disease of unknown cause. To investigate the infectious etiology of Kawasaki disease, we initiated a prospective case-control study to investigate possible links between common viral infections and Kawasaki disease. METHODS: We enrolled 226 children with KD and 226 age- and sex-matched healthy children from February 2004 to March 2010. Throat and nasopharyngeal swabs were taken for both viral isolation and polymerase chain reaction (PCR) for various viruses. RESULTS: The mean age of the 226 KD cases was 2.07 years, and the male to female ratio was 1.43 (133 boys to 93 girls). Their mean fever duration was 7.5 days with a mean peak temperature of 39.7°C. In addition to the typical symptoms of fever, neck lymphadenopathy, lip fissure and/or strawberry tongue, skin rash, nonpurulent bulbar conjunctivitis, palm/sole erythema, and induration followed by periungual desquamation, these KD cases also exhibited cough (69%), rhinorrhea (58%), and diarrhea (45%). Cases of KD had a significantly higher positive rate of viral isolation in comparison with the control group (7.5% vs. 2.2%, p = 0.02). Compared with the control group, cases of KD were more likely to have overall positive rates of viral PCR (50.4% vs. 16.4%, p < 0.001) and for various viruses including enterovirus (16.8% vs. 4.4%, p < 0.001), adenovirus (8.0% vs. 1.8%, p = 0.007), human rhinovirus (26.5% vs. 9.7%, p < 0.001), and coronavirus (7.1% vs. 0.9%, p = 0.003). CONCLUSION: We found that some common respiratory viruses, such as adenoviruses, enteroviruses, rhinoviruses, and coronaviruses, were associated with KD cases.


id: cord-293714-s6ezxi5r
title: The role of infection in Kawasaki syndrome
author: Principi, Nicola
date: 2013-04-18
txt: ./txt/cord-293714-s6ezxi5r.txt
cache: ./cache/cord-293714-s6ezxi5r.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0163445313000777
doi: 10.1016/j.jinf.2013.04.004
summary:
  Further findings that strongly support an infectious origin of KS are those of Orenstein et al., who used light microscopy and TEM to study tissue specimens from 32 autopsies, eight heart transplants and an excised coronary aneurysm of patients with KS and identified three different vasculopathic processes: acute self-limited necrotising arteritis (NA), subacute/chronic vasculitis, and luminal myofibroplastic proliferation. More recently, Japanese and Taiwanese groups independently reported a significant association between KS and polymorphisms in the intergenic region on chromosome 8p23-p22 between B lymphoid kinase (BLK ), a tyrosine kinase involved in B-cell receptor signal transduction and FAM167A, a functionally uncharacterized gene. 117 They found that polymorphisms at BLK gene together with genetic abnormalities at CD40, were associated with KS at genomewide significance (p < 5.5 Â 10 À8 ) confirming the role of immune activation and inflammation in the pathogenesis of the syndrome. Association of vascular endothelial growth factor (VEGF) and VEGF receptor gene polymorphisms with coronary artery lesions of Kawasaki disease

abstract:
  OBJECTIVES: To analyse the evidence suggesting a possible infectious origin of Kawasaki syndrome (KS). METHODS: PubMed was searched for all of the studies published over the last 15 years using the key words “Kawasaki syndrome” or “mucocutaneous lymph node syndrome” and “infectious disease” or “genetics” or “vasculitis” or “pathogenesis”. RESULTS: Various levels of evidence support the hypothesis that KS is a complex disease triggered by an infection due to one or more pathogens. Viruses or bacteria may be the primum movens, although no specific infectious agent can be considered definitely etiological. A number of genetic polymorphisms have been identified in subjects with KS, but none of them can currently be considered a real marker of susceptibility. CONCLUSIONS: Various data suggest that KS is intimately related to infectious diseases and that its clinical expression is influenced by predisposing genetic backgrounds, but our knowledge of the infectious agent(s) involved and the genetic characteristics of susceptible children remains only partial. Further studies are needed to address the many still open questions concerning the disease.


id: cord-294729-c9f0iokr
author: Orr, William B.
date: 2020-10-01
txt: ./txt/cord-294729-c9f0iokr.txt
cache: ./cache/cord-294729-c9f0iokr.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1097/cce.0000000000000236
doi: 10.1097/cce.0000000000000236
summary:
  Conclusion: Our representative case of a patient with coronavirus disease-19-associated multisystem inflammatory syndrome in children without robust hyperinflammation and a delayed finding of coronary artery dilatation compared with reported case series highlights the need for further mechanistic understanding of coronavirus disease-19 disease and subsequent multisystem inflammatory syndrome in children or Kawasaki disease development. Key Words: coronavirus disease-19; immune suppression; Kawasaki disease; multisystem inflammatory syndrome in children; research S ignificant disease burden in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been relatively uncommon in children with less than 5% of cases in the United States and globally under 18 years old (1) (2) (3) (4) (5) (6) . However, although children appear to have a less severe acute disease course, worldwide cases of a postinfectious multisystem inflammatory syndrome in children (MIS-C) and possible atypical Kawasaki-like disease attributed to SARS-CoV-2 infection have arisen (8) (9) (10) .

title:
  Delayed Development of Coronary Artery Dilitation in Suspected Severe Acute Respiratory Syndrome Coronavirus 2 Multisystem Inflammatory Syndrome: More Research Needed

abstract:
  Although significant disease burden in the severe acute respiratory syndrome coronavirus 2 pandemic has been relatively uncommon in children, worldwide cases of a postinfectious multisystem inflammatory syndrome in children and possible atypical Kawasaki-like disease attributing to severe acute respiratory syndrome coronavirus 2 infection have arisen. Original thinking for coronavirus disease-19 disease was that an overwhelming proinflammatory response drove disease pathogenesis. Emerging reports suggest that a robust immune suppression may be more relevant and predominant. Recently reported data on children with multisystem inflammatory syndrome in children have demonstrated a heterogeneity of immune phenotypes among these patients, with concern for a strong initial proinflammatory state; however, data are lacking to support this. Likewise, understanding development of certain clinical findings to changes in the immune system is lacking. CASE SUMMARY: We report a 12-year-old multiracial male with negative coronavirus disease-19 nasopharyngeal RNA polymerase chain reaction testing but positive severe acute respiratory syndrome coronavirus 2 serology, subsequent development of vasodilatory shock with myocardial depression, and subsequent delayed development of coronary artery dilatation after resolution of myocardial depression. Unlike previous reported cases of multisystem inflammatory syndrome in children, he exhibited profound lymphopenia without specific inflammatory cytokines elevations, whereas nonspecific markers (ferritin and C-reactive protein) were increased. He subsequently was discharged on day 12 of hospitalization with complete recovery. CONCLUSION: Our representative case of a patient with coronavirus disease-19-associated multisystem inflammatory syndrome in children without robust hyperinflammation and a delayed finding of coronary artery dilatation compared with reported case series highlights the need for further mechanistic understanding of coronavirus disease-19 disease and subsequent multisystem inflammatory syndrome in children or Kawasaki disease development. This report offers a number of disease mechanisms and clinical evolution considerations for further elucidation to guide development of potential therapies.


id: cord-299870-4ulmbn1r
title: Anakinra for Treatment-Resistant Kawasaki Disease: Evidence from a Literature Review
author: Ferrara, Giovanna
date: 2020-09-03
txt: ./txt/cord-299870-4ulmbn1r.txt
cache: ./cache/cord-299870-4ulmbn1r.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32885390/
doi: 10.1007/s40272-020-00421-3
summary:
  Intravenous immunoglobulin (IVIG) in association with aspirin represents the main treatment for KD, and administration of these treatments within the first 10 days following fever onset has been associated with a fivefold reduction in the risk of coronary artery aneurysms (CAA) [1] . The first report on the use of anti-IL-1 in KD dates back to 2012 [20] and described a 2-year-old boy with classic KD who developed myocarditis with reduction of the ejection fraction to 20%, without coronary artery inflammation, 2 days after the first dose of IVIG. The main reason for the use of anakinra was persistent fever (8/11), followed by gradual dilatation of the coronary arteries (7/11), persistence of clinical (2/11) or laboratory abnormalities (6/11), and severe myocarditis with KD shock syndrome in one case. This study supports the early use of anakinra in cases refractory to IVIG, demonstrating that it is quickly effective on KD symptoms, inflammation parameters, and dilatation of the coronary arteries in most patients, with good tolerability.

abstract:
  Kawasaki disease (KD) is one of the most common vasculitides of childhood and the main cause of acquired heart disease in developed countries. Intravenous immunoglobulin (IVIG) in association with aspirin represents the main treatment for KD. However, 10–20% of patients fail to respond to standard treatment and have an increased risk of cardiac complications. There is currently no accepted protocol for treatment of resistant cases. Several authors highlighted the role of interleukin-1 (IL-1) as a mediator of inflammation in KD and suggested the possibility of using IL-1 or its receptor as a target of therapy. The use of IL-1 inhibitors in patients with KD has been reported in the scientific literature, but data are largely limited to individual case reports and small case series. We summarized the scientific literature related to the use of anakinra, analyzing preclinical and clinical data. Thirty-eight patients have been described so far, most of them with KD-related complications. Twenty-two were described in case reports and case series, while 16 were patients from the completed KAWAKINRA phase IIa study. Almost all patients received clinical benefit, and no relevant side effects were noted. Based on this evidence, in our opinion, anakinra may be considered as an option after the failure of the first IVIG infusion, especially in patients with coronary involvement.


id: cord-300216-3mvfiuwc
author: Montenegro-Villalobos, Jiulliana
date: 2020-09-02
txt: ./txt/cord-300216-3mvfiuwc.txt
cache: ./cache/cord-300216-3mvfiuwc.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.7759/cureus.10212
doi: 10.7759/cureus.10212
summary:
  title: Subconjunctival Acute Bilateral Hemorrhages Due to Kawasaki Disease in a Costa Rican Girl: An Unusual Clinical Manifestation of the Disease Among the ocular manifestations in these patients, bilateral non-suppurative conjunctival injection and uveitis are the most common. We describe a six-year-old Costa Rican girl with acute Kawasaki disease who developed severe bilateral conjunctival injection with subsequent bilateral subconjunctival hemorrhages. To our knowledge, this is the first report from Latin America and among the few in the literature of a child in whom severe bilateral subconjunctival hemorrhages occur as a manifestation of Kawasaki disease. Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired cardiac disease in children, with approximately 80% of cases occurring in children in the first five years of age. Rare ocular manifestations in an 11-year-old girl with incomplete Kawasaki disease: a case report

title:
  Subconjunctival Acute Bilateral Hemorrhages Due to Kawasaki Disease in a Costa Rican Girl: An Unusual Clinical Manifestation of the Disease

abstract:
  Kawasaki disease is an acute systemic vasculitis and is the leading cause of acquired cardiac disease in children. Among the ocular manifestations in these patients, bilateral non-suppurative conjunctival injection and uveitis are the most common. We describe a six-year-old Costa Rican girl with acute Kawasaki disease who developed severe bilateral conjunctival injection with subsequent bilateral subconjunctival hemorrhages. For her ocular involvement, she was treated expectantly, and after six weeks there was complete resolution. To our knowledge, this is the first report from Latin America and among the few in the literature of a child in whom severe bilateral subconjunctival hemorrhages occur as a manifestation of Kawasaki disease.


id: cord-301107-0njnjqeb
title: The Clinics of HHV‐6 infection in COVID‐19 pandemic: Pityriasis rosea and Kawasaki disease
author: Dursun, Recep
date: 2020-05-31
txt: ./txt/cord-301107-0njnjqeb.txt
cache: ./cache/cord-301107-0njnjqeb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32475003/
doi: 10.1111/dth.13730
summary:
  After pandemic, the number of patients with Pityriasis rosea and Kawasaki disease increased significantly in patients who applied to the dermatology outpatient clinic. Herein, we wanted to aim to evaluate whether two diseases (Pityriasis rosea and Kawasaki disease), in which Human Herpesvirus 6 (HHV-6) was held responsible for etiopathogenesis, after the COVID-19 pandemic. After pandemic, the number of patients with Pityriasis rosea increased significantly in patients who applied to the dermatology outpatient clinic (p:0,000). After pandemic, the number of patients with Kawasaki disease increased significantly in patients who applied to the dermatology outpatient clinic (p:0,009). In our study, it was found that the rate of Pityriasis rosae patients who applied to the dermatology outpatient clinic this year during the pandemic period increased approximately 5 times compared to the same time last year. In our study, there was a 10-fold increase in the rate of patients with Kawasaki disease who applied to the dermatology outpatient clinic compared to the previous year.

abstract:
  A new type of coronavirus family (SARS‐CoV‐2), which can be found in humans and animals, with many varieties and clinical symptoms, was first seen in Wuhan, China in late 2019, under the name novel Coronavirus Disease 2019 (COVID‐19). In the literature, cutaneous symptoms related to the disease are generally emphasized. However, it is not yet known whether this new SARS‐CoV‐2 virus, which has entered our lives, plays a role in the etiopathogenesis of dermatological diseases. The patients who were admitted to the dermatology outpatient clinic between 1 April and May 15, 2019, and on 1 April and May 15, 2020 were retrospectively analyzed by searching the hospital automation system and patient files. The reason for the same months to be included in the study was to exclude seasonal effects on the diseases. After pandemic, the number of patients with Pityriasis rosea and Kawasaki disease increased significantly in patients who applied to the dermatology outpatient clinic. Our study is the first study showing pityriasis rosea increase during the pandemic period. We think that this increase is related to HHV‐6 reactivation. Herein, we wanted to draw attention to two diseases in which Human Herpes 6 (HHV‐6) was accused in etiopathogenesis: Kawasaki disease and Pityriasis rosea. This article is protected by copyright. All rights reserved.


id: cord-301160-7ik3iszp
author: Lee, Kyung-Yil
date: 2012-03-01
txt: ./txt/cord-301160-7ik3iszp.txt
cache: ./cache/cord-301160-7ik3iszp.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3349/ymj.2012.53.2.262
doi: 10.3349/ymj.2012.53.2.262
summary:
  Therefore, circulating immune cells, especially T cells, control the inflammation of the majority of the affected regions of KD patients without sequelae, but they also may be involved in the progression of the disease, such as in the case of CALs. Epidemiological and clinical data suggest that KD is an immunological reaction to infectious triggers occurring in genetically susceptible children. Many genetic studies in different countries have evaluated variants in candidate KD genes, and a number of variants, including inositol 1,4,5 triphosphate 3-kinase (ITPKC) and caspase-3, risk of CALs. For example, a severely affected patient who is persistently febrile for a week, showing constant low levels of platelet with high levels of AST and ALT in followup examination, may still not have reached the peak stage of inflammation, suggesting a higher possibility of more severe CALs. Laboratory findings are now mandatory for diagnosis of incomplete KD.

title:
  Kawasaki Disease: Laboratory Findings and an Immunopathogenesis on the Premise of a "Protein Homeostasis System"

abstract:
  Kawasaki disease (KD) is a self-limited systemic inflammatory illness, and coronary artery lesions (CALs) are a major complication determining the prognosis of the disease. Epidemiologic studies in Asian children suggest that the etiologic agent(s) of KD may be associated with environmental changes. Laboratory findings are useful for the diagnosis of incomplete KD, and they can guide the next-step in treatment of initial intravenous immunoglobulin non-responders. CALs seem to develop in the early stages of the disease before a peak in inflammation. Therefore early treatment, before the peak in inflammation, is mandatory to reduce the risk of CAL progression and severity of CALs. The immunopathogenesis of KD is more likely that of acute rheumatic fever than scarlet fever. A hypothetical pathogenesis of KD is proposed under the premise of a "protein homeostasis system"; where innate and adaptive immune cells control pathogenic proteins that are toxic to host cells at a molecular level. After an infection of unknown KD pathogen(s), the pathogenic proteins produced from an unknown focus, spread and bind to endothelial cells of coronary arteries as main target cells. To control the action of pathogenic proteins and/or substances from the injured cells, immune cells are activated. Initially, non-specific T cells and non-specific antibodies are involved in this reaction, while hyperactivated immune cells produce various cytokines, leading to a cytokine imbalance associated with further endothelial cell injury. After the emergence of specific T cells and specific antibodies against the pathogenic proteins, tissue injury ceases and a repair reaction begins with the immune cells.


id: cord-304533-qwbbsg14
title: An adult presentation consistent with PIMS-TS
author: Jones, Imogen
date: 2020-07-10
txt: ./txt/cord-304533-qwbbsg14.txt
cache: ./cache/cord-304533-qwbbsg14.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S2665991320302344
doi: 10.1016/s2665-9913(20)30234-4
abstract: nan
summary:
  key: cord-304533-qwbbsg14 cord_uid: qwbbsg14 The patient had no previous his tory of COVID19 symptoms or con tact with known COVID19 cases. Adult and paediatric specialists conferred and concluded that the most likely diagnosis was Kawasaki like disease on the PIMSTS spectrum. Kawasaki dis ease has been described in adults in association with viral infection. 4, 5 To the best of our knowledge, this is the first reported case of adult Kawasaki like disease related to SARSCoV2 infection. There is an urgent need to recognise and fully characterise PIMS TS in young adults to improve our understanding of pathogenesis, guide treatment decisions, and prevent sequelae in these patients. An outbreak of severe Kawasakilike disease at the Italian epicentre of SARSCoV2 epidemic: an observational cohort study A case of complete adultonset Kawasaki disease: a review of pathogenesis and classification Kawasakilike syndromes in HIVinfected adults


id: cord-309317-cgs0sui7
title: Autoimmune and inflammatory diseases following COVID-19
author: Galeotti, Caroline
date: 2020-06-04
txt: ./txt/cord-309317-cgs0sui7.txt
cache: ./cache/cord-309317-cgs0sui7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41584-020-0448-7
doi: 10.1038/s41584-020-0448-7
summary:
  Emerging reports show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection precedes the appearance of various autoimmune and autoinflammatory diseases, including paediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), thus adding to the growing mystery of this virus and raising questions about the nature of its link with autoimmune and autoinflammatory sequelae. Several emerging reports show that coronavirus disease 2019 (COVID-19), a pandemic respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), could lead to autoimmune and autoinflammatory diseases, such as paedi atric inflammatory multisystemic syndrome (PIMS; which includes Kawasaki-like disease, Kawasaki disease shock syndrome, toxic shock syndrome, myocarditis and macrophage activation syndrome) in children [1] [2] [3] [4] [5] [6] . In the USA, the New York City Health Department on 4 May 2020 reported that 15 children aged 2-15 years had presented with symptoms of MIS-C, including persistent fever and increased levels of inflammatory markers, and many also had rash, abdominal pain, vomiting or diarrhea; ten of the 15 child ren were positive for SARS-CoV-2 infection 6 .

abstract:
  Emerging reports show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection precedes the appearance of various autoimmune and autoinflammatory diseases, including paediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), thus adding to the growing mystery of this virus and raising questions about the nature of its link with autoimmune and autoinflammatory sequelae.


id: cord-312486-rumqopg0
title: On the genetics and immunopathogenesis of COVID-19
author: Jacob, Chaim Oscar
date: 2020-09-10
txt: ./txt/cord-312486-rumqopg0.txt
cache: ./cache/cord-312486-rumqopg0.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1521661620307518
doi: 10.1016/j.clim.2020.108591
summary:
  The question is whether ACE2 expression levels are pertinent to SARS-CoV-2 infection only in the tissues relevant to viral entry and the lungs as its major target, [44, 45] or, given that COVID-19 in its severe form is a systemic disease with multi-organ disfunction [46, 47] , ACE2 expression levels may be important in multiple organs and tissues other than those of the respiratory system. However, the activation of multiple complement pathways, dysregulated neutrophil responses, endothelial injury, and hypercoagulability appear to be interlinked with SARS-CoV-2 infection and instead serve to drive the severity of the disease [91] . Regarding SLE, the prototypic systemic autoimmune disease, a group of investigators suggested that inherent epigenetic dysregulation causing hypomethylation and overexpression of ACE2, the functional receptor for SARS-CoV-2, might facilitate viral J o u r n a l P r e -p r o o f entry, viremia, and increased likelihood of cytokine storm in such patients [153] .

abstract:
  Most severe cases with COVID-19, especially those with pulmonary failure, are not a consequence of viral burden and/or failure of the ‘adaptive’ immune response to subdue the pathogen by utilizing an adequate ‘adaptive’ immune defense. Rather it is a consequence of immunopathology, resulting from imbalanced innate immune response, which may not be linked to pathogen burden at all. In fact, it might be described as an autoinflammatory disease. The Kawasaki-like disease seen in children with SARS-CoV-2 exposure might be another example of similar mechanism.


id: cord-314662-nem6dw34
author: Nakra, Natasha A.
date: 2020-07-01
txt: ./txt/cord-314662-nem6dw34.txt
cache: ./cache/cord-314662-nem6dw34.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/children7070069
doi: 10.3390/children7070069
summary:
  Initial reports surfaced in the UK [3] and Italy [4] , followed by New York and other parts of the U.S. Preliminary accounts of the features of this syndrome resemble those of known entities such as Kawasaki Disease (KD), toxic shock syndrome (TSS), and secondary hemophagocytic lymphohistiocytosis (SHLH)/macrophage activation syndrome (MAS). Early consultation of specialists to assist in management, such as intensive care, cardiology, rheumatology, infectious diseases, allergy/immunology, neurology Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; pro-BNP, pro-B-type natriuretic peptide; BUN, blood urea nitrogen; CRP, C-reactive protein; CT, computed tomography; ESR, erythrocyte sedimentation rate; GI, gastrointestinal; HLH, hemophagocytic lymphohistiocytosis; IL, interleukin; MIS-C, multisystem inflammatory syndrome in children; NK, natural killer; NP, nasopharyngeal; PT, prothrombin time; PTT, partial thromboplastin time; RT-PCR, reverse transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

title:
  Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management

abstract:
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in the multisystem inflammatory syndrome in children (MIS-C). The clinical presentation of MIS-C includes fever, severe illness, and the involvement of two or more organ systems, in combination with laboratory evidence of inflammation and laboratory or epidemiologic evidence of SARS-CoV-2 infection. Some features of MIS-C resemble Kawasaki Disease, toxic shock syndrome, and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. The relationship of MIS-C to SARS-CoV-2 infection suggests that the pathogenesis involves post-infectious immune dysregulation. Patients with MIS-C should ideally be managed in a pediatric intensive care environment since rapid clinical deterioration may occur. Specific immunomodulatory therapy depends on the clinical presentation. The relationship between the immune response to SARS-CoV-2 vaccines in development and MIS-C requires further study.


id: cord-315001-1ui27pkc
title: Discovering Associations: Kawasaki Disease and COVID-19
author: Peterson, Nicholas
date: 2020-09-28
txt: ./txt/cord-315001-1ui27pkc.txt
cache: ./cache/cord-315001-1ui27pkc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33062362/
doi: 10.1155/2020/8880242
summary:
  Due to her prolonged fever, she was tested for COVID-19 which was positive; however, she did not develop respiratory symptoms during her illness. At the time of manuscript submission, this is the second case report to our knowledge showing an association between Kawasaki Disease and SARS-CoV-2 virus, both of which are poorly understood diseases in the pediatric population. This case highlights the value of testing pediatric patients for COVID-19 who present with fever in the absence of other symptoms to improve epidemiologic measures during the ongoing pandemic, and it also adds to a foundation of cases for future research on the presence of a link between Kawasaki Disease and COVID-19. We present a case showing an association between Kawasaki disease and the SARS-CoV-2 virus. is case highlights the value of testing patients for COVID-19 during evaluation for Kawasaki disease (KD). is case highlights the value of testing patients for COVID-19 during evaluation for possible Kawasaki disease.

abstract:
  The COVID-19 pandemic has resulted in over 3.6 million confirmed cases and over 254,000 deaths worldwide. It has been theorized that children who are asymptomatic or who do not display significant respiratory symptoms are potential vectors for community transmission of the SARS-CoV-2 virus. This is incompletely understood due to the current lack of widespread testing in the pediatric population. We describe a case of a 2-year-old female who presented with symptoms of prolonged fever, conjunctivitis, extremity edema, rash, dry/cracked lips, fussiness and fatigue, and a notable absence of respiratory symptoms. She was diagnosed with and treated for Kawasaki disease. Due to her prolonged fever, she was tested for COVID-19 which was positive; however, she did not develop respiratory symptoms during her illness. At the time of manuscript submission, this is the second case report to our knowledge showing an association between Kawasaki Disease and SARS-CoV-2 virus, both of which are poorly understood diseases in the pediatric population. This case highlights the value of testing pediatric patients for COVID-19 who present with fever in the absence of other symptoms to improve epidemiologic measures during the ongoing pandemic, and it also adds to a foundation of cases for future research on the presence of a link between Kawasaki Disease and COVID-19.


id: cord-323202-kcy8xoos
author: Burns, Jane C.
date: 2020-09-22
txt: ./txt/cord-323202-kcy8xoos.txt
cache: ./cache/cord-323202-kcy8xoos.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32976897/
doi: 10.1016/j.jpeds.2020.09.043
summary:
  The observed and synthetic KD clusters were compared with respect to demographic and clinical characteristics and median values for standard laboratory data using univariate analysis and a multivariate, Rotated Empirical Orthogonal Function Analysis (REOFs). CONCLUSIONS: Cases of Kawasaki disease within a cluster were more similar with respect to demographic and clinical features, and levels of inflammation than would be expected by chance. In the univariate analysis, cluster-level averages of demographic and clinical characteristics were compared between the set of 47 true KD clusters and 100 sets of 47 synthetic clusters of equal size created either by randomly shuffling membership of cluster cases (referred to as shuffled clusters) or by randomly creating clusters from non-cluster cases of Kawasaki disease within the same season as the true cluster (referred to as control clusters). (Figure 2 ; available at www.jpeds.com) Striking differences were noted between individual true clusters and synthetic clusters for the following variables: age, ESR, and the presence of enlarged lymph nodes or strawberry tongue.

title:
  Temporal Clusters of Kawasaki Disease Cases Share Distinct Phenotypes That Suggest Response to Diverse Triggers

abstract:
  OBJECTIVE: To test the hypothesis that cases of Kawasaki disease within a temporal cluster have a similar pattern of host response that is distinct from cases of Kawasaki disease in different observed clusters and randomly constructed clusters. STUDY DESIGN: We designed a case-control study to analyze 47 clusters derived from 1332 patients with Kawasaki disease over a 17-yr. period (2002-2019) from a single clinical site and compared the cluster characteristics with two control groups of synthetic KD clusters. We defined a “true” KD cluster as at least 5 patients within a 7-day moving window. The observed and synthetic KD clusters were compared with respect to demographic and clinical characteristics and median values for standard laboratory data using univariate analysis and a multivariate, Rotated Empirical Orthogonal Function Analysis (REOFs). RESULTS: In a univariate analysis, the median values for age, coronary artery Z score, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and age-adjusted hemoglobin for several of the true KD clusters exceeded the 95th percentile for the two synthetic clusters. REOFs revealed distinct patterns of demographic and clinical measures within clusters. CONCLUSIONS: Cases of Kawasaki disease within a cluster were more similar with respect to demographic and clinical features, and levels of inflammation than would be expected by chance. These observations suggest that different triggers and/or different intensity of exposures result in clusters of cases of Kawasaki disease that share a similar response pattern. Analyzing cases within clusters or cases who share demographic and clinical features may lead to new insights into the etiology of KD.


id: cord-331249-jrzgqq8q
title: Enfermedad de kawasaki
author: del Castillo Martín, Fernando
date: 2006-06-30
txt: ./txt/cord-331249-jrzgqq8q.txt
cache: ./cache/cord-331249-jrzgqq8q.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1577356606750825
doi: 10.1016/s1577-3566(06)75082-5
summary:
  Para que un caso pueda ser diagnosticado de enfermedad de Kawasaki incompleta, debe tener al menos 5 días de fiebre, 2 o 3 criterios clínicos, elevación de los reactantes de fase aguda (proteína C reactiva y/o velocidad de sedimentación) y al menos 3 de las siguientes alteraciones analíticas: albúmina ≤ 3 g/dl, anemia para la edad del niño, elevación de alaninaminotransferasa, plaquetas > 450.000 después de 7 días de fiebre, leucocitos ≥ 15.000/µl y en orina ≥ 10 células/campo. Hay autores que incluso proponen un tratamiento si el niño es un lactante con fiebre sin foco de más de 5 días de duración, acompañada de aumento de la proteína C reactiva, neutrofilia y trombocitosis después de 7 días de fiebre, pero muy especialmente si tiene al menos uno de los siguientes signos: inyección conjuntival, enrojecimiento de labios o exantema 48 .

abstract:
  Resumen La enfermedad de Kawasaki es una vasculitis sistémica de etiología desconocida que afecta principalmente a niños menores de 5 años. Es actualmente la primera causa de cardiopatía adquirida en la infancia en los países desarrollados, lo que la convierte en una enfermedad de suma trascendencia en el momento actual. No se conoce su etiología, aunque existen fuertes sospechas de que sea infecciosa. El diagnóstico se realiza por criterios clínicos de fiebre persistente de al menos 5 días de duración y 4 de 5 criterios clínicos: cambios en extremidades, exantemas polimorfos, inyección conjuntival no exudativa, cambios en los labios y la mucosa oral y adenopatías>1,5cm, habitualmente unilateral. La complicación más frecuente es la dilatación y los aneurismas de las arterias coronarias, la cual ocurre en el 20-25% de los niños no tratados. El tratamiento estándar de la enfermedad es con gammaglobulina intravenosa en dosis de 2g/kg, antes de los 10 días del comienzo de la enfermedad, más ácido acetilsalicílico oral en dosis antiinflamatorias. El riesgo de lesión coronaria en los niños tratados es del 3-5%. Abstract Kawasaki disease is a systemic vasculitis of unknow etiology that occurs predominantly in children under the age of 5 years. Kawasaki disease is the most common cause of acquired heart disease in children in the developed world. The exact cause has not yet been established but there is considerable support for it to be due to an infectious agent. The diagnosis of Kawasaki disease is based in clinical criteria: fever persisting at least 5 days and the presence of at least 4 principal features: changes of extremities, polymorphous exanthem, bilateral bulbar conjunctival injection without exudate, changes in lips and oral cavity and cervical lymphadenopathy>1.5cm, usually unilateral. The most common complication is coronary arterial aneurysm and coronay arterial dilatation that occurs in 20-25% untreated children. Standard treatment for Kawasaki disease include intravenous immunoglobulin as a single 2g/kg dose within the first 10 days and oral acetilsalycilic acid. The risk of coronary damage in treated patient is 3-5%.


id: cord-333145-a20dlaxn
title: Association of an IGHV3-66 gene variant with Kawasaki disease
author: Johnson, Todd A.
date: 2020-10-26
txt: ./txt/cord-333145-a20dlaxn.txt
cache: ./cache/cord-333145-a20dlaxn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33106546/
doi: 10.1038/s10038-020-00864-z
summary:
  In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10(−9)). Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD. Instead, 7 out of 12 groups of SNVs in the 6p21 region examined in the Stage 2 analyses showed significant association in the metaanalyses of the data sets in the three GWAS as well as in the follow-up studies ( Table 1 and Supplementary Fig. 3A ).

abstract:
  In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10(−9)). Investigation of nonsynonymous SNVs of the IGHV cluster in 9335 Japanese subjects identified the C allele of rs6423677, located in IGHV3-66, as the most significant reproducible association (OR = 1.25, P = 6.8 × 10(−10) in 3603 cases and 5731 controls). We observed highly skewed allelic usage of IGHV3-66, wherein the rs6423677 A allele was nearly abolished in the transcripts in peripheral blood mononuclear cells of both KD patients and healthy adults. Association of the high-expression allele with KD strongly indicates some active roles of B-cells or endogenous immunoglobulins in the disease pathogenesis. Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD.


id: cord-342372-2g9sq36w
title: The Clinical Diagnosis and Management of Kawasaki Disease: a Review and Update
author: Zhu, Frank H.
date: 2016-09-28
txt: ./txt/cord-342372-2g9sq36w.txt
cache: ./cache/cord-342372-2g9sq36w.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s11908-016-0538-5
doi: 10.1007/s11908-016-0538-5
summary:
  The use of corticosteroids in patients with KD is currently reserved for children who have received ≥2 infusions of IVIG on the basis that effects of steroid therapy on coronary artery abnormalities were uncertain at the time of publication of KD treatment guidelines in 2004. In Japan, the study on the efficacy of IVIG and steroids in patients with severe presentation of KD (RAISE study), a multicenter, prospective, randomized, open-label, blinded-endpoints trial, showed combination treatment with IVIG and prednisolone had significant advantages over IVIG alone in the prevention of coronary artery abnormalities with rapid defervescence of fever and normalization of inflammatory markers [41•] . The earlier initiation of IVIG and corticosteroid therapy with subsequent increased steroid treatment duration was associated with significantly lower rates of coronary artery abnormalities in the RAISE study. Treatment with infliximab in patients with refractory Kawasaki disease was associated with shorter duration of fever and hospitalization when compared to second dose of IVIG in this randomized

abstract:
  Kawasaki disease is an acute, self-limited vasculitis of childhood and has become the leading cause of acquired pediatric heart disease in the USA. Prompt treatment is essential in reducing cardiac-related morbidity and mortality. The underlying etiology remains unknown. The disease itself may be the characteristic manifestation of a common pathway of immune-mediated vascular inflammation in susceptible hosts. The characteristic clinical features of fever for at least 5 days with bilateral nonpurulent conjunctivitis, rash, changes in lips and oral cavity, changes in peripheral extremities, and cervical lymphadenopathy remain the mainstay of diagnosis. Supplementary laboratory criteria can aid in the diagnosis, particularly in cases of incomplete clinical presentation. Diagnosis of Kawasaki disease can be challenging as the clinical presentation can be mistaken for a variety of other pediatric illnesses. Standard of care consists of intravenous immune globulin and aspirin. Corticosteroids, infliximab, and cyclosporine A have been used as adjunct therapy for Kawasaki disease refractory to initial treatment. There is ongoing research into the use of these agents in the initial therapy of Kawasaki disease.


id: cord-343387-7el80yby
title: Kawasaki disease epidemic: pitfalls
author: Gallizzi, Romina
date: 2020-08-27
txt: ./txt/cord-343387-7el80yby.txt
cache: ./cache/cord-343387-7el80yby.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s13052-020-00887-4
doi: 10.1186/s13052-020-00887-4
summary:
  Recent reports have described in the pediatric population a new type of hyperinflammatory response manifested following contact with SARS-CoV-2, with some of the clinical features attributable to Kawasaki disease (KD). Although today little is known about the etiology of KD, the most accepted hypothesis is that of a probable viral etiology, therefore, even the SARS-CoV-2 virus could trigger, in genetically predisposed subjects, an exaggerated inflammatory response that is clinically evident like the one described in KD. In this context the scientific community is wondering about a possible correlation between SARS-CoV-2 virus infection and the onset of Kawasaki-like diseases. They suggest that this clinical picture represents a new phenomenon that affects previously asymptomatic children with SARS-CoV-2 infection manifesting itself as a hyperinflammatory multi-organ involvement syndrome similar to a shock syndrome in KD [8] . Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study

abstract:
  Recent reports have described in the pediatric population a new type of hyperinflammatory response manifested following contact with SARS-CoV-2, with some of the clinical features attributable to Kawasaki disease (KD). The purpose of this commentary is to remark on a possible recent association between SARS-CoV-2 and KD. Although today little is known about the etiology of KD, the most accepted hypothesis is that of a probable viral etiology, therefore, even the SARS-CoV-2 virus could trigger, in genetically predisposed subjects, an exaggerated inflammatory response that is clinically evident like the one described in KD.


id: cord-353229-k3zerr83
title: Kawasaki-like disease in children with COVID-19
author: Akca, Ummusen Kaya
date: 2020-09-16
txt: ./txt/cord-353229-k3zerr83.txt
cache: ./cache/cord-353229-k3zerr83.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s00296-020-04701-6
doi: 10.1007/s00296-020-04701-6
summary:
  Herein, we report the characteristics of four patients with Kawasaki-like phenotype associated with COVID-19 from Turkey and analyze the features of similar published cases through a systematic literature review. Diagnosis of complete KD was based on the criteria of the American Heart Association (AHA): the presence of fever for at least 5 days accompanied by the presence of at least four of the following five findings: bilateral non-exudative conjunctival injection, unilateral cervical lymphadenopathy, changes in the lips and oral cavity, skin rash, and changes in extremities, including indurative angioedema and desquamation [18] . Children with persistent fever, inflammation (neutrophilia, high CRP, and lymphopenia), and single or multi-organ dysfunction have been identified in the UK as "Pediatric Multisystem Inflammatory Syndrome in relation to SARSCoV-2 (PMIS-TS)" regardless of the SARS-CoV-2 RT-PCR test results [73] . Pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort

abstract:
  Children with Coronavirus disease 2019 (COVID-19) are being reported to have manifestations of hyperinflammatory states and/or Kawasaki-like disease. In this study, we investigated children with typical and atypical Kawasaki disease (KD) likely to be associated with COVID-19. We have reported four children with Kawasaki-like disease probably associated with COVID-19. The clinical features were consistent with incomplete KD in three patients. SARS-CoV-2 RT-PCR was positive in one and the serology was positive in one patient with negative RT-PCR. Corticosteroids, anakinra, intravenous immunoglobulin (IVIG), and acetylsalicylic acid were used in the treatment. Three patients recovered after the treatment while one patient died. The literature review revealed 36 articles describing 320 children with Kawasaki-like disease associated with COVID-19. SARS-CoV-2 RT-PCR was negative in 120 (65.5%) of 183 patients while the serology was positive in 130 (83.8%) of 155 patients. The therapeutic options have included IVIG, acetylsalicylic acid, tocilizumab, anakinra, enoxaparin, and methylprednisolone. Pediatric COVID-19 cases may present with atypical/incomplete Kawasaki-like disease. Thus, pediatricians need to be aware of such atypical presentations resembling KD for early diagnosis of COVID-19.


