Kawasaki disease pathophysiology: Difference between revisions

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{{Kawasaki disease}}
{{Kawasaki disease}}


{{CMG}}; {{AE}} {{SH}}
{{CMG}}; {{AE}} {{SH}}, {{Sab}}
==Overview==
==Overview==
The exact pathogenesis of Kawasaki disease is not fully understood. However, it is thought that Kawasaki disease is caused by either environmental, [[genetic]], or [[viral]] causes. Kawasaki disease is defined as the [[systemic inflammation]] of the medium sized arteries and in multiple organs and tissues, which can lead to associated conditions such as [[Hepatitis (patient information)|hepatitis]], [[interstitial pneumonitis]], [[abdominal pain]], [[vomiting]], [[diarrhea]], [[gallbladder]] hydrops, [[aseptic meningitis]], [[irritability]], [[myocarditis]], [[pericarditis]], [[valvulitis]], [[pyuria]], [[pancreatitis]], and [[lymphadenopathy]]. On gross pathology, large or giant [[Coronary artery aneurysm|coronary artery aneurysms]], [[Thrombus|thrombi]] containing [[Aneurysm|aneurysms]], decreases in luminal diameter, [[stenosis]] of the lumen and chronic [[inflamation]] are noted. On microscopic histopathological analysis of autopsied cases of Kawasaki disease, intracytoplasmic [[inclusion bodies]] are frequently observed in [[ciliated]] [[Bronchiole|bronchial]] [[epithelial cells]].
The exact pathogenesis of Kawasaki disease is not fully understood. However, it is thought that Kawasaki disease is caused by either environmental, [[genetic]], or [[viral]] causes. Kawasaki disease is defined as the [[systemic inflammation]] of the medium sized arteries and in multiple [[Organ (anatomy)|organs]] and [[Tissue (biology)|tissues]], which can lead to associated conditions such as [[Hepatitis (patient information)|hepatitis]], [[interstitial pneumonitis]], [[abdominal pain]], [[vomiting]], [[diarrhea]], [[gallbladder]] hydrops, [[aseptic meningitis]], [[irritability]], [[myocarditis]], [[pericarditis]], [[valvulitis]], [[pyuria]], [[pancreatitis]], and [[lymphadenopathy]]. On [[gross pathology]], large or giant [[Coronary artery aneurysm|coronary artery aneurysms]], [[Thrombus|thrombi]] containing [[Aneurysm|aneurysms]], decreases in luminal diameter, [[stenosis]] of the lumen and chronic [[inflamation]] are noted. On [[microscopic]] [[histopathological]] [[analysis]] of [[Autopsy|autopsied]] cases of Kawasaki disease, intracytoplasmic [[inclusion bodies]] are frequently observed in [[ciliated]] [[Bronchiole|bronchial]] [[epithelial cells]].
==Pathophysiology==
==Pathophysiology==


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* The exact pathogenesis of Kawasaki disease is not fully understood.
* The exact pathogenesis of Kawasaki disease is not fully understood.
* It is thought that Kawasaki disease is caused by either environmental, viral or [[genetic|genetic mutations]] such as, [[FCGR2A]], [[CASP3]], [[HLA-A2|HLAclass II]], [[BLK (gene)|BLK]], IPTKC and [[CD40]].
* It is thought that Kawasaki disease is caused by either environmental, viral, or [[genetic|genetic mutations]] in [[FCGR2A]], [[CASP3]], [[HLA-A2|HLAclass II]], [[BLK (gene)|BLK]], IPTKC and [[CD40]].


==Genetics==
==Genetics==
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! style="background:#4479BA; color: #FFFFFF;" |Potential Significance
! style="background:#4479BA; color: #FFFFFF;" |Potential Significance
|-
|-
| style="background:#DCDCDC;" |[[FCGR2A]]<ref name="KhorDavila2011">{{cite journal|last1=Khor|first1=C. C.|last2=Davila|first2=S.|last3=Shimizu|first3=C.|last4=Sheng|first4=S.|last5=Matsubara|first5=T.|last6=Suzuki|first6=Y.|last7=Newburger|first7=J. W.|last8=Baker|first8=A.|last9=Burgner|first9=D.|last10=Breunis|first10=W.|last11=Kuijpers|first11=T.|last12=Wright|first12=V. J.|last13=Levin|first13=M.|last14=Hibberd|first14=M. L.|last15=Burns|first15=J. C.|title=Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease|journal=Journal of Medical Genetics|volume=48|issue=7|year=2011|pages=467–472|issn=0022-2593|doi=10.1136/jmg.2010.086611}}</ref>
! style="background:#DCDCDC;" |[[FCGR2A]]<ref name="KhorDavila2011">{{cite journal|last1=Khor|first1=C. C.|last2=Davila|first2=S.|last3=Shimizu|first3=C.|last4=Sheng|first4=S.|last5=Matsubara|first5=T.|last6=Suzuki|first6=Y.|last7=Newburger|first7=J. W.|last8=Baker|first8=A.|last9=Burgner|first9=D.|last10=Breunis|first10=W.|last11=Kuijpers|first11=T.|last12=Wright|first12=V. J.|last13=Levin|first13=M.|last14=Hibberd|first14=M. L.|last15=Burns|first15=J. C.|title=Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease|journal=Journal of Medical Genetics|volume=48|issue=7|year=2011|pages=467–472|issn=0022-2593|doi=10.1136/jmg.2010.086611}}</ref>
| style="background:#DCDCDC;" |1q23
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |[[Genome-wide association study|GWAS]]
* 1q23
| style="background:#DCDCDC;" |European descent, Taiwanese, Koreans, Han Chinese
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |Low-affinity receptor for [[Fc receptor|Fc]] fragment of [[Immunoglobulin G|IgG]]; risk [[allele]] has lower binding affinity
* [[Genome-wide association study|GWAS]]
| style="background:#DCDCDC;" |
* European descent, Taiwanese, Koreans, Han Chinese
| style="background:#DCDCDC;" |
* Low-affinity receptor for [[Fc receptor|Fc]] fragment of [[Immunoglobulin G|IgG]]; risk [[allele]] has lower binding affinity
|-
|-
| style="background:#DCDCDC;" |[[CASP3]]<ref name="OnouchiOzaki2010">{{cite journal|last1=Onouchi|first1=Yoshihiro|last2=Ozaki|first2=Kouichi|last3=Buns|first3=Jane C.|last4=Shimizu|first4=Chisato|last5=Hamada|first5=Hiromichi|last6=Honda|first6=Takafumi|last7=Terai|first7=Masaru|last8=Honda|first8=Akihito|last9=Takeuchi|first9=Takashi|last10=Shibuta|first10=Shoichi|last11=Suenaga|first11=Tomohiro|last12=Suzuki|first12=Hiroyuki|last13=Higashi|first13=Kouji|last14=Yasukawa|first14=Kumi|last15=Suzuki|first15=Yoichi|last16=Sasago|first16=Kumiko|last17=Kemmotsu|first17=Yasushi|last18=Takatsuki|first18=Shinichi|last19=Saji|first19=Tsutomu|last20=Yoshikawa|first20=Tetsushi|last21=Nagai|first21=Toshiro|last22=Hamamoto|first22=Kunihiro|last23=Kishi|first23=Fumio|last24=Ouchi|first24=Kazunobu|last25=Sato|first25=Yoshitake|last26=Newburger|first26=Jane W.|last27=Baker|first27=Annette L.|last28=Shulman|first28=Stanford T.|last29=Rowley|first29=Anne H.|last30=Yashiro|first30=Mayumi|last31=Nakamura|first31=Yoshikazu|last32=Wakui|first32=Keiko|last33=Fukushima|first33=Yoshimitsu|last34=Fujino|first34=Akihiro|last35=Tsunoda|first35=Tatsuhiko|last36=Kawasaki|first36=Tomisaku|last37=Hata|first37=Akira|last38=Nakamura|first38=Yusuke|last39=Tanaka|first39=Toshihiro|title=Common variants in CASP3 confer susceptibility to Kawasaki disease|journal=Human Molecular Genetics|volume=19|issue=14|year=2010|pages=2898–2906|issn=1460-2083|doi=10.1093/hmg/ddq176}}</ref>
! style="background:#DCDCDC;" |[[CASP3]]<ref name="OnouchiOzaki2010">{{cite journal|last1=Onouchi|first1=Yoshihiro|last2=Ozaki|first2=Kouichi|last3=Buns|first3=Jane C.|last4=Shimizu|first4=Chisato|last5=Hamada|first5=Hiromichi|last6=Honda|first6=Takafumi|last7=Terai|first7=Masaru|last8=Honda|first8=Akihito|last9=Takeuchi|first9=Takashi|last10=Shibuta|first10=Shoichi|last11=Suenaga|first11=Tomohiro|last12=Suzuki|first12=Hiroyuki|last13=Higashi|first13=Kouji|last14=Yasukawa|first14=Kumi|last15=Suzuki|first15=Yoichi|last16=Sasago|first16=Kumiko|last17=Kemmotsu|first17=Yasushi|last18=Takatsuki|first18=Shinichi|last19=Saji|first19=Tsutomu|last20=Yoshikawa|first20=Tetsushi|last21=Nagai|first21=Toshiro|last22=Hamamoto|first22=Kunihiro|last23=Kishi|first23=Fumio|last24=Ouchi|first24=Kazunobu|last25=Sato|first25=Yoshitake|last26=Newburger|first26=Jane W.|last27=Baker|first27=Annette L.|last28=Shulman|first28=Stanford T.|last29=Rowley|first29=Anne H.|last30=Yashiro|first30=Mayumi|last31=Nakamura|first31=Yoshikazu|last32=Wakui|first32=Keiko|last33=Fukushima|first33=Yoshimitsu|last34=Fujino|first34=Akihiro|last35=Tsunoda|first35=Tatsuhiko|last36=Kawasaki|first36=Tomisaku|last37=Hata|first37=Akira|last38=Nakamura|first38=Yusuke|last39=Tanaka|first39=Toshihiro|title=Common variants in CASP3 confer susceptibility to Kawasaki disease|journal=Human Molecular Genetics|volume=19|issue=14|year=2010|pages=2898–2906|issn=1460-2083|doi=10.1093/hmg/ddq176}}</ref>
| style="background:#DCDCDC;" |4q34-35
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |Linkage analysis
* 4q34-35
Candidate gene study
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |Japanese, Taiwanese, Koreans, Chinese, Euro-Americans
* Linkage analysis
| style="background:#DCDCDC;" |Mediates [[apoptosis]] in immune cells and [[Cardiomyocyte|cardiomyocytes]]
* Candidate gene study
Risk [[allele]] decreases [[gene transcription]]
| style="background:#DCDCDC;" |
* Japanese, Taiwanese, Koreans, Chinese, Euro-Americans
| style="background:#DCDCDC;" |
* Mediates [[apoptosis]] in immune cells and [[Cardiomyocyte|cardiomyocytes]]
* Risk [[allele]] decreases [[gene transcription]]
|-
|-
| style="background:#DCDCDC;" |[[HLA-A2|HLAclass II]]<ref name="OnouchiOzaki2012">{{cite journal|last1=Onouchi|first1=Yoshihiro|last2=Ozaki|first2=Kouichi|last3=Burns|first3=Jane C|last4=Shimizu|first4=Chisato|last5=Terai|first5=Masaru|last6=Hamada|first6=Hiromichi|last7=Honda|first7=Takafumi|last8=Suzuki|first8=Hiroyuki|last9=Suenaga|first9=Tomohiro|last10=Takeuchi|first10=Takashi|last11=Yoshikawa|first11=Norishige|last12=Suzuki|first12=Yoichi|last13=Yasukawa|first13=Kumi|last14=Ebata|first14=Ryota|last15=Higashi|first15=Kouji|last16=Saji|first16=Tsutomu|last17=Kemmotsu|first17=Yasushi|last18=Takatsuki|first18=Shinichi|last19=Ouchi|first19=Kazunobu|last20=Kishi|first20=Fumio|last21=Yoshikawa|first21=Tetsushi|last22=Nagai|first22=Toshiro|last23=Hamamoto|first23=Kunihiro|last24=Sato|first24=Yoshitake|last25=Honda|first25=Akihito|last26=Kobayashi|first26=Hironobu|last27=Sato|first27=Junichi|last28=Shibuta|first28=Shoichi|last29=Miyawaki|first29=Masakazu|last30=Oishi|first30=Ko|last31=Yamaga|first31=Hironobu|last32=Aoyagi|first32=Noriyuki|last33=Iwahashi|first33=Seiji|last34=Miyashita|first34=Ritsuko|last35=Murata|first35=Yuji|last36=Sasago|first36=Kumiko|last37=Takahashi|first37=Atsushi|last38=Kamatani|first38=Naoyuki|last39=Kubo|first39=Michiaki|last40=Tsunoda|first40=Tatsuhiko|last41=Hata|first41=Akira|last42=Nakamura|first42=Yusuke|last43=Tanaka|first43=Toshihiro|title=A genome-wide association study identifies three new risk loci for Kawasaki disease|journal=Nature Genetics|volume=44|issue=5|year=2012|pages=517–521|issn=1061-4036|doi=10.1038/ng.2220}}</ref>
! style="background:#DCDCDC;" |[[HLA-A2|HLAclass II]]<ref name="OnouchiOzaki2012">{{cite journal|last1=Onouchi|first1=Yoshihiro|last2=Ozaki|first2=Kouichi|last3=Burns|first3=Jane C|last4=Shimizu|first4=Chisato|last5=Terai|first5=Masaru|last6=Hamada|first6=Hiromichi|last7=Honda|first7=Takafumi|last8=Suzuki|first8=Hiroyuki|last9=Suenaga|first9=Tomohiro|last10=Takeuchi|first10=Takashi|last11=Yoshikawa|first11=Norishige|last12=Suzuki|first12=Yoichi|last13=Yasukawa|first13=Kumi|last14=Ebata|first14=Ryota|last15=Higashi|first15=Kouji|last16=Saji|first16=Tsutomu|last17=Kemmotsu|first17=Yasushi|last18=Takatsuki|first18=Shinichi|last19=Ouchi|first19=Kazunobu|last20=Kishi|first20=Fumio|last21=Yoshikawa|first21=Tetsushi|last22=Nagai|first22=Toshiro|last23=Hamamoto|first23=Kunihiro|last24=Sato|first24=Yoshitake|last25=Honda|first25=Akihito|last26=Kobayashi|first26=Hironobu|last27=Sato|first27=Junichi|last28=Shibuta|first28=Shoichi|last29=Miyawaki|first29=Masakazu|last30=Oishi|first30=Ko|last31=Yamaga|first31=Hironobu|last32=Aoyagi|first32=Noriyuki|last33=Iwahashi|first33=Seiji|last34=Miyashita|first34=Ritsuko|last35=Murata|first35=Yuji|last36=Sasago|first36=Kumiko|last37=Takahashi|first37=Atsushi|last38=Kamatani|first38=Naoyuki|last39=Kubo|first39=Michiaki|last40=Tsunoda|first40=Tatsuhiko|last41=Hata|first41=Akira|last42=Nakamura|first42=Yusuke|last43=Tanaka|first43=Toshihiro|title=A genome-wide association study identifies three new risk loci for Kawasaki disease|journal=Nature Genetics|volume=44|issue=5|year=2012|pages=517–521|issn=1061-4036|doi=10.1038/ng.2220}}</ref>
| style="background:#DCDCDC;" |6p21.3
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |[[Genome-wide association study|GWAS]]
* 6p21.3
| style="background:#DCDCDC;" |Japanese, Taiwanese, Koreans
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |Activation marker for [[immune cells]]; [[antigen presentation]]
* [[Genome-wide association study|GWAS]]
| style="background:#DCDCDC;" |
* Japanese, Taiwanese, Koreans
| style="background:#DCDCDC;" |
* Activation marker for [[immune cells]]; [[antigen presentation]]
|-
|-
| style="background:#DCDCDC;" |[[BLK (gene)|BLK]]<ref name="OnouchiOzaki20122">{{cite journal|last1=Onouchi|first1=Yoshihiro|last2=Ozaki|first2=Kouichi|last3=Burns|first3=Jane C|last4=Shimizu|first4=Chisato|last5=Terai|first5=Masaru|last6=Hamada|first6=Hiromichi|last7=Honda|first7=Takafumi|last8=Suzuki|first8=Hiroyuki|last9=Suenaga|first9=Tomohiro|last10=Takeuchi|first10=Takashi|last11=Yoshikawa|first11=Norishige|last12=Suzuki|first12=Yoichi|last13=Yasukawa|first13=Kumi|last14=Ebata|first14=Ryota|last15=Higashi|first15=Kouji|last16=Saji|first16=Tsutomu|last17=Kemmotsu|first17=Yasushi|last18=Takatsuki|first18=Shinichi|last19=Ouchi|first19=Kazunobu|last20=Kishi|first20=Fumio|last21=Yoshikawa|first21=Tetsushi|last22=Nagai|first22=Toshiro|last23=Hamamoto|first23=Kunihiro|last24=Sato|first24=Yoshitake|last25=Honda|first25=Akihito|last26=Kobayashi|first26=Hironobu|last27=Sato|first27=Junichi|last28=Shibuta|first28=Shoichi|last29=Miyawaki|first29=Masakazu|last30=Oishi|first30=Ko|last31=Yamaga|first31=Hironobu|last32=Aoyagi|first32=Noriyuki|last33=Iwahashi|first33=Seiji|last34=Miyashita|first34=Ritsuko|last35=Murata|first35=Yuji|last36=Sasago|first36=Kumiko|last37=Takahashi|first37=Atsushi|last38=Kamatani|first38=Naoyuki|last39=Kubo|first39=Michiaki|last40=Tsunoda|first40=Tatsuhiko|last41=Hata|first41=Akira|last42=Nakamura|first42=Yusuke|last43=Tanaka|first43=Toshihiro|title=A genome-wide association study identifies three new risk loci for Kawasaki disease|journal=Nature Genetics|volume=44|issue=5|year=2012|pages=517–521|issn=1061-4036|doi=10.1038/ng.2220}}</ref>
! style="background:#DCDCDC;" |[[BLK (gene)|BLK]]<ref name="OnouchiOzaki20122">{{cite journal|last1=Onouchi|first1=Yoshihiro|last2=Ozaki|first2=Kouichi|last3=Burns|first3=Jane C|last4=Shimizu|first4=Chisato|last5=Terai|first5=Masaru|last6=Hamada|first6=Hiromichi|last7=Honda|first7=Takafumi|last8=Suzuki|first8=Hiroyuki|last9=Suenaga|first9=Tomohiro|last10=Takeuchi|first10=Takashi|last11=Yoshikawa|first11=Norishige|last12=Suzuki|first12=Yoichi|last13=Yasukawa|first13=Kumi|last14=Ebata|first14=Ryota|last15=Higashi|first15=Kouji|last16=Saji|first16=Tsutomu|last17=Kemmotsu|first17=Yasushi|last18=Takatsuki|first18=Shinichi|last19=Ouchi|first19=Kazunobu|last20=Kishi|first20=Fumio|last21=Yoshikawa|first21=Tetsushi|last22=Nagai|first22=Toshiro|last23=Hamamoto|first23=Kunihiro|last24=Sato|first24=Yoshitake|last25=Honda|first25=Akihito|last26=Kobayashi|first26=Hironobu|last27=Sato|first27=Junichi|last28=Shibuta|first28=Shoichi|last29=Miyawaki|first29=Masakazu|last30=Oishi|first30=Ko|last31=Yamaga|first31=Hironobu|last32=Aoyagi|first32=Noriyuki|last33=Iwahashi|first33=Seiji|last34=Miyashita|first34=Ritsuko|last35=Murata|first35=Yuji|last36=Sasago|first36=Kumiko|last37=Takahashi|first37=Atsushi|last38=Kamatani|first38=Naoyuki|last39=Kubo|first39=Michiaki|last40=Tsunoda|first40=Tatsuhiko|last41=Hata|first41=Akira|last42=Nakamura|first42=Yusuke|last43=Tanaka|first43=Toshihiro|title=A genome-wide association study identifies three new risk loci for Kawasaki disease|journal=Nature Genetics|volume=44|issue=5|year=2012|pages=517–521|issn=1061-4036|doi=10.1038/ng.2220}}</ref>
| style="background:#DCDCDC;" |8p23-22
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |[[Genome-wide association study|GWAS]]
* 8p23-22
| style="background:#DCDCDC;" |Japanese, Taiwanese, Koreans
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |[[B-cell]] receptor [[signal transduction]]
* [[Genome-wide association study|GWAS]]
| style="background:#DCDCDC;" |
* Japanese, Taiwanese, Koreans
| style="background:#DCDCDC;" |
* [[B-cell]] receptor [[signal transduction]]
|-
|-
| style="background:#DCDCDC;" |IPTKC<ref name="OnouchiGunji2007">{{cite journal|last1=Onouchi|first1=Yoshihiro|last2=Gunji|first2=Tomohiko|last3=Burns|first3=Jane C|last4=Shimizu|first4=Chisato|last5=Newburger|first5=Jane W|last6=Yashiro|first6=Mayumi|last7=Nakamura|first7=Yoshikazu|last8=Yanagawa|first8=Hiroshi|last9=Wakui|first9=Keiko|last10=Fukushima|first10=Yoshimitsu|last11=Kishi|first11=Fumio|last12=Hamamoto|first12=Kunihiro|last13=Terai|first13=Masaru|last14=Sato|first14=Yoshitake|last15=Ouchi|first15=Kazunobu|last16=Saji|first16=Tsutomu|last17=Nariai|first17=Akiyoshi|last18=Kaburagi|first18=Yoichi|last19=Yoshikawa|first19=Tetsushi|last20=Suzuki|first20=Kyoko|last21=Tanaka|first21=Takeo|last22=Nagai|first22=Toshiro|last23=Cho|first23=Hideo|last24=Fujino|first24=Akihiro|last25=Sekine|first25=Akihiro|last26=Nakamichi|first26=Reiichiro|last27=Tsunoda|first27=Tatsuhiko|last28=Kawasaki|first28=Tomisaku|last29=Nakamura|first29=Yusuke|last30=Hata|first30=Akira|title=ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms|journal=Nature Genetics|volume=40|issue=1|year=2007|pages=35–42|issn=1061-4036|doi=10.1038/ng.2007.59}}</ref>
! style="background:#DCDCDC;" |IPTKC<ref name="OnouchiGunji2007">{{cite journal|last1=Onouchi|first1=Yoshihiro|last2=Gunji|first2=Tomohiko|last3=Burns|first3=Jane C|last4=Shimizu|first4=Chisato|last5=Newburger|first5=Jane W|last6=Yashiro|first6=Mayumi|last7=Nakamura|first7=Yoshikazu|last8=Yanagawa|first8=Hiroshi|last9=Wakui|first9=Keiko|last10=Fukushima|first10=Yoshimitsu|last11=Kishi|first11=Fumio|last12=Hamamoto|first12=Kunihiro|last13=Terai|first13=Masaru|last14=Sato|first14=Yoshitake|last15=Ouchi|first15=Kazunobu|last16=Saji|first16=Tsutomu|last17=Nariai|first17=Akiyoshi|last18=Kaburagi|first18=Yoichi|last19=Yoshikawa|first19=Tetsushi|last20=Suzuki|first20=Kyoko|last21=Tanaka|first21=Takeo|last22=Nagai|first22=Toshiro|last23=Cho|first23=Hideo|last24=Fujino|first24=Akihiro|last25=Sekine|first25=Akihiro|last26=Nakamichi|first26=Reiichiro|last27=Tsunoda|first27=Tatsuhiko|last28=Kawasaki|first28=Tomisaku|last29=Nakamura|first29=Yusuke|last30=Hata|first30=Akira|title=ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms|journal=Nature Genetics|volume=40|issue=1|year=2007|pages=35–42|issn=1061-4036|doi=10.1038/ng.2007.59}}</ref>
| style="background:#DCDCDC;" |19q13.2
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |Linkage analysis
* 19q13.2
[[Transmission disequilibrium test|TDT]]
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |Japanese, Taiwanese, Koreans, Chinese, Euro- Americans
* Linkage analysis
| style="background:#DCDCDC;" |Negative regulator of [[calcineurin]]-[[NFAT]] signaling pathway; risk [[allele]] increases signaling
* [[Transmission disequilibrium test|TDT]]
| style="background:#DCDCDC;" |
* Japanese, Taiwanese, Koreans, Chinese, Euro- Americans
| style="background:#DCDCDC;" |
* Negative regulator of [[calcineurin]]-[[NFAT]] signaling pathway; risk [[allele]] increases signaling
|-
|-
| style="background:#DCDCDC;" |[[CD40]]<ref name="OnouchiOzaki20123">{{cite journal|last1=Onouchi|first1=Yoshihiro|last2=Ozaki|first2=Kouichi|last3=Burns|first3=Jane C|last4=Shimizu|first4=Chisato|last5=Terai|first5=Masaru|last6=Hamada|first6=Hiromichi|last7=Honda|first7=Takafumi|last8=Suzuki|first8=Hiroyuki|last9=Suenaga|first9=Tomohiro|last10=Takeuchi|first10=Takashi|last11=Yoshikawa|first11=Norishige|last12=Suzuki|first12=Yoichi|last13=Yasukawa|first13=Kumi|last14=Ebata|first14=Ryota|last15=Higashi|first15=Kouji|last16=Saji|first16=Tsutomu|last17=Kemmotsu|first17=Yasushi|last18=Takatsuki|first18=Shinichi|last19=Ouchi|first19=Kazunobu|last20=Kishi|first20=Fumio|last21=Yoshikawa|first21=Tetsushi|last22=Nagai|first22=Toshiro|last23=Hamamoto|first23=Kunihiro|last24=Sato|first24=Yoshitake|last25=Honda|first25=Akihito|last26=Kobayashi|first26=Hironobu|last27=Sato|first27=Junichi|last28=Shibuta|first28=Shoichi|last29=Miyawaki|first29=Masakazu|last30=Oishi|first30=Ko|last31=Yamaga|first31=Hironobu|last32=Aoyagi|first32=Noriyuki|last33=Iwahashi|first33=Seiji|last34=Miyashita|first34=Ritsuko|last35=Murata|first35=Yuji|last36=Sasago|first36=Kumiko|last37=Takahashi|first37=Atsushi|last38=Kamatani|first38=Naoyuki|last39=Kubo|first39=Michiaki|last40=Tsunoda|first40=Tatsuhiko|last41=Hata|first41=Akira|last42=Nakamura|first42=Yusuke|last43=Tanaka|first43=Toshihiro|title=A genome-wide association study identifies three new risk loci for Kawasaki disease|journal=Nature Genetics|volume=44|issue=5|year=2012|pages=517–521|issn=1061-4036|doi=10.1038/ng.2220}}</ref>
! style="background:#DCDCDC;" |[[CD40]]<ref name="OnouchiOzaki20123">{{cite journal|last1=Onouchi|first1=Yoshihiro|last2=Ozaki|first2=Kouichi|last3=Burns|first3=Jane C|last4=Shimizu|first4=Chisato|last5=Terai|first5=Masaru|last6=Hamada|first6=Hiromichi|last7=Honda|first7=Takafumi|last8=Suzuki|first8=Hiroyuki|last9=Suenaga|first9=Tomohiro|last10=Takeuchi|first10=Takashi|last11=Yoshikawa|first11=Norishige|last12=Suzuki|first12=Yoichi|last13=Yasukawa|first13=Kumi|last14=Ebata|first14=Ryota|last15=Higashi|first15=Kouji|last16=Saji|first16=Tsutomu|last17=Kemmotsu|first17=Yasushi|last18=Takatsuki|first18=Shinichi|last19=Ouchi|first19=Kazunobu|last20=Kishi|first20=Fumio|last21=Yoshikawa|first21=Tetsushi|last22=Nagai|first22=Toshiro|last23=Hamamoto|first23=Kunihiro|last24=Sato|first24=Yoshitake|last25=Honda|first25=Akihito|last26=Kobayashi|first26=Hironobu|last27=Sato|first27=Junichi|last28=Shibuta|first28=Shoichi|last29=Miyawaki|first29=Masakazu|last30=Oishi|first30=Ko|last31=Yamaga|first31=Hironobu|last32=Aoyagi|first32=Noriyuki|last33=Iwahashi|first33=Seiji|last34=Miyashita|first34=Ritsuko|last35=Murata|first35=Yuji|last36=Sasago|first36=Kumiko|last37=Takahashi|first37=Atsushi|last38=Kamatani|first38=Naoyuki|last39=Kubo|first39=Michiaki|last40=Tsunoda|first40=Tatsuhiko|last41=Hata|first41=Akira|last42=Nakamura|first42=Yusuke|last43=Tanaka|first43=Toshihiro|title=A genome-wide association study identifies three new risk loci for Kawasaki disease|journal=Nature Genetics|volume=44|issue=5|year=2012|pages=517–521|issn=1061-4036|doi=10.1038/ng.2220}}</ref>
| style="background:#DCDCDC;" |20q12-13.2
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |[[Genome-wide association study|GWAS]]
* 20q12-13.2
| style="background:#DCDCDC;" |Japanese, Taiwanese, Koreans
| style="background:#DCDCDC;" |
| style="background:#DCDCDC;" |Risk alleles associated with increased [[Translation (genetics)|translation]]
* [[Genome-wide association study|GWAS]]
| style="background:#DCDCDC;" |
* Japanese, Taiwanese, Koreans
| style="background:#DCDCDC;" |
* Risk alleles associated with increased [[Translation (genetics)|translation]]
|-
|-
| colspan="5" |'''Abbreviations''': [[BLK (gene)|BLK]]; [[B cell|B-cell]] lymphoid kinase, [[CASP3]];[[Caspase 3]], [[FCGR1A|FCGR]]; Fcγ receptor, [[Genome-wide association study|GWAS]]; [[Genome-wide association study]], [[Human leukocyte antigen|HLA]]; [[human leukocyte antigen]], [[Immunoglobulin G|IgG]]; [[immunoglobulin G]], [[ITPKC]]; [[Inositol 1,4,5-triphosphate|inositol 1,4,5-trisphosphate kinase-C]], [[Kawasaki disease|KD; Kawasaki disease]], [[NFAT|NFAT; nuclear factor of activated T cells]], and [[Transmission disequilibrium test|TDT; transmission disequilibrium test.]]
| colspan="5" |'''Abbreviations''': [[BLK (gene)|BLK]]; [[B cell|B-cell]] lymphoid kinase, [[CASP3]];[[Caspase 3]], [[FCGR1A|FCGR]]; Fcγ receptor, [[Genome-wide association study|GWAS]]; [[Genome-wide association study]], [[Human leukocyte antigen|HLA]]; [[human leukocyte antigen]], [[Immunoglobulin G|IgG]]; [[immunoglobulin G]], [[ITPKC]]; [[Inositol 1,4,5-triphosphate|inositol 1,4,5-trisphosphate kinase-C]], [[Kawasaki disease|KD; Kawasaki disease]], [[NFAT|NFAT; nuclear factor of activated T cells]], and [[Transmission disequilibrium test|TDT; transmission disequilibrium test.]]
Line 75: Line 99:
! style="background:#4479BA; color: #FFFFFF;" |Associated conditions
! style="background:#4479BA; color: #FFFFFF;" |Associated conditions
|-
|-
| style="background:#DCDCDC;" | [[Liver]]
! style="background:#DCDCDC;" |[[Liver]]
| style="background:#DCDCDC;" | [[Hepatitis]]
| style="background:#DCDCDC;" |
* [[Hepatitis]]
|-
|-
| style="background:#DCDCDC;" | [[Lung]]
! style="background:#DCDCDC;" |[[Lung]]
| style="background:#DCDCDC;" | [[Interstitial pneumonitis]]
| style="background:#DCDCDC;" |
* [[Interstitial pneumonitis]]
|-
|-
| style="background:#DCDCDC;" | [[Gastrointestinal tract]]
! style="background:#DCDCDC;" |[[Gastrointestinal tract]]
| style="background:#DCDCDC;" | [[Abdominal pain]]
| style="background:#DCDCDC;" |
[[Diarrhea]]
* [[Abdominal pain]]
 
* [[Diarrhea]]
[[Vomiting]]
* [[Vomiting]]
 
* [[Gallbladder]] hydrops
[[Gallbladder]] hydrops
|-
|-
| style="background:#DCDCDC;" | [[Meninges]]
! style="background:#DCDCDC;" |[[Meninges]]
| style="background:#DCDCDC;" | [[Aseptic meningitis]]
| style="background:#DCDCDC;" |
[[Irritability]]
* [[Aseptic meningitis]]
* [[Irritability]]
|-
|-
| style="background:#DCDCDC;" | [[Heart]]
! style="background:#DCDCDC;" |[[Heart]]
| style="background:#DCDCDC;" | [[Myocarditis]]
| style="background:#DCDCDC;" |
[[Pericarditis]]
* [[Myocarditis]]
 
* [[Pericarditis]]
[[Valvulitis]]
* [[Valvulitis]]
|-
|-
| style="background:#DCDCDC;" | [[Urinary tract]]
! style="background:#DCDCDC;" |[[Urinary tract]]
| style="background:#DCDCDC;" | [[Pyuria]]
| style="background:#DCDCDC;" |
* [[Pyuria]]
|-
|-
| style="background:#DCDCDC;" | [[Pancreas]]
! style="background:#DCDCDC;" |[[Pancreas]]
| style="background:#DCDCDC;" | [[Pancreatitis]]
| style="background:#DCDCDC;" |
* [[Pancreatitis]]
|-
|-
| style="background:#DCDCDC;" | [[Lymph node|Lymph nodes]]
! style="background:#DCDCDC;" |[[Lymph node|Lymph nodes]]
| style="background:#DCDCDC;" | [[Lymphadenopathy]]
| style="background:#DCDCDC;" |
* [[Lymphadenopathy]]
|}
|}


Line 116: Line 145:
**Chronic [[vasculitis]]
**Chronic [[vasculitis]]
**Luminal [[Myofibroblast|myofibroblastic]] proliferation
**Luminal [[Myofibroblast|myofibroblastic]] proliferation
===Images===
[[File:Kawasaki symptoms D.jpg|300px|thumb|left| Erythema of the palms, which is often accompanied by painful, brawny edema of the dorsa of the hands.<ref>By Kawasaki_symptoms.jpg: Dong Soo Kimderivative work: Natr (talk) - Kawasaki_symptoms.jpg, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=12776158</ref>]]
[[File:Kawasaki tongue.jpg|300px|thumb|center| Strawberry tongue and bright red, swollen lips with vertical cracking and bleeding.<ref>By Kawasaki_symptoms.jpg: Dong Soo Kimderivative work: Natr (talk) - Kawasaki_symptoms.jpg, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=12776137</ref>]]
[[File:Kawasaki.png|800px|left|thumb| (A) Bilateral, non-exudative conjunctival injection with perilimbal sparing. (B) Strawberry tongue and bright red, swollen lips with vertical cracking and bleeding. (C) Erythematous rash involving perineum. (D) Erythema of the palms, which is often accompanied by painful, brawny edema of the dorsa of the hands. (E) Erythema of the soles, and swelling dorsa of the feet. (F) Desquamation of the fingers. (G) Erythema and induration at the site of a previous vaccination with Bacille Calmette-Gurin (BCG). (H) Perianal erythematous desquamation.<ref>By Dong Soo Kim - Kawasaki disease., CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=9962875</ref>]]
<br style="clear:left">


==Microscopic Pathology==
==Microscopic Pathology==

Latest revision as of 20:53, 12 February 2020

Kawasaki disease Microchapters

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

Overview

The exact pathogenesis of Kawasaki disease is not fully understood. However, it is thought that Kawasaki disease is caused by either environmental, genetic, or viral causes. Kawasaki disease is defined as the systemic inflammation of the medium sized arteries and in multiple organs and tissues, which can lead to associated conditions such as hepatitis, interstitial pneumonitis, abdominal pain, vomiting, diarrhea, gallbladder hydrops, aseptic meningitis, irritability, myocarditis, pericarditis, valvulitis, pyuria, pancreatitis, and lymphadenopathy. On gross pathology, large or giant coronary artery aneurysms, thrombi containing aneurysms, decreases in luminal diameter, stenosis of the lumen and chronic inflamation are noted. On microscopic histopathological analysis of autopsied cases of Kawasaki disease, intracytoplasmic inclusion bodies are frequently observed in ciliated bronchial epithelial cells.

Pathophysiology

Pathogenesis

Genetics

In independent cohort studies, the genes which have been identified to lead to the development of Kawasaki disease include:[1]

Adapted from the AHA Scientific Statement on the diagnosis, treatment, and long term management of Kawasaki disease[1]
Gene Chromosome Location Genetic Methods Validation Populations Potential Significance
FCGR2A[2]
  • 1q23
  • European descent, Taiwanese, Koreans, Han Chinese
  • Low-affinity receptor for Fc fragment of IgG; risk allele has lower binding affinity
CASP3[3]
  • 4q34-35
  • Linkage analysis
  • Candidate gene study
  • Japanese, Taiwanese, Koreans, Chinese, Euro-Americans
HLAclass II[4]
  • 6p21.3
  • Japanese, Taiwanese, Koreans
BLK[5]
  • 8p23-22
  • Japanese, Taiwanese, Koreans
IPTKC[6]
  • 19q13.2
  • Linkage analysis
  • TDT
  • Japanese, Taiwanese, Koreans, Chinese, Euro- Americans
CD40[7]
  • 20q12-13.2
  • Japanese, Taiwanese, Koreans
Abbreviations: BLK; B-cell lymphoid kinase, CASP3;Caspase 3, FCGR; Fcγ receptor, GWAS; Genome-wide association study, HLA; human leukocyte antigen, IgG; immunoglobulin G, ITPKC; inositol 1,4,5-trisphosphate kinase-C, KD; Kawasaki disease, NFAT; nuclear factor of activated T cells, and TDT; transmission disequilibrium test.

Associated Conditions

  • Inflammation of the coronary arteries leads to the most important clinical outcomes.[8][9]
  • Kawasaki disease is defined by the systemic inflammation of the medium-sized arteries, multiple organs and tissues.
  • The systemic inflammation of the medium-sized arteries, organs and tissues can lead to the following associated conditions:
Organ and Tissue Associated conditions
Liver
Lung
Gastrointestinal tract
Meninges
Heart
Urinary tract
Pancreas
Lymph nodes

Gross Pathology

Images

Erythema of the palms, which is often accompanied by painful, brawny edema of the dorsa of the hands.[11]
Strawberry tongue and bright red, swollen lips with vertical cracking and bleeding.[12]
(A) Bilateral, non-exudative conjunctival injection with perilimbal sparing. (B) Strawberry tongue and bright red, swollen lips with vertical cracking and bleeding. (C) Erythematous rash involving perineum. (D) Erythema of the palms, which is often accompanied by painful, brawny edema of the dorsa of the hands. (E) Erythema of the soles, and swelling dorsa of the feet. (F) Desquamation of the fingers. (G) Erythema and induration at the site of a previous vaccination with Bacille Calmette-Gurin (BCG). (H) Perianal erythematous desquamation.[13]


Microscopic Pathology

References

  1. ↑ 1.0 1.1 McCrindle, Brian W.; Rowley, Anne H.; Newburger, Jane W.; Burns, Jane C.; Bolger, Anne F.; Gewitz, Michael; Baker, Annette L.; Jackson, Mary Anne; Takahashi, Masato; Shah, Pinak B.; Kobayashi, Tohru; Wu, Mei-Hwan; Saji, Tsutomu T.; Pahl, Elfriede (2017). "Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association". Circulation. 135 (17): e927–e999. doi:10.1161/CIR.0000000000000484. ISSN 0009-7322.
  2. ↑ Khor, C. C.; Davila, S.; Shimizu, C.; Sheng, S.; Matsubara, T.; Suzuki, Y.; Newburger, J. W.; Baker, A.; Burgner, D.; Breunis, W.; Kuijpers, T.; Wright, V. J.; Levin, M.; Hibberd, M. L.; Burns, J. C. (2011). "Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease". Journal of Medical Genetics. 48 (7): 467–472. doi:10.1136/jmg.2010.086611. ISSN 0022-2593.
  3. ↑ Onouchi, Yoshihiro; Ozaki, Kouichi; Buns, Jane C.; Shimizu, Chisato; Hamada, Hiromichi; Honda, Takafumi; Terai, Masaru; Honda, Akihito; Takeuchi, Takashi; Shibuta, Shoichi; Suenaga, Tomohiro; Suzuki, Hiroyuki; Higashi, Kouji; Yasukawa, Kumi; Suzuki, Yoichi; Sasago, Kumiko; Kemmotsu, Yasushi; Takatsuki, Shinichi; Saji, Tsutomu; Yoshikawa, Tetsushi; Nagai, Toshiro; Hamamoto, Kunihiro; Kishi, Fumio; Ouchi, Kazunobu; Sato, Yoshitake; Newburger, Jane W.; Baker, Annette L.; Shulman, Stanford T.; Rowley, Anne H.; Yashiro, Mayumi; Nakamura, Yoshikazu; Wakui, Keiko; Fukushima, Yoshimitsu; Fujino, Akihiro; Tsunoda, Tatsuhiko; Kawasaki, Tomisaku; Hata, Akira; Nakamura, Yusuke; Tanaka, Toshihiro (2010). "Common variants in CASP3 confer susceptibility to Kawasaki disease". Human Molecular Genetics. 19 (14): 2898–2906. doi:10.1093/hmg/ddq176. ISSN 1460-2083.
  4. ↑ Onouchi, Yoshihiro; Ozaki, Kouichi; Burns, Jane C; Shimizu, Chisato; Terai, Masaru; Hamada, Hiromichi; Honda, Takafumi; Suzuki, Hiroyuki; Suenaga, Tomohiro; Takeuchi, Takashi; Yoshikawa, Norishige; Suzuki, Yoichi; Yasukawa, Kumi; Ebata, Ryota; Higashi, Kouji; Saji, Tsutomu; Kemmotsu, Yasushi; Takatsuki, Shinichi; Ouchi, Kazunobu; Kishi, Fumio; Yoshikawa, Tetsushi; Nagai, Toshiro; Hamamoto, Kunihiro; Sato, Yoshitake; Honda, Akihito; Kobayashi, Hironobu; Sato, Junichi; Shibuta, Shoichi; Miyawaki, Masakazu; Oishi, Ko; Yamaga, Hironobu; Aoyagi, Noriyuki; Iwahashi, Seiji; Miyashita, Ritsuko; Murata, Yuji; Sasago, Kumiko; Takahashi, Atsushi; Kamatani, Naoyuki; Kubo, Michiaki; Tsunoda, Tatsuhiko; Hata, Akira; Nakamura, Yusuke; Tanaka, Toshihiro (2012). "A genome-wide association study identifies three new risk loci for Kawasaki disease". Nature Genetics. 44 (5): 517–521. doi:10.1038/ng.2220. ISSN 1061-4036.
  5. ↑ Onouchi, Yoshihiro; Ozaki, Kouichi; Burns, Jane C; Shimizu, Chisato; Terai, Masaru; Hamada, Hiromichi; Honda, Takafumi; Suzuki, Hiroyuki; Suenaga, Tomohiro; Takeuchi, Takashi; Yoshikawa, Norishige; Suzuki, Yoichi; Yasukawa, Kumi; Ebata, Ryota; Higashi, Kouji; Saji, Tsutomu; Kemmotsu, Yasushi; Takatsuki, Shinichi; Ouchi, Kazunobu; Kishi, Fumio; Yoshikawa, Tetsushi; Nagai, Toshiro; Hamamoto, Kunihiro; Sato, Yoshitake; Honda, Akihito; Kobayashi, Hironobu; Sato, Junichi; Shibuta, Shoichi; Miyawaki, Masakazu; Oishi, Ko; Yamaga, Hironobu; Aoyagi, Noriyuki; Iwahashi, Seiji; Miyashita, Ritsuko; Murata, Yuji; Sasago, Kumiko; Takahashi, Atsushi; Kamatani, Naoyuki; Kubo, Michiaki; Tsunoda, Tatsuhiko; Hata, Akira; Nakamura, Yusuke; Tanaka, Toshihiro (2012). "A genome-wide association study identifies three new risk loci for Kawasaki disease". Nature Genetics. 44 (5): 517–521. doi:10.1038/ng.2220. ISSN 1061-4036.
  6. ↑ Onouchi, Yoshihiro; Gunji, Tomohiko; Burns, Jane C; Shimizu, Chisato; Newburger, Jane W; Yashiro, Mayumi; Nakamura, Yoshikazu; Yanagawa, Hiroshi; Wakui, Keiko; Fukushima, Yoshimitsu; Kishi, Fumio; Hamamoto, Kunihiro; Terai, Masaru; Sato, Yoshitake; Ouchi, Kazunobu; Saji, Tsutomu; Nariai, Akiyoshi; Kaburagi, Yoichi; Yoshikawa, Tetsushi; Suzuki, Kyoko; Tanaka, Takeo; Nagai, Toshiro; Cho, Hideo; Fujino, Akihiro; Sekine, Akihiro; Nakamichi, Reiichiro; Tsunoda, Tatsuhiko; Kawasaki, Tomisaku; Nakamura, Yusuke; Hata, Akira (2007). "ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms". Nature Genetics. 40 (1): 35–42. doi:10.1038/ng.2007.59. ISSN 1061-4036.
  7. ↑ Onouchi, Yoshihiro; Ozaki, Kouichi; Burns, Jane C; Shimizu, Chisato; Terai, Masaru; Hamada, Hiromichi; Honda, Takafumi; Suzuki, Hiroyuki; Suenaga, Tomohiro; Takeuchi, Takashi; Yoshikawa, Norishige; Suzuki, Yoichi; Yasukawa, Kumi; Ebata, Ryota; Higashi, Kouji; Saji, Tsutomu; Kemmotsu, Yasushi; Takatsuki, Shinichi; Ouchi, Kazunobu; Kishi, Fumio; Yoshikawa, Tetsushi; Nagai, Toshiro; Hamamoto, Kunihiro; Sato, Yoshitake; Honda, Akihito; Kobayashi, Hironobu; Sato, Junichi; Shibuta, Shoichi; Miyawaki, Masakazu; Oishi, Ko; Yamaga, Hironobu; Aoyagi, Noriyuki; Iwahashi, Seiji; Miyashita, Ritsuko; Murata, Yuji; Sasago, Kumiko; Takahashi, Atsushi; Kamatani, Naoyuki; Kubo, Michiaki; Tsunoda, Tatsuhiko; Hata, Akira; Nakamura, Yusuke; Tanaka, Toshihiro (2012). "A genome-wide association study identifies three new risk loci for Kawasaki disease". Nature Genetics. 44 (5): 517–521. doi:10.1038/ng.2220. ISSN 1061-4036.
  8. ↑ McCrindle, Brian W.; Rowley, Anne H.; Newburger, Jane W.; Burns, Jane C.; Bolger, Anne F.; Gewitz, Michael; Baker, Annette L.; Jackson, Mary Anne; Takahashi, Masato; Shah, Pinak B.; Kobayashi, Tohru; Wu, Mei-Hwan; Saji, Tsutomu T.; Pahl, Elfriede (2017). "Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association". Circulation. 135 (17): e927–e999. doi:10.1161/CIR.0000000000000484. ISSN 0009-7322.
  9. ↑ Amano S, Hazama F, Hamashima Y (July 1979). "Pathology of Kawasaki disease: I. Pathology and morphogenesis of the vascular changes". Jpn. Circ. J. 43 (7): 633–43. PMID 41111.
  10. ↑ McCrindle, Brian W.; Rowley, Anne H.; Newburger, Jane W.; Burns, Jane C.; Bolger, Anne F.; Gewitz, Michael; Baker, Annette L.; Jackson, Mary Anne; Takahashi, Masato; Shah, Pinak B.; Kobayashi, Tohru; Wu, Mei-Hwan; Saji, Tsutomu T.; Pahl, Elfriede (2017). "Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association". Circulation. 135 (17): e927–e999. doi:10.1161/CIR.0000000000000484. ISSN 0009-7322.
  11. ↑ By Kawasaki_symptoms.jpg: Dong Soo Kimderivative work: Natr (talk) - Kawasaki_symptoms.jpg, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=12776158
  12. ↑ By Kawasaki_symptoms.jpg: Dong Soo Kimderivative work: Natr (talk) - Kawasaki_symptoms.jpg, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=12776137
  13. ↑ By Dong Soo Kim - Kawasaki disease., CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=9962875
  14. ↑ Rowley AH, Baker SC, Shulman ST, Garcia FL, Fox LM, Kos IM, Crawford SE, Russo PA, Hammadeh R, Takahashi K, Orenstein JM (February 2008). "RNA-containing cytoplasmic inclusion bodies in ciliated bronchial epithelium months to years after acute Kawasaki disease". PLoS ONE. 3 (2): e1582. doi:10.1371/journal.pone.0001582. PMC 2216059. PMID 18270572.

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