Kawasaki disease pathophysiology: Difference between revisions

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Revision as of 18:26, 11 April 2018

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

Overview

The exact pathogenesis of Kawasaki disease is not fully understood. However it is thought that Kawasaki disease is caused by either environmental, genetic such as, FCGR2A, CASP3, HLAclass II, BLK, IPTKC and CD40, and viral. The Kawasaki disease is defined as the systemic inflammation of the medium sized arteries and in multiple organs and tissues which can lead to the associated conditions like 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 luminal diamieter, stenosis of the lumen and chronic inflamation are the usual findings of Kawasaki disease. On microscopic histopathological analysis of autopsied cases of Kawasaki disease, intracytoplasmic inclusion bodies are frequently observed in ciliated bronchial epithelial cells.

Pathophysiology

Pathogenesis

The exact pathogenesis of Kawasaki disease is not fully understood.

Genetics

In independent cohort studies the genes which are suspected :^[1]

Gene	Chromosome Location	Genetic Methods	Validation Populations	Potential Significance	Reference and Year
Adapted from the AHA Scientific Statement on the diagnosis, treatment, and long term management of Kawasaki disease^[1]
FCGR2A	1q23	GWAS	European descent, Taiwanese, Koreans, Han Chinese	Low-affinity receptor for Fc fragment of IgG; risk allele has lower binding affinity	Khor et al^[2]2011
CASP3	4q34-35	Linkage analysis Candidate gene study	Japanese, Taiwanese, Koreans, Chinese, Euro-Americans	Mediates apoptosis in immune cells and cardiomyocytes Risk allele decreases gene transcription	Onouchi et al^[3] 2010
HLAclass II	6p21.3	GWAS	Japanese, Taiwanese, Koreans	Activation marker for immune cells; antigen presentation	Onouchi et al^[4] 2012
BLK	8p23-22	GWAS	Japanese, Taiwanese, Koreans	B-cell receptor signal transduction	Onouchi et al^[5] 2012
IPTKC	19q13.2	Linkage analysis TDT	Japanese, Taiwanese, Koreans, Chinese, Euro- Americans	Negative regulator of calcineurin-NFAT signaling pathway; risk allele increases signaling	Onouchi et al^[6] 2008
CD40	20q12-13.2	GWAS	Japanese, Taiwanese, Koreans	Risk alleles associated with increased translation	Onouchi et al^[7] 2012
BLK indicates 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 lead to most important clinical outcomes.
Kawasaki disease is defined by the systemic inflammation of the medium sized arteries and in multiple organs and tissues.
The systemic inflammation of the medium sized arteries organs and tissues can lead to the following associated conditions:^[8]^[9]

Organ and Tissue	Associated conditions
Liver	Hepatitis
Lung	Interstitial pneumonitis
Gastrointestinal tract	Abdominal pain Diarrhea Vomiting Gallbladder hydrops
Meninges	Aseptic meningitis Irritability
Heart	Myocarditis Pericarditis Valvulitis
Urinary tract	Pyuria
Pancreas	Pancreatitis
Lymph nodes	Lymphadenopathy

Gross Pathology

On gross pathology, large or giant coronary artery aneurysms, thrombi containing aneurysms, decreases luminal diamieter, stenosis of the lumen and chronic inflamation are the usual findings of Kawasaki disease.^[10]
The Kawasaki disease mainly involved the muscular arteries and is characterized by the following processes:
Necrotizing arteritis
Subacute vasculitis
Chronic Vasculitis
Luminal myofibroblastic proliferation

Microscopic Pathology

On microscopic histopathological analysis of autopsied cases of Kawasaki disease, intracytoplasmic inclusion bodies are frequently observed in ciliated bronchial epithelial cells.^[11]

References

↑ ^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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

Template:WH Template:WS

[McCrindleRowley2017-1] 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.

[KhorDavila2011-2] 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.

[OnouchiOzaki2010-3] 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.

[OnouchiOzaki2012-4] 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.

[OnouchiOzaki20122-5] 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.

[OnouchiGunji2007-6] 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.

[OnouchiOzaki20123-7] 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.

[McCrindleRowley20172-8] 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.

[pmid41111-9] 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.

[McCrindleRowley20173-10] 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.

[pmid18270572-11] 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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@@ Line 4: / Line 4: @@
 {{CMG}}; {{AE}} {{SH}}
 ==Overview==
-The exact pathogenesis of Kawasaki disease is not fully understood. However it is thought that Kawasaki disease  is caused by either environmental, [[genetic]], and [[viral]].
+The exact pathogenesis of Kawasaki disease is not fully understood. However it is thought that Kawasaki disease  is caused by either environmental, [[genetic]] such as, [[FCGR2A]], [[CASP3]], [[HLA-A2|HLAclass II]], [[BLK (gene)|BLK]], IPTKC and [[CD40]],  and [[viral]]. The Kawasaki disease is defined as the systemic inflammation of the medium sized arteries and in multiple organs and tissues which can lead to the associated conditions like [[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 luminal diamieter, [[stenosis]] of the lumen and chronic [[inflamation]] are the usual findings of Kawasaki disease. On microscopic histopathological analysis of autopsied cases of Kawasaki disease, intracytoplasmic [[inclusion bodies]] are frequently observed in [[ciliated]] [[Bronchiole|bronchial]] [[epithelial cells]].
 ==Pathophysiology==
@@ Line 11: / Line 13: @@
 ==Genetics==
-In independent cohort studies the genes which are suspected in susceptibility to Kawasaki disease with replication are:<ref name="McCrindleRowley2017">{{cite journal|last1=McCrindle|first1=Brian W.|last2=Rowley|first2=Anne H.|last3=Newburger|first3=Jane W.|last4=Burns|first4=Jane C.|last5=Bolger|first5=Anne F.|last6=Gewitz|first6=Michael|last7=Baker|first7=Annette L.|last8=Jackson|first8=Mary Anne|last9=Takahashi|first9=Masato|last10=Shah|first10=Pinak B.|last11=Kobayashi|first11=Tohru|last12=Wu|first12=Mei-Hwan|last13=Saji|first13=Tsutomu T.|last14=Pahl|first14=Elfriede|title=Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association|journal=Circulation|volume=135|issue=17|year=2017|pages=e927–e999|issn=0009-7322|doi=10.1161/CIR.0000000000000484}}</ref>
+In independent cohort studies the genes which are suspected :<ref name="McCrindleRowley2017">{{cite journal|last1=McCrindle|first1=Brian W.|last2=Rowley|first2=Anne H.|last3=Newburger|first3=Jane W.|last4=Burns|first4=Jane C.|last5=Bolger|first5=Anne F.|last6=Gewitz|first6=Michael|last7=Baker|first7=Annette L.|last8=Jackson|first8=Mary Anne|last9=Takahashi|first9=Masato|last10=Shah|first10=Pinak B.|last11=Kobayashi|first11=Tohru|last12=Wu|first12=Mei-Hwan|last13=Saji|first13=Tsutomu T.|last14=Pahl|first14=Elfriede|title=Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association|journal=Circulation|volume=135|issue=17|year=2017|pages=e927–e999|issn=0009-7322|doi=10.1161/CIR.0000000000000484}}</ref>
 {|
 |-
@@ Line 23: / Line 25: @@
 ! style="background:#4479BA; color: #FFFFFF;" |Reference and Year
 |-
-| style="background:#DCDCDC;" |''[[FCGR2A]]''
+| style="background:#DCDCDC;" |[[FCGR2A]]
 | style="background:#DCDCDC;" |1q23
 | style="background:#DCDCDC;" |[[Genome-wide association study|GWAS]]
@@ Line 30: / Line 32: @@
 | style="background:#DCDCDC;" |Khor et al<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>2011
 |-
-| style="background:#DCDCDC;" |''[[CASP3]]''
+| style="background:#DCDCDC;" |[[CASP3]]
 | style="background:#DCDCDC;" |4q34-35
 | style="background:#DCDCDC;" |Linkage analysis
@@ Line 39: / Line 41: @@
 | style="background:#DCDCDC;" |Onouchi et al<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> 2010
 |-
-| style="background:#DCDCDC;" |[[HLA-A2|''HLA''class II]]
+| style="background:#DCDCDC;" |[[HLA-A2|HLAclass II]]
 | style="background:#DCDCDC;" |6p21.3
 | style="background:#DCDCDC;" |[[Genome-wide association study|GWAS]]
@@ Line 46: / Line 48: @@
 | style="background:#DCDCDC;" |Onouchi et al<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> 2012
 |-
-| style="background:#DCDCDC;" |''[[BLK (gene)|BLK]]''
+| style="background:#DCDCDC;" |[[BLK (gene)|BLK]]
 | style="background:#DCDCDC;" |8p23-22
 | style="background:#DCDCDC;" |[[Genome-wide association study|GWAS]]
@@ Line 53: / Line 55: @@
 | style="background:#DCDCDC;" |Onouchi et al<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> 2012
 |-
-| style="background:#DCDCDC;" |''IPTKC''
+| style="background:#DCDCDC;" |IPTKC
 | style="background:#DCDCDC;" |19q13.2
 | style="background:#DCDCDC;" |Linkage analysis
@@ Line 61: / Line 63: @@
 | style="background:#DCDCDC;" |Onouchi et al<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> 2008
 |-
-| style="background:#DCDCDC;" |''[[CD40]]''
+| style="background:#DCDCDC;" |[[CD40]]
 | style="background:#DCDCDC;" |20q12-13.2
 | style="background:#DCDCDC;" |[[Genome-wide association study|GWAS]]
@@ Line 114: / Line 116: @@
 ==Gross Pathology==
-*On gross pathology, large or giant coronary artery aneurysms, thrombi containing aneurysms, decreases luminal diamieter, stenosis of the lumen and chronic inflamation are the usual findings of Kawasaki disease.<ref name="McCrindleRowley20173">{{cite journal|last1=McCrindle|first1=Brian W.|last2=Rowley|first2=Anne H.|last3=Newburger|first3=Jane W.|last4=Burns|first4=Jane C.|last5=Bolger|first5=Anne F.|last6=Gewitz|first6=Michael|last7=Baker|first7=Annette L.|last8=Jackson|first8=Mary Anne|last9=Takahashi|first9=Masato|last10=Shah|first10=Pinak B.|last11=Kobayashi|first11=Tohru|last12=Wu|first12=Mei-Hwan|last13=Saji|first13=Tsutomu T.|last14=Pahl|first14=Elfriede|title=Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association|journal=Circulation|volume=135|issue=17|year=2017|pages=e927–e999|issn=0009-7322|doi=10.1161/CIR.0000000000000484}}</ref>
+*On gross pathology, large or giant [[Coronary artery aneurysm|coronary artery aneurysms]], [[Thrombus|thrombi]] containing [[Aneurysm|aneurysms]], decreases luminal diamieter, [[stenosis]] of the lumen and chronic [[inflamation]] are the usual findings of Kawasaki disease.<ref name="McCrindleRowley20173">{{cite journal|last1=McCrindle|first1=Brian W.|last2=Rowley|first2=Anne H.|last3=Newburger|first3=Jane W.|last4=Burns|first4=Jane C.|last5=Bolger|first5=Anne F.|last6=Gewitz|first6=Michael|last7=Baker|first7=Annette L.|last8=Jackson|first8=Mary Anne|last9=Takahashi|first9=Masato|last10=Shah|first10=Pinak B.|last11=Kobayashi|first11=Tohru|last12=Wu|first12=Mei-Hwan|last13=Saji|first13=Tsutomu T.|last14=Pahl|first14=Elfriede|title=Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association|journal=Circulation|volume=135|issue=17|year=2017|pages=e927–e999|issn=0009-7322|doi=10.1161/CIR.0000000000000484}}</ref>
 *The Kawasaki disease mainly involved the muscular arteries and is characterized by the following processes:
-*Necrotizing arteritis
+*[[Necrosis|Necrotizing]] [[arteritis]]
-*Subacute vasculitis
+*Subacute [[vasculitis]]
-*Chronic Vasculitis
+*Chronic [[Vasculitis]]
-*Luminal myofibroblastic proliferation
+*Luminal [[Myofibroblast|myofibroblastic]] proliferation
 ==Microscopic Pathology==
-*On microscopic histopathological analysis of autopsied cases of Kawasaki disease, intracytoplasmic inclusion bodies are frequently observed in ciliated bronchial epithelial cells.<ref name="pmid18270572">{{cite journal |vauthors=Rowley AH, Baker SC, Shulman ST, Garcia FL, Fox LM, Kos IM, Crawford SE, Russo PA, Hammadeh R, Takahashi K, Orenstein JM |title=RNA-containing cytoplasmic inclusion bodies in ciliated bronchial epithelium months to years after acute Kawasaki disease |journal=PLoS ONE |volume=3 |issue=2 |pages=e1582 |date=February 2008 |pmid=18270572 |pmc=2216059 |doi=10.1371/journal.pone.0001582 |url=}}</ref>
+*On microscopic histopathological analysis of autopsied cases of Kawasaki disease, intracytoplasmic [[inclusion bodies]] are frequently observed in [[ciliated]] [[Bronchiole|bronchial]] [[epithelial cells]].<ref name="pmid18270572">{{cite journal |vauthors=Rowley AH, Baker SC, Shulman ST, Garcia FL, Fox LM, Kos IM, Crawford SE, Russo PA, Hammadeh R, Takahashi K, Orenstein JM |title=RNA-containing cytoplasmic inclusion bodies in ciliated bronchial epithelium months to years after acute Kawasaki disease |journal=PLoS ONE |volume=3 |issue=2 |pages=e1582 |date=February 2008 |pmid=18270572 |pmc=2216059 |doi=10.1371/journal.pone.0001582 |url=}}</ref>
 ==References==
 {{Reflist|2}}