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{{AE}} {{SHA}}


{{SHA}}
<br />
 
== Overview ==
[[Esophagitis]] is the inflammation of the esophagus.[https://en.wikipedia.org/wiki/Esophagitis]
 
== Historical Perspective ==


== Classification ==


* Esophagitis  may be classified into 5 subtypes/groups:<ref name=":0" />
** Reflux esophagitis
**Infectious esophagitis
***Fungal
****[[Candida]]
*** Viral
**** Herpes simplex
**** Cytomegalovirus
** Drug-induced esophagitis
** Eosinophilic esophagitis
** Caustic esophagitis


<br />
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
{| class="wikitable"
|+
|+
!A
!1
|-
|-
|B
| colspan="9" style="background: #4479BA; text-align: center;" |{{fontcolor|#000|Some Differential Diagnosis of Asperger Syndrome
|
(Modified Table from The Investigation and Differential Diagnosis of Asperger Syndrome in Adults)<ref name="pmid24290364" /> '''}}
|- style="padding: 5px 5px; background: #4479BA;" align="center" |
| style="padding: 5px 5px; background: #4479BA;" align="center" |
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Asperger Syndrome'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Schizoid Personality Disorder'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Schizotypal Personality Disorder'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Avoidant Personality Disorder'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Social Phobia'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Obsessive Personality Disorder'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Obsessive-compulsive disorder (OCD)'''
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Attention deficit–hyperactivity disorder (ADHD)'''
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal social interaction'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal verbal communication'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal facial expression/gestures/prosody'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal eye contact'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal theory of mind'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal empathy'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal interests/rituals/compulsions'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal attention'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal  psychomotor function'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal self-injurious behavior'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- <br />
|-
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal psychotic manifestations'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
|-
|-
|C
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal social interaction in childhood'''
|
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
|-
|-
|D
| style="padding: 5px 5px; background: #4479BA;" align="center" |'''Abnormal biographical stress factors'''
|
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | -
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +
| style="padding: 5px 5px; background: #DCDCDC;" align="center" | +/- 
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |  +/- 
|}
|}


== Pathophysiology ==


== Clinical Features ==


== Differentiating Esophagitis from other Diseases ==


== Epidemiology and Demographics ==


=== Age ===


* Esophagitis is more commonly observed among adults.
== Cytokine Storm ==


=== Gender ===


* Esophagitis  affects men and women equally.
Cytokine storm is an immune reaction that is characterized by dysregulated and excessive release of proinflammatory [[Cytokine|cytokines]].<ref name="pmid22390970">{{cite journal| author=Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG| title=Into the eye of the cytokine storm. | journal=Microbiol Mol Biol Rev | year= 2012 | volume= 76 | issue= 1 | pages= 16-32 | pmid=22390970 | doi=10.1128/MMBR.05015-11 | pmc=3294426 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22390970  }} </ref>


=== Race ===
=== Cytokines Involved in Cytokine Storm ===


* There is no racial predilection for esophagitis .
*[[Cytokine|Cytokines]] are small [[Protein|proteins]] that are released for [[cell signaling]].<ref name="pmid22390970" />
*[[Cytokine|Cytokines]] types and their actions include:<ref name="pmid22390970" />
**'''Interferons''' '''(INFs)'''
*** Key role in [[Innate immune system|innate immunity]]
*** Regulation of the production of antiviral [[Protein|proteins]]
*** Regulation of the production of antiproliferative [[Protein|proteins]]
**'''Interleukins''' '''(ILs)'''
*** Regulation of immune cell [[differentiation]] and activation  
*** May be pro- or anti-[[Inflammation|inflammatory]]  
**'''Chemokines'''
*** Act as chemoattractants
*** Recruitment of [[White blood cells|leukocytes]]
**'''Colony-stimulating factors'''  
*** Induction of [[Hematopoietic stem cell|hematopoietic progenitor cell]] [[Cell growth|proliferation]] and [[differentiation]]  
**'''Tumor necrosis factor (TNF)''' 
*** Activation of [[T cell|T cells]] ([[Cytotoxic T cell|cytotoxic]])


== Risk Factors ==
*


* Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
*  
*
*


== Natural History, Complications and Prognosis ==
=== Pathogenesis of Cytokine Storm ===


*Prognosis is generally good.  
* Cytokine storm is an immune reaction that is characterized by dysregulated and excessive release of proinflammatory [[Cytokine|cytokines]].<ref name="pmid22390970" />
*If left untreated, [#%] of patients with esophagitis may progress to develop scarring in the esophagus.
* During [[sepsis]], cytokine storm may be the cause of tissue or organ injury.<ref name="pmid28555385">{{cite journal| author=Chousterman BG, Swirski FK, Weber GF| title=Cytokine storm and sepsis disease pathogenesis. | journal=Semin Immunopathol | year= 2017 | volume= 39 | issue= 5 | pages= 517-528 | pmid=28555385 | doi=10.1007/s00281-017-0639-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28555385  }} </ref>
*Common complications of esophagitis include esophageal ulcers, Barrett's esophagus, and esophageal cancer.


== Diagnosis ==
*Cytokine storm causes [[inflammation]], which in the beginning of the disease is [[local]] and later spreads around by the [[systemic circulation]]. This is followed by repair and restoration of tissues, [[Organ (anatomy)|organs]] and their functions. However, in severe or some [[Inflammation|inflammations]], the repair is with [[fibrosis]] which may lead to permanent dysfunction of organs.<ref name="pmid22390970" />
*Lung damage caused by pathogens (such as [[SARS-CoV]] and [[influenza virus]]) may lead to acute lung injury (ALI) or [[Acute respiratory distress syndrome|acute respiratory distress syndrome (ARDS)]].
* [[Cytokine|Cytokines]] profiles change over time in patients with [[sepsis]]:<ref name="pmid22390970" />
** In the early stages of the infection (minutes to hours),  [[Cytokine|cytokines]]  such as [[Tumor necrosis factors|TNF]] and [[IL-1]], and [[Chemokine|chemokines]] such as [[Interleukin 8|IL-8]] and [[CCL2|MCP-1 (CCL2)]] increase.
** Then, an increase in [[Interleukin 6|IL-6]] is followed.
** Later, [[Interleukin 10|IL-10]] (anti-[[Inflammation|inflammatory]] cytokine) increases.


=== Diagnostic Criteria ===
* Proinflammatory [[Cytokine|cytokines]] that have a role in [[Acute respiratory distress syndrome|ARDS]] include:<ref name="pmid15657466">{{cite journal| author=Jiang Y, Xu J, Zhou C, Wu Z, Zhong S, Liu J | display-authors=etal| title=Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome. | journal=Am J Respir Crit Care Med | year= 2005 | volume= 171 | issue= 8 | pages= 850-7 | pmid=15657466 | doi=10.1164/rccm.200407-857OC | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15657466  }} </ref><ref name="pmid17374415">{{cite journal| author=Cameron MJ, Bermejo-Martin JF, Danesh A, Muller MP, Kelvin DJ| title=Human immunopathogenesis of severe acute respiratory syndrome (SARS). | journal=Virus Res | year= 2008 | volume= 133 | issue= 1 | pages= 13-9 | pmid=17374415 | doi=10.1016/j.virusres.2007.02.014 | pmc=7114310 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17374415  }} </ref><ref name="pmid15655079">{{cite journal| author=Reghunathan R, Jayapal M, Hsu LY, Chng HH, Tai D, Leung BP | display-authors=etal| title=Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome. | journal=BMC Immunol | year= 2005 | volume= 6 | issue=  | pages= 2 | pmid=15655079 | doi=10.1186/1471-2172-6-2 | pmc=546205 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15655079  }} </ref><ref name="pmid32283152">{{cite journal| author=Ye Q, Wang B, Mao J| title=The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. | journal=J Infect | year= 2020 | volume= 80 | issue= 6 | pages= 607-613 | pmid=32283152 | doi=10.1016/j.jinf.2020.03.037 | pmc=7194613 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32283152  }} </ref>
**IL-1β
**[[Interleukin 6|IL-6]]
**[[IL-8|IL-8 (CXCL8)]]
**[[CCL2|CCL-2 (MCP-1)]]
**[[CCL3|CCL-3 (Macrophage inflammatory protein-1A)]]
**[[CCL5|CCL-5]]
**IFNγ -induced protein 10 (IP-10, CXCL10)
**[[Granulocyte macrophage colony stimulating factor|Granulocytemacrophage colony-stimulating factor (GM-CSF)]]


=== Symptoms ===
* Cytokine storm (dysregulated and excessive release of [[Cytokine|cytokines]]) has been associated with [[Acute respiratory distress syndrome|ARDS]] in [[SARS coronavirus|SARS coronavirus (SARS-CoV)]] and [[Middle East respiratory syndrome coronavirus infection causes|MERS coronavirus (MERS-CoV)]] infections.<ref name="pmid28466096">{{cite journal| author=Channappanavar R, Perlman S| title=Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. | journal=Semin Immunopathol | year= 2017 | volume= 39 | issue= 5 | pages= 529-539 | pmid=28466096 | doi=10.1007/s00281-017-0629-x | pmc=7079893 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28466096  }} </ref>
* <s>There have been reports on an association between cytokine storm and severity of [[COVID-19]] infection and COVID-19-associated-ARDS.</s>


* Symptoms of esophagitis may include the following:
*It has been suggested that  the [[pathogenesis]] of severe [[COVID-19]] infection may be due to cytokine storm and suppression of [[T helper cell|Th1]] antiviral responses since the following findings have been reported to be associated with severe [[COVID-19]] infection:<ref name="pmid32361250">{{cite journal| author=Liu J, Li S, Liu J, Liang B, Wang X, Wang H | display-authors=etal| title=Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. | journal=EBioMedicine | year= 2020 | volume= 55 | issue=  | pages= 102763 | pmid=32361250 | doi=10.1016/j.ebiom.2020.102763 | pmc=7165294 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32361250  }} </ref><ref name="pmid32388462">{{cite journal| author=Kuppalli K, Rasmussen AL| title=A glimpse into the eye of the COVID-19 cytokine storm. | journal=EBioMedicine | year= 2020 | volume= 55 | issue=  | pages= 102789 | pmid=32388462 | doi=10.1016/j.ebiom.2020.102789 | pmc=7204696 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32388462  }} </ref>
** Epigastric pain
**Increase in pro-inflammatory [[Cytokine|cytokines]] (such as [[Interleukin 6|IL-6]])
** Nausea or vomitting
**Increase in [[Interleukin 10|IL-10]] (a [[cytokine]] produced by  [[T helper cell|Th2]]) and suppression in [[T helper cell|Th1]] antiviral responses
** Dysphagia
**Decrease in [[Cytotoxic T cell|CD+8 T-cells]]
** Cough


=== Physical Examination ===
*It has been reported that in patients with [[COVID-19]] there is increase in IL-1B, IFN-γ , IP-10, and [[CCL2|monocyte hemoattractant protein 1 (MCP-1)]] and [[COVID-19]]  patients in the [[Intensive care unit|intensive care unit (ICU)]] have increased levels of [[granulocyte  colony-stimulating factor]], IP-10, [[CCL2|MCP-1]], macrophage inflammatory  protein-1A, and [[Tumor necrosis factor-alpha|TNF-α]] compared to those in general wards. However, in contrast to [[Severe acute respiratory syndrome|SARS infection]], patients with [[COVID-19]] infection have high levels of  [[Interleukin 4|IL-4]] and [[Interleukin 10|IL-10]] (secreted  by [[Th2|Th2 cells]]), which are antiinflammatory [[Cytokine|cytokines]].<ref name="pmid31986264">{{cite journal| author=Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y | display-authors=etal| title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. | journal=Lancet | year= 2020 | volume= 395 | issue= 10223 | pages= 497-506 | pmid=31986264 | doi=10.1016/S0140-6736(20)30183-5 | pmc=7159299 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31986264  }} </ref>


=== Laboratory Findings ===


=== Imaging Findings ===
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+
!colspan="9" style="background: #4479BA; text-align: center;" |{{fontcolor|#000|'''Cytokines Involved in COVID-19-Associated-Cytokine Storm'''}}
|-
| rowspan="5" style="padding: 5px 5px; background: #4479BA;" align="center" |{{fontcolor|#000|'''Proinflammatory'''}}
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Interferones'''
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
* IFN-γ
|-
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Interleukines'''
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
*IL-1β
* IL-6
|-
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Chemokines'''
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
*CCL-2 (MCP-1)
* CCL-3 (Macrophage inflammatory protein-1A)
* CCL-5
* IL-8 (CXCL8)
* IP-10 (CXCL10)
|-
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Colony-stimulating'''
'''factors  '''
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
* GM-CSF
|-
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Tumor necrosis'''
'''factor  '''
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
* TNF-α
|-
|style="padding: 5px 5px; background: #4479BA;" align="center" |{{fontcolor|#000|'''Anti-inflammatory'''}}
|style="padding: 5px 5px; background: #4479BA;" align="center" |'''Interleukines'''
|style="padding: 5px 5px; background: #DCDCDC;" align="left" |
*IL-4
* IL-10
|}


=== Other Diagnostic Studies ===
==Overview==


== Treatment ==
==COVID-19-Associated Hematologic Findings==


=== Medical Therapy ===
*[[Leukocytosis]]
*Increase in [[C-reactive protein|C-reactive protein (CRP)]]
*Increase in [[procalcitonin]]
*Increase in [[ferritin]]
*Increase in [[Aspartate aminotransferase|aspartate aminotransferase (AST)]]
*Increase in [[Alanine aminotransferase|alanine aminotransferase (ALT)]]
*Increase in [[Lactate dehydrogenase|lactate dehydrogenase (LDH)]]
*Increase in monocyte volume distribution width (MDW)
*Increase in total [[bilirubin]]
*Increase in creatinine
*Increase in cardiac [[Troponin|troponins]]
*Decrease in [[albumin]]
*Increase in [[Interleukin-6|interleukin-6 (IL-6)]]
*[[Thrombocytosis]]


=== Surgery ===
==Pathophysiology and Causes==


=== Prevention ===
*CRP is an [[Acute phase protein|acute phase reactant]] that increases in conditions with inflammation.<ref name="pmid32311826">{{cite journal| author=Frater JL, Zini G, d'Onofrio G, Rogers HJ| title=COVID-19 and the clinical hematology laboratory. | journal=Int J Lab Hematol | year= 2020 | volume= 42 Suppl 1 | issue=  | pages= 11-18 | pmid=32311826 | doi=10.1111/ijlh.13229 | pmc=7264622 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32311826  }} </ref>
*In [[sepsis]], the activation and adherence of [[Monocyte|monocytes]] increase [[procalcitonin]], therefore [[procalcitonin]] in a biomarker for sepsis and septic shock.<ref name="pmid24982830">{{cite journal| author=Meisner M| title=Update on procalcitonin measurements. | journal=Ann Lab Med | year= 2014 | volume= 34 | issue= 4 | pages= 263-73 | pmid=24982830 | doi=10.3343/alm.2014.34.4.263 | pmc=4071182 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24982830  }} </ref>
*[[Alanine transaminase|ALT]] is produced by liver cells and is increased in liver conditions.<ref name="pmid32311826" />
*[[Lactate dehydrogenase|LDH]] is expressed in almost all cells and an increase in [[LDH]] could be seen in damage to any of the cell types.<ref name="pmid32311826" />
*[[Bilirubin]]  is produced by liver cells and increases in liver and biliary conditions.<ref name="pmid32311826" />
*Creatinin is produced in the liver and excreted by the kidneys; [[creatinine]] increases when there is decrease in [[glomerular filtration rate]].<ref name="pmid32311826" />
*Increase in cardiac [[Troponin|troponins]] are used for diagnosing myocardial infarction and [[Acute coronary syndromes|acute coronary syndrome]] .<ref name="pmid32311826" />
*[[Albumin]] may be decreased in many conditions such as [[sepsis]], renal disease or [[malnutrition]].<ref name="pmid32311826" />


* Effective measures for the primary prevention of esophagitis include finding the cause, life style modifications like avoiding caffeine, alcohol, smoking and fatty food, and drinking  fluids when taking medical drugs.
==Epidemiology==


== References ==
*[[Leukocytosis]] is seen in 11.4% of patients with severe [[COVID-19]] infection compared to 4.8% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623">{{cite journal| author=Lippi G, Plebani M| title=The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. | journal=Clin Chem Lab Med | year= 2020 | volume= 58 | issue= 7 | pages= 1063-1069 | pmid=32191623 | doi=10.1515/cclm-2020-0240 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32191623  }} </ref>
<references />
*Increase in CRP is seen in 81.5% of patients with severe [[COVID-19]] infection compared to 56.4% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
   
*Increase in [[procalcitonin]] is seen in 13.7% of patients with severe [[COVID-19]] infection compared to 3.7% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
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*Increase in [[Aspartate transaminase|AST]] is seen in 39.4% of patients with severe [[COVID-19]] infection compared to 18.2% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
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*Increase in [[ALT]] is seen in 28.1% of patients with severe [[COVID-19]] infection compared to 19.8% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
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*Increase in [[Lactate dehydrogenase|LDH]] is seen in 58.1% of patients with severe [[COVID-19]] infection compared to 37.2% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
*MDW was found to be increased in all patients with COVID-19 infection, particularly in those with the worst conditions.<ref name="pmid32191623" />
*Increase in total bilirubin is seen in 13.3% of patients with severe [[COVID-19]] infection compared to 9.9% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
*Increase in [[creatinine]] is seen in 4.3% of patients with severe [[COVID-19]] infection compared to 1% of patients with non-severe infection.<ref name="pmid32109013" /><ref name="pmid32191623" />
*[[Thrombocytosis]] has been reported in 4% of patients with [[COVID-19]] infection.<ref name="pmid32007143">{{cite journal| author=Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y | display-authors=etal| title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. | journal=Lancet | year= 2020 | volume= 395 | issue= 10223 | pages= 507-513 | pmid=32007143 | doi=10.1016/S0140-6736(20)30211-7 | pmc=7135076 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32007143  }} </ref>


<br />
==Clinical Significance==
Laboratory findings in [[COVID-19]] infection may indicate clinical abnormalities, including:
 
*In patients with [[COVID-19]] infection, leukocytosis may be an indication of a bacterial infection or superinfection.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in [[CRP]] may be an indication of severe viral infection or [[sepsis]] and [[viremia]].<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in [[procalcitonin]] may be an indication of bacterial infection or [[superinfection]].<ref name="pmid32191623" />
*There have been different reports regarding the association of increase in [[ferritin]] with death in COVID-19 infection; for example, there has been a report that increase in [[ferritin]] is associated with [[Acute respiratory distress syndrome|acute respiratory distress syndrome (ARDS)]] but not death<ref name="pmid32167524">{{cite journal| author=Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S | display-authors=etal| title=Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. | journal=JAMA Intern Med | year= 2020 | volume=  | issue=  | pages=  | pmid=32167524 | doi=10.1001/jamainternmed.2020.0994 | pmc=7070509 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32167524  }} </ref>, while another one reports an association between increase in [[ferritin]] and death in COVID-19 infection<ref name="pmid32171076">{{cite journal| author=Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z | display-authors=etal| title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. | journal=Lancet | year= 2020 | volume= 395 | issue= 10229 | pages= 1054-1062 | pmid=32171076 | doi=10.1016/S0140-6736(20)30566-3 | pmc=7270627 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32171076  }} </ref>
*In patients with [[COVID-19]] infection, increase in [[aminotransferases]] may indicate injury to the [[liver]] or multi-system damage.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in [[aminotransferases]] may indicate injury to the liver or multi-system damage.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in [[Lactate dehydrogenase|LDH]] may indicate injury to the lungs or multi-system damage.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in total bilirubin may indicate injury to the liver.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in [[creatinine]] may indicate injury to the kidneys.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, increase in cardiac troponins may indicate cardiac injury.<ref name="pmid32191623" />
*In patients with [[COVID-19]] infection, decrease in [[albumin]] may indicate liver function abnormality.<ref name="pmid32191623" />
*Increase in [[IL-6]] has been reported to be associated with death in  [[COVID-19]] infection.<ref name="pmid32167524" />
 
 
 
 
==References==
{{reflist|2}}
 
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Latest revision as of 08:38, 17 July 2020

Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[1]



Some Differential Diagnosis of Asperger Syndrome

(Modified Table from The Investigation and Differential Diagnosis of Asperger Syndrome in Adults)[1]

Asperger Syndrome Schizoid Personality Disorder Schizotypal Personality Disorder Avoidant Personality Disorder Social Phobia Obsessive Personality Disorder Obsessive-compulsive disorder (OCD) Attention deficit–hyperactivity disorder (ADHD)
Abnormal social interaction + + + + + + + +
Abnormal verbal communication + + + - - - - -
Abnormal facial expression/gestures/prosody + + + + +/-  - - +/- 
Abnormal eye contact + + +/-  + +/-  - - +/- 
Abnormal theory of mind + +/-  +/-  +/-  +/-  +/-  - +/- 
Abnormal empathy + +/-  +/-  - - +/-  - +/- 
Abnormal interests/rituals/compulsions + +/-  +/-  - - + + -
Abnormal attention +/-  - - - - - - +
Abnormal psychomotor function + - +/-  - - - - +/- 
Abnormal self-injurious behavior +/- +/-  +/-  - - - - +/- 
Abnormal psychotic manifestations +/- - +/-  - - - - -
Abnormal social interaction in childhood + +/-  +/-  +/-  - - - +
Abnormal biographical stress factors - + +/-  + +/-  + +/-  +/- 




Cytokine Storm

Cytokine storm is an immune reaction that is characterized by dysregulated and excessive release of proinflammatory cytokines.[2]

Cytokines Involved in Cytokine Storm

Pathogenesis of Cytokine Storm

  • Cytokine storm is an immune reaction that is characterized by dysregulated and excessive release of proinflammatory cytokines.[2]
  • During sepsis, cytokine storm may be the cause of tissue or organ injury.[3]
  • It has been suggested that the pathogenesis of severe COVID-19 infection may be due to cytokine storm and suppression of Th1 antiviral responses since the following findings have been reported to be associated with severe COVID-19 infection:[9][10]


Cytokines Involved in COVID-19-Associated-Cytokine Storm
Proinflammatory Interferones
  • IFN-γ
Interleukines
  • IL-1β
  • IL-6
Chemokines
  • CCL-2 (MCP-1)
  • CCL-3 (Macrophage inflammatory protein-1A)
  • CCL-5
  • IL-8 (CXCL8)
  • IP-10 (CXCL10)
Colony-stimulating

factors  

  • GM-CSF
Tumor necrosis

factor  

  • TNF-α
Anti-inflammatory Interleukines
  • IL-4
  • IL-10

Overview

COVID-19-Associated Hematologic Findings

Pathophysiology and Causes

Epidemiology

  • Leukocytosis is seen in 11.4% of patients with severe COVID-19 infection compared to 4.8% of patients with non-severe infection.[14][15]
  • Increase in CRP is seen in 81.5% of patients with severe COVID-19 infection compared to 56.4% of patients with non-severe infection.[14][15]
  • Increase in procalcitonin is seen in 13.7% of patients with severe COVID-19 infection compared to 3.7% of patients with non-severe infection.[14][15]
  • Increase in AST is seen in 39.4% of patients with severe COVID-19 infection compared to 18.2% of patients with non-severe infection.[14][15]
  • Increase in ALT is seen in 28.1% of patients with severe COVID-19 infection compared to 19.8% of patients with non-severe infection.[14][15]
  • Increase in LDH is seen in 58.1% of patients with severe COVID-19 infection compared to 37.2% of patients with non-severe infection.[14][15]
  • MDW was found to be increased in all patients with COVID-19 infection, particularly in those with the worst conditions.[15]
  • Increase in total bilirubin is seen in 13.3% of patients with severe COVID-19 infection compared to 9.9% of patients with non-severe infection.[14][15]
  • Increase in creatinine is seen in 4.3% of patients with severe COVID-19 infection compared to 1% of patients with non-severe infection.[14][15]
  • Thrombocytosis has been reported in 4% of patients with COVID-19 infection.[16]

Clinical Significance

Laboratory findings in COVID-19 infection may indicate clinical abnormalities, including:

  • In patients with COVID-19 infection, leukocytosis may be an indication of a bacterial infection or superinfection.[15]
  • In patients with COVID-19 infection, increase in CRP may be an indication of severe viral infection or sepsis and viremia.[15]
  • In patients with COVID-19 infection, increase in procalcitonin may be an indication of bacterial infection or superinfection.[15]
  • There have been different reports regarding the association of increase in ferritin with death in COVID-19 infection; for example, there has been a report that increase in ferritin is associated with acute respiratory distress syndrome (ARDS) but not death[17], while another one reports an association between increase in ferritin and death in COVID-19 infection[18]
  • In patients with COVID-19 infection, increase in aminotransferases may indicate injury to the liver or multi-system damage.[15]
  • In patients with COVID-19 infection, increase in aminotransferases may indicate injury to the liver or multi-system damage.[15]
  • In patients with COVID-19 infection, increase in LDH may indicate injury to the lungs or multi-system damage.[15]
  • In patients with COVID-19 infection, increase in total bilirubin may indicate injury to the liver.[15]
  • In patients with COVID-19 infection, increase in creatinine may indicate injury to the kidneys.[15]
  • In patients with COVID-19 infection, increase in cardiac troponins may indicate cardiac injury.[15]
  • In patients with COVID-19 infection, decrease in albumin may indicate liver function abnormality.[15]
  • Increase in IL-6 has been reported to be associated with death in COVID-19 infection.[17]



References

  1. 2.0 2.1 2.2 2.3 2.4 2.5 Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG (2012). "Into the eye of the cytokine storm". Microbiol Mol Biol Rev. 76 (1): 16–32. doi:10.1128/MMBR.05015-11. PMC 3294426. PMID 22390970.
  2. Chousterman BG, Swirski FK, Weber GF (2017). "Cytokine storm and sepsis disease pathogenesis". Semin Immunopathol. 39 (5): 517–528. doi:10.1007/s00281-017-0639-8. PMID 28555385.
  3. Jiang Y, Xu J, Zhou C, Wu Z, Zhong S, Liu J; et al. (2005). "Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome". Am J Respir Crit Care Med. 171 (8): 850–7. doi:10.1164/rccm.200407-857OC. PMID 15657466.
  4. Cameron MJ, Bermejo-Martin JF, Danesh A, Muller MP, Kelvin DJ (2008). "Human immunopathogenesis of severe acute respiratory syndrome (SARS)". Virus Res. 133 (1): 13–9. doi:10.1016/j.virusres.2007.02.014. PMC 7114310 Check |pmc= value (help). PMID 17374415.
  5. Reghunathan R, Jayapal M, Hsu LY, Chng HH, Tai D, Leung BP; et al. (2005). "Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome". BMC Immunol. 6: 2. doi:10.1186/1471-2172-6-2. PMC 546205. PMID 15655079.
  6. Ye Q, Wang B, Mao J (2020). "The pathogenesis and treatment of the `Cytokine Storm' in COVID-19". J Infect. 80 (6): 607–613. doi:10.1016/j.jinf.2020.03.037. PMC 7194613 Check |pmc= value (help). PMID 32283152 Check |pmid= value (help).
  7. Channappanavar R, Perlman S (2017). "Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology". Semin Immunopathol. 39 (5): 529–539. doi:10.1007/s00281-017-0629-x. PMC 7079893 Check |pmc= value (help). PMID 28466096.
  8. Liu J, Li S, Liu J, Liang B, Wang X, Wang H; et al. (2020). "Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients". EBioMedicine. 55: 102763. doi:10.1016/j.ebiom.2020.102763. PMC 7165294 Check |pmc= value (help). PMID 32361250 Check |pmid= value (help).
  9. Kuppalli K, Rasmussen AL (2020). "A glimpse into the eye of the COVID-19 cytokine storm". EBioMedicine. 55: 102789. doi:10.1016/j.ebiom.2020.102789. PMC 7204696 Check |pmc= value (help). PMID 32388462 Check |pmid= value (help).
  10. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y; et al. (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. PMC 7159299 Check |pmc= value (help). PMID 31986264.
  11. 12.0 12.1 12.2 12.3 12.4 12.5 12.6 Frater JL, Zini G, d'Onofrio G, Rogers HJ (2020). "COVID-19 and the clinical hematology laboratory". Int J Lab Hematol. 42 Suppl 1: 11–18. doi:10.1111/ijlh.13229. PMC 7264622 Check |pmc= value (help). PMID 32311826 Check |pmid= value (help).
  12. Meisner M (2014). "Update on procalcitonin measurements". Ann Lab Med. 34 (4): 263–73. doi:10.3343/alm.2014.34.4.263. PMC 4071182. PMID 24982830.
  13. 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7
  14. 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 15.12 15.13 15.14 15.15 15.16 15.17 15.18 Lippi G, Plebani M (2020). "The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks". Clin Chem Lab Med. 58 (7): 1063–1069. doi:10.1515/cclm-2020-0240. PMID 32191623 Check |pmid= value (help).
  15. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y; et al. (2020). "Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study". Lancet. 395 (10223): 507–513. doi:10.1016/S0140-6736(20)30211-7. PMC 7135076 Check |pmc= value (help). PMID 32007143 Check |pmid= value (help).
  16. 17.0 17.1 Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S; et al. (2020). "Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China". JAMA Intern Med. doi:10.1001/jamainternmed.2020.0994. PMC 7070509 Check |pmc= value (help). PMID 32167524 Check |pmid= value (help).
  17. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z; et al. (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. PMC 7270627 Check |pmc= value (help). PMID 32171076 Check |pmid= value (help).


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