Chickenpox pathophysiology: Difference between revisions

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==Overview==
==Overview==


Chickenpox is a highly contagious disease contracted by the inhalation of aerosolized nasopharyngeal secretions droplets or through direct contact with the vesicles from an infected host. It takes from 10 to 21 days after exposure to a person with chickenpox or shingles for someone to develop chickenpox. Viral proliferation occurs in regional lymph nodes of the upper respiratory tract leading to viremia. Viremia is characterized by diffuse viral invasion of capillary endothelial cells and the epidermis. VZV infection of cells of the malpighian layer produces both intercellular and intracellular edema, resulting in the characteristic vesicle.
[[Chickenpox]] is a highly [[Infectious disease|contagious disease]] contracted by the [[inhalation]] of [[Aerosol|aerosolized]] [[nasopharyngeal]] [[Secretion|secretions]] or through direct contact with the [[Vesicle|vesicles]] from an [[Infection (disambiguation)|infected]] host. Chicken pox has an [[incubation period]] of 10-21 days. [[Viral replication|Viral proliferation]] occurs in regional [[Lymph node|lymph nodes]] of the [[upper respiratory tract]] leading to [[viremia]]. [[Viremia]] is characterized by diffuse [[Virus|viral]] [[invasion]] of [[capillary]] [[Endothelium|endothelial]] cells and the [[Epidermis (skin)|epidermis]]. [[Chickenpox|VZV infection]] of cells of the [[malpighian layer]] produces both [[Intercellular space|intercellular]] and [[intracellular]] [[edema]], resulting in the characteristic [[Vesicles|vesicles.]]


==Pathophysiology==
==Pathophysiology==
Chickenpox is contracted by the inhalation of aerosolized nasopharyngeal secretions droplets from an infected host. The highly contagious nature of VZV explains the epidemics of chickenpox that spread through schools as one child who is infected quickly spreads the virus to many classmates. High viral titers are found in the vesicles of chickenpox; hence, the viral transmission may also occur through direct contact with these vesicles and the risk is lower comparatively.
[[Chickenpox]] is contracted by the [[inhalation]] of [[Aerosol|aerosolized]] [[Nasopharynx|nasopharyngeal]] [[Secretion|secretions]] from an [[Infection (disambiguation)|infected]] host. The highly [[contagious]] nature of [[Varicella zoster virus|VZV]] explains the [[Epidemic|epidemics]] of [[chickenpox]] that spread through schools, as one child who is [[Infection (disambiguation)|infected]] quickly spreads the [[virus]] to many classmates.
 
===Transmission===
===Transmission===
*The virus spreads easily from people with chickenpox to others who have never had the disease or received the chickenpox vaccine. The virus spreads in the air when an infected person [[coughs]] or [[sneezes]]. It can also be spread by touching or [[breathing]] in the virus particles that come from chickenpox [[blisters]].
*The mode of transmission is by [[inhalation]] of [[Aerosol|aerosolized]] [[nasopharyngeal]] [[Secretion|secretions]] from an [[Infection (disambiguation)|infected]] host.<ref name="pmid2829675">{{cite journal| author=Straus SE, Ostrove JM, Inchauspé G, Felser JM, Freifeld A, Croen KD et al.| title=NIH conference. Varicella-zoster virus infections. Biology, natural history, treatment, and prevention. | journal=Ann Intern Med | year= 1988 | volume= 108 | issue= 2 | pages= 221-37 | pmid=2829675 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2829675  }} </ref>
*Chickenpox can also be spread from people with [[shingles]]. Varicella-zoster  virus also causes shingles. A person with shingles can spread the virus to  others who have never had chickenpox or received the chickenpox vaccine. In  these cases, the exposed person might develop chickenpox.
*[[Chickenpox]] can also be spread from people with [[shingles]] by direct contact.
*A person with chickenpox can spread the disease from 1 to 2 days before they get the rash until all their chickenpox blisters have formed [[scabs]].
*[[Viral shedding]] occurs 1-2 days prior to development of the [[rash]] and continues until all their [[chickenpox]] [[blisters]] have formed [[Scab|scabs]].
*If a person vaccinated for chickenpox gets the [[disease]], they can still spread it to others.
*[[Nosocomial]] transmission of ''[[Varicella-zoster virus]]'' ([[Varicella zoster virus|VZV]]) has also been reported.<ref name="pmid7351951">{{cite journal| author=Leclair JM, Zaia JA, Levin MJ, Congdon RG, Goldmann DA| title=Airborne transmission of chickenpox in a hospital. | journal=N Engl J Med | year= 1980 | volume= 302 | issue= 8 | pages= 450-3 | pmid=7351951 | doi=10.1056/NEJM198002213020807 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7351951  }} </ref>
*For most people, getting chickenpox once provides [[immunity]] for life. However, for a few people, they can get chickenpox more than once, although this is not common.
*[[Nosocomial]] transmission of ''Varicella-zoster virus'' (VZV) is well-recognized and can be life threatening to certain groups of patients. Reports of nosocomial transmission are relatively uncommon in the United States since introduction of [[varicella vaccine]].


===Incubation Period===
===Incubation Period===
*It takes from 10 to 21 days after exposure to a person with [[chickenpox]] or [[shingles]] for someone to develop chickenpox.
*The [[incubation period]] of [[chickenpox]] is typically from 14 to 16 days. However, the interval may vary from 10 to 21 days.<ref name="pmid17046469">{{cite journal| author=Heininger U, Seward JF| title=Varicella. | journal=Lancet | year= 2006 | volume= 368 | issue= 9544 | pages= 1365-76 | pmid=17046469 | doi=10.1016/S0140-6736(06)69561-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17046469  }} </ref>
 
*The [[infectivity]] period begins 48 hours prior to the appearance of the [[rash]] and lasts till crusts appear.


===Dissemination===
===Dissemination===
*After initial inhalation of contaminated aerosolized droplets, the virus infects the [[conjunctiva]]e or the [[mucosa]]e of the [[upper respiratory tract]]. Viral proliferation occurs in regional [[lymph node]]s of the upper respiratory tract 2-4 days after initial infection and is followed by primary viremia on postinfection days 4-6.
*After initial [[inhalation]] of [[Contamination|contaminated]] [[Aerosol|aerosolized]] [[Droplet|droplets]], the [[virus]] [[Infect|infects]] the [[conjunctiva]]e and the [[mucosa]]e of the [[upper respiratory tract]].  
*[[Viral replication|Viral proliferation]] occurs in regional [[lymph node]]s of the [[upper respiratory tract]] 2-4 days after initial [[Infection (disambiguation)|infection]], and is followed by primary [[viremia]].  
 
==Pathogenesis==


===Pathogenesis===
*[[Viral replication]] occurs in the [[liver]], [[spleen]], followed by a secondary [[viremia]] 14-16 days post infection. Secondary [[viremia]] is characterized by diffuse [[Virus|viral]] [[invasion]] of [[capillary]] [[Endothelium|endothelial cells]] and the [[Epidermis (skin)|epidermis]].
*[[Varicella zoster virus|VZV infection]] of cells of the [[malpighian layer]] produces both [[Intercellular space|intercellular]] and [[intracellular]] [[edema]], resulting in the characteristic [[Vesicles|vesicles.]]
*Exposure to [[Varicella zoster virus|VZV]] initiates the production of host [[immunoglobulin G]] ([[IgG]]), [[immunoglobulin M]] ([[IgM]]), and [[immunoglobulin A]] ([[IgA]]) [[Antibody|antibodies]]; [[IgG]] [[antibodies]] persist for life and confer [[Immunity (medical)|immunity]].
*After primary [[Infection (disambiguation)|infection]], [[Varicella zoster virus|VZV]] then remains latent in the [[Dorsal root ganglion|dorsal ganglion]] cells of the [[Sensory nerve|sensory nerves]].
*Reactivation of [[Varicella zoster virus|VZV]] results in the clinically distinct syndrome of [[herpes zoster]] ([[shingles]]).


*A second round of viral replication occurs in the body's internal organs, most notably the [[liver]] and the [[spleen]], followed by a secondary [[viremia]] 14-16 days postinfection. This secondary viremia is characterized by diffuse viral invasion of [[capillary]] [[Endothelium|endothelial cells]] and the [[Epidermis (skin)|epidermis]]. VZV infection of cells of the [[malpighian layer]] produces both intercellular and intracellular [[edema]], resulting in the characteristic vesicle.
==Genetics==
There is no genetic predisposition associated with [[chickenpox]]. Similarities in sibling response to [[varicella vaccine]] are supportive of the hypothesis that [[genetic]] factors play a role in the [[Antibody responses|antibody response]] to the [[varicella vaccine]].<ref name="pmid17414391">{{cite journal |vauthors=Klein NP, Fireman B, Enright A, Ray P, Black S, Dekker CL |title=A role for genetics in the immune response to the varicella vaccine |journal=Pediatr. Infect. Dis. J. |volume=26 |issue=4 |pages=300–5 |year=2007 |pmid=17414391 |doi=10.1097/01.inf.0000257454.74513.07 |url=}}</ref>


*Exposure to VZV in a healthy child initiates the production of host [[immunoglobulin G]] (IgG), [[immunoglobulin M]] (IgM), and [[immunoglobulin A]] (IgA) [[Antibody|antibodies]]; IgG antibodies persist for life and confer immunity.
==Associated Conditions==
*[[Thrombocytopenia]]<ref name="MuthuM.B.2013">{{cite journal|last1=Muthu|first1=Valliappan|last2=M.B.|first2=Adarsh|last3=Kumar|first3=P. Sathish|last4=Varma|first4=Subhash|last5=Malhotra|first5=Pankaj|title=Varicella zoster virus-related pancytopenia|journal=International Journal of Infectious Diseases|volume=17|issue=12|year=2013|pages=e1264|issn=12019712|doi=10.1016/j.ijid.2013.06.010}}</ref>


*[[Cell-mediated immunity|Cell-mediated immune responses]] are also important in limiting the scope and the duration of primary varicella infection. After primary infection, VZV is hypothesized to spread from [[mucosa]]l and [[Epidermis (skin)|epidermal]] lesions to local [[sensory nerve]]s. VZV then remains latent in the [[Dorsal root ganglion|dorsal ganglion]] cells of the sensory nerves.
*[[Pancytopenia]]<ref name="MuthuM.B.2013">{{cite journal|last1=Muthu|first1=Valliappan|last2=M.B.|first2=Adarsh|last3=Kumar|first3=P. Sathish|last4=Varma|first4=Subhash|last5=Malhotra|first5=Pankaj|title=Varicella zoster virus-related pancytopenia|journal=International Journal of Infectious Diseases|volume=17|issue=12|year=2013|pages=e1264|issn=12019712|doi=10.1016/j.ijid.2013.06.010}}</ref>


*'''Reactivation of VZV''' results in the clinically distinct syndrome of herpes zoster ([[shingles]]).
*Red eye in [[chickenpox]]: varicella-related acute [[anterior uveitis]]<ref name="pmid22778248">{{cite journal| author=Johnston NR| title=Red eye in chickenpox: varicella-related acute anterior uveitis in a child. | journal=BMJ Case Rep | year= 2010 | volume= 2010 | issue=  | pages=  | pmid=22778248 | doi=10.1136/bcr.01.2010.2678 | pmc=3029245 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22778248  }} </ref>


==Gross Pathology==
==Gross Pathology==
The following gross pathological images depict the progression of the disease based on the distribution of rash.


<gallery>
=== Rash findings ===
The typical rash in chickenpox may show the following findings:
* Superficial
* Unilocular
* Umblicated
* Area of inflammation around rash


Image:Chickenpox U1.jpg|Girl with a secondary skin infection due to chickenpox
* Pleomorphism (papules, vesicles and crusts may be seen simultaneously at the same area)
Image:Chickenpox U4.jpg|Chickenpox in unvaccinated adult.
Image:Chickenpox U3.jpg|Chickenpox in an unvaccinated adult.
Image:CHICKENPOX_IN_UNVACCINATED_CHILD.jpg|Chickenpox in unvaccinated child.
Image: Varicella 10.jpeg| Vasculitis leukocytoclasia. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Varicella 02.jpeg| Varicella <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
</gallery>


==Microscopic Pathology==


===Microscopic Pathology===
=== Rash findings ===
Skin lesions in chickenpox may show the following findings:
* Multi-nucleated giant cells
* Steel-gray nuclei with accentuation of nucleoplasm at their periphery
* Necrosis
* Acantholysis
* Vascular dilation


<gallery>
<gallery>
Image:Chickenpox M1.jpg|Varicella virus grown in a tissue culture; magnified 500X.
Image:Chickenpox M2.jpg|Electron micrograph of a varicella (chickenpox) virus.<ref name="urlHome - Public Health Image Library (PHIL)">{{cite web |url=http://phil.cdc.gov/phil/home.asp |title=Home - Public Health Image Library (PHIL) |format= |work= |accessdate=}}</ref>


Image: VZV14.jpeg| Transmission electron micrograph (TEM) of a Varicella (Chickenpox) Virus. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: VZV14.jpeg| Transmission electron micrograph (TEM) of a Varicella (Chickenpox) Virus. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Line 66: Line 77:


Image: VZV06.jpeg| Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes found in a human skin tissue specimen that included a varicella zoster virus lesion (500x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: VZV06.jpeg| Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes found in a human skin tissue specimen that included a varicella zoster virus lesion (500x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: VZV05.jpeg| Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes found in a human skin tissue specimen that included a varicella zoster virus lesion (1200x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


Image: VZV04.jpeg| Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes found in a human skin tissue specimen that included a varicella zoster virus lesion (1200x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: VZV04.jpeg| Hematoxylin-eosin (H&E)-stained photomicrograph reveals some of the cytoarchitectural histopathologic changes found in a human skin tissue specimen that included a varicella zoster virus lesion (1200x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
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Latest revision as of 20:53, 29 July 2020


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S[2]

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Overview

Chickenpox is a highly contagious disease contracted by the inhalation of aerosolized nasopharyngeal secretions or through direct contact with the vesicles from an infected host. Chicken pox has an incubation period of 10-21 days. Viral proliferation occurs in regional lymph nodes of the upper respiratory tract leading to viremia. Viremia is characterized by diffuse viral invasion of capillary endothelial cells and the epidermis. VZV infection of cells of the malpighian layer produces both intercellular and intracellular edema, resulting in the characteristic vesicles.

Pathophysiology

Chickenpox is contracted by the inhalation of aerosolized nasopharyngeal secretions from an infected host. The highly contagious nature of VZV explains the epidemics of chickenpox that spread through schools, as one child who is infected quickly spreads the virus to many classmates.

Transmission

Incubation Period

  • The infectivity period begins 48 hours prior to the appearance of the rash and lasts till crusts appear.

Dissemination

Pathogenesis

Genetics

There is no genetic predisposition associated with chickenpox. Similarities in sibling response to varicella vaccine are supportive of the hypothesis that genetic factors play a role in the antibody response to the varicella vaccine.[4]

Associated Conditions

Gross Pathology

Rash findings

The typical rash in chickenpox may show the following findings:

  • Superficial
  • Unilocular
  • Umblicated
  • Area of inflammation around rash
  • Pleomorphism (papules, vesicles and crusts may be seen simultaneously at the same area)

Microscopic Pathology

Rash findings

Skin lesions in chickenpox may show the following findings:

  • Multi-nucleated giant cells
  • Steel-gray nuclei with accentuation of nucleoplasm at their periphery
  • Necrosis
  • Acantholysis
  • Vascular dilation

References

  1. Straus SE, Ostrove JM, Inchauspé G, Felser JM, Freifeld A, Croen KD; et al. (1988). "NIH conference. Varicella-zoster virus infections. Biology, natural history, treatment, and prevention". Ann Intern Med. 108 (2): 221–37. PMID 2829675.
  2. Leclair JM, Zaia JA, Levin MJ, Congdon RG, Goldmann DA (1980). "Airborne transmission of chickenpox in a hospital". N Engl J Med. 302 (8): 450–3. doi:10.1056/NEJM198002213020807. PMID 7351951.
  3. Heininger U, Seward JF (2006). "Varicella". Lancet. 368 (9544): 1365–76. doi:10.1016/S0140-6736(06)69561-5. PMID 17046469.
  4. Klein NP, Fireman B, Enright A, Ray P, Black S, Dekker CL (2007). "A role for genetics in the immune response to the varicella vaccine". Pediatr. Infect. Dis. J. 26 (4): 300–5. doi:10.1097/01.inf.0000257454.74513.07. PMID 17414391.
  5. 5.0 5.1 Muthu, Valliappan; M.B., Adarsh; Kumar, P. Sathish; Varma, Subhash; Malhotra, Pankaj (2013). "Varicella zoster virus-related pancytopenia". International Journal of Infectious Diseases. 17 (12): e1264. doi:10.1016/j.ijid.2013.06.010. ISSN 1201-9712.
  6. Johnston NR (2010). "Red eye in chickenpox: varicella-related acute anterior uveitis in a child". BMJ Case Rep. 2010. doi:10.1136/bcr.01.2010.2678. PMC 3029245. PMID 22778248.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 7.6 "Public Health Image Library (PHIL)".