Smallpox pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
[[Smallpox virus]] may be transmitted | [[Smallpox virus]] may be transmitted from contaminated surfaces or aerosolized particles. It is capable of inducing harm by evading the host's [[immune system]] and replicating inside host's [[cells]]. The [[virus]] may cause 3 forms of the disease: 1) ''ordinary''; 2) ''flat-type''; or 3) ''hemorrhagic [[smallpox]]''. It [[infection|infects]] different [[cells]] of the body, being known by it's propensity to cause characteristic pock like lesions on the [[skin]]. | ||
==Transmission== | ==Transmission== | ||
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==Gross Pathology== | ==Gross Pathology== | ||
Depending on the status of the patient's [[immune system]], there | Depending on the status of the patient's [[immune system]], there are 3 forms of [[smallpox]]:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref> | ||
===Ordinary Smallpox=== | ===Ordinary Smallpox=== | ||
Ordinary smallpox is characterized by the following progression of lesions:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref> | |||
* Initial [[Hypopigmentation|hypopigmented]] [[macules]], which appear first in the [[mouth]] | * Initial [[Hypopigmentation|hypopigmented]] [[macules]], which appear first in the [[mouth]] | ||
* [[Macules]] progress into [[papules]] and subsequently to [[vesicles]] | * [[Macules]] progress into [[papules]] and subsequently to [[vesicles]] | ||
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===Flat-type Smallpox=== | ===Flat-type Smallpox=== | ||
Flat-type smallpox is characterized by the following progression of lesions:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref> | |||
* Delayed appearance of [[macules]] | * Delayed appearance of [[macules]] | ||
* Slow progression of the lesions, usually with flat and soft appearance | * Slow progression of the lesions, usually with flat and soft appearance | ||
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===Hemorrhagic-type smallpox=== | ===Hemorrhagic-type smallpox=== | ||
Hemorrhagic-type smallpox is characterized by the following progression of lesions:<ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 0443068399 }}</ref> | |||
* [[Skin]] [[petechiae]] | * [[Skin]] [[petechiae]] | ||
* [[Mucous membrane]] and [[conjunctival]] [[bleeding]] | * [[Mucous membrane]] and [[conjunctival]] [[bleeding]] | ||
| Line 93: | Line 93: | ||
The typical [[skin]] [[vesicles]] observed in [[smallpox]] occur following:<ref>{{cite book | last = Cecil | first = Russell | title = Goldman's Cecil medicine | publisher = Elsevier/Saunders | location = Philadelphia | year = 2012 | isbn = 1437716040 }}</ref> | The typical [[skin]] [[vesicles]] observed in [[smallpox]] occur following:<ref>{{cite book | last = Cecil | first = Russell | title = Goldman's Cecil medicine | publisher = Elsevier/Saunders | location = Philadelphia | year = 2012 | isbn = 1437716040 }}</ref> | ||
* [[Viral infection]] of the [[epidermal]] [[cell]] | * [[Viral infection]] of the [[epidermal]] [[cell]] | ||
* [[Cells]] in [[malpighian layer]] | * [[Cells]] in [[malpighian layer]] entering balloon degeneration, from formation of [[vacuoles]] | ||
* [[Cytoplasmic]] enlargement | * [[Cytoplasmic]] enlargement leading to loss of [[nuclear]] material | ||
* Destruction of upper and middle layers of [[stratum spinosum]] | * Destruction of upper and middle layers of [[stratum spinosum]] | ||
* Formation of [[ | * Formation of [[vesicles]], with high [[viral]] index | ||
On the other hand, in the [[infected]] [[mucous]] surfaces, the [[viral]] proliferation and absence of the [[stratum corneum]] lead to the formation of [[ulcers]]. These ultimately lead to the release of greater loads of [[virus]] | On the other hand, in the [[infected]] [[mucous]] surfaces, the [[viral]] proliferation and absence of the [[stratum corneum]], lead to the formation of [[ulcers]]. These ultimately lead to the release of greater loads of [[virus]] into the [[oropharynx]].<ref>{{cite book | last = Cecil | first = Russell | title = Goldman's Cecil medicine | publisher = Elsevier/Saunders | location = Philadelphia | year = 2012 | isbn = 1437716040 }}</ref> | ||
===Histopathology=== | ===Histopathology=== | ||
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====B-type, or Guarnieri bodies==== | ====B-type, or Guarnieri bodies==== | ||
* | * In areas of active [[viral replication]] | ||
* Present in [[infections]] by all poxviruses | * Present in [[infections]] by all poxviruses | ||
* Appear as [[basophilic]] bodies near the [[nucleus]] on hematoxylin and eosin-stained samples | * Appear as [[basophilic]] bodies near the [[nucleus]] on hematoxylin and eosin-stained samples | ||
* Evident at [[epithelial cells]] underlying [[vesicles]] and [[pustules]] | * Evident at [[epithelial cells]] underlying [[vesicles]] and [[pustules]] | ||
== | ==Gallery== | ||
<gallery> | <gallery> | ||
Image:Smallpox-1.jpg|Hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. <SMALL><SMALL>''[http://phil.cdc.gov/phil/ Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL> | Image:Smallpox-1.jpg|Hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. <SMALL><SMALL>''[http://phil.cdc.gov/phil/ Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.]''<ref name="PHIL">{{Cite web | title = Public Health Image Library (PHIL), Centers for Disease Control and Prevention | url = http://phil.cdc.gov/phil/}}</ref></SMALL></SMALL> | ||
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[[Category:Needs overview]] | [[Category:Needs overview]] | ||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Pediatrics]] | [[Category:Pediatrics]] | ||
[[Category:Smallpox]] | [[Category:Smallpox]] | ||
Latest revision as of 19:04, 18 September 2017
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Smallpox Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Smallpox pathophysiology On the Web |
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American Roentgen Ray Society Images of Smallpox pathophysiology |
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Risk calculators and risk factors for Smallpox pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Overview
Smallpox virus may be transmitted from contaminated surfaces or aerosolized particles. It is capable of inducing harm by evading the host's immune system and replicating inside host's cells. The virus may cause 3 forms of the disease: 1) ordinary; 2) flat-type; or 3) hemorrhagic smallpox. It infects different cells of the body, being known by it's propensity to cause characteristic pock like lesions on the skin.
Transmission
Smallpox virus is transmitted by:[1]
- Physical contact
- Contact with infected body fluids
- Contact with infected objects
- Air through aerosolized particles
Genetics
Smallpox pathogenicity is due to its ability to evade the host's immune system. Most proteins responsible for the pathogenesis of the virus are located at the terminal DNA regions of the virus.
Genetic comparisons of the smallpox virus with the vaccinia virus allowed to observe certain genetic changes that may be responsible for the virulence of the smallpox virus. However, without studying the gene transcripts, it is not possible to draw objective conclusions.[2]
Pathogenesis
The smallpox virus commonly enters the body through the upper respiratory tract, invading the oropharyngeal and respiratory mucosa.[3] Other possible ports of entry include: skin, conjunctiva as well as through the placenta.[4] Although the viral scabs may contain life viruses, they are commonly contained within thickened material, which limits transmission.
Once in the respiratory mucosa, the infection commonly progresses as:[5][4][6]
- Asymptomatic respiratory mucosa infection
- Viral replication within respiratory epithelium
- Transient primary asymptomatic viraemia
- Virus enters macrophages and spreads to lymph nodes and reticuloendothelial system, where it replicates during 4 - 14 days
- Exuberant secondary viraemia, leading to symptom onset
During secondary viraemia the virus infects mucous cells of the pharynx and mouth, and endothelium of the capillaries of the dermis, causing skin lesions. Other organs with high viral loads include:[6]
Before development of the rash, the first lesions appear on the oropharyngeal mucosa, at which time the virus is released through the mucosal secretions, making that patient infectious.
Skin lesions develop due to migration of macrophages to the infected areas of the dermis, leading to edema and necrosis. With the influx of more polymorphonuclear cells, skin pustules will develop.[5]
The immune system responds to the viremia with activation of lymphocytes T and B and concomitant production of:[6]
- Neutralizing antibodies, during first week of disease, remaining for many years
- Hemagglutination-inhibition antibodies, by the 16th day of infection, beginning to decrease after 1 year
- Complement-fixation antibodies, by the 18th day of infection, beginning to decrease after 1 year
- Memory T cells, remaining for 50 years
Death by smallpox was commonly due to toxemia, following:[5]
Gross Pathology
Depending on the status of the patient's immune system, there are 3 forms of smallpox:[7]
Ordinary Smallpox
Ordinary smallpox is characterized by the following progression of lesions:[8]
- Initial hypopigmented macules, which appear first in the mouth
- Macules progress into papules and subsequently to vesicles
- Vesicles become pustules
- At the 14th day, pustules loose liquid content and become crusted
- At the 3rd week, most crusts will separate (palms and soles last)
This form of smallpox is typical of an immunocompetent patient, in whom the immune system is able to inhibit viral replication.
Flat-type Smallpox
Flat-type smallpox is characterized by the following progression of lesions:[9]
- Delayed appearance of macules
- Slow progression of the lesions, usually with flat and soft appearance
- Possible slough of skin sections
Most cases are fatal with presence of severe toxemia. This form of smallpox is typical of patients with weak cellular immune response to the virus.
Hemorrhagic-type smallpox
Hemorrhagic-type smallpox is characterized by the following progression of lesions:[10]
- Skin petechiae
- Mucous membrane and conjunctival bleeding
- Subcutaneous hemorrhage gives skin and conjunctivae deep red appearance
- Organ bleeding
- Early death by multi organ failure, usually before appearance of maculae.
This rare form of smallpox is typical of patients with severely compromised immune response, in which there is intense viral replication in the bone marrow and spleen. It is also associated with intense toxemia.
Microscopic Pathology
The typical skin vesicles observed in smallpox occur following:[11]
- Viral infection of the epidermal cell
- Cells in malpighian layer entering balloon degeneration, from formation of vacuoles
- Cytoplasmic enlargement leading to loss of nuclear material
- Destruction of upper and middle layers of stratum spinosum
- Formation of vesicles, with high viral index
On the other hand, in the infected mucous surfaces, the viral proliferation and absence of the stratum corneum, lead to the formation of ulcers. These ultimately lead to the release of greater loads of virus into the oropharynx.[12]
Histopathology
Poxviruses are characterized by cytoplasmic inclusions, however, these do not identify specifically the smallpox virus on a biopsy. There are 2 types of inclusion bodies:[13]
A-type
Typical of some viruses of the:
- Genus Orthopoxvirus:
- Cowpox virus
- Ectromelia virus
- Genus Avipoxvirus
B-type, or Guarnieri bodies
- In areas of active viral replication
- Present in infections by all poxviruses
- Appear as basophilic bodies near the nucleus on hematoxylin and eosin-stained samples
- Evident at epithelial cells underlying vesicles and pustules
Gallery
-
![Hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/images/8/8f/Smallpox-1.jpg)
Hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]
-
![hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/images/0/0b/Smallpox-2.jpg)
hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]
-
![This is a chickenpox scab (left), and smallpox scab (right) viewed in profile as a demonstration in comparative morphology. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/images/3/30/Smallpox-5.jpg)
This is a chickenpox scab (left), and smallpox scab (right) viewed in profile as a demonstration in comparative morphology. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]
-
![This image depicts three mounted chickenpox scabs seen from the side revealing the superficiality of these scabs when morphologically compared to a smallpox scab.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/images/3/3c/Smallpox-7.jpg)
This image depicts three mounted chickenpox scabs seen from the side revealing the superficiality of these scabs when morphologically compared to a smallpox scab.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]
-
![Viewed from above, this image depicts a smallpox scab (left), and chickenpox scab (right) as a demonstration in comparative morphology. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/images/e/e9/Smallpox-9.jpg)
Viewed from above, this image depicts a smallpox scab (left), and chickenpox scab (right) as a demonstration in comparative morphology. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]
-
![Cytoarchitectural pathologic changes found in a sample of skin tissue from a eczema vaccinatum lesion, which had manifested itself after this patient had received a smallpox vaccination.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/images/8/8a/Smallpox-74.jpg)
Cytoarchitectural pathologic changes found in a sample of skin tissue from a eczema vaccinatum lesion, which had manifested itself after this patient had received a smallpox vaccination.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]
-
![Cytoarchitectural pathologic changes found in a sample of skin tissue from a eczema vaccinatum lesion, which had manifested itself after this patient had received a smallpox vaccination.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/images/6/61/Smallpox-76.jpg)
Cytoarchitectural pathologic changes found in a sample of skin tissue from a eczema vaccinatum lesion, which had manifested itself after this patient had received a smallpox vaccination.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]
![Hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/index.php/File:Smallpox-1.jpg)
![hematoxylin and eosin (H&E)-stained tissue sample, reveals some of the histopathologic changes found in a human skin tissue sample from the site of a smallpox lesion. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/index.php/File:Smallpox-2.jpg)
![This is a chickenpox scab (left), and smallpox scab (right) viewed in profile as a demonstration in comparative morphology. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/index.php/File:Smallpox-5.jpg)
![This image depicts three mounted chickenpox scabs seen from the side revealing the superficiality of these scabs when morphologically compared to a smallpox scab.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/index.php/File:Smallpox-7.jpg)
![Viewed from above, this image depicts a smallpox scab (left), and chickenpox scab (right) as a demonstration in comparative morphology. Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/index.php/File:Smallpox-9.jpg)
![Cytoarchitectural pathologic changes found in a sample of skin tissue from a eczema vaccinatum lesion, which had manifested itself after this patient had received a smallpox vaccination.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/index.php/File:Smallpox-74.jpg)
![Cytoarchitectural pathologic changes found in a sample of skin tissue from a eczema vaccinatum lesion, which had manifested itself after this patient had received a smallpox vaccination.Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.[14]](/index.php/File:Smallpox-76.jpg)
References
- ↑ "Smallpox disease overview".
- ↑ Massung RF, Liu LI, Qi J, Knight JC, Yuran TE, Kerlavage AR; et al. (1994). "Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975". Virology. 201 (2): 215–40. doi:10.1006/viro.1994.1288. PMID 8184534.
- ↑ Cecil, Russell (2012). Goldman's Cecil medicine. Philadelphia: Elsevier/Saunders. ISBN 1437716040.
- ↑ 4.0 4.1 "Smallpox and its Eradication" (PDF).
- ↑ 5.0 5.1 5.2 Moore, Zack S; Seward, Jane F; Lane, J Michael (2006). "Smallpox". The Lancet. 367 (9508): 425–435. doi:10.1016/S0140-6736(06)68143-9. ISSN 0140-6736.
- ↑ 6.0 6.1 6.2 Breman, Joel G.; Henderson, D.A. (2002). "Diagnosis and Management of Smallpox". New England Journal of Medicine. 346 (17): 1300–1308. doi:10.1056/NEJMra020025. ISSN 0028-4793.
- ↑ Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
- ↑ Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
- ↑ Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
- ↑ Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
- ↑ Cecil, Russell (2012). Goldman's Cecil medicine. Philadelphia: Elsevier/Saunders. ISBN 1437716040.
- ↑ Cecil, Russell (2012). Goldman's Cecil medicine. Philadelphia: Elsevier/Saunders. ISBN 1437716040.
- ↑ Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
- ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 "Public Health Image Library (PHIL), Centers for Disease Control and Prevention".