Hand-foot-and-mouth disease pathophysiology: Difference between revisions

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{{Hand-foot-and-mouth disease}}
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==Overview==
==Overview==


HFMD usually affects infants and children, and is quite common. It is highly contagious and is spread through direct contact with the mucus or feces of an infected person. It typically occurs in small epidemics in nursery schools or kindergartens, usually during the summer and autumn months.
[[Hand-foot-and-mouth disease|HFMD]] usually affects [[Infant|infants]] and children, and is quite common. It is highly [[contagious]] and is spread through direct contact with the [[mucus]] or [[feces]] of an infected person. It typically occurs in small [[epidemics]] in nursery schools or kindergartens, usually during the summer and autumn months.


== Pathophysiology==
== Pathophysiology==
*HFMD outbreaks typically occur during summer and autumn months in the United states.<ref name=HFMD>CDC HFMD https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6112a5.htm (2012) Accessed on October 20, 2016</ref>  
*[[Hand-foot-and-mouth disease|HFMD]] outbreaks typically occur during summer and autumn months in the United states.<ref name=HFMD>CDC https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6112a5.htm (2012) Accessed on October 20, 2016</ref>  


'''Mode of transmission'''
'''Mode of transmission'''
*HFMD is a contagious disease that is spread from person to person by:<ref name=HFMD>CDC HFMD http://www.cdc.gov/hand-foot-mouth/about/transmission.html(2015) Accessed on October 20, 2016</ref>  
*HFMD is a contagious disease that is spread from person to person by:<ref name=HFMD>CDC http://www.cdc.gov/hand-foot-mouth/about/transmission.html(2015) Accessed on October 20, 2016</ref><ref name="pmid13585281">{{cite journal| author=ROBINSON CR, DOANE FW, RHODES AJ| title=Report of an outbreak of febrile illness with pharyngeal lesions and exanthem: Toronto, summer 1957; isolation of group A Coxsackie virus. | journal=Can Med Assoc J | year= 1958 | volume= 79 | issue= 8 | pages= 615-21 | pmid=13585281 | doi= | pmc=1830188 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13585281  }} </ref><ref name="pmid22456122">{{cite journal| author=Centers for Disease Control and Prevention (CDC)| title=Notes from the field: severe hand, foot, and mouth disease associated with coxsackievirus A6 - Alabama, Connecticut, California, and Nevada, November 2011-February 2012. | journal=MMWR Morb Mortal Wkly Rep | year= 2012 | volume= 61 | issue= 12 | pages= 213-4 | pmid=22456122 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22456122  }} </ref><ref name="pmid27701445">{{cite journal| author=Zhao J, Li X| title=Determinants of the Transmission Variation of Hand, Foot and Mouth Disease in China. | journal=PLoS One | year= 2016 | volume= 11 | issue= 10 | pages= e0163789 | pmid=27701445 | doi=10.1371/journal.pone.0163789 | pmc=5049751 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27701445  }} </ref><ref name="pmid27618078">{{cite journal| author=Chang PC, Chen SC, Chen KT| title=The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development. | journal=Int J Environ Res Public Health | year= 2016 | volume= 13 | issue= 9 | pages=  | pmid=27618078 | doi=10.3390/ijerph13090890 | pmc=5036723 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27618078  }} </ref>
:*Close personal contact
:*Close personal contact
:*The air (Nasopharyngeal secretions)
:*[[Nasopharyngeal]] [[secretions]]
:*Contact with feces (fecal-oral transmission)
:*Contact with [[feces]] (fecal-oral transmission)
:*Contact with contaminated objects and surfaces
:*Contact with contaminated objects and surfaces
:*Contaminated water (Swimming pools not properly treated with chlorine)
:*Contaminated water (Swimming pools not properly treated with chlorine)
*The virus can be isolated from the following sources:
*The [[virus]] can be isolated from the following sources:
:*Nose and throat secretions (such as saliva, sputum, or nasal mucus)
:*[[Nose]] and [[throat]] [[secretions]] (such as [[saliva]], [[sputum]], or nasal mucus)
:*Blister fluid, and
:*Blister fluid
:*Feces (stool)
:*[[Feces]] (stool)
*Following the disease, the infected person (symptomatic or asymptomatic) is most contagious during the first week of illness but can spread disease for days or weeks after symptoms go away.
*Following the disease, the infected person (symptomatic or asymptomatic) is most [[contagious]] during the first week of illness but can spread disease for days or weeks after symptoms go away.
*Hand, foot, and mouth disease is not transmitted to or from pets or other animals.
*[[Hand-foot-and-mouth disease|Hand foot and mouth disease]] is not transmitted to or from pets or other animals.
*Factors affecting the transmission:
:*Level of [[hygiene]]
:*Water quality
:*Extent of crowding
:*Seasonal variations
:**Tropical and subtropical: Circulation of virus tends to be year long, with more outbreaks in rainy season
:**Temperate regions: Autumn and spring


===Pathogenesis===
===Pathogenesis===
The pathogenesis of HFMD caused by EV71 includes:
The exact pathogenesis of [[Hand-foot-and-mouth disease|HFMD]] is not fully understood.The pathogenesis of [[Hand-foot-and-mouth disease|HFMD]] caused by EV71 includes:<ref name="pmid20961813">{{cite journal| author=Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH| title=Virology, epidemiology, pathogenesis, and control of enterovirus 71. | journal=Lancet Infect Dis | year= 2010 | volume= 10 | issue= 11 | pages= 778-90 | pmid=20961813 | doi=10.1016/S1473-3099(10)70194-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20961813  }} </ref><ref name="pmid13682692">{{cite journal| author=ALSOP J, FLEWETT TH, FOSTER JR| title="Hand-foot-and-mouth disease" in Birmingham in 1959. | journal=Br Med J | year= 1960 | volume= 2 | issue= 5214 | pages= 1708-11 | pmid=13682692 | doi= | pmc=2098292 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13682692  }} </ref>
*
 
===Gross pathology===


*EV71 replicates in the [[lymphoid]] tissues of the [[oropharyngeal]] cavity([[Tonsil|tonsils]]), [[small bowel]](payer's patches) and regional lymph nodes(deep cervical and mesenteric nodes) leading to a mild [[viremia]].
*Most of the viruses are destroyed in these [[lymphatic tissues]] and the patients remain asymptomatic.
*Patients present with clinical symptoms when the [[virus]] disseminates to other organs like [[Reticuloendothelial system|reticuloendothelial]] system([[liver]], [[spleen]], [[Bone marrow|bone marrow,]] [[lymph node]]), [[heart]], [[lung]], [[pancreas]], [[skin]], [[mucous membranes]] and [[CNS]].
*The virus is typically shed for between two and four weeks, and sometimes for as long as 12 weeks post-infection.
*Replication also occurs in the [[Upper respiratory tract|upper respiratory trac]]<nowiki/>t and the [[virus]] has been recovered from throat swabs for up to two weeks post-infection.
*The relationship between pathogenesis and distribution of viral entry receptors (scavenger receptor B2, [[P-selectin]] glycoprotein ligand-1 and sialic acid-linked glycans) and host factors, such as gender and age group, is unknown.
*The pathogenesis of EV71 depends on following factors:
'''Viral factors'''
[[Viral]] [[virulence]] factors are still unknown.
'''Host factors'''
*Inflammatory factors: High levels of following factors are seen in pulmonary edema.
:*[[Interleukin 6]] (IL-6)
:*[[Tumor necrosis factor alpha]]
:*Interleukin-1 beta (IL-12)
:*[[Interleukin-10]](IL-10)
:*Monocyte chemo attractant protein (MCP-1)
:*Monokine induced by interferon gamma (MIG)
*[[Cell-mediated immunity|Cell mediated immunity]]
:*Reduction in [[T-lymphocytes|T-lymphocyte]]<nowiki/>s and [[Natural killer cell|NK cells]]
*[[HLA|Human Leukocyte antigen(HLA)]]
:*[[HLA]]-A33: Associated with increased susceptibility of EV71 in Asian population
:*[[HLA]]-A2: Increased risk of cardiopulmonary complications


===Microscopic pathology===
===Microscopic pathology===
 
*Microscopic examination of the vesicular lesions will demonstrate loose strands of fibrin, lymphocytes and neutrophils in the vesicular fluid. The presence of acantholysis in the epidermis and perivascular infiltration of leukocytes is seen in hand foot and mouth disease. The absence of intracelluar inclusion bodies differentiates it from the herpes simplex infection.<ref name="pmid5694203">{{cite journal| author=Miller GD, Tindall JP| title=Hand-foot-and-mouth disease. | journal=JAMA | year= 1968 | volume= 203 | issue= 10 | pages= 827-30 | pmid=5694203 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5694203  }} </ref>
Viruses from the group called [[enterovirus]]es cause [[HFMD]] ([[Hand-foot-and-mouth disease]]). The most common cause is coxsackievirus A16; sometimes, HFMD is caused by enterovirus 71 or other enteroviruses. The enterovirus group includes [[poliovirus]]es, [[coxsackievirus]]es, [[echovirus]]es and other [[enterovirus]]es.
 
HFMD begins with a mild [[fever]], poor appetite, [[malaise]] ("feeling sick"), and frequently a sore throat. One or 2 days after the fever begins, painful sores develop in the mouth. They begin as small red spots that blister and then often become ulcers. They are usually located on the tongue, gums, and inside of the cheeks. The skin [[rash]] develops over 1 to 2 days with flat or raised red spots, some with blisters. The [[rash]] does not itch, and it is usually located on the palms of the hands and soles of the feet. It may also appear on the buttocks. A person with HFMD may have only the rash or the mouth ulcers.
 
HFMD usually affects infants and children, and is quite common. It is highly contagious and is spread through direct contact with the mucus or feces of an infected person. The disease is not spread from pets. Transmission is by direct contact with nose and throat discharges, saliva, fluid from blisters, or stools of an infected person. Most of the transmission occurs in the first week of illness. It typically occurs in small epidemics in nursery schools or kindergartens, usually during the summer and autumn months.
 
The time between infection and the development of symptoms is about 3 - 7 days.


==References==
==References==
{{Reflist|2}}
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[[Category:Dermatology]]
[[Category:Otolaryngology]]

Latest revision as of 21:57, 29 July 2020

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

Overview

HFMD usually affects infants and children, and is quite common. It is highly contagious and is spread through direct contact with the mucus or feces of an infected person. It typically occurs in small epidemics in nursery schools or kindergartens, usually during the summer and autumn months.

Pathophysiology

  • HFMD outbreaks typically occur during summer and autumn months in the United states.[1]

Mode of transmission

  • HFMD is a contagious disease that is spread from person to person by:[1][2][3][4][5]
  • Close personal contact
  • Nasopharyngeal secretions
  • Contact with feces (fecal-oral transmission)
  • Contact with contaminated objects and surfaces
  • Contaminated water (Swimming pools not properly treated with chlorine)
  • The virus can be isolated from the following sources:
  • Following the disease, the infected person (symptomatic or asymptomatic) is most contagious during the first week of illness but can spread disease for days or weeks after symptoms go away.
  • Hand foot and mouth disease is not transmitted to or from pets or other animals.
  • Factors affecting the transmission:
  • Level of hygiene
  • Water quality
  • Extent of crowding
  • Seasonal variations
    • Tropical and subtropical: Circulation of virus tends to be year long, with more outbreaks in rainy season
    • Temperate regions: Autumn and spring

Pathogenesis

The exact pathogenesis of HFMD is not fully understood.The pathogenesis of HFMD caused by EV71 includes:[6][7]

  • EV71 replicates in the lymphoid tissues of the oropharyngeal cavity(tonsils), small bowel(payer's patches) and regional lymph nodes(deep cervical and mesenteric nodes) leading to a mild viremia.
  • Most of the viruses are destroyed in these lymphatic tissues and the patients remain asymptomatic.
  • Patients present with clinical symptoms when the virus disseminates to other organs like reticuloendothelial system(liver, spleen, bone marrow, lymph node), heart, lung, pancreas, skin, mucous membranes and CNS.
  • The virus is typically shed for between two and four weeks, and sometimes for as long as 12 weeks post-infection.
  • Replication also occurs in the upper respiratory tract and the virus has been recovered from throat swabs for up to two weeks post-infection.
  • The relationship between pathogenesis and distribution of viral entry receptors (scavenger receptor B2, P-selectin glycoprotein ligand-1 and sialic acid-linked glycans) and host factors, such as gender and age group, is unknown.
  • The pathogenesis of EV71 depends on following factors:

Viral factors Viral virulence factors are still unknown. Host factors

  • Inflammatory factors: High levels of following factors are seen in pulmonary edema.
  • HLA-A33: Associated with increased susceptibility of EV71 in Asian population
  • HLA-A2: Increased risk of cardiopulmonary complications

Microscopic pathology

  • Microscopic examination of the vesicular lesions will demonstrate loose strands of fibrin, lymphocytes and neutrophils in the vesicular fluid. The presence of acantholysis in the epidermis and perivascular infiltration of leukocytes is seen in hand foot and mouth disease. The absence of intracelluar inclusion bodies differentiates it from the herpes simplex infection.[8]

References

  1. ↑ 1.0 1.1 CDC https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6112a5.htm (2012) Accessed on October 20, 2016
  2. ↑ ROBINSON CR, DOANE FW, RHODES AJ (1958). "Report of an outbreak of febrile illness with pharyngeal lesions and exanthem: Toronto, summer 1957; isolation of group A Coxsackie virus". Can Med Assoc J. 79 (8): 615–21. PMC 1830188. PMID 13585281.
  3. ↑ Centers for Disease Control and Prevention (CDC) (2012). "Notes from the field: severe hand, foot, and mouth disease associated with coxsackievirus A6 - Alabama, Connecticut, California, and Nevada, November 2011-February 2012". MMWR Morb Mortal Wkly Rep. 61 (12): 213–4. PMID 22456122.
  4. ↑ Zhao J, Li X (2016). "Determinants of the Transmission Variation of Hand, Foot and Mouth Disease in China". PLoS One. 11 (10): e0163789. doi:10.1371/journal.pone.0163789. PMC 5049751. PMID 27701445.
  5. ↑ Chang PC, Chen SC, Chen KT (2016). "The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development". Int J Environ Res Public Health. 13 (9). doi:10.3390/ijerph13090890. PMC 5036723. PMID 27618078.
  6. ↑ Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH (2010). "Virology, epidemiology, pathogenesis, and control of enterovirus 71". Lancet Infect Dis. 10 (11): 778–90. doi:10.1016/S1473-3099(10)70194-8. PMID 20961813.
  7. ↑ ALSOP J, FLEWETT TH, FOSTER JR (1960). ""Hand-foot-and-mouth disease" in Birmingham in 1959". Br Med J. 2 (5214): 1708–11. PMC 2098292. PMID 13682692.
  8. ↑ Miller GD, Tindall JP (1968). "Hand-foot-and-mouth disease". JAMA. 203 (10): 827–30. PMID 5694203.

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