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==Overview==
==Overview==
Rheumatic fever is the result of an autoimmunological sequela to a virulent ''[[Streptococcus pyogenes]]'' infection in a patient who was immunologically sensitized from prior infections.During a streptococcal infection, activated antigen presenting cells, such as [[macrophage]]s, present the bacterial antigen to helper T cells. [[Helper T cell]]s subsequently activate B cells and induce the production of antibodies against the cell wall of [[streptococcus]]. However the antibodies may also act against the myocardium and joints, producing the symptoms of rheumatic fever.<ref name=WPatho> Rheumatic Fever. Wikipedia (2015). http://www.mayoclinic.org/diseases-conditions/rheumatic-fever/basics/causes/con-20031399 Accessed on October 12, 2015 </ref>
[[Rheumatic fever]] is the result of an autoimmunological sequela to a virulent ''[[Streptococcus pyogenes]]'' [[infection]] in a [[patient]] who was immunologically sensitized from prior [[infections]]. During a streptococcal [[infection]], activated [[antigen-presenting cell]]s, such as [[macrophage]]s, present the [[bacterial]] [[antigen]] to [[helper T cells]]. [[Helper T cells]] subsequently activate [[B cells]] and induce the production of [[antibodies]] against the [[cell wall]] of ''[[Streptococcus]]''. However the [[antibodies]] also act against the [[myocardium]] and [[joint]]s, producing the [[symptoms]] of rheumatic fever.


==Pathophysiology==
==Pathophysiology==
===Pathogenesis===
===Pathogenesis===
Rheumatic fever is the result of an autoimmunological sequela to a virulent ''[[Streptococcus pyogenes]]'' infection in a patient who was immunologically sensitized from prior infections. The systemic disease affects the periarteriolar connective tissue and can occur after an untreated Group A streptococcal [[pharyngeal]] infection. It is believed to be caused by antibody [[cross-reactivity]] which is a [[Hypersensitivity#Type 2 - antibody-dependent|Type II hypersensitivity reaction]].<ref name=WPatho> Rheumatic Fever. Wikipedia (2015). http://www.mayoclinic.org/diseases-conditions/rheumatic-fever/basics/causes/con-20031399 Accessed on October 12, 2015 </ref>
*Rheumatic fever is the result of an autoimmunological sequelae to a virulent ''[[Streptococcus pyogenes]]'' infection in a [[patient]] who was immunologically sensitized from prior [[infections]], affecting [[periarteriolar]] [[connective tissue]].
*During a [[streptococcal infection]], activated [[antigen-presenting cell]]s, such as [[macrophage]]s, present the [[bacterial]] [[antigen]] to [[helper T cell]]s.
**[[Helper T cell]]s subsequently activate [[B cells]] and induce the production of [[antibodies]] against the cell wall of ''[[Streptococcus]]''.
*However the [[antibodies]] may also act against the [[myocardium]] and [[joints]], producing the [[symptoms]] of rheumatic fever.
**Contrary to the immunological protection developed during most [[infections]], [[infections]] by ''Streptococcus pyogenes'' cause both a protective [[immunological]] and [[pathological]] autoimmunological stimulation.
**Repeated [[infections]] by ''[[Streptococcus pyogenes]]'' will cause both a heightened protective and [[pathological]] [[immune]] response


Usually, self reactive [[B cell]]s remain anergic in the periphery without [[T cell]] co-stimulation. During a streptococcal infection, activated antigen presenting cells, such as [[macrophage]]s, present the bacterial antigen to helper T cells. [[Helper T cell]]s subsequently activate B cells and induce the production of antibodies against the cell wall of [[streptococcus]]. However the antibodies may also act against the myocardium and joints, producing the symptoms of rheumatic fever.
===Acute rheumatic fever===
*[[Lesions]] may occur in [[endocardium]], [[myocardium]], or [[pericardium]].
**The [[inflammation]] may cause serofibrinous [[pericardial]] exudates described as “bread-and-butter” [[pericarditis]], which usually resolves without sequelae.
*Involvement of the [[endocardium]] typically results in [[fibrinoid necrosis]] and [[verrucae]] formation along the lines of closure of the [[heart valve]]s.
**These warty projections and irregular thickenings are known as [[MacCallum plaques]].<ref name="pmid18306530">{{cite journal| author=Chopra P, Gulwani H| title=Pathology and pathogenesis of rheumatic heart disease. | journal=Indian J Pathol Microbiol | year= 2007 | volume= 50 | issue= 4 | pages= 685-97 | pmid=18306530 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18306530  }} </ref>


Contrary to the immunological protection developed during most infections, infections by ''Streptococcus pyogenes'' cause both a protective immunological and pathological autoimmunological stimulation. Repeated infections by ''Streptococcus pyogenes'' will cause both a heightened protective and pathological immune response. The immune response helps in combating the streptococcal infection. However, the autoimmunological response causes an inflammatory, systemic, disease process, rheumatic fever.  
===Chronic rheumatic fever===
*[[Lesions]] may occur in the [[mitral valve]].
*[[Valve]] thickening may result in [[stenosis]] or [[regurgitation]].


In acute rheumatic fever, these lesions may occur in endocardium, myocardium or pericardium.  The inflammation may cause a serofibrinous pericardial exudates described as “bread-and-butter” [[pericarditis]], which usually resolves without sequelae.  Involvement of the endocardium typically results in [[fibrinoid necrosis]] and verrucae formation along the lines of closure of the left heart valves. Warty projections arise from the deposition, while subendothelial lesions may induce irregular thickenings called [[MacCallum plaques]].<ref name="pmid18306530">{{cite journal| author=Chopra P, Gulwani H| title=Pathology and pathogenesis of rheumatic heart disease. | journal=Indian J Pathol Microbiol | year= 2007 | volume= 50 | issue= 4 | pages= 685-97 | pmid=18306530 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18306530  }} </ref>
===Gross===
 
On [[gross]] [[pathology]], the following are characteristic findings of rheumatic fever:<ref name="LIBRE"> Rheumatic Heart Disease. Libre Pathology (2015). http://librepathology.org/wiki/index.php/Heart_valves#Rheumatic_heart_disease Accessed on October 12, 2015 </ref>
===Gross and Microscopic Pathology===
====Gross====
On gross pathology, the following features are characteristic findings of rheumatic fever:<ref name=LIBRE> Rheumatic Heart Disease. Libre Pathology (2015). http://librepathology.org/wiki/index.php/Heart_valves#Rheumatic_heart_disease Accessed on October 12, 2015 </ref>
*"Fish-mouth appearance"
*"Fish-mouth appearance"
**Slit-like morphology; elliptical cross-sectional flow area (mitral valve) with abnormally small semi-minor axis axis due to valve thickening
**Slit-like [[morphology]]; elliptical cross-sectional flow area ([[mitral valve]]) with abnormally small semi-minor axis
*Significant valvular thickening
*Significant [[valvular]] thickening
*Thickening and shortening of the [[chorda tympani]]
*Thickening and shortening of the [[chorda tympani]]


====Microscopic histopathological analysis====
===Microscopic histopathological analysis===
On microscopic histopathological analysis, the following features are characteristic findings of rheumatic fever:<ref name=LIBRE> Rheumatic Heart Disease. Libre Pathology (2015). http://librepathology.org/wiki/index.php/Heart_valves#Rheumatic_heart_disease Accessed on October 12, 2015 </ref><ref name="robbins">{{cite book |author=Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Robbins, Stanley L.; Abbas, Abul K. |title=Robbins and Cotran pathologic basis of disease |publisher=Elsevier Saunders |location=St. Louis, MO |year=2005 |pages= |isbn=0-7216-0187-1 |oclc= |doi=}}</ref><ref name="robbins">{{cite book |author=Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Robbins, Stanley L.; Abbas, Abul K. |title=Robbins and Cotran pathologic basis of disease |publisher=Elsevier Saunders |location=St. Louis, MO |year=2005 |pages= |isbn=0-7216-0187-1 |oclc= |doi=}}</ref>
On [[microscopic]] [[histopathological]] [[analysis]], the following are characteristic findings of rheumatic fever:<ref name="LIBRE"> Rheumatic Heart Disease. Libre Pathology (2015). http://librepathology.org/wiki/index.php/Heart_valves#Rheumatic_heart_disease Accessed on October 12, 2015 </ref><ref name="robbins">{{cite book |author=Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Robbins, Stanley L.; Abbas, Abul K. |title=Robbins and Cotran pathologic basis of disease |publisher=Elsevier Saunders |location=St. Louis, MO |year=2005 |pages= |isbn=0-7216-0187-1 |oclc= |doi=}}</ref>
*[[Anitschkow cell|Caterpillar cells]]
*[[Anitschkow cell|Caterpillar cells]]
**Abundant [[eosinophilic]] [[cytoplasm]]
**Abundant [[eosinophilic]] [[cytoplasm]]
**Moderately-poorly defined cell border
**Moderately-poorly defined [[cell]] border
**Well-defined central [[ovoid]] nucleus with a prominent wavy ribbon-like chromatin
**Well-defined central [[ovoid]] [[nucleus]] with a prominent wavy ribbon-like [[chromatin]]
*[[Aschoff bodies]] found within the heart
*[[Aschoff bodies]] found within the [[heart]]
**Jumbled [[collagen]], eosinophilic
**Jumbled, [[eosinophilic]] [[collagen]]
**Surrounded by T cells
**Surrounded by [[T cells]]


===Images===
===Images===
The following are gross and microscopic images associated with rheumatic fever:<ref name=RFPath> Pathology Education Instructional Resource. University of Alabama at Birmingham (2014). Images courtesy of Propessor Peter Anderson DVM PhD and published with permission of PEIR, Department of Pathology, University of Alabama at Birmingham. http://www.peir.net Accessed on October 12, 2015.</ref>
The following are gross and microscopic images associated with rheumatic fever:<ref name="RFPath"> Pathology Education Instructional Resource. University of Alabama at Birmingham (2014). Images courtesy of Propessor Peter Anderson DVM PhD and published with permission of PEIR, Department of Pathology, University of Alabama at Birmingham. http://www.peir.net Accessed on October 12, 2015.</ref>


<gallery>
<gallery>
Image:Rheumatic fever 001.jpg|[[Aortic stenosis]] ([[Tricuspid]] aorta): gross, an example of aortic stenosis due to rheumatic fever  
Image:Rheumatic fever 001.jpg|[[Aortic stenosis]] ([[Tricuspid]] aorta): gross, an example of aortic stenosis due to rheumatic fever.


Image:Rheumatic fever 002.jpg|[[Mitral]] scarring: gross, an example of mitral scarring due to rheumatic fever (healing phase of an infectious lesion)  
Image:Rheumatic fever 002.jpg|[[Mitral]] scarring: gross, an example of mitral scarring due to rheumatic fever (healing phase of an infectious lesion).


Image:Rheumatic mitral valvulitis.jpg|Rheumatic [[mitral]] [[valvulitis]]: gross, rheumatic mitral valvulitis: Gross, an example of [[fibrosis]], [[chorda tympani|chorda]] thickening and shortening with [[thrombus]] around the large left atrium
Image:Rheumatic mitral valvulitis.jpg|Rheumatic [[mitral]] [[valvulitis]]: gross, an example of [[fibrosis]], [[chorda tympani|chorda]] thickening and shortening with [[thrombus]] around the large left atrium.


Image:ARF mitral valve.jpg|Rheumatic [[mitral]] [[valvulitis]]: Gross, an example of acute rheumatic fever lesion along line of closure of mitral valve  
Image:ARF mitral valve.jpg|Rheumatic [[mitral]] [[valvulitis]]: gross, an example of acute rheumatic fever lesion along line of closure of [[mitral valve]].


Image:Rheumatic fever 003.jpg|[[Mitral]] valve: gross, acute rheumatic fever  
Image:Rheumatic fever 003.jpg|[[Mitral]] valve: gross, acute rheumatic fever.


Image:Rheumatic fever 004.jpg|[[Aschoff bodies]]: microscopic histopathological analysis, Aschoff bodies in rheumatic heart disease
Image:Rheumatic fever 004.jpg|[[Aschoff bodies]]: microscopic histopathological analysis, [[Aschoff bodies]] in rheumatic heart disease.
</gallery>
</gallery>


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[[Category:Cardiology]]
[[Category:Cardiology]]
[[Category:Bacterial diseases]]
[[Category:Rheumatology]]
[[Category:Rheumatology]]
[[Category:Primary care]]
[[Category:Disease]]
{{WH}}
{{WS}}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Lance Christiansen, D.O.; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Anthony Gallo, B.S. [3]

Overview

Rheumatic fever is the result of an autoimmunological sequela to a virulent Streptococcus pyogenes infection in a patient who was immunologically sensitized from prior infections. During a streptococcal infection, activated antigen-presenting cells, such as macrophages, present the bacterial antigen to helper T cells. Helper T cells subsequently activate B cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies also act against the myocardium and joints, producing the symptoms of rheumatic fever.

Pathophysiology

Pathogenesis

Acute rheumatic fever

Chronic rheumatic fever

Gross

On gross pathology, the following are characteristic findings of rheumatic fever:[2]

Microscopic histopathological analysis

On microscopic histopathological analysis, the following are characteristic findings of rheumatic fever:[2][3]

Images

The following are gross and microscopic images associated with rheumatic fever:[4]

References

  1. Chopra P, Gulwani H (2007). "Pathology and pathogenesis of rheumatic heart disease". Indian J Pathol Microbiol. 50 (4): 685–97. PMID 18306530.
  2. 2.0 2.1 Rheumatic Heart Disease. Libre Pathology (2015). http://librepathology.org/wiki/index.php/Heart_valves#Rheumatic_heart_disease Accessed on October 12, 2015
  3. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, MO: Elsevier Saunders. ISBN 0-7216-0187-1.
  4. Pathology Education Instructional Resource. University of Alabama at Birmingham (2014). Images courtesy of Propessor Peter Anderson DVM PhD and published with permission of PEIR, Department of Pathology, University of Alabama at Birmingham. http://www.peir.net Accessed on October 12, 2015.