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| ==Pathophysiology== | | ==Pathophysiology== |
| [[Image:Rheumatoid arthritis joint.gif|thumb|left|Joint abnormalities in rheumatoid arthritis]]
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| *'''Possible role of infections'''
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| **Some infectious organisms mentioned in this context have been ''[[Mycoplasma]]'', ''Erysipelothrix'', [[Epstein-Barr virus]], [[parvovirus|parvovirus B19]] and [[rubella]], [[adenovirus]], [[Herpesvirus]], have been implicated in the pathophysiology of RA.<ref name="pmid18484700">{{cite journal |author=Kozireva SV, Zestkova JV, Mikazane HJ, ''et al.'' |title=Incidence and clinical significance of parvovirus B19 infection in patients with rheumatoid arthritis |journal=[[The Journal of Rheumatology]] |volume=35 |issue=7 |pages=1265–70 |year=2008 |month=July |pmid=18484700 |doi= |url=http://www.jrheum.org/cgi/pmidlookup?view=long&pmid=18484700 |accessdate=2012-04-26}}</ref> <ref name="pmid22293286">{{cite journal |author=Davis JM, Knutson KL, Skinner JA, ''et al.'' |title=A profile of immune response to herpesvirus is associated with radiographic joint damage in rheumatoid arthritis |journal=[[Arthritis Research & Therapy]] |volume=14 |issue=1 |pages=R24 |year=2012 |month=January |pmid=22293286 |doi=10.1186/ar3706 |url=http://arthritis-research.com/content/14/1/R24 |accessdate=2012-04-26}}</ref> <ref name="pmid22183424">{{cite journal |author=Pierer M, Rothe K, Quandt D, ''et al.'' |title=Anti-cytomegalovirus seropositivity in rheumatoid arthritis is associated with more severe joint destruction and more frequent joint surgery |journal=[[Arthritis and Rheumatism]] |volume= |issue= |pages= |year=2011 |month=December |pmid=22183424 |doi=10.1002/art.34346 |url=http://dx.doi.org/10.1002/art.34346 |accessdate=2012-04-26}}</ref> <ref name="pmid22011088">{{cite journal |author=Goldstein BL, Chibnik LB, Karlson EW, Costenbader KH |title=Epstein-Barr virus serologic abnormalities and risk of rheumatoid arthritis among women |journal=[[Autoimmunity]] |volume=45 |issue=2 |pages=161–8 |year=2012 |month=March |pmid=22011088 |doi=10.3109/08916934.2011.616557 |url=http://informahealthcare.com/doi/abs/10.3109/08916934.2011.616557 |accessdate=2012-04-26}}</ref>
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| **[[Periodontitis]] and Rheumatoid arthritis
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| ***Various studies have elucidated the co-relation between [[periodontitis]] and Rheumatoid arthritis because of the similarities .<ref name="pmid12956651">{{cite journal |author=Mercado FB, Marshall RI, Bartold PM |title=Inter-relationships between rheumatoid arthritis and periodontal disease. A review |journal=[[Journal of Clinical Periodontology]] |volume=30 |issue=9 |pages=761–72 |year=2003 |month=September |pmid=12956651 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0303-6979&date=2003&volume=30&issue=9&spage=761 |accessdate=2012-04-26}}</ref>
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| ***It was found to be more common and severe in patients with RA, but did not correlate with the disease severity. The presence of [[periodontitis]] in these patients was also associated with seropositivity for [[Rheumatoid factor]], the anti-cyclic citrullinated peptide antibody (anti-CCP)and antibodies to [[Porphyromonas gingivalis]] as well. <ref name="pmid20151800">{{cite journal |author=Dissick A, Redman RS, Jones M, ''et al.'' |title=Association of periodontitis with rheumatoid arthritis: a pilot study |journal=[[Journal of Periodontology]] |volume=81 |issue=2 |pages=223–30 |year=2010 |month=February |pmid=20151800 |doi=10.1902/jop.2009.090309 |url=http://www.joponline.org/doi/abs/10.1902/jop.2009.090309?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-04-26}}</ref> <ref name="pmid18848647">{{cite journal |author=Mikuls TR, Payne JB, Reinhardt RA, ''et al.'' |title=Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis |journal=[[International Immunopharmacology]] |volume=9 |issue=1 |pages=38–42 |year=2009 |month=January |pmid=18848647 |pmc=2748386 |doi=10.1016/j.intimp.2008.09.008 |url=http://linkinghub.elsevier.com/retrieve/pii/S1567-5769(08)00291-9 |accessdate=2012-04-26}}</ref>
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| *'''[[Smoking]]'''
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| **[[Smoking]] is one of the most important independent risk factors for radiographic progression of RA. It is associated with an earlier disease onset and shared epitope HLA DRB1.<ref name="pmid22045838">{{cite journal |author=Ruiz-Esquide V, Gómez-Puerta JA, Cañete JD, ''et al.'' |title=Effects of smoking on disease activity and radiographic progression in early rheumatoid arthritis |journal=[[The Journal of Rheumatology]] |volume=38 |issue=12 |pages=2536–9 |year=2011 |month=December |pmid=22045838 |doi=10.3899/jrheum.110410 |url=http://www.jrheum.org/cgi/pmidlookup?view=long&pmid=22045838 |accessdate=2012-04-26}}</ref> <ref name="pmid20112396">{{cite journal |author=Bang SY, Lee KH, Cho SK, Lee HS, Lee KW, Bae SC |title=Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA-DRB1 shared epitope, regardless of rheumatoid factor or anti-cyclic citrullinated peptide antibody status |journal=[[Arthritis and Rheumatism]] |volume=62 |issue=2 |pages=369–77 |year=2010 |month=February |pmid=20112396 |doi=10.1002/art.27272 |url=http://dx.doi.org/10.1002/art.27272 |accessdate=2012-04-26}}</ref> However, short term cessation in smoking does not appear to alter the progression of disease activity over time.<ref name="pmid22422494">{{cite journal |author=Fisher MC, Hochberg MC, El-Taha M, Kremer JM, Peng C, Greenberg JD |title=Smoking, Smoking Cessation, and Disease Activity in a Large Cohort of Patients with Rheumatoid Arthritis |journal=[[The Journal of Rheumatology]] |volume= |issue= |pages= |year=2012 |month=March |pmid=22422494 |doi=10.3899/jrheum.110852 |url=http://www.jrheum.org/cgi/pmidlookup?view=long&pmid=22422494 |accessdate=2012-04-26}}</ref>
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| **Genetic variations in NAT2 appear to mediate the risk RA imposed by smoking in African American population.<ref name="pmid21989592">{{cite journal |author=Mikuls TR, Levan T, Gould KA, ''et al.'' |title=Impact of interactions of cigarette smoking with NAT2 polymorphisms on rheumatoid arthritis risk in African Americans |journal=[[Arthritis and Rheumatism]] |volume=64 |issue=3 |pages=655–64 |year=2012 |month=March |pmid=21989592 |doi=10.1002/art.33408 |url=http://dx.doi.org/10.1002/art.33408 |accessdate=2012-04-26}}</ref>
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| *'''Effects of lifestyle'''
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| **There is also no clear evidence that physical and emotional effects, stress and improper diet could be a trigger for the disease. The many negative findings suggest that either the trigger is different from patient to patient, or that the trigger might in fact be a chance event. <ref>Edwards JC, Cambridge G, Abrahams VM. Do self-perpetuating B lymphocytes drive human autoimmune disease? Immunology. 1999;97:188-96.</ref>
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| *'''Genetic associations'''
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| **It has also become clear from recent studies that these genetic factors may interact with the most clearly defined environmental risk factor for rheumatoid arthritis, namely cigarette smoking <ref>Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L. A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum. 2004;50:3085-92.</ref>
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| *'''Hormonal factors'''
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| **Sex hormones also appear to play a role in pathophysiology of RA, partly the reason for increased incidence of RA in women.
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| **The symptoms of RA may alleviate during the luteal phase of the [[menstrual cycle]] when the [[progesterone]] levels peak.<ref name="pmid9665348">{{cite journal |author=Case AM, Reid RL |title=Effects of the menstrual cycle on medical disorders |journal=[[Archives of Internal Medicine]] |volume=158 |issue=13 |pages=1405–12 |year=1998 |month=July |pmid=9665348 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=9665348 |accessdate=2012-04-26}}</ref>
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| **[[Breast feeding]] also appears to exacerbate symptoms. As the immediate [[postnatal|postpartum]] period also imposes a risk for disease activity flare up, the exact role of breast feeding in RA is difficult to delineate.
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| *'''Occupational risks'''
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| **[[Silicon dioxide|Silica]] and [[asbestos]] exposure have been associated with development of RA.<ref name="pmid19966090">{{cite journal |author=Stolt P, Yahya A, Bengtsson C, ''et al.'' |title=Silica exposure among male current smokers is associated with a high risk of developing ACPA-positive rheumatoid arthritis |journal=[[Annals of the Rheumatic Diseases]] |volume=69 |issue=6 |pages=1072–6 |year=2010 |month=June |pmid=19966090 |doi=10.1136/ard.2009.114694 |url=http://ard.bmj.com/cgi/pmidlookup?view=long&pmid=19966090 |accessdate=2012-04-26}}</ref> <ref name="pmid15319232">{{cite journal |author=Stolt P, Källberg H, Lundberg I, Sjögren B, Klareskog L, Alfredsson L |title=Silica exposure is associated with increased risk of developing rheumatoid arthritis: results from the Swedish EIRA study |journal=[[Annals of the Rheumatic Diseases]] |volume=64 |issue=4 |pages=582–6 |year=2005 |month=April |pmid=15319232 |pmc=1755463 |doi=10.1136/ard.2004.022053 |url=http://ard.bmj.com/cgi/pmidlookup?view=long&pmid=15319232 |accessdate=2012-04-26}}</ref>
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| *'''Other factors'''
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| **[[Obesity]] and high consumption of red meat also seems to play a role in increased disease severity.<ref name="pmid22514156">{{cite journal |author=Crowson CS, Matteson EL, Davis JM, Gabriel SE |title=Obesity fuels the upsurge in rheumatoid arthritis |journal=[[Arthritis Care & Research]] |volume= |issue= |pages= |year=2012 |month=April |pmid=22514156 |doi=10.1002/acr.21660 |url=http://dx.doi.org/10.1002/acr.21660 |accessdate=2012-04-26}}</ref> <ref name="pmid19318947">{{cite journal |author=Liao KP, Alfredsson L, Karlson EW |title=Environmental influences on risk for rheumatoid arthritis |journal=[[Current Opinion in Rheumatology]] |volume=21 |issue=3 |pages=279–83 |year=2009 |month=May |pmid=19318947 |pmc=2898190 |doi=10.1097/BOR.0b013e32832a2e16 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1040-8711&volume=21&issue=3&spage=279 |accessdate=2012-04-26}}</ref>
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| **Role of [[oral contraceptive]] pills and [[vitamin D]] is found to be equivocal.<ref name="pmid19318947">{{cite journal |author=Liao KP, Alfredsson L, Karlson EW |title=Environmental influences on risk for rheumatoid arthritis |journal=[[Current Opinion in Rheumatology]] |volume=21 |issue=3 |pages=279–83 |year=2009 |month=May |pmid=19318947 |pmc=2898190 |doi=10.1097/BOR.0b013e32832a2e16 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1040-8711&volume=21&issue=3&spage=279 |accessdate=2012-04-26}}</ref>
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| ==References== | | ==References== |
| {{Reflist|2}} | | {{Reflist|2}} |