Rheumatoid arthritis natural history, complications and prognosis: Difference between revisions

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{{Rheumatoid arthritis}}
{{Rheumatoid arthritis}}
{{CMG}} {{AE}} ; {{MKK}}
{{CMG}};{{AE}} {{MKK}}


==Overview==
==Overview==
The symptoms of [[rheumatoid arthritis]]  usually develop in the third to fourth decade of life. Symptoms such as fatigue, small joint pain and morning stiffness are seen initially, the stiffness may last more than 1 hour. Complications of [[rheumatoid arthritis]] may involve various organ systems. Cardiac complications include pericarditis, congestive heart failure, endocarditis, and myocardial infarction. Pulmonary complications include pleurisy, [[alveolitis]], [[pleural effusion]], and [[pulmonary fibrosis]]. Rheumatological complications include [[joint]] deformities, [[Felty's syndrome]], [[sjögren's syndrome]], [[osteoporosis]],  and atlantoaxial subluxation. Ophthalmology complications include [[scleritis]] and [[keratitis]]. Renal complications include [[chronic renal failure]] from [[amyloidosis]]. Nervous system complications like [[peripheral neuropathy]], [[quadriplegia]], and [[mononeuritis multiplex]] may also be seen. Prognosis is generally good with early diagnosis and treatment. The 10-year disability rate of patients with rheumatoid arthritis is approximately 40%.


===Natural History===
==Natural History==
*The symptoms of [[rheumatoid arthritis]]  usually develop in the first/ second/ third decade of life, and start with symptoms such as ___.
*The symptoms of [[rheumatoid arthritis]]  usually develop in the third to fourth decade of life. Symptoms such as [[fatigue]], small [[joint]] pain and morning stiffness lasting more than 1 hour may be seen.
*The symptoms of (disease name) typically develop ___ years after exposure to ___.  
*If left untreated, patients with [[rheumatoid arthritis]] may progress to develop extra-[[articular]] manifestation.
*If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].


==Complications==
==Complications==
The complication of [[rheumatoid arthritis]] are given below:<ref name="pmid17870035">{{cite journal |vauthors=Young A, Koduri G |title=Extra-articular manifestations and complications of rheumatoid arthritis |journal=Best Pract Res Clin Rheumatol |volume=21 |issue=5 |pages=907–27 |date=October 2007 |pmid=17870035 |doi=10.1016/j.berh.2007.05.007 |url=}}</ref><ref name="pmid19448378">{{cite journal |vauthors=Al-Ghamdi A, Attar SM |title=Extra-articular manifestations of rheumatoid arthritis: a hospital-based study |journal=Ann Saudi Med |volume=29 |issue=3 |pages=189–93 |date=2009 |pmid=19448378 |pmc=2813651 |doi= |url=}}</ref>
===Rheumatological===
===Rheumatological===
The rheumatological complications of rheumatoid arthritis include:
*Joint deformitites
*Joint deformitites
*[[Felty's syndrome]]
*[[Felty's syndrome]]
*[[Sjögren's syndrome]]
*[[Sjögren's syndrome]]
===Cardiac complications===
===Cardiac complications===
The cardiac complications of rheumatoid arthritis include:
*[[Pericarditis]]
*[[Pericarditis]]
*[[Congestive heart failure]]
*[[Congestive heart failure]]
*[[Endocarditis]]
*[[Endocarditis]]
*[[Myocardial infarction]]
*[[Myocardial infarction]]
===Cardiovascular disease===
Paitents with RA are at increased risk of vascular disease.<ref name="pmid12628952">{{cite journal |vauthors=Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC |title=Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis |journal=Circulation |volume=107 |issue=9 |pages=1303–7 |date=March 2003 |pmid=12628952 |doi= |url=}}</ref><ref name="pmid16877533">{{cite journal |vauthors=Turesson C, McClelland RL, Christianson TJ, Matteson EL |title=Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis |journal=Ann. Rheum. Dis. |volume=66 |issue=1 |pages=70–5 |date=January 2007 |pmid=16877533 |pmc=1798415 |doi=10.1136/ard.2006.052506 |url=}}</ref><ref name="pmid16490910">{{cite journal |vauthors=Roman MJ, Moeller E, Davis A, Paget SA, Crow MK, Lockshin MD, Sammaritano L, Devereux RB, Schwartz JE, Levine DM, Salmon JE |title=Preclinical carotid atherosclerosis in patients with rheumatoid arthritis |journal=Ann. Intern. Med. |volume=144 |issue=4 |pages=249–56 |date=February 2006 |pmid=16490910 |doi= |url=}}</ref>
The degree of increase in risk is hard to estimate as meta-analyses of the cohorts note that many studies did not adjust for cardiovascular risk factors. This includes the meta-analysis by Dadoun<ref name="pmid22459416">{{cite journal| author=Dadoun S, Zeboulon-Ktorza N, Combescure C, Elhai M, Rozenberg S, Gossec L | display-authors=etal| title=Mortality in rheumatoid arthritis over the last fifty years: systematic review and meta-analysis. | journal=Joint Bone Spine | year= 2013 | volume= 80 | issue= 1 | pages= 29-33 | pmid=22459416 | doi=10.1016/j.jbspin.2012.02.005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22459416  }} </ref> cited by the EULAR guidelines<ref name="pmid27697765">{{cite journal| author=Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJ | display-authors=etal| title=EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. | journal=Ann Rheum Dis | year= 2017 | volume= 76 | issue= 1 | pages= 17-28 | pmid=27697765 | doi=10.1136/annrheumdis-2016-209775 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27697765  }} </ref> and the meta-analysis by Aviña-Zubieta<ref name="pmid19035419">{{cite journal| author=Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D| title=Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. | journal=Arthritis Rheum | year= 2008 | volume= 59 | issue= 12 | pages= 1690-7 | pmid=19035419 | doi=10.1002/art.24092 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19035419  }} </ref> cited by the American Heart Association<ref name="pmid30586774">{{cite journal| author=Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS | display-authors=etal| title=2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. | journal=Circulation | year= 2019 | volume= 139 | issue= 25 | pages= e1082-e1143 | pmid=30586774 | doi=10.1161/CIR.0000000000000625 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30586774  }} </ref>.
Thus, while EULAR recommends multiplying cardiac risk in RA patients by 1.5, this does not seem supported by the analysis cited by EULAR.
===Pulmonary complications===
===Pulmonary complications===
*[[Pleurisy]],
The pulmonary complications of rheumatoid arthritis include:<ref name="pmid16192902">{{cite journal |vauthors=Bharadwaj A, Haroon N |title=Interstitial lung disease and neuropathy as predominant extra-articular manifestations in patients with rheumatoid arthritis: a prospective study |journal=Med. Sci. Monit. |volume=11 |issue=10 |pages=CR498–502 |date=October 2005 |pmid=16192902 |doi= |url=}}</ref><ref name="pmid16765714">{{cite journal |vauthors=Balbir-Gurman A, Yigla M, Nahir AM, Braun-Moscovici Y |title=Rheumatoid pleural effusion |journal=Semin. Arthritis Rheum. |volume=35 |issue=6 |pages=368–78 |date=June 2006 |pmid=16765714 |doi=10.1016/j.semarthrit.2006.03.002 |url=}}</ref><ref name="pmid19892679">{{cite journal |vauthors=Kim EJ, Collard HR, King TE |title=Rheumatoid arthritis-associated interstitial lung disease: the relevance of histopathologic and radiographic pattern |journal=Chest |volume=136 |issue=5 |pages=1397–1405 |date=November 2009 |pmid=19892679 |pmc=2818853 |doi=10.1378/chest.09-0444 |url=}}</ref>
*[[Alveolitis]],
*[[Pleurisy]]
*[[Pulmonary effusion]]
*[[Alveolitis]]
*[[Pleural effusion]]
*[[Pulmonary fibrosis]]
*[[Pulmonary fibrosis]]
===Eye complications===
===Ocular complications===
*[[Scleritis]], and
The ocular complications of rheumatoid arthritis include:
*[[subcutaneous tissue|Subcutaneous]] [[nodule (medicine)|nodule]]s
*[[Scleritis]]
*[[Keratitis]]
===Renal complications===
===Renal complications===
The renal complications of rheumatoid arthritis include:
*[[Chronic renal failure]] from [[amyloidosis]]
*[[Chronic renal failure]] from [[amyloidosis]]
===Nervous system complications===
===Neurological complications===
The neurological complications of rheumatoid arthritis include:<ref name="pmid8265831">{{cite journal |vauthors=Chang DJ, Paget SA |title=Neurologic complications of rheumatoid arthritis |journal=Rheum. Dis. Clin. North Am. |volume=19 |issue=4 |pages=955–73 |date=November 1993 |pmid=8265831 |doi= |url=}}</ref><ref name="pmid11225133">{{cite journal |vauthors=Nadkar MY, Agarwal R, Samant RS, Chhugani SJ, Idgunji SS, Iyer S, Borges NE |title=Neuropathy in rheumatoid arthritis |journal=J Assoc Physicians India |volume=49 |issue= |pages=217–20 |date=February 2001 |pmid=11225133 |doi= |url=}}</ref>
*[[Peripheral neuropathy]] and [[mononeuritis multiplex]]
*[[Peripheral neuropathy]] and [[mononeuritis multiplex]]
*[[Quadriplegia]]
*[[Quadriplegia]]
===Orthopedic complications===
===Orthopedic complications===
*Erosion of the odontoid process and or/transverse ligaments in the [[cervical spine]]
The orthopedic complications of rheumatoid arthritis include:<ref name="pmid12111629">{{cite journal |vauthors=Laiho K, Kaarela K, Kauppi M |title=Cervical spine disorders in patients with rheumatoid arthritis and amyloidosis |journal=Clin. Rheumatol. |volume=21 |issue=3 |pages=227–30 |date=June 2002 |pmid=12111629 |doi= |url=}}</ref>
*Erosion of the odontoid process and transverse ligaments in the [[cervical spine]]
*[[Osteoporosis]]
*[[Osteoporosis]]
*Atlanto-axial subluxation
*Atlanto-axial subluxation
===Hematological complications===
===Hematologic complications===
The hematologic complications of rheumatoid arthritis include:
*[[Lymphoma]]
*[[Lymphoma]]
*[[Anemia]]
*[[Anemia]]
===Dermatological complications===
The dermatological complications of rheumatoid arthritis include:<ref name="pmid17023257">{{cite journal |vauthors=Genta MS, Genta RM, Gabay C |title=Systemic rheumatoid vasculitis: a review |journal=Semin. Arthritis Rheum. |volume=36 |issue=2 |pages=88–98 |date=October 2006 |pmid=17023257 |doi=10.1016/j.semarthrit.2006.04.006 |url=}}</ref><ref name="pmid15262699">{{cite journal |vauthors=Charles CA, Bialy TL, Falabella AF, Eaglstein WH, Kerdel FA, Kirsner RS |title=Poor prognosis of arthritis-associated pyoderma gangrenosum |journal=Arch Dermatol |volume=140 |issue=7 |pages=861–4 |date=July 2004 |pmid=15262699 |doi=10.1001/archderm.140.7.861 |url=}}</ref>
*[[Splinter haemorrhages]]
*Periungual infarcts
*Leg [[ulcers]]
*Digital [[gangrene]]
*[[Pyoderma gangrenosum]]
==Prognosis==
==Prognosis==
The course of the disease varies greatly from patient to patient. Some patients have mild short-term symptoms, but in most the disease is progressive for life. Around 20%-30% will have subcutaneous nodules (known as rheumatoid nodules); this is associated with a poor prognosis. 
*Prognosis is generally good with early diagnosis and treatment, and 10-year disability rate of patients with rheumatoid arthritis is approximately 40%.
 
===Disability===
*Daily living activities are impaired in most patients.
*After 5 years of disease, approximately 33% of patients will not be working
*After 10 years, approximately half will have substantial functional disability.  
 
===Prognostic factors===
===Prognostic factors===
*Poor prognostic factors include persistent synovitis, early erosive disease, extra-articular findings (including subcutaneous rheumatoid nodules), positive serum RF findings, positive serum anti-CCP autoantibodies, carriership of HLA-DR4 "Shared Epitope" alleles, family history of RA, poor functional status, socioeconomic factors, elevated acute phase response (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and increased clinical severity.
*Poor prognostic factors are:<ref name="pmid16572283">{{cite journal |vauthors=Agrawal S, Misra R, Aggarwal A |title=Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA |journal=Clin. Rheumatol. |volume=26 |issue=2 |pages=201–4 |date=February 2007 |pmid=16572283 |doi=10.1007/s10067-006-0275-5 |url=}}</ref><ref name="pmid12695154">{{cite journal |vauthors=Vencovský J, Machácek S, Sedová L, Kafková J, Gatterová J, Pesáková V, Růzicková S |title=Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis |journal=Ann. Rheum. Dis. |volume=62 |issue=5 |pages=427–30 |date=May 2003 |pmid=12695154 |pmc=1754544 |doi= |url=}}</ref>
 
**Insidious onset of symptoms
===Mortality===
**Female sex
Estimates of the life-shortening effect of RA vary; most sources cite a lifespan reduction of 5 to 10 years; the [[National Institutes of Health]] has estimated a lifespan reduction of 10 to 20 years.<ref>[www.nih.gov/about/researchresultsforthepublic/arthritis.pdf Rheumatoid arthritis prognosis]</ref> According to the UK's National Rheumatoid Arthritis Society, "Young age at onset, long disease duration, the concurrent presence of other health problems (called co-morbidity), and characteristics of severe RA – such as poor functional ability or overall health status, a lot of joint damage on x-rays, the need for hospitalisation or involvement of organs other than the joints – have been shown to associate with higher mortality". <ref>[http://www.rheumatoid.org.uk/article.php?article_id=112 Excess mortality in rheumatoid arthritis]</ref> Positive responses to treatment may indicate a better prognosis. A 2005 study by the [[Mayo Clinic]] noted that RA patients suffer a doubled risk of heart disease,<ref>[http://www.mayoclinic.org/news2005-rst/2654.html The second largest contributor of mortality is cerebrovascular disease. Increased risk of heart disease in rheumatoid arthritis patients]</ref> independent of other risk factors such as [[diabetes]], alcohol abuse, and elevated [[cholesterol]], blood pressure and [[body mass index]]. The mechanism by which RA causes this increased risk remains unknown; the presence of chronic inflammation has been proposed as a contributing factor. <ref>[http://www.hopkins-arthritis.org/news-archive/2002/cardiac.html Cardiac disease in rheumatoid arthritis]</ref>
**Age less than 30 years
**HLA-DRB1*04/04 genotype
**High serum levels of autoantibodies
**Extra-articular symptoms
**Systemic symptoms
**Cigarette smoking
**Lack of formal education
**Lower socioeconomic status


==References==
==References==

Latest revision as of 18:38, 17 April 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Overview

The symptoms of rheumatoid arthritis usually develop in the third to fourth decade of life. Symptoms such as fatigue, small joint pain and morning stiffness are seen initially, the stiffness may last more than 1 hour. Complications of rheumatoid arthritis may involve various organ systems. Cardiac complications include pericarditis, congestive heart failure, endocarditis, and myocardial infarction. Pulmonary complications include pleurisy, alveolitis, pleural effusion, and pulmonary fibrosis. Rheumatological complications include joint deformities, Felty's syndrome, sjögren's syndrome, osteoporosis, and atlantoaxial subluxation. Ophthalmology complications include scleritis and keratitis. Renal complications include chronic renal failure from amyloidosis. Nervous system complications like peripheral neuropathy, quadriplegia, and mononeuritis multiplex may also be seen. Prognosis is generally good with early diagnosis and treatment. The 10-year disability rate of patients with rheumatoid arthritis is approximately 40%.

Natural History

Complications

The complication of rheumatoid arthritis are given below:[1][2]

Rheumatological

The rheumatological complications of rheumatoid arthritis include:

Cardiac complications

The cardiac complications of rheumatoid arthritis include:

Cardiovascular disease

Paitents with RA are at increased risk of vascular disease.[3][4][5]

The degree of increase in risk is hard to estimate as meta-analyses of the cohorts note that many studies did not adjust for cardiovascular risk factors. This includes the meta-analysis by Dadoun[6] cited by the EULAR guidelines[7] and the meta-analysis by Aviña-Zubieta[8] cited by the American Heart Association[9].

Thus, while EULAR recommends multiplying cardiac risk in RA patients by 1.5, this does not seem supported by the analysis cited by EULAR.

Pulmonary complications

The pulmonary complications of rheumatoid arthritis include:[10][11][12]

Ocular complications

The ocular complications of rheumatoid arthritis include:

Renal complications

The renal complications of rheumatoid arthritis include:

Neurological complications

The neurological complications of rheumatoid arthritis include:[13][14]

Orthopedic complications

The orthopedic complications of rheumatoid arthritis include:[15]

Hematologic complications

The hematologic complications of rheumatoid arthritis include:

Dermatological complications

The dermatological complications of rheumatoid arthritis include:[16][17]

Prognosis

  • Prognosis is generally good with early diagnosis and treatment, and 10-year disability rate of patients with rheumatoid arthritis is approximately 40%.

Prognostic factors

  • Poor prognostic factors are:[18][19]
    • Insidious onset of symptoms
    • Female sex
    • Age less than 30 years
    • HLA-DRB1*04/04 genotype
    • High serum levels of autoantibodies
    • Extra-articular symptoms
    • Systemic symptoms
    • Cigarette smoking
    • Lack of formal education
    • Lower socioeconomic status

References

  1. ↑ Young A, Koduri G (October 2007). "Extra-articular manifestations and complications of rheumatoid arthritis". Best Pract Res Clin Rheumatol. 21 (5): 907–27. doi:10.1016/j.berh.2007.05.007. PMID 17870035.
  2. ↑ Al-Ghamdi A, Attar SM (2009). "Extra-articular manifestations of rheumatoid arthritis: a hospital-based study". Ann Saudi Med. 29 (3): 189–93. PMC 2813651. PMID 19448378.
  3. ↑ Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC (March 2003). "Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis". Circulation. 107 (9): 1303–7. PMID 12628952.
  4. ↑ Turesson C, McClelland RL, Christianson TJ, Matteson EL (January 2007). "Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis". Ann. Rheum. Dis. 66 (1): 70–5. doi:10.1136/ard.2006.052506. PMC 1798415. PMID 16877533.
  5. ↑ Roman MJ, Moeller E, Davis A, Paget SA, Crow MK, Lockshin MD, Sammaritano L, Devereux RB, Schwartz JE, Levine DM, Salmon JE (February 2006). "Preclinical carotid atherosclerosis in patients with rheumatoid arthritis". Ann. Intern. Med. 144 (4): 249–56. PMID 16490910.
  6. ↑ Dadoun S, Zeboulon-Ktorza N, Combescure C, Elhai M, Rozenberg S, Gossec L; et al. (2013). "Mortality in rheumatoid arthritis over the last fifty years: systematic review and meta-analysis". Joint Bone Spine. 80 (1): 29–33. doi:10.1016/j.jbspin.2012.02.005. PMID 22459416.
  7. ↑ Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJ; et al. (2017). "EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update". Ann Rheum Dis. 76 (1): 17–28. doi:10.1136/annrheumdis-2016-209775. PMID 27697765.
  8. ↑ Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D (2008). "Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies". Arthritis Rheum. 59 (12): 1690–7. doi:10.1002/art.24092. PMID 19035419.
  9. ↑ Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS; et al. (2019). "2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines". Circulation. 139 (25): e1082–e1143. doi:10.1161/CIR.0000000000000625. PMID 30586774.
  10. ↑ Bharadwaj A, Haroon N (October 2005). "Interstitial lung disease and neuropathy as predominant extra-articular manifestations in patients with rheumatoid arthritis: a prospective study". Med. Sci. Monit. 11 (10): CR498–502. PMID 16192902.
  11. ↑ Balbir-Gurman A, Yigla M, Nahir AM, Braun-Moscovici Y (June 2006). "Rheumatoid pleural effusion". Semin. Arthritis Rheum. 35 (6): 368–78. doi:10.1016/j.semarthrit.2006.03.002. PMID 16765714.
  12. ↑ Kim EJ, Collard HR, King TE (November 2009). "Rheumatoid arthritis-associated interstitial lung disease: the relevance of histopathologic and radiographic pattern". Chest. 136 (5): 1397–1405. doi:10.1378/chest.09-0444. PMC 2818853. PMID 19892679.
  13. ↑ Chang DJ, Paget SA (November 1993). "Neurologic complications of rheumatoid arthritis". Rheum. Dis. Clin. North Am. 19 (4): 955–73. PMID 8265831.
  14. ↑ Nadkar MY, Agarwal R, Samant RS, Chhugani SJ, Idgunji SS, Iyer S, Borges NE (February 2001). "Neuropathy in rheumatoid arthritis". J Assoc Physicians India. 49: 217–20. PMID 11225133.
  15. ↑ Laiho K, Kaarela K, Kauppi M (June 2002). "Cervical spine disorders in patients with rheumatoid arthritis and amyloidosis". Clin. Rheumatol. 21 (3): 227–30. PMID 12111629.
  16. ↑ Genta MS, Genta RM, Gabay C (October 2006). "Systemic rheumatoid vasculitis: a review". Semin. Arthritis Rheum. 36 (2): 88–98. doi:10.1016/j.semarthrit.2006.04.006. PMID 17023257.
  17. ↑ Charles CA, Bialy TL, Falabella AF, Eaglstein WH, Kerdel FA, Kirsner RS (July 2004). "Poor prognosis of arthritis-associated pyoderma gangrenosum". Arch Dermatol. 140 (7): 861–4. doi:10.1001/archderm.140.7.861. PMID 15262699.
  18. ↑ Agrawal S, Misra R, Aggarwal A (February 2007). "Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA". Clin. Rheumatol. 26 (2): 201–4. doi:10.1007/s10067-006-0275-5. PMID 16572283.
  19. ↑ Vencovský J, Machácek S, Sedová L, Kafková J, Gatterová J, Pesáková V, Růzicková S (May 2003). "Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis". Ann. Rheum. Dis. 62 (5): 427–30. PMC 1754544. PMID 12695154.

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