advances in identifying genetic and non genetic risk factors of rheumatoid arthritis l.
Skip this Video
Loading SlideShow in 5 Seconds..
Advances in identifying genetic and non-genetic risk factors of rheumatoid arthritis PowerPoint Presentation
Download Presentation
Advances in identifying genetic and non-genetic risk factors of rheumatoid arthritis

Loading in 2 Seconds...

play fullscreen
1 / 17

Advances in identifying genetic and non-genetic risk factors of rheumatoid arthritis - PowerPoint PPT Presentation

  • Uploaded on

Advances in identifying genetic and non-genetic risk factors of rheumatoid arthritis. Jessica Larson Advisor: Sam Powdrill, PA-C. Objectives. Review of epidemiology & pathophysiology of RA Understand functional impairment

I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
Download Presentation

PowerPoint Slideshow about 'Advances in identifying genetic and non-genetic risk factors of rheumatoid arthritis' - DoraAna

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
advances in identifying genetic and non genetic risk factors of rheumatoid arthritis

Advances in identifying genetic and non-genetic risk factors of rheumatoid arthritis

Jessica Larson

Advisor: Sam Powdrill, PA-C

  • Review of epidemiology & pathophysiology of RA
  • Understand functional impairment
  • Learn risk factors that determine the onset & severity in development of RA
  • Pre-RA red flags
  • How to advise patient in clinic to reduce or prolong outcome of RA
  • Most common inflammatory polyarthritis
  • One percent or 2.1 million adults in US
  • Women 2-3x more affected than men
  • Age of onset is 40-60 years old
  • Smokers 4x more likely to develop
  • First-degree relative prevalence rate is 2-3x more like to develop
  • Mortality is higher, in severe RA mortality approaches that of CHF or Hodgkin disease
pathophysiology review
Pathophysiology Review

functional impairment
Functional Impairment

functional impairment6
Functional Impairment

Morning stiffness

>1 hour

functional impairment7
Functional Impairment

Arthritis of >3

of the following joints:

PIP, MCP, wrist,

elbow, knee, ankle,

and MTP joints

functional impairment8
Functional Impairment


involvement of joints

functional impairment9
Functional Impairment

Rheumatoid nodules

functional impairment10
Functional Impairment

Positive serum

rheumatoid factor

functional impairment11
Functional Impairment

Radiographic changes

including erosions

or bony decalcification

risk factors13

HLA - DR complex

DR-1 & DR-4


HLA - I kappa BL



Neuroendocrine imbalances:

Low sex hormones

Low cortisol levels

Vascular endothelial alterations in men

Immunologic markers

Risk Factors
pre ra red flags
Pre-RA red flags

CCP antibody immunological markers appear many years (as many as 12) before onset of RA with increased risks if:

  • Smoking (>20 pack-years)
  • Coffee consumption (>10 cups/day)
  • Ever use of oral contraceptives
  • First-degree relative of schizophrenia
  • Obesity (3x risk)
  • Age of menarche >15 years old (2x risk)
what can pas do
What can PAs do?
  • If there is a family history of RA, it is especially important to NOT SMOKE
  • Anti-CCP test is a blood test that can be ordered by the PA
    • RF is ~81-87% specific post-onset
    • CCP is ~96% specific and available earlier
  • Tell them to stay active and loose weight
  • Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315-324.
  • Barrera P, et al. Noninherited maternal antigens do not increase the susceptibility for familial rheumatoid arthritis. European Consortium on Rheumatoid Arthritis Families (ECRAF). Rheumatol. 2001 May;28(5):968-74. PMID: 1136122
  • Berg L, Ronnelid J, Sanjeevi CB, Lampa J, Klareskog L. Interferon-gamma production in response to in vitro stimulation with collagen type II in rheumatoid arthritis is associated with HLA-DRB1(*)0401 and HLA-DQ8. Arthritis Res. 2000;2(1):75-84. PMID: 11219392
  • Combe B, Eliaou JF. Can the prognosis of early rheumatoid arthritis be predicted? Presse Med. 1995 May 20;24(18):839-41. PMID: 7638113
  • Cornelis F, Faure S, Martinez M, Prud’homme JF, Fritz P, Dib C, et al. New susceptibility locus for rheumatoid arthritis suggested by RA susceptibility genes in multicase families 915 a genome-wide linkage study. Proc Natl Acad Sci U S A 1998;95: 10746–50.
  • Costenbader KH, Feskanich D, Mandl LA, Karlson EW. Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am J Med. 2006 Jun;119(6):503.e1-9. )PMID: 16750964
  • Cutolo M, Villaggio B, Foppiani L, Briata M, Sulli A, Pizzorni C, Faelli F, Prete C, Felli L, Seriolo B, Giusti M. The hypothalamic-pituitary-adrenal and gonadal axes in rheumatoid arthritis. Ann N Y Acad Sci. 2000;917:835-43. Review. PMID: 11268413
  • Evans TI, Han J, Singh R, Moxley G. The genotypic distribution of shared-epitope DRB1 alleles suggests a recessive mode of inheritance of the rheumatoid arthritis disease-susceptibility gene. Arthritis Rheum. 1995 Dec;38(12):1754-61. PMID: 884934
  • Goronzy JJ, Weyand CM. Interplay of T lymphocytes and HLA-DR molecules in rheumatoid arthritis. Curr Opin Rheumatol. 1993 Mar;5(2):169-77. Review. PMID: 8452767
  • Geenen R, Van Middendorp H, Bijlsma JW. Related Articles, The impact of stressors on health status and hypothalamic-pituitary-adrenal axis and autonomic nervous system responsiveness in rheumatoid arthritis. Ann N Y Acad Sci. 2006 Jun;1069:77-97. PMID: 16855136
  • Harney S, Newton J, Milicic A, Brown MA, Wordsworth BP. Non-inherited maternal HLA alleles are associated with rheumatoid arthritis. Rheumatology (Oxford). 2003 Jan;42(1):171-4. PMID: 12509632)
  • Harris ED Jr. Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med 1990;322:1277–89.
  • Hutchinsona D, Shepstoneb L, et al., Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA, Ann Rheum Dis 2001;60:223-227
  • van der Horst-Bruinsma IE, Hazes JM, Schreuder GM, Radstake TR, Barrera P, van de Putte LB, Mustamu D, van Schaardenburg D, Breedveld FC, de Vries RR. Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis. Ann Rheum Dis. 1998 Nov;57(11):672-5. PMID: 9924209
  • van Jaarsveld CH, Otten HG, Jacobs JW, Kruize AA, Brus HL, Bijlsma JW. Is there an indication for HLA-DR typing for individual patients with rheumatoid arthritis? Clin Exp Rheumatol. 1998 Jul-Aug;16(4):483-8. Review. PMID: 9706434
  • Jawaheer D, Seldin MF, Amos CI, et. Al. Screening the genome for rheumatoid arthritis susceptibility genes: a replication study and combined analysis of 512 multicase families. Arthritis Rheum. 2003 Apr;48(4):906-16.
  • Jawaheer D, Seldin MF, Amos CI, Chen WV, Shigeta R, Monteiro J, et al. A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases. Am J Hum Genet 2001;68:927–36.
  • Kilding R, Wilson AG. Mapping of a novel susceptibility gene for rheumatoid arthritis in the telomeric MHC region. Cytokine. 2005 Oct 21;32(2):71-5. Epub 2005 Sep 30. Review. PMID: 1619916
  • Klareskog L, Padyukov L, Lorentzen J, Alfredsson L. Related Articles, Mechanisms of disease: Genetic susceptibility and environmental triggers in the development of rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Aug;2(8):425-33. Review.PMID: 16932734)
  • Matsumoto A. Rheumatoid arthritis, a clinical presentation. Johns Hopkins University website.
  • MacKay K, Eyre S, Myerscough A, Milicic A, Barton A, Laval S, et al. Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom. Arthritis Rheum 2002;46:632–9
  • Masi AT, Bijlsma JW, Chikanza IC, Pitzalis C, Cutolo M. Neuroendocrine, immunologic, and microvascular systems interactions in rheumatoid arthritis: physiopathogenetic and therapeutic perspectives. Semin Arthritis Rheum. 1999 Oct;29(2):65-81. Review. PMID: 10553979)
  • Masi AT, Aldag JC, Jacobs JW. Rheumatoid arthritis: neuroendocrine immune integrated physiopathogenetic perspectives and therapy. Rheum Dis Clin North Am. 2005 Feb;31(1):131-60, x. Review. PMID: 15639060)
  • Masi AT, Aldag JC. Integrated neuroendocrine immune risk factors in relation to rheumatoid arthritis: should rheumatologists now adopt a model of a multiyear, presymptomatic phase? Scand J Rheumatol. 2005 Sep-Oct;34(5):342-52. Review. PMID: 16234181)
  • Masi AT, Aldag JC, Chatterton RT. Sex hormones and risks of rheumatoid arthritis and developmental or environmental influences. Ann N Y Acad Sci. 2006 Jun;1069:223-35. Review. PMID: 16855149)
references cont
References (cont)
  • Mattey DL, Dawes PT, Gonzalez-Gay MA, Garcia-Porrua C, Thomson W, Hajeer AH, Ollier WE. HLA-DRB1 alleles encoding an aspartic acid at position 70 protect against development of rheumatoid arthritis.J Rheumatol. 2001 Feb;28(2):232-9. PMID: 11246655
  • Okamoto K, Makino S, Yoshikawa Y, Takaki A, Nagatsuka Y, Ota M, Tamiya G, Kimura A, Bahram S, Inoko H. Identification of I kappa BL as the second major histocompatibility complex-linked susceptibility locus for rheumatoid arthritis. Am J Hum Genet. 2003 Feb;72(2):303-12. Epub 2002 Dec 31.
  • Ollier W, Thomson W. Population genetics of rheumatoid arthritis. Rheum Dis Clin North Am 1992;18:741–59.
  • Pedersen M, Jacobsen S, Klarlund M, Pedersen BV, Wiik A, Wohlfahrt J, Frisch M. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides. Arthritis Res Ther. 2006;8(4):R133. PMID: 1687251
  • Scand J Rheumatol, HLA antigens in rheumatoid arthritis patients with and without a family history of polyarthritis.. 1985;14(4):375-80. PMID: 4081661
  • Stastny P. Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med 1978;298:869–71.
  • Stolt P, Bengtsson C, Nordmark B, Lindblad S, Lundberg I, Klareskog L, Alfredsson L; EIRA study group. Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from a population based case-control study, using incident cases. Ann Rheum Dis. 2003 Sep;62(9):835-41. Review. PMID: 12922955)
  • de Vries RR, Huizinga TW, Toes RE. Redefining the HLA and RA association: to be or not to be anti-CCP positive. J Autoimmun. 2005;25 Suppl:21-5. Epub 2005 Oct 27. Review. PMID: 16257178
  • Weyand CM, Klimiuk PA, Goronzy JJ. Heterogeneity of rheumatoid arthritis: from phenotypes to genotypes. Springer Semin Immunopathol. 1998;20(1-2):5-22.