Rheumatoid arthritis is a common autoimmune disease that causes inflammation in the joints. It can lead to joint damage, deformity, disability, and reduced life expectancy if left untreated. It is characterized by symmetric inflammation of small and medium-sized joints. Extra-articular manifestations can include lung, heart, eye, and skin involvement. Diagnosis is based on symptoms, laboratory tests for rheumatoid factor and anti-CCP antibodies, and imaging of affected joints. Early, aggressive treatment is important to prevent long-term damage.

1. RHEUMATOID ARTHRITIS
A COMMON
AUTOIMMUNE DISEASE
DIANA GIRNITA MD PhD
RHEUMATOLOGY
TRIHEALTH PHYSICIAN PARTNERS

2. Learning objectives
 Understanding the most common clinical
presentation of RA, laboratory testing and
differential diagnosis
 Understanding that RA is a systemic disease
with emphasis on the increased cardiovascular
risk
 Current treatment options in RA and the
importance of early aggressive treatment

3. RA chronic, systemic disease
◻ Rheumatoid arthritis (RA) is a symmetric,
inflammatory, peripheral polyarthritis
◻ If untreated, inflammation can lead to joint
destruction, deformity, significant disability and
shortened life expectancy.

4. Epidemiology
◻ Annual incidence: 30/ 100,000 persons
worldwide.
◻ Female predominance ( F: M is 5:1 < age 50)
◻ Can develop at any age
◻ Peak age of onset 30 to 55 years

5. PATHOGENESIS

6. Genetic Factors
◻ Account for 60% of an individual’s susceptibility to
RA
◻ HLA-DR genes (DR4, DR1, DR14) account for 30%
to 40% of genetic predisposition
◻ Genetic loci outside the MHC have been
associated with an increased risk
◻ Polymorphisms of PTPN22, TRAF1-C5, STAT4,
TNFAIP3, and PADI4

7. Hormones?
◻ Reduced risk in women who have had children/
breastfed > 1 year
◻ Disease activity often subsides during pregnancy
and flares postpartum

8. Environmental Factors
◻ Smoking the best characterized
environmental risk factor increases
the OR for developing RA 12-fold in
susceptible monozygotic twins, 2.5-
fold in dizygotic twins, and 1.8-fold in
smokers (>20 pack-yrs). This risk
persists for 10 to 20 years after a
person quits smoking.
◻ Periodontal disease
◻ Asbestos/ silica exposure
◻ Parvovirus/ EBV virus –low evidence

9. RF and CCP
◻ The presence of Rheumatoid factor (RF) or anti-
CCP (citric citrullinated peptides) antibodies in the
blood is associated with increased risk of RA
◻ RF is absent in 30% of patients with rheumatoid
arthritis; present in 10% of healthy individuals
◻ Anti-CCP antibodies are absent in 40% of patients
with the disease.

11. CLINICAL PRESENTATION

12. RA is a systemic disease
 Joints
 Heart
 Lungs
 Brain
 Bones
 Eyes
 GI
 Skin
 Kidney

13. “Classic” RA
◻ Symmetric, bilateral polyarthritis of small,
medium, and large joints
◻ Morning stiffness >1h
Most common joints affected in RA
Rheumatology secrets, 3rd ed, 2016

14. Symmetric, bilateral synovitis PIPs, MCPs

15. MCPs and PIPs synovitis
35yo F with
bilateral
MCP, PIPs
synovitis,
especially
2nd and 3rd
PIP
Personal library of RA patients

16. Symmetric deformities
40yo female
presented
with bilateral
MCP
synovitis and
“boutonniere
” deformity of
4th digit
Personal library of RA patients

17. RA-deformities of the hands
A.”Butonniere” deformity“
B. “Swan neck deformity” -
hyperextension of the PIP
and extension of the DIP
Kelleys’ Rheumatology Chapter 70, Clinical
RA

18. RA–late disease
Personal library of RA patients
“Butonniere” deformities in late RA
disease

19. Hands - Ulnar deviation
Rheumatolo
gy Image
bank-ACR
website

20. RA mutilans – late stage
Rheumatology Image bank-ACR website

21. RA nodulosis
Rheumatology Image bank-ACR website

22. Other forms of RA
◻ Palindromic rheumatism — episodic, one to
several joints affected sequentially for hours to
days, alternating with symptom-free periods
◻ Monoarthritis — Persistent single joint
arthritis (wrist, knee, shoulder, hip, or ankle)

23. RA extra-articular manifestations
Ocular
Brain
Heart
Pulmonary
GI
Renal
Skin

24. Extra-articular manifestations

25. Ocular involvement
Episcleritis Scleromalacia
Rheumatology Image bank-ACR website

26. Scleromalacia perforans –severe, uncontrolled RA
Personal library of RA patients

27. 78yo patient with longstanding RA. MRI of the brain showed diffuse
leptomeningeal enhancement over the right frontal and parietal lobes.
Leptomeningeal biopsy showed a granulomatous inflammatory reaction
(arrow) consistent with rheumatoid pachymeningitis.
Brain - Pachimeningitis
Rheumatology Image bank-ACR website

28. Cardiac involvement
Rheumatology Image bank-ACR website

29. Lung involvement –interstitial lung disease
52 YO M,
seropositive RA
who presented
with dyspnea
and hypoxemia.
Chest X-ray w/
increased
interstitial
markings with
volume loss and
tracheal
deviation.
CT scan-
honeycombing
and traction
bronchiectasis
consistent with
ILD associated
with RA.
Rheumatology Image bank-ACR website

30. RA pulmonary nodules
Rheumatology Image bank-ACR website

31. Caplan’s syndrome refers to a type of large nodule formation found in
lungs of patients, many of whom are coal miners with rheumatoid
arthritis (Multiple nodules (3 cm or more in diameter in both lungs).
The remaining pulmonary parenchyma demonstrates micronodularity
typical of pneumoconiosis and fibrosis. There is marked prominence of
RA-Caplan’s Syndrome

32. Skin involvement –vasculitis
Images demonstrates of the finger from a woman with RA complicated
by systemic vasculitis numerous ischemic lesions.
Note the swan-neck deformity from erosive RA.
Rheumatology Image bank-ACR website

33. Sternoclavicular Joint
Girnita DM- Case Report: Sternoclavicular Erosions in a Patient with Uncontrolled RA;
The Rheumatologist, December 17, 2015 issue

34. Renal involvement
Girnita DM et al. Case report: Rheumatoid Arthritis & Autoimmune
Glomerulonephritis; The Rheumatologist; June 13, 2016
 69-year-old African
American female with
25 years’ history of
seropositive, erosive
RA with nephrotic
syndrome and
worsening Cr.
 Renal Biopsy :
immune mediated
MPGN, no signs of
vasculitis

35. RA - DIAGNOSIS

36. ACR 2010 Criteria for RA Classification
RA>= 6/10
criteria
ARTHRITIS &
RHEUMATISM
Vol. 62, No. 9,
September 2010, pp
2569–2581

37. Imaging in RA

38. Plain XRAYs
◻ Marginal erosions
◻ Symmetric joint-
space narrowing
◻ Periarticular
osteopenia
◻ Baseline and every 2
years

39. RA at diagnosis and 10 years later
10 years later-progression of osteopenia,
development of ulnar deviation,
subluxation of MCP and loss of joint
space.
Rheumatology Image bank-ACR website
At diagnosis: juxtaarticular
osteopenia.

40. Feet involvement
 Marginal
erosions
 Osteopenia
 Lateral
deviation, and
subluxation of
all the MTPs
 Hallux valgus
Rheumatology Image bank-ACR website

41. Elbows and Knees
Elbow erosion Knee erosion
Rheumatology Image bank-ACR website

42. Ultrasound detects synovitis and early bone erosions.
Rheumatology Image bank-ACR website

43. MRI detects bone erosions earlier than Xrays
Rheumatology Image bank-ACR website

44. Cervical spine involvement
MRI cervical spine
demonstrating pannus
formation of the C1–C2
articulation (long arrow)
and impingement of the
odontoid on the spinal
cord (arrow).
Rheumatology Image bank-ACR website

45. Cervical Spine, Atlantoaxial Subluxation
The lateral radiograph in flexion
shows separation between the
anterior inferior aspect of C1
and the odontoid process of
greater than 2.5 mm.
Rheumatology Image bank-ACR website

46. Differential diagnosis
Spondylarthropaties -Ankylosing spondylitis,
psoriatic arthritis, inflammatory bowel disease,
reactive arthritis
CTD-SLE, Sjogren, scleroderma, sarcoidosis
Crystal induced arthritidis (CPPD, Gout)
Infections (Hepatitis B, C, HIV, parvovirus, Lyme,
bacterial endocarditis)
Polymyalgia rheumatica/Giant cell artheritis
Osteoarthritis

47. Rheumatoid arthritis vs Osteoarthritis

48. The significance of RF and anti-
CCP

49. Rheumatoid factor (RF)
 RF -70% to 80% with a specificity of 86% for RA
 High-titer RF appears to be a better predictor of a
severe disease course
 Stronger correlation with extraarticular manifestations
(ILD) and subcutaneous nodules, and with increased
mortality
 The RF titer does not correlate with disease activity so
it does not have to be repeated
 Positive RF - hepatitis C (40%), SLE (20%), Sjögren’s
syndrome (70%), and subacute bacterial endocarditis

50. High titer of RF more erosive disease
van Zeben D et al. Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of
a follow up study. Ann Rheum Dis. 1992;51(9):1029.
Numberoferosions

51. Anti-CCP better specificity than
RF
Nishimura K et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and
rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007 Jun 5;146(11):797-808.
Zeng X et al. Diagnostic value of anti-cyclic citrullinated Peptide antibody in patients with rheumatoid
arthritis. J Rheumatol. 2003;30(7):1451. Ann Rheum Dis. 2006 Jul; 65(7): 845–851.

52. Other autoimmune tests
 ANA: +30%; patients tend to have more severe
disease and a poorer prognosis;+ secondary
Sjögren’s syndrome.
 ANCA: usually negative. If it is positive, it should not
have specificity against PR3 or myeloperoxidase.
 Complement (C3, C4, CH50): normal or elevated. If
it is low, consider a disease other than RA.

53. Poor outcome/ severe disease
RF ;anti-CCP + and poor functional status at presentation
Generalized polyarthritis (small and large joints >13 joints)
Extraarticular disease(nodules and vasculitis)
Persistently elevated ESR or CRP; ANA +
Radiographic erosions within 2 years of disease onset
HLA-DR4 genetic marker
Education level <11th grade (frequently have a manual labor job
contributing to joint damage)

54. Increased cardiovascular risk in RA

55. US - Mortality Data
 1997, RA accounted for 22% of all
deaths due to arthritis and other
rheumatic conditions in the US
 40% of all deaths in RA patients are
due to CV causes (ischemic heart
disease, stroke, premature death)
Sacks JJ, Helmick CG, Langmaid G. Deaths from arthritis and other rheumatic conditions, United States, 1979-1998 1.
J.Rheumatol. 2004;31(9):1823-1828; Symmons DP, Gabriel SE. Epidemiology of CVD in rheumatic disease, with a focus
on RA and SLE. Nat Rev Rheumatol. 2011;7(7):399-408.

56. Wolfe F et al. The mortality in RA. Arthritis & Rheumatism; 37 (4) 481-494, 1994
Increased mortality in RA patients

57. Premature
atherosclerosis
MI, Stroke in RA
Roman MJ. Preclinical carotid atherosclerosis in patients
with RA Ann Intern Med. 2006;144:249-256.
Solomon DH et al, Circulation. 2003;107:1303-1307

58. Unrecognized MI in RA patients
Maradit-Kremers et al. Arthritis Rheum. 2005 Mar;52(3):722-32.

59. Increased risk of MI, stroke and CV death
in RA patients
Solomon DH et al. Ann Rheum Dis 2006; 65:1608-1612

60. Increased risk of Heart failure in RA
Nicola PJ et al. The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years.
Arthritis Rheum. 2005 Feb;52(2):412-20. Crowson C et al. ARTHRITIS & RHEUMATISM 2005(10:52), pp 3039–3044

61. TREATMENT IN RA

62. Early, aggressive treatment is the key in RA
 Once the diagnosis of RA is established, all patients
(with rare exception) should begin DMARD therapy
 Bone erosions and joint space narrowing develop
within the first 2 years of disease in most patients
and are progressive from that point onward
 Patients with evidence of active disease (synovitis,
morning stiffness, etc.), bony erosions or deformities,
or extraarticular disease

63. DMARD
(disease modifying anti-rheumatic drugs)
 Drug must change the course of the disease for
at least 1 year as evidenced by
 sustained improvement in physical function
 decreased inflammatory synovitis
 slowing or prevention of joint destruction

64. DMARDs

65. Abbas AK et al, Basic Immunology: Functions and Disorders of the Immune System

67. Cytokine-
targeted
therapies
TNF
inhibitors
Etanercept, Infliximab,
Adalimumab, Golimumab,
Certolizumab
IL-1 inhibitors Anakinra
IL-6 inhibitors Tocilizumab, Sarilumab
IL12/23
IL-17
Ustekinumab
Secukinumab, Ixekizumab
Jak inhibitors Tofacitinib, Baricitinib
B-cell targeted
therapies
Rituximab (anti-CD 20)
B cell growth factor inhibitors: Belimumab
T-cell targeted
therapies
Abatacept (anti-CD80/ 86)

68. TNF alpha -inhibitors

69. IL-6 inhibitors (Tocilizumab)

70. JAK inhibitors (Tofacinib)
Koenders MI et al.Novel therapeutic targets in rheumatoid arthritis, Trends in Pharmacological Science,
2015, vol36:4, p189-195

71. T cell targeted therapy (Abatacept)

72. B-cell targeted therapy
(Rituximab)

73. 2015 ACR
guidelines
for RA
treatment
Singh JI et al, Arthritis Care & Research
2015, American College of Rheumatology

74. Wheel of empiric therapy
Kelley's Textbook of Rheumatology, 9th edition, Treatment in RA

75. Triple therapy HCQ+SSZ+MTX
 Improved disease
activity of triple
therapy vs
monotherapy

76. TEAR trial - Etanercept vs triple therapy
Moreland LW et al. A randomized comparative effectiveness study of oral triple therapy vs
etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment
of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum. 2012 September ; 64(9): 2824–2835.

77. PREMIER trial- Adalimumab+methotrexate is
superior to either alone
Breedveld FC, Weisman MH, Kavanaugh AF, et al: A multicenter, randomized, double-blind clinical trial of
combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in
patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment, Arthritis
Rheum 54:26–37, 2006

78. Effect of Biologic therapies in RA

79. Targeted therapies changed the
course of RA
No
deformities
No
synovectomies/
splinting
Resolution
of nodules
Less RA
lung
Less
Mortality
from CVD
Low
incidence of
lymphoma

80. The role of the PCP
PCP
Rheumatologi
st
Patient
Recognize disease early, early
referral
Monitor and aggresively treat CV
risk factors
Monitor and treat osteoporosis
Immunization prior DMARDs/ biologics
Recognize side effects from
medication

81. Rheumatoid arthritis: SUMMARY
 Autoimmune disease -SYSTMIC effect (joints, heart,
lung, eyes, etc)
 RF and CCP are helpful in diagnosis, but remains a
CLINICAL diagnosis
 Treatment needs to start early and had been proven
to help restore the functional capacity of patients
 Targeted therapies have changed the course of
Rheumatoid arthritis
 Arthritis foundation website www.arthritis.org

82. THANK YOU!