This document discusses rheumatoid arthritis (RA), including its etiology, classification criteria, clinical features, diagnostic testing, complications, and treatment approaches. RA is a chronic inflammatory disorder that primarily involves synovial joints, with symmetric involvement of hands/feet typically seen. Diagnosis relies on clinical exam showing inflamed joints and laboratory tests like rheumatoid factor and anti-CCP antibodies. If left untreated, RA can cause long-term joint damage and functional disability. Treatment involves medications like NSAIDs, DMARDs, steroids, and biologics to reduce inflammation and prevent structural damage.

1. Puneet Bajaj, M.D., M.P.H.
Assistant Professor of Medicine
Rheumatic Diseases Division

2. RA is a chronic, systemic, inflammatory disorder of unknown etiology
that primarily involves synovial joints

3.  Hereditary
 Environmental
Triggers:
 Eg, cigarette
smoking,
infection, or
trauma

4. • Inflammatory synovitis
• Palpable synovial swelling or tenderness
• Morning stiffness >1 hour
• Symmetrical and polyarticular
• Typically involves wrists, MCP, and PIP joints
• Typically spares certain joints
▪ Thoracolumbar spine
▪ DIPs of the fingers and IPs of the toes

5.  2010 ACR-EULAR
Classification
Criteria for RA
 A score of ≥6/10 is
needed for
classification of a
patient as having
definite RA

6.  Prominent ulnar
deviation in the right
hand
 MCP and PIP
swelling in both
hands
 Synovitis of left wrist

7.  Soft synovial swelling
 Synovitis and volar
subluxation at the
MCP joints
 Synovitis of the wrists
 Early swan neck
deformities

8.  Rheumatoid nodules
 Felty’s syndrome (neutropenia, splenomegaly)
 Rheumatoid vasculitis
 Eye:
 Episcleritis
 Scleritis (pain, tenderness, photophobia)
 Interstitial lung disease
 Amyloidosis (long-standing poorly controlled
dz)
 RA is independent risk factor for CAD

9. • RF (IgM against the Fc portion of IgG)
• Specificity approx. 80%
• 45% positive in first 6 months
• 85% positive with established disease
• Not specific for RA
• Hep C (mixed cryoglobulinemia)
• Sjögren syndrome
• SLE
• May be present in up to 10% of healthy persons
• Anti-CCP antibodies
• more specific – 95%

10.  Xrays
 Periarticular
osteopenia
 Erosions
 Symmetric
joint-space
narrowing
 MRI & US are more
sensitive to dx
synovitis &
erosions.

11. • Long-standing rheumatoid arthritis
• May have NO symptoms
• Manipulation under anesthesia can cause
spinal cord injury
• Flexion and extension X-rays of the C spine
Klippel. Primer on Rheum Dis. 13th edition. 2008:114

12. • Damage occurs early in most patients
• 50% show joint space narrowing or erosions in the
first 2 years
• By 10 years, 50% of young working patients are
disabled

13. • Assess current activity
• Morning stiffness, synovitis, ESR/CRP
• Degree of damage
• X-rays: Joint space narrowing and erosions
• Functional status
• Assess prior Rx responses and side effects

14. • Education
• Educating the patient about their disease
• Exercise/Physical Therapy
• Vaccination
• Influenza and pneumococcal vaccines are advised.
• Live vaccines
• should be avoided in patients on biologic therapies
• considered safe with nonbiologic DMARDs and low-dose
prednisone
2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic
drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res, 64: 625–639.

15. • NSAIDs
• Not DMARDs
• Low-dose prednisone (10 mg qd)
• May substitute for NSAID
• Used as bridge therapy
• Intra-articular steroids
• Useful for flares

16. • Disease modifying drugs (DMARDs)
• Sulfasalazine, hydroxychloroquine
▪ May use in patients with low dz activity
• Methotrexate/Leflunamide
▪ MTX is the gold standard therapy
• Triple Therapy
• HCQ, SSZ & MTX
• Cyclophosphamide
▪ Effective for vasculitis, less so for arthritis
Klippel. Primer on Rheum Dis. 13th edition. 2008:133.

17. • Anti-TNF drugs (First line biologics)
• Infliximab
• Etanercept
• Adalimumab
• Golimumab
• Certolizumab pegol
• Side Effects of anti-TNF agents.
• Infections (Hep B/TB reactivation)
• CHF exacerbation
• Demyelinating dz
• Drug induced lupus

18. • Tocilizumab – IL6 inhibitor
• Increase lipids, GI perforation, HZ reactivation,
improve anemia.
• Abatacept – inhibits T cell co-stimulation
• COPD exacerbation
• Tofacitinib – interferes with JAK-STAT
pathway
• Increase lipids, HZ reactivation
• Rituximab – anti CD 20
• Risk for developing PML

19.  Most women demonstrate clinical improvement
during pregnancy
 Flares are common during the postpartum period
 MTX must be discontinued 3 mths prior to
conception.
 Leflunomide must be discontinued 2 yrs prior to
conception
 cholestyramine may be used to hasten the elimination.
 SSZ can cause reversible oligospermia; men should
discontinue it for 3 months prior to conception
 HCQ & SSZ are often used during pregnancy.

21.  A 32 YO woman seeks preconception counseling. She
was diagnosed with RA 1 year ago. She has no other
pertinent personal or family medical history. Disease
activity is controlled with methotrexate. She also
takes FA.
 On PE, vital signs are normal. On MSK examination,
there is no synovitis or bony abnormalities. The
remainder of the examination is normal.
 Laboratory studies, including ESR and CRP level, are
normal; RF and anti-CCP antibodies are positive.
Urine pregnancy test results are negative.
 Radiographs of the hands, feet, & C spine are normal.

22.  Which of the following is the most appropriate
management?
A. Discontinue methotrexate before conception
B. Discontinue methotrexate when conception is
confirmed
C. Maintain methotrexate through pregnancy at
current dose
D. Maintain methotrexate through pregnancy
with dose adjustment
 Women with RA who are taking MTX must
discontinue it 3 months before conception.

23.  A 52 YO man is evaluated for an 8-week history of
pain and 2 hours of morning stiffness of the hands
that improves with activity. The patient has no
pertinent personal or FH. He takes no medications.
 On PE, vital signs are normal. Synovitis is noted at the
MCP joints of the second through fifth digits
bilaterally with swelling, tenderness, and pain on
range of motion. The remainder of the examination is
normal.
 Laboratory studies, including CBC, chemistries, LFTs,
TSH, CRP, and UA, are normal; ESR is 13 mm/h, and
RF is negative. Parvovirus serology results are
negative.
 Radiographs of the hands are normal.

24.  Which of the following antibody assays is
most helpful in establishing this patient's
diagnosis?
A. Anti–cyclic citrullinated peptide antibodies
B. Antimitochondrial antibodies
C. Antineutrophil cytoplasmic antibodies
D. Antinuclear antibodies
 RF may be negative in early RA. Anti–CCP
antibodies are a highly specific marker for RA.

25.  A 64YO man is evaluated during a routine f/u visit for a 5-year h/o RA.
Four months ago, he began IV tocilizumab to manage synovitis that was
not responding to treatment with etanercept; his last infusion was
administered 2 weeks ago. The patient also has hypertension. FH is
notable for his father, brother, and uncle with coronary artery disease.
Other medications are enalapril, HCTZ, methotrexate, prednisone, and
naproxen as needed.
 On PE, temperature is 37.0 °C (98.6 °F), BP is 130/84 mm Hg, pulse rate is
80/min and regular, and RR is 16/min. Auscultation of the heart and lungs
is normal, and no edema is present. No synovitis is present on MSK
examination. The remainder of the examination is unremarkable.
 Laboratory studies performed before each infusion reveal normal CBC,
LFTs, and serum creatinine levels. A lipid profile obtained 6 months ago
revealed a total cholesterol level of 180 mg/dL (4.7 mmol/L) and a LDL
cholesterol level of 98 mg/dL (2.5 mmol/L).
 Results from a tuberculin skin test obtained before starting tocilizumab
treatment were negative.

26.  Which of the following is the most
appropriate test to perform next?
A. Echocardiography
B. Electrocardiography
C. Lipid profile
D. Serum aminotransferase levels
E. Serum immunoglobulin levels
 Periodic monitoring for changes in lipid status
is indicated for patients receiving
tocilizumab.

27.  A 42 YO man is evaluated for morning stiffness of the
wrists lasting up to 1 hour. He was diagnosed with RA
4 months ago and was started on methotrexate and
titrated to maximum dose 3 months ago with partial
response. He also takes prednisone as needed for joint
pain and FA daily.
 On PE, vital signs are normal. MSK examination
reveals swelling, tenderness, and pain on range of
motion of the wrists. No rash or joint deformities are
noted. The remainder of the examination is normal.
 Laboratory studies reveal a CRP of 3.1 mg/dL; anti–
CCP antibodies are positive.

28.  Which of the following is the most
appropriate treatment?
A. Add adalimumab
B. Discontinue folic acid
C. Discontinue methotrexate; begin infliximab
D. Discontinue methotrexate; begin
sulfasalazine
E. Maintain current regimen
 Use of methotrexate with a TNF α inhibitor is
associated with further reductions in disease
activity and radiographic progression

30.  Age: 75% of persons over age 70 have OA
 Female sex
 Obesity (most important modifiable risk
factor)
 Hereditary
 Trauma
 Neuromuscular dysfunction
 Metabolic disorders

31.  Pain is related to use
 Pain gets worse during
the day
 Minimal morning
stiffness (<20 min) and
after inactivity
 Range of motion
decreases
 Joint instability
 Bony enlargement
 Crepitus
 Variable swelling
and/or instability

32.  Primary OA typically
involves variable
number of joints in
characteristic
locations, as shown

34. Oxford Textbook
of Medicine

35.  No specific tests
 No associated laboratory abnormalities;
eg, sedimentation rate

36.  Joint space
narrowing (medial is
more common)
 Marginal
osteophytes
 Subchondral cysts
 Bony sclerosis
 Malalignment

37.  Radiograph shows
severe changes
 Most common
location in hand
 May cause
significant loss of
function

38.  X-ray shows
osteophytes,
subchondral
sclerosis, and
complete loss of
joint space
 Patients often
present with deep
groin pain that
radiates into the
medial thigh

39. • Consider secondary causes of OA
• Previous trauma and/or overuse
• Neuromuscular disease, especially diabetic or
other neuropathies
• Metabolic disorders,
• CPPD (calcium pyrophosphate deposition disease)
• Hemochromatosis
• MCPs with hook like osteophytes
• Order iron studies
• Genetic tests: HFEmutations (C282Y)

40.  Hemochromatosis
 Hyperparathyroidism
 Hypothyroidism
 Hypophosphatasia
 Hypomagnesemia

41.  Flares of joint
inflammation involve
PIP & DIP joints
 Associated with
erythema, swelling, &
severe pain.
 Radiographs reveal
erosions of these joints
(Sea gull appearance)

42. • Goal: decrease pain to increase function
• Progressive exercise to
• Increase function
• Increase endurance and strength
• Reduce fall risk
• Patient education:
• Weight loss
• Heat/cold modalities

43.  Use of a cane can significantly unload a knee /hip
& improve gait, mobility, & pain.
 Proper Positioning
 Placed in the hand contralateral to the symptomatic
joint.
 The top of your cane should reach to the crease in
your wrist when you stand up straight.
 Elbow should bend a bit (10-15 deg.) when holding the
cane.
 Walking
 Cane & injured leg swing & strike the ground at the
same time.

44.  Nonopioid analgesics
 Topical agents
 Intra-articular agents
 Opioid analgesics

45. • Surgery
• Arthroscopy
• Osteotomy
• Total joint replacement
• Decision is based on the patient's sx & quality
of life, rather than the radiographic severity

47.  A 76 YO woman is evaluated for a 3-month history of left knee pain
of moderate intensity that worsens with ambulation. She reports
minimal pain at rest & no nocturnal pain. There are no clicking or
locking symptoms. She has tried naproxen and ibuprofen but
developed dyspepsia; acetaminophen provides mild to moderate
relief. The patient has HTN, HLD, and chronic stable angina.
Medications are lisinopril, metoprolol, simvastatin, low-dose
aspirin, and nitroglycerin as needed.
 On PE, VS are normal. BMI is 32. ROM of the left knee elicits
crepitus. There is a small effusion without redness or warmth &
tenderness to palpation along the medial joint line. Testing for
meniscal or ligamentous injury is negative.
 Lab studies, including CBC & ESR, are normal.
 Radiographs of the knee reveal medial tibiofemoral compartment
joint-space narrowing and sclerosis; small medial osteophytes are
present.

48.  Which of the following is the next best step in
management?
A. Add celecoxib
B. Add glucosamine sulfate
C. MRI of the knee
D. Weight loss and exercise
 Obesity is the most important modifiable risk
factor for knee OA.

49.  A 58 YO man is evaluated for a 6-year history of
hand pain accompanied by morning stiffness
lasting 30 minutes & a 2-year history of bilateral
hip pain. He takes naproxen, which moderately
relieves the pain.
 On PE, VS are normal. There is tenderness of
both wrists and the MCP joints and pain on
flexion and internal rotation of the hips. The
wrists and hips have limited range of motion.
 Radiographs reveal joint-space narrowing at the
hips, MCP joints, and proximal interphalangeal
joints; osteophytes are seen at the MCP and hip
joints.

50.  Which of the following tests is likely to
confirm diagnosis?
A. Antinuclear antibody assay
B. Rheumatoid factor
C. Serum transferrin saturation
D. Serum uric acid level
 Secondary OA involving the MCP joints
should specifically raise suspicion for
hemochromatosis.

51.  A 72 YO woman is evaluated for a 6-month history of increasing
pain and swelling of the hands and fingers associated with a 20-
year history of OA. The pain is worse with activity, and she now
has difficulty opening jars and buttoning her shirt. She states
that diclofenac no longer provides relief.
 On PE, temperature is 37.0 °C (98.6 °F), BP is 148/78 mm Hg,
PR is 88/min, and RR is 18/min. MSK exam reveals bilateral firm
swelling and tenderness of the second and third proximal IP
joints. The left third distal IP joint is swollen and red. The
remainder of the examination is unremarkable.
 Laboratory studies reveal an ESR of 36 mm/h.
 Radiographs of the hands reveal joint-space narrowing of the
proximal and distal IP joints with multiple osteophytes; erosive
changes of the distal IP joints are noted.

52.  Which of the following is the most likely
diagnosis?
A. Erosive hand osteoarthritis
B. Psoriatic arthritis
C. Rheumatoid arthritis
D. Tophaceous gout
 Erosive hand OA involves proximal and distal
IP joints that are associated with erythema,
swelling, and severe pain. Erosions in DIPs
should raise suspicion for erosive OA or PsA.

53.  American College of Rheumatology (ACR)
 ACR: Image Bank
 ACR: Rheum2Learn
https://www.rheumatology.org/education/tra
ining/Rheum2Learn.asp
 Primer on Rheumatic Diseases
 ACP – MKSAP 16