Rheumatoid Arthritis

"Rheumatoid arthritis is a chronic systemic

inflammatory disorder of unknown cause that
primarily affects the synovial joints. It is
characterized by persistent symmetric
polyarthritis, leading to joint destruction,
deformity, and loss of function."
Classification according to duration
• Early RA
Duration: Less than 6 months
Emphasis is on early diagnosis and treatment to prevent joint damage.
Disease may still be evolving—prognosis may improve with early
intervention.

• Established RA
Duration: More than 6 months
Persistent inflammation and symptoms, with higher risk of joint erosion
and deformities.
May show more definite radiographic and serologic features.

• Chronic RA (also commonly referred to in clinical context)

Often used for long-standing disease, typically beyond several years
Associated with significant structural damage and possible extra-articular
involvement.
✅ Joint Involvement in RA (Commonly Involved):
[Link] joints of the hands:
• Metacarpophalangeal (MCP) joints
• Proximal interphalangeal (PIP) joints
• Wrist joints (radiocarpal and intercarpal)
[Link] joints of the feet:
• Metatarsophalangeal (MTP) joints
[Link] joints (later in disease):
• Knees
• Elbows
• Shoulders
• Ankles
• Hips
[Link] spine (especially C1-C2 articulation)
❌ Joints Not Typically Involved in RA:
[Link] interphalangeal (DIP) joints of the fingers
These are more commonly affected in osteoarthritis and
psoriatic arthritis
[Link] spine
Rarely involved in RA (unlike ankylosing spondylitis,
which affects the sacroiliac joints and lumbar spine)
[Link] joints
 Pathogenesis
1. Genetic Predisposition
HLA-DR4 and HLA-DR1 alleles (MHC class II) are strongly associated.
These genes contribute to antigen presentation and T-cell activation.
2. Environmental Triggers
Smoking is the strongest known environmental risk factor.
Other possible triggers: microbial antigens (e.g., Porphyromonas gingivalis in periodontitis).
3. Autoimmunity Activation
Loss of tolerance to self-antigens (e.g., citrullinated peptides).
Autoantibodies produced:
Rheumatoid Factor (RF): IgM antibody against the Fc portion of IgG.
Anti-cyclic citrullinated peptide (anti-CCP) antibodies: more specific for RA.
4. Role of T cells and Cytokines
CD4+ T helper cells (especially Th1 and Th17) are activated in synovium.
These cells release cytokines:
TNF-α, IL-1, IL-6 → promote inflammation.
IL-17 → recruits neutrophils, amplifies synovial inflammation.
✅ Components of DAS-28:
It includes the following four parameters:
Tender Joint Count (TJC28)
Out of 28 joints
Swollen Joint Count (SJC28)
Out of 28 joints
Patient's Global Health Assessment (GH)
On a Visual Analogue Scale (VAS), usually 0–100 mm
Erythrocyte Sedimentation Rate (ESR) or C-Reactive Protein (CRP)

DAS-28 Score Disease Activity Level

> 5.1 High disease activity
3.2 – 5.1 Moderate disease activity
2.6 – 3.2 Low disease activity
< 2.6 Remission
✅ ACR/EULAR Boolean-Based Remission Criteria (2011):
A patient is considered to be in remission if all of the following 4 conditions are
met:
Tender Joint Count (TJC28) ≤ 1
Swollen Joint Count (SJC28) ≤ 1
C-Reactive Protein (CRP) ≤ 1 mg/dL
Patient Global Assessment (PtGA) ≤ 1 (on a 0–10 scale)

🔍 Notes:
These criteria use 28-joint counts (TJC28 and SJC28).
Patient Global Assessment reflects how the patient feels about their disease
activity.
If any one of the above is >1, the patient does not meet Boolean remission
criteria.

📌 Why Use Boolean Criteria?

They are more strict and precise.
Ensure near-complete control of disease activity.
May be harder to achieve, but align better with true remission (especially in
clinical trials).
**Undifferentiated Arthritis or UA) refers to:
A condition where a patient has clinical signs of inflammatory arthritis
but does not fulfill the full classification criteria for any specific rheumatic
disease like RA, SLE, or PsA.
•May have joint pain, stiffness, mild swelling
•May have positive or negative RF or anti-CCP
•Often involves 1–2 joints, or atypical presentation
•No erosions, systemic symptoms, or symmetric polyarthritis yet
🔄 Possible Outcomes of Undifferentiated RA:
1. ✅ Remission or Resolution (~30–50%)
Spontaneous remission is possible, especially in:
Seronegative cases (RF and anti-CCP negative)
Low inflammation (normal ESR/CRP)
Short symptom duration
Mild or monoarticular joint involvement

2. 🔁 Persistent Undifferentiated Arthritis

The disease stays active but does not evolve into a well-defined diagnosis.
Patient continues to have non-specific arthritis.

3. ❌ Progression to Rheumatoid Arthritis (RA) (~30–50%)

More likely if:
RF and/or anti-CCP positive
Multiple joint involvement, especially small joints
Elevated ESR/CRP
Morning stiffness > 30 minutes
Joint symptoms lasting > 6 weeks
Factor Risk of Progression
Positive anti-CCP antibody High ↑↑
Positive Rheumatoid Factor Moderate ↑
Synovitis on Ultrasound/MRI High ↑↑
Elevated ESR/CRP Moderate ↑
Small joint involvement Moderate ↑
Smoking Moderate ↑
Early treatment with DMARDs Reduces risk ↓
 🔍 Clinical Features of Rheumatoid Arthritis (RA)

🦴 1. Articular (Joint) Manifestations

✅ Key Features:
Symmetric polyarthritis (hallmark feature)
Most commonly affects:
Small joints: MCP, PIP, MTP
Wrists, elbows, shoulders, knees, ankles
DIP joints typically spared
⏰ Morning stiffness > 1 hour
Improves with activity, worsens with rest
🔄 Joint swelling, tenderness, warmth
Persistent synovitis may lead to deformities
🦴 Common Joint Deformities in Chronic RA:
Ulnar deviation
Swan neck deformity
Boutonnière deformity
Z-line deformity of the thumb
 Extra-articular menifestation
System Manifestation

Rheumatoid nodules (usually over

Skin
pressure points like elbows)

Keratoconjunctivitis sicca (part of

Eyes
secondary Sjögren’s)
Interstitial lung disease, pleural
Lungs
effusion, nodules
Pericarditis, increased risk of
Heart
atherosclerosis
Anemia of chronic disease, Felty’s
Hematologic syndrome (RA + splenomegaly +
neutropenia)

Peripheral neuropathy, entrapment

Nervous system
syndromes (e.g., carpal tunnel)

Rare but serious; affects skin, nerves,

Vasculitis
organs
Investigation Purpose/Findings
Positive in 70–80% of RA
Rheumatoid Factor (RF)
cases (not specific)
Specific for RA, correlated
Anti-CCP antibodies with severe disease
Reflects inflammation;
ESR / CRP elevated in active disease
Anemia of chronic disease,
CBC thrombocytosis
Joint erosions, soft tissue
X-rays swelling, joint narrowing
Detect synovitis, effusions,
Ultrasound / MRI early erosions
Cloudy fluid with elevated
Synovial Fluid Analysis WBCs, low glucose (no
crystals)
Genetic marker; associated
HLA-DR4 with RA but not diagnostic
Treatment Purpose Common Side Effects
GI ulcers, renal toxicity,
NSAIDs Symptomatic relief
cardiovascular risk
Weight gain,
Corticosteroids Acute flare management hyperglycemia,
osteoporosis, infections

Methotrexate Disease-modifying, slows Bone marrow suppression,

RA liver toxicity, lung disease
Retinopathy, GI upset, skin
Hydroxychloroquine Disease-modifying, mild RA rash

TNF inhibitors Biologic, reduce Increased infections,

inflammation lymphoma, heart failure
Biologic, reduce Liver toxicity, infections, GI
IL-6 inhibitors
inflammation upset

JAK inhibitors Oral DMARDs, target Infections, blood count

cytokines abnormalities, blood clots
 Treatment Regimen

[Link]+Steroid
[Link]+Steroid+Hydroxychloroquine/Salfasalazine/Both+Low dose
7.5mg Steroid every morning
[Link]+Biologics
[Link]+JAK-I

**Biologics- **JAK-I
•Etanercept •(Enbrel)
Tofacitinib
•Infliximab (Remicade)
•Baricitinib
•Adalimumab (Humira)