Rheumatoid Arthritis

Dr (Brig) YD Singh
MBBS, MD (Medicine), FIACM, DIT

Professor & Head, unit of Medicine,

Faculty of Medicine, AIMST University
 Rheumatoid arthritis (RA) : Introduction
• Chronic inflammatory polyarthritis
– Autoimmune disorder
– Intermittent & relapsing course
• Attacks mainly synovial joints
– Destroying them by chronic inflammatory processes
• Development of deformities of joints
• Has many extra articular manifestations
• Early diagnosis essential to prevent deformities
– DMARDs (Diseases Modifying Anti Rheumatoid
Drugs) are available
– More potent drug available (Monoclonal antibodies)
• RA is NOW a Treatable Disorder !!

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 RA: Genetic & Risk Factors
• Genetic risk factors
– Seen 2 to 4 times more in first degree relatives
– Strong association with HLA-DR4
• Patients with DR4 tend to have severe disease
• Non genetic risk factors
– Male to Female ratio 1:3
– Chronic gingivitis by Porphyromonas gingivalis
• Causes persistent low-grade inflammation and alteration in
citrullination of our mucosal proteins
• Citrullination = conversion of amino acid Arginine to
Citrulline using enzyme called peptidyl-arginine-de-iminase
(PADI) ( present in bacteria P. Gingivalis)
• Finally, immune response triggered through production of
Anti- Citrullinated Protein Antibody (ACPA) = key player in
pathogenesis of RA

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 RA : Epidemiology & Aetiology

• Disease prevalence 0.8% (0.3 to 2.1%)

– All racial groups affected
– Peak age of onset 30 to 50 years
• Aetiology
– Exact cause of RA is not known
– Autoimmune disorder
– It seems to involve a complex interplay between
genetic factors, environmental triggers, and
stochastic factors
• Infectious agents or their products have been implicated
without conclusive evidence

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 RA : Pathogenesis (01)
• Synovium is primary site of inflammation
• Pathogenesis is a step-wise evolution of
disease in phases spread over several years
– Pre-articular phase (>10 years)
– Transition phase
• To clinically detectable Articular inflammation
– Finally self perpetuating cycle of chronic synovitis
• Associated with cartilage & bone damage and
• Extra-articular features
– TNF-α (produced by synovial macrophages) is
master cytokine = triggers an inflammatory cascade
• Imbalance between pro- and anti-inflammatory cytokines is
an important mechanism of self-perpetuating chronic
inflammatory synovitis in RA

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 RA : Pathogenesis (02)

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 RA : Pathogenesis (03)

Cytokine imbalance in Rheumatoid joint

with preponderance in proinflammatory cytokines
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 RA : Pattern of Onset
• Most common onset of symptoms of joint pains
and swelling = insidious
– Evolving slowly in a fluctuating manner, over weeks
to months
• Starts as Oligoarthritis (<5 joints) & becomes Polyarthritis
• Most common Bilateral symmetrical small joints hands/ feet
• Much less commonly = sudden explosive onset
of polyarthritis within a few days
• Least common “Palindromic Rheumatism”
– Transient self-limited episodes of mono- or
polyarthritis lasting days to weeks
• Nearly 50% of such patients evolve into RA over time
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 RA : Joints Involvement pattern
• Early disease = most commonly
– Metacarpophalangeal (MCP) joints, Interphalangeal
(IP) joints of thumbs, Proximal Interphalangeal (PIP)
joints of fingers, Wrists, Mid-foot joints & Meta-
tarsophalangeal (MTP) joints affected in that order
– May involve TMJ / C1-2 articulation
• Spares DIP joints (involved in OA & psoriatic arthritis )
• Spares rest of spine
– Soft swelling on dorsum of wrist due to tenosynovitis
is an early sign
• Pain, swelling, morning stiffness – improves as
day progresses
• Main target in RA are 14 joint-groups namely
– MCP, PIP, Wrist, Elbow, Knee, Ankle and MTP
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 RA: Clinical Features
• Clinical features of RA can be divided as
– Articular
– Para-articular
– Extra-articular features
• Articular features usually present as
– Symmetrical, small joints, inflammatory, additive,
polyarthritis affecting wrists and small joints of
hands and feet
• Para-articular features
– Common manifestation = Tenosynovitis in tendon
sheaths around wrists & in hands
• Major cause of hand weakness &
• Carpal tunnel syndrome
• Extra- Articular features
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 Signs of RA in the hands/wrist

• Synovitis involving the wrists,metacarpo-

phalangeal and proximal inter- phalangeal
joints with sparing of the distal
interphalangeal joints.
• Ulnar deviation of fingers (subluxation
/dislocation at the MCP joints).
• Swan neck deformity: hyperextension of PIP
joints with flexion of MCP and DIP joints.

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 Various Joints Deformities in RA
• Progressive disease causes
– Progressive structural damage leading to deformity,
subluxation, & ankylosis / disintegration of joints
• Deformities seen in established RA
– ‘Ulnar deviation’ = at MCP joints
• Subluxation /dislocation at the MCP joints
– ‘Swan-neck’ deformity
• Characterised with flexion of DIP and MCP joints with
hyperextension of PIP joint
– ‘Boutonnière deformity’
– ‘Z’ deformity of thumb
– Subluxation of distal Radio-ulnar joint
– ‘Cock-up’ toe deformity
– Hammer toes and
– ‘Rocker bottom’ deformity
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 Clawed fingers in RA

Boutonniere deformity

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 Ulner deviation of fingers
at MCP joints

‘Swan-neck’ deformity of
the fingers

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 Deformities in Rheumatoid Arthritis

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 Hallux valgus deformity

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 Triggering of fingers

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 Physical Exam of Hand in RA

• Decreased grip strength

• Tenosinovitis
• Boxing glove edema
• Boutonniere deformity
• Swan neck deformities
• Carpal tunnel
• Ulnar deviation
• Extensor tendon rupture

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 Rheumatoid nodules
• Common at sites of pressure
– Extensor aspect elbows, wrists, achilles tendon,
fingers, occiput area scalp
– Often unilateral
• Associated with more severe disease
• Always Rheumatoid factor positive

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 Extra-articular manifestations (01)
• General = Low grade fever, Lymphadenopathy
– Weight loss, Fatigue, Xerostomia (parotids involved)
• Dermatologic = Palmar erythema, Nodules
– Vasculitis, Raynaud’s phenomenon
– Pyoderma gangrenosum
• Ocular = Episcleritis/ Scleritis
– Scleromalacia perforans, choroid and retinal nodules
– Kerato-conjunctivitis sicca
• Due to Lacrimal gland involvement
• Lungs: Pl effusion, Rheumatoid nodule
– Interstitial lung disease, Bronchiolitis obliterans
• Kidneys: Secondary amyloidosis
– May cause Nephrotic syndrome
– NSAID toxicity
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 Xerostomia (Dry Mouth)

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 Rheumatoid Vasculitis

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 Raynaud’s Phenomenon

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Pyoderma gangrenosum on the lower leg

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 Xerophthalmia (Dry Eyes)

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 Scleritis

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 Pleural Effusion

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 Interstitial Lung Disease in RA

Rheumatoid nodule in the lungs

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 Extra-articular manifestations (02)

• Cardiac
– Pericarditis, Myocarditis, Coronary vasculitis,
nodules on valves
• Neuromuscular
– Entrapment neuropathy, peripheral neuropathy,
mononeuritis multiplex
• Hematologic
– Felty’s syndrome, Lymphomas
• Others
– Sjogren’s syndrome, Amyloidosis

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 Wrist drop(Mono neuritis multiplex)

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 Foot drop(Mononeuritis multiplex)

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 Carpal Tunnel Syndrome

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 Felty’s syndrome

• Classic triad
– RA, Splenomegaly, Leukopenia
• Neutropenia (<2000/mm3)
• Thrombocytopenia may occur
• Complications
– Infections, non-healing leg ulcers
• Usually require no additional treatment for
cytopenias

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 Complications of Rheumatoid Arthritis

• Complications include:
– Carpal tunnel syndrome, Baker’s cyst,
– Vasculitis, Subcutaneous nodules,
– Sjögren’s syndrome, Peripheral neuropathy,
– Cardiac and pulmonary involvement,
– Felty’s syndrome, and anemia
– Osteopenia, Osteoporosis
• Disabilities of Rheumatoid Arthritis
– Name all deformities of joints

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 Sjögren's syndrome

• Sjögren's ("SHOW-grins") syndrome

– Chronic disease in which white blood cells attack
the moisture-producing glands.
• The hallmark symptoms are
– Dry eyes and dry mouth,
• It is a systemic disease, affecting many
organs and may cause fatigue
• It is one of the most prevalent autoimmune
disorders

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 Classical presentation : RA

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 1987 American College of Rheumatology
(ACR) criteria for classification of RA

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 ACR Criteria for Diagnosis

• Four or more of the following criteria must be

present:
– Morning stiffness > 1 hour
– Arthritis of > 3 joint areas
– Arthritis of hand joints (MCPs, PIPs, wrists)
– Symmetric swelling (arthritis)
– Serum rheumatoid factor
– Rheumatoid nodules
– Radiographic changes
• First four criteria must be present for 6
weeks or more

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 ACR & European Leagues of Associations against
Rheumatism (EULAR) new (2010) classification criteria

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 Investigations for suspected RA
• Routine laboratory tests at baseline
– Assessing degree of systemic inflammation
– Organ specific toxicities from prior drug use
• Systemic inflammation
– ESR (Westergren method) & Sensitive-CRP levels
– Platelets: May be normal or elevated
• Acute phase reactant
• Complete Blood Count (CBC)
– Hemoglobin = May be anemic
• Normocytic normochromic anaemia of chr disease
• Organ Function assessment
– Renal assessment
– Liver function tests
• Radiology of joints and baseline Xray chest
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 Auto-antibodies in RA
• Rheumatoid factors (RFs)
– Antibodies against IgG, IgM, IgA
– IgM antibodies directed against Fc domain of IgG
• Routinely tested
– RF positive (IgM) = severe disease & poor outcome
– Only 70% of patients with clinically diagnosed RA
• Have significant titres of RF & Classified as Seropositive RA
– Non-specific, also seen in
• SLE, Sjögren's, Sarcoidosis, Chronic infections.
• Anti-Citrullinated Peptide Antibody (ACPA)
– More specific than RF for RA (95%)

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 Xray Hands in RA

• Typical changes of RA on radiology

– Loss of joint space & erosions in most joints
– Complete disorganisation of the wrist joints
• Erosions
• Particularly look for
5th MC & MT, ulnar styloid &
Scaphoid /trapezium

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 Joint Imaging in RA
• Valuable tool for diagnosing RA
– Also for tracking progression of any joint damage.
• Plain Radiography
– Initial finding = Juxtaarticular osteopenia, soft tissue
swelling, symmetric joint space loss, & subchondral
erosions
• Frequently in wrists & hands (MCPs and PIPs) & feet (MTPs)
(lateral aspect of fifth MTP is often targeted first)
– X-ray imaging of advanced RA may reveal signs of
severe destruction, including joint subluxation.
• MRI: Offers greatest sensitivity for detecting
– Synovitis & joint effusions / early bone changes
– Presence of bone marrow oedema has been
recognized to be an early sign of inflammatory joint
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 The Importance of Early Diagnosis

• RA is progressive and destructive

• Structural damage/disability occurs within
first 2 to 3 years of disease
• Slower progression of disease linked to early
treatment
• Early treatment prevents disability

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 Goals of Therapy

• Control disease activity

• Alleviate pain
• Maintain function for essential daily activities
• Maximize quality of life
• Halt / Slow progression / rate of joint damage
• Prevent complications & deformities

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 RA - Management

• Nonpharmacologic
– Rest
• fatigue, splinting
– Pain relief
• Heat, cold, ultrasound, paraffin bath local, massage
– Physical therapy (physiotherapy)
– Occupational therapy
• Mind diversion and financial independence)
– Patient education
• To better understand the disease process

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 Disease Modifying Anti-Rheumatic
Drugs(DMARD)
• Generally, if pain and swelling persist after 2 to
4 mo of disease despite treatment with aspirin
or other NSAIDs (DMARD to start within 6
months)
– Add a disease-modifying drugs
» Hydroxychloroquine
» Sulfasalazine
» Methotrexate : an immunosuppressive drug now
used very early as disease-modifying drugs of
first choice
» Leflunomide

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 An overview of treatment strategy for RA

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 Corticosteroids in RA

• Corticosteroids = offer most effective short-

term relief as anti-inflammatory drugs.
– Corticosteroids do not prevent progression of
disease or joint destruction
• Severe rebound follows the withdrawal of
corticosteroids in active disease
• To be used as bridging therapy with
Mehtrexate
– It takes few weeks to show response with Mx

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 Immunosuppressive drugs

• Immunosuppressive drugs
– Methotrexate
– Azathioprine
– Cyclosporine
– They are increasingly used in management active RA
• They can suppress inflammation and allow
reduction of corticosteroid doses
• Major side effects can occur, including liver
disease, pneumonitis, bone marrow
suppression
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 Combination therapy
Using 2 to 3 DMARDs at a time
works better than using a single
DMARD
 Common DMARD
Combinations
• Triple Therapy
– Methotrexate, Sulfasalazine, Hydroxychloroquine
• Double Therapy
– Methotrexate & Leflunomide
– Methotrexate & Sulfasalazine
– Methotrexate & Hydroxychloroquine
– Methotrexate & Gold
– Sulfasalazine &Hydroxychloroquine( Plaquenil).

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 Tumour Necrosis Factor (TNF)
(Cytokines)
• TNF is a potent inflammatory cytokine
– Produced mainly by macrophages and monocytes
– Major contributor to inflammatory and destructive
changes that occur in RA
– Blockade of TNF results in a reduction in a number
of other pro-inflammatory cytokines (IL-1, IL-6, IL-8)
• Anti TNF alfa antibodies are now used in
treatment of RA (Costly + side effects)
– Etanercept 25mg subcut twice a week
– Infliximab 3-10mg/kg iv every 4-8 weeks
– Adalimumab 40mg subcut alternate weeks
• Halt / slow down the disease progression
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 Role of Surgery

• Synovectomy of wrists or finger tendon

sheath of the hands required for pain relief or
to prevent tendon rupture.
• Arthroscopic synovectomy may help
preserve joint function if drugs have been
unsuccessful.

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 Progression and Prognosis

• There is increased mortality in RA patients,

highest in those with severe disease.
• Average life span is reduced by 8-15 years by
RA and 5 year survival for patients with
severe disease is only 50%.
• 40% of patients disabled within 3 years
– New anti TNF antibodies treatment disability is
greatly reduced and prolonged the longivity

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 Remission in RA

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 Thank you

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