• 35 yrs female, giving history of pain in first

metacarpophalangeal and distal

interphalangeal joints of second and third
digits on right hand for 7 weeks. Her RA
factor is low positive, ESR is 10mmhg,
CRP <1. Her mother is known case of
Rheumatoid Arthritis.
• On the basis of information given, would
you label her as having Rheumatoid
Arthritis?
 RHEUMATOID
ARTHRITIS
• Chronic systemic inflammatory disease
• Unknown cause
• Age: 4th-5th decade(F), 6th-8th decade(M)
• Female: male 3:1(M=F in older age)
• First degree relative 2-3times higher risk
• Monozygotic twins 15-20%, dizygotic 3%
 ETIOLOGY
Genetic
HLA DR4,
DR1,
DW15,
PTPN22
TRAF 5
Environmental
Infectious smoking
Periodontal
pathogens, RA
EBV, CMV

Hormonal Immunologic
Hyperprolacti
nemia
 PATHOPHYSIOLOGY
• Lymphocytes, macrophages, dendritic cells ,
plasma cells  synovial infiltration  lymphoid
follicles  T+B cells interaction

B-cells Marcrophage
activation
TNF,
IL1,6,
15
Cytokines+
RF/ACPA
 Cartilage
Osteoclast
and bone
&
destructio
chondrocyt
n
e activation
Hypoxic Neoangio-
joint genesis

TNF,
IL1,6,
15
Pannus Cartilage
Synovial formatio and bone
fibroblast Soft n destruction
activation tissue/car
tilage
damage
+synovial
swelling Bony
ankylosis
 CLINICAL
PRESENTATION
• Insidious onset
• Symmetrical polyarthritis(PIP, MCP, MTP,
wrists, ankles, knee, C1C2)
• Signs of inflammation+
• Morning stiffness >30 mins
• May begin with fever, myalgia, weakness,
arthralgia
• Spontaneous remission is uncommon
• Occasionally palindromic
Rheumatoid Arthritis-Distribution

Latinis, K., et al
The Washington
Manual Rheumatology
Subspecialty Consult.,
LWW, 2003.
Osteoarthritis-
Distribution

Bouchard’s

Heberden’s

Latinis, K., Dao, K, Shepherd,

R, Gutierrez, E, Velazquez, C.
The Washington Manual
Rheumatology Subspecialty
Consult., LWW, 2003.
 ARTICULAR
• Swan neck deformities
• Boutonniere deformities
• Z-deformity
• Dorsal subluxation of ulna
• Triggering of fingers
• Calceneovalgus deformity
• Flat foot d/t rupture of tibialis post tendon
• Baker’s cyst
 RA Vs. OA
Features Rheumatoid Arthritis Osteoarthritis

Age of onset Can happen at any age Usually later in life

Speed of onset Rapid- weeks to months Slow- over years

Distribution Symmetrical Initially asymmetrical

polyarthritis monoarthritis
polyarthritis
Joints affected Small joints of hands Weight bearing joints-
and feet knees, hips
Duration of morning Stiffness worse in the Stiffness <1hour and worse
stiffness morning >1hour at the end of the day (after
activity)
Systemic symptoms Fatigue, fever, night -
sweats
 EXTRAARTICULAR
FEATURES
ORGAN MANIFESTATION

MUSCULOSKELETAL Myopathy, bursitis, tenosynovitis, osteoporosis,

HEMATOLOGICAL Anemia of chronic disease, eosinophilia,

thrombocytosis, leukopenia(felty syndrome), iron def
anemia
LYMPHATIC Felty syndrome, splenomegaly, lymphadenopathy,
increased risk of lymphoma

CUTANEOUS Subcutaneous nodules, purpura, palmer erythema,

ulcers, sinuses, fistulae, pyoderma gangreneosum
ORGAN MANIFESTATION
OCULAR Keratoconjunctivitis sicca, episcleritis, uveitis,
nodular scleritis, scleromalacia

VASCULITIS Purpura, ulcers, digital infarcts, digital arteritis,

mononueritis multiplex, visceral arteritis

CARDIAC MI, valvular lesions (common).

Peri/endo/myocarditis, conduction defects, coronary
vasculitis.
PULMONARY Pleural effusions, nodules, Pulmonary fibrosis,
Caplan syndrome

NEUROLOGICAL Compression neuropathy e.g. Carpal tunnel

syndrome, myelopathy, cord compression, peripheral
neuropathy
RENAL Not direct, medications, amyloidosis, associated
diseases

GIT Not direct, splenomegaly (felty syndrome)

CRITERIA TO DIAGNOSE
RA
 D/D
• Polymyalgia • Fibromyalgia
Rheumatica
• Lyme Disease
• Psoriatic Arthritis
• Myelodysplastic Syndrome

• Osteoarthritis • Sjogren Syndrome

• Sarcoidosis
• Paraneoplastic Syndromes

• Systemic Lupus • Polychondritis

Erythematosus (SLE)
How will you Investigate?
• CBC
• ESR
• CRP
• RA FACTOR (70%)
• ANTI CCP ANTIBODY (70%, 95% SPECIFIC)
• ANA
• JOINT ASPIRATION
• U/S
• MRI
• XRAYS
RADIOLOGICAL
FINDINGS
Osteopenia

Loss of joint
space

Baker’s cyst

Erosions
 RADIOLOGICAL
FINDINGS
• Usually normal
• EARLY: hands/feet  soft tissue swelling& juxta
articular demineralization.
• LATER: joint space narrowing, erosions(first at ulnar
styloid)
• CERVICAL SPINE: subluxation
• D: demineralization
• E: erosions
• N: narrowing of space
• S: soft tissue swelling
• S: subluxation
DISEASE ACTIVITY
MEASUREMENT
DISEASE PROGRESSION
MEASUREMENT
 FUNCTIONAL STATUS
• Class I – Completely able to perform usual activities
of daily living
• Class II – Able to perform usual self-care and
vocational activities but limited in avocational
activities
• Class III – Able to perform usual self-care activities
but limited in vocational and avocational activities
• Class IV – Limited in ability to perform usual self-care,
vocational, and avocational activities
MANAGEMENT
 WHAT ARE YOUR
OBJECTIVES
• Reduction of inflammation
• Reduction of pain
• Preservation of function
• Prevention of deformity

• Patients with active disease should be monitored

every 3 months, and treatment should be adjusted
if there is no improvement at 6 months
• Exclude latent TB in patients who are candidates of
biological agents
 RA

Pharmacological Surgical Non pharmacological

EXCERSICE
DMARDS NSAIDS SYNOVECTOMY DIET
TENOSYNOVECTOM MASSAGE
Y COUNSELLING
TENDON STRESS REDUCTION
REALIGNMENT
PHYSICAL
ARTHROPLASTY THERPARY
ARTHRODESIS HEAT&COLD
RECONSTRUCTIVE APPLICATION
SURGERY ASSISTIVE DEVICES
 DMARDS

SYNTHETIC

BIOLOGICAL
CORTICOSTEROIDS

*TNF INHIBITORS
METHOTREXATE ABATACEPT
ORAL SULFASALAZINE
INTRAARTCULAR RITUXIMAB
LEFLONAMIDE
INTRAMUSCULAR ANTIMALARIALS TOCLIZUMAB
MINOCYCLINE
TOFACITINIB

* TNF INHIBITORS: ETANERCEPT, INFLIXIMAB,

ADALIMUMAB, GOLIMUMAB, CERTOLIZUMAB
DRUG MECHANIS DOSE/MAX INCREASE S/E CONTRAIN MONITORI
M OF DOSE DOSE DICATION NG F/UP
ACTION S

Methotrexate Inhibits 5-25mg/wk 2.5 in 2-4 GI, Hepatitis, CBC/LFT

(use with DNA weeks stomatitis, pregnancy, every 3
folic synthesis & rash, lactation months
acid/leucovor cell division hepatotoxict
in) y, acute
pneumonitis
, marrow
suppression,
carcinogenic

Sulfasalazine Unknown 500mg, 2- GI, rash, Aspirin CBC/ LFT

(orange 4g/day hepatitis, hypersensiti Monthly for
staining of neutropenia, vity, 3 months
urine and pancytopeni lactation than every 3
contact lens) a, hemolysis months
in G6PD def

Leflunomide Blocks T- 10-20mg/d GI, rash, Pregnancy, CBC/LFT/BP

(loading dose cell division alopecia, males who 2-4weekly
of 100mg on 3 hepatitis, wish to
days can be hypertensio become
given) n,carcinogen father,l
ic, wt loss acttaion
DRUG MOA DOSE/MAX S/E CONTRAIND MONITORIN
DOSE ICATIONS G

Antimalarials unknown 200-400mg/d Rash, nausea, Hypersensitivi VA/fundoscop

(mild cases) diarrhea, ty, y
headache, Porphyrias, annualy
corneal Psoriasis,
deposits, lacttaion
Retinopathy,sk
eletal, cardaic
myopathies

Minocycline Unclear, 200mg/d dizziness Hypersensitivi

(early mild antiinflammat ty
cases), better ory, ihibits
during first destructive
year enzyme like
collagenes

Tofacitinib Janus Kinase 3 5-/10md BD Screen for

(severe inhibitor Latent TB
disease,
refractory to
MTX)
DRUG DOSE/MAX S/E CONTRAINDI MONITORING
DOSE CATIONS
Increased risk of mailgnancy esp basal cell carcinoma of skin, accelerate progression of cancers.
Risk of vascular disease is reduced.

Etanercept Decoy receptor 50mg/week Minor irritation at

for TNF alpha, SC inj. Site,
Soluble demyelination like
recombinant MS
TNFR: FC
fusion protein
Acute and chronic Screen for
infections, latent TB
Infliximab Chimeric 3-10mg/kg Increased Demyelinating
Monoclonal IV, 2,6,10,14 mortality in heart illness, class III, IV
Antibody weeks, than failure trials, heart failure,
every 8 weeks anaphylaxis, Anti Recent
dsDNA malignancies
Antibodies to TNF
Adalimumab Human 40mg/ alternate Minor irritation at
Monoclonal weeks inj. site
antibody, binds SC
to TNF
Golimumab Human anti- 50mg/ month
TNF SC
Monoclonal
Antibody
Certolizumab Pegylated 200-400mg/2-
Monoclonal 4weeks
Antibody TNF SC
DRUG MOA DOSE

Abatacept Blocks T-cell costimulation, 125mg SC weekly

(refractory to MTX and TNFi) Recombinant protein fragnebt
of Fc domain of human IgG and
extracelluar domain of T-cell
inhibitory receptor

Rituximab Depletes B cell, 2 intravenous (IV) infusions of

(refractory to treatment with
TNFi)
Toclizumab
(refractory to mtx, TNFi)
Incrased risk of infection
Humanized mouse monoclonal
antibody
Blocks receptor for IL6,
monoclonal antibody
1000 mg, separated by 2 weeks,
in combination with MTX.
Methylpred, chlorphenaramine
and paracetamol 30 mins before
8mg/kg monthly
IV

Anakinra IL1 receptor antagonist, 100mg/day

Recombinant, nonglycosylated SC
 OTHER MEDICATIONS
• Penicillamine
• Sodium thioaurate
• Ciclosporin

• Combination of DMARDs
 RA IN PREGNANCY
• No special monitoring
• Flares are reduced
• Postpartum flares
• Counsel about teratogenicity
• Avoid NSAIDS
• Discontinue MTX and Leflunomide 3 months before
pregnancy and check levels of leflunomide
• SAFE IN PREGNANCY:
o STEROIDS
o SULFASALAZINE
o HYDROXYCHLOROQUINE
o AZATHIOPRINE
o CICLOSPORIN

• NOT SAFE IN PREGNANCY:

o METHOTREXATE
o LEFLUNOMIDE
o CYCLOPHOSPHAMIDE
o GOLD
o PENICILLAMINE
o NSAIDS IN 3RD TRIMESTER
 VACCINATION
• Administer all killed vaccines (pneumococcal,
intramuscular influenza, and HBV) and human
papillomavirus (HPV) recombinant vaccine
BEFORE STARTING OR WHILE ON TREATMENT

• The herpes zoster virus (HZV) live attenuated

vaccine should only be administered before starting
treatment.
 POOR PROGNOSTIC
FACTORS
• HLA-DRB1*04/04 genotype
• High serum titer of autoantibodies (eg, RF and
ACPA)
• Extra-articular manifestations
• Large number of involved joints
• Age younger than 30 years
• Female sex
• Systemic symptoms
• Insidious onset
• Smoking
• overall mortality in patients with RA =2.5 times higher
• Increased risk of cardiovascular disease 8-15 yrs
reduction in life span
• Within 3 yrs 40% disabled
• Within 20 yrs 80% severly disbaled
 FELTY SYNDROME
• RA, splenomegaly, agranulocytopenia
• >50-70 yrs, f>m, long standing RA
• Extraarticular manifestations are more common
• Serious infections, splenic infarcts
• Highr titers of RF, ANA (67%), antihistones, p-
ANCA(77%)
• Complications: splenic rupture, portal hypertension,
life threatening infections
• Steroids, methotrexate, colony stimulating factors
• Splenectomy: severe disease, failure to medical
therpay, recurrent infections
• 35 yrs female, giving history of pain in first
metacarpophalangeal and distal interphalangeal
joints of second and third digits on right hand for 7
weeks. Her RA factor is low positive, ESR is 10mmhg,
CRP <1. Her mother is known case of Rheumatoid
Arthritis.
• On the basis of information given, would you label
her as having Rheumatoid Arthritis?
• Hint: her score is??
• Ans: