Definition
A chronic systemic, autoimmune inflammatory disease of unknown cause
Epidemiology
1% of population
M:F = 1:3
Peak onset 40 years
Most common inflammatory arthropathy
Aetiology
Autoimmune
- trigger not identified
- cell mediated immune response
Combination of
1. External trigger ? Infection
2. Genetic susceptibility
Pathogenesis
Associated with HLA DR4
- 70 % RA
Shared epitope concept AA67-74 on Ag presenting gene
- marker of disease severity
- can have double dose of marker
Exogenous agent alters IgG to become antigenic
Plasma Cells produce RF directed against IgG
- synovium acts as lymphoid organ
- local plasma cells produce RF
- Antibody-Antigen complexes formed
- stimulate complement
- 2° destructive inflammatory cascade / lymphokines, IL1
Rheumatoid Factor
IgM antibody directed at Fc region of IgG
- 80% with RA
- high titre correlates with severe disease
Present in 5% general population
- seen in SLE / Sjorgrens / TB / Syphilus / Hep c
Pathology
1. Synovitis
- type B Synoviocyte undergoes almost malignant like transformation
- T Cell driven
- release metalloproteinases directly
- cartilage destruction
2. Synovial Fluid production
- predominate cell is PMN not lymphocyte
- PMN's amplify inflammation but synovitis is most important event in tissue destruction
3. Pannus
- proliferating synovium
- spreads over surface of cartilage
- causes direct destruction of cartilage
Clinical
Most commonly present with
- malaise
- fever
- fatigue
Symmetrical pain & swelling in hands, wrists & feet
Four Presentations
1. Slowly progressive polyarthritis
- gradually worsens over months
2. Episodic polyarthritis
- acute swelling of one joint
- resolves with asymptomatic interval
- intervals become shorter until polyarthritis develops
3. Monoarticular or Oligoarticular Arthritis
- swollen large joint
- polyarthritis develops later
4. Fulminating Polyarthritis
- elderly
- acute onset with widespread joint involvement
Four Outcomes
Short - Lived & No disability 25%
Mild Disability 25%
Progressive 40%
- variable progressive deformity
Severe 10%
- gross deformity / severe disability / rapid progression
Symptoms
Articular
- early morning joint stiffness
- joint swelling
- polyarthralgia - initially fingers, then wrists, feet, knees & GHJ
Systemic symptoms
- weight loss
- fever
- malaise
Nodules
- occur in 20% of patients
- pathognomonic
- associated with IgM RF
- most common occur on subcutaneous surface of forearms
- also pleura & lung / larynx / pericardium & myocardium / sclera
Ocular
- red eyes
- sceleritis / keratoconjunctivitis sicca
Pulmonary
- rheumatoid nodules
- if associated with pneumoconiosis / Caplan's Syndrome
- pleurisy
- diffuse interstitial fibrosis
Cardiac
- pericarditis
- nodules causing valvular insufficiency / conduction defects
Lymphadenopathy
- nodes draining affected joints
- nodes at a distance due to hyperactivity of RES
Myopathy
Neuropathy
- sensory polyneuropathy
- motor & sensory polyneuropathy
Cervical Myelopathy
- cord compression 2° atlantoaxial instability
- SMO / SAS
Entrapment Neuropathies
- CTS
- ulnar / cubital tunnel syndrome
Vasculitis
- obliterative endarteritis
- Raynaud's
Anaemia of Chronic Disease
- normocytic normochromic
Felty's Syndrome
Combination RA / Splenomegaly / Neutropenia
Other features are
- lymphadenopathy
- skin pigmentation
- chronic leg ulceration
- thrombocytopaenia
- haemolytic anaemia
Sjogren's Syndrome
Combination of
- dry eyes / keratoconjunctivitis sicca
- dry mouth / xerostomia
- connective tissue disorder - RA in 50%
Histology
Synovial Biopsy
- non specific chronic inflammation
DDx
Seronegative Spondyloarthropathies (Reiters / AS / Psoriasis / Enterocolitis)
Crystal Arthropathies (Gout / CPPD / HADD)
CT Diseases (JRA / SLE)
Polymyalgia Rheumatica
Sarcoidosis
Dx Crtieria 1987 Am College of Rheumatology
Need 4/7 MAX RANS
1. Morning Stiffness
2. Arthritis of 3 areas > 6/52
3. X-ray changes
4. Rh factor
5. Arthritis of Hand > 6/52
6. Nodules
7. Symmetric Arthritis > 6/52
Medical Management
1. Symptom Modifying Drugs
NSAID
First-line therapy
- alleviates pain & swelling
Side Effects
- troublesome
- skin rashes / gastric ulceration / renal dysfunction
2. Disease Modifying drugs (DMARDs)
Effects
Effective in 50-80%
- improve symptoms & signs in medium term
- some slowing of progress of disease
- toxicity is problem
Gold Salts
Inhibit monocyte function
- IM route / PO less toxic but less effective
- need close monitoring / toxicity in 30-40%
- pancytopenia & ARF
- screening with FBC & urinalysis
Penicillamine
Modulates lymphocyte function
- toxicity in 50%
- similar profile to gold
Antimalarials
Stabilise lysosomal membranes
- inhibit IL-1 function
- Chloroquine & Hydroxycholoroquine
- less life-threatening toxicity
- can cause macular degeneration
Sulphasalazine
Anti-Folate activity
- fewer side effects
MTX / Methotrexate
70% of patient respond
- main problem is pneumonitis
- more rarely liver fibrosis / marrow suppression
- 3-4% incidence nausea, stomatitis, nodules
Should MTX be stopped for surgery
- cessation can cause flare up which is difficult to treat
- without cessation risk of wound healing problems and infection
3. Corticosteroids
Effects
Dramatically effective
- long-term side effects - osteoporosis, HTN & DM
Indications
- refractory disease
- severe non articular manifestations of RA
Complications
- impaired wound healing
- increased risk of infection
- post-op hypotension
- wound dehiscence
- cover required by replacement of oral dose with IV Hydrocortisone
4. Biological Agents / Immune Modulators
Effects
Modify the inflammatory cascade
Have dramatically changed the face of rheumatoid arthritis
Multiple studies demonstrating
- improved remission
- reduction in inflammation
- slowing of radiographic progression
A. TNF Alpha Antagonists
Etanercept, adalimumab, infliximab
- administered IV or subcut
- varying half lives
Side effects
- increased opportunistic infections
- TB, pneumocystis
- aspergillosis, candidiasis
Surgery
- unknown if increases infection risk etc
- recommend withhold for major OT
B. IL 1 Receptor Antagonists
Anakinra
Side effects
- nil obvious increase in opportunistic infections
Recommendations for surgery as above