Rheumatoid Arthritis

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