Epidemiology

  • Incidence: 40.00 cases per 100,000 person-years
  • Peak incidence: 30-40 years
  • Sex ratio: more common in females 3:1
Condition Relative
incidence
Osteoarthritis of the hand150.00
Polymyalgia rheumatica2.10
Rheumatoid arthritis1
Psoriatic arthropathy0.20
Systemic lupus erythematosus0.13
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

Aetiology
  • some ethnic differences e.g. high in Native Americans
  • associated with HLA-DR4 (especially Felty's syndrome)

Clinical features

Typical features
  • swollen, painful joints in hands and feet
  • stiffness worse in the morning
  • gradually gets worse with larger joints becoming involved
  • presentation usually insidiously develops over a few months
  • positive 'squeeze test' - discomfort on squeezing across the metacarpal or metatarsal joints

Swan neck and boutonnière deformities are late features of rheumatoid arthritis and unlikely to be present in a recently diagnosed patient.

Other presentations:
  • acute onset with marked systemic disturbance
  • relapsing/remitting monoarthritis of different large joints (palindromic rheumatism)

Investigations

Rheumatoid factor

Rheumatoid factor (RF) is a circulating antibody (usually IgM) which reacts with the Fc portion of the patients own IgG

RF can be detected by either
  • Rose-Waaler test: sheep red cell agglutination
  • Latex agglutination test (less specific)

RF is positive in 70-80% of patients with rheumatoid arthritis, high titre levels are associated with severe progressive disease (but NOT a marker of disease activity)

Other conditions associated with a positive RF include:
  • Sjogren's syndrome (around 100%)
  • Felty's syndrome (around 100%)
  • infective endocarditis (= 50%)
  • SLE (= 20-30%)
  • systemic sclerosis (= 30%)
  • general population (= 5%)
  • rarely: TB, HBV, EBV, leprosy


Anti-cyclic citrullinated peptide antibody

Anti-cyclic citrullinated peptide antibody may be detectable up to 10 years before the development of rheumatoid arthritis. It may therefore play a key role in the future of rheumatoid arthritis, allowing early detection of patients suitable for aggressive anti-TNF therapy. It has a sensitivity similar to rheumatoid factor (around 70%) with a much higher specificity of 90-95%.

NICE recommends that patients with suspected rheumatoid arthritis who are rheumatoid factor negative should be test for anti-CCP antibodies.


X-ray changes

Early x-ray findings
  • loss of joint space
  • juxta-articular osteoporosis
  • soft-tissue swelling

Late x-ray findings
  • periarticular erosions
  • subluxation

Diagnosis

NICE have stated that clinical diagnosis is more important than criteria such as those defined by the American College of Rheumatology.

2010 American College of Rheumatology criteria

Target population. Patients who
  • 1) have at least 1 joint with definite clinical synovitis
  • 2) with the synovitis not better explained by another disease

Classification criteria for rheumatoid arthritis (add score of categories A-D;
a score of 6/10 is needed definite rheumatoid arthritis)

Key

FactorScoring
A. Joint involvement
1 large joint0
2 - 10 large joints1
1 - 3 small joints (with or without involvement of large joints)2
4 - 10 small joints (with or without involvement of large joints)3
10 joints (at least 1 small joint)5
B. Serology (at least 1 test result is needed for classification)
Negative RF and negative ACPA0
Low-positive RF or low-positive ACPA2
High-positive RF or high-positive ACPA3
C. Acute-phase reactants (at least 1 test result is needed for classification)
Normal CRP and normal ESR0
Abnormal CRP or abnormal ESR1
D. Duration of symptoms
< 6 weeks0
> 6 weeks1

Management

The management of rheumatoid arthritis (RA) has been revolutionised by the introduction of disease-modifying therapies in the past decade.

Patients with evidence of joint inflammation should start a combination of disease-modifying drugs (DMARD) as soon as possible. Other important treatment options include analgesia, physiotherapy and surgery.

Initial therapy
  • In 2018 NICE updated their rheumatoid arthritis guidelines. They now recommend DMARD monotherapy +/- a short-course of bridging prednisolone. In the past dual DMARD therapy was advocated as the initial step.

Monitoring response to treatment
  • NICE recommends using a combination of CRP and disease activity (using a composite score such as DAS28) to assess response to treatment

DMARDs
  • methotrexate is the most widely used DMARD. Monitoring of FBC & LFTs is essential due to the risk of myelosuppression and liver cirrhosis. Other important side-effects include pneumonitis
  • sulfasalazine
  • leflunomide
  • hydroxychloroquine

TNF-inhibitors
  • the current indication for a TNF-inhibitor is an inadequate response to at least two DMARDs including methotrexate
  • etanercept: recombinant human protein, acts as a decoy receptor for TNF-α, subcutaneous administration, can cause demyelination, risks include reactivation of tuberculosis
  • infliximab: monoclonal antibody, binds to TNF-α and prevents it from binding with TNF receptors, intravenous administration, risks include reactivation of tuberculosis
  • adalimumab: monoclonal antibody, subcutaneous administration

Rituximab
  • anti-CD20 monoclonal antibody, results in B-cell depletion
  • two 1g intravenous infusions are given two weeks apart
  • infusion reactions are common

Abatacept
  • fusion protein that modulates a key signal required for activation of T lymphocytes
  • leads to decreased T-cell proliferation and cytokine production
  • given as an infusion
  • not currently recommend by NICE

Complications

A wide variety of extra-articular complications occur in patients with rheumatoid arthritis (RA):
  • respiratory: pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans, methotrexate pneumonitis, pleurisy
  • ocular: keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration, keratitis, steroid-induced cataracts, chloroquine retinopathy
  • osteoporosis
  • ischaemic heart disease: RA carries a similar risk to type 2 diabetes mellitus
  • increased risk of infections
  • depression

Less common
  • Felty's syndrome (RA + splenomegaly + low white cell count)
  • amyloidosis

Respiratory complications

A variety of respiratory problems may be seen in patients with rheumatoid arthritis:
  • pulmonary fibrosis
  • pleural effusion
  • pulmonary nodules
  • bronchiolitis obliterans
  • complications of drug therapy e.g. methotrexate pneumonitis
  • pleurisy
  • Caplan's syndrome - massive fibrotic nodules with occupational coal dust exposure
  • infection (possibly atypical) secondary to immunosuppression

Ocular complications

Ocular manifestations of rheumatoid arthritis are common, with 25% of patients having eye problems

Ocular manifestations
  • keratoconjunctivitis sicca (most common)
  • episcleritis (erythema)
  • scleritis (erythema and pain)
  • corneal ulceration
  • keratitis

Iatrogenic
  • steroid-induced cataracts
  • chloroquine retinopathy

Prognosis

A number of features have been shown to predict a poor prognosis in patients with rheumatoid arthritis, as listed below

Poor prognostic features
  • rheumatoid factor positive
  • poor functional status at presentation
  • HLA DR4
  • X-ray: early erosions (e.g. after < 2 years)
  • extra articular features e.g. nodules
  • insidious onset
  • anti-CCP antibodies

In terms of gender there seems to be a split in what the established sources state is associated with a poor prognosis. However both the American College of Rheumatology and the recent NICE guidelines (which looked at a huge number of prognosis studies) seem to conclude that female gender is associated with a poor prognosis.