Rheumatoid arthritis

Definition

  • Chronic inflammatory condition primarily affecting the small joints of the hands and feet

Risk Factors

  • Genetic

  • Smoking?

Differential diagnosis

Epidemiology

  • Prevalence 1% to 2%

  • Incidence 0.25 - 0.4 per 1000 person years

  • Patients are usually in their 50s when diagnosed

  • In younger patients, females have a 2:1 predominance but as age increases this becomes closer to 1:1.

Aetiology

  • Aetiology is unclear

  • The presence of major histocompatibility complex class II allele HLA (human leukocyte antigen) DRw4 is more common in patients with RA

    • The product of RA-related HLA alleles shares an amino acid sequence that has been named the shared epitope and seems to be involved in the pathogenesis of RA

  • Certain genetic variants of PTPN22 and other genes were identified as a risk factor for RA. [10]

  • An infection as a triggering factor for RA in genetically susceptible individuals has been proposed but no specific infectious agent has been identified so far

Clinical features

  • active symmetric arthritis lasting >6 weeks

  • age 50-55 years

  • female

  • joint pain and swelling

  • rheumatoid nodules over the extensor surfaces of tendons

    • Only seen in very active disease

  • symptoms worse in the morning

Pathophysiology

  • Inflamed synovium is central to the pathogenesis

    • Increased angiogenesis

    • Cellular hyperplasia

    • Influx of inflammatory cells

    • Changes in the expression of cell surface adhesion molecules

    • Many cytokines

    • Development of pannus

  • Synovial lining becomes hyperplastic, with infiltration of the sublining with mononuclear cells including T-cells, B cells, macrophages and plasma cells

  • This formation of locally invasive synovial tissue is characteristic and it is involved in causing the erosions seen in RA

  • Cytokines affect all phases of the inflammatory process

    • Tumour necrosis factor (TNF) and interleukin (IL-1) seem to be the most abundant in the joint

    • Both are stimulators of proliferation, metalloproteinase expression, adhesion molecule expression, and further secretion of other cytokines

  • High levels of metalloproteinase activity are thought to contribute to joint destruction

  • Angiogenesis is active and leads to new blood vessels proliferating to provide for the hypertrophic synovium

  • This very inflammatory setting, when not treated, leads to the eventual destruction of the involved joint.

Investigations

  • Rheumatoid factor (RF)

    • One of the autoantibodies frequently seen in patients with RA

    • Can be seen with other conditions like hepatitis C, chronic infections and other rheumatological conditions

    • Approximately 30% of RA patients are RF negative

    • Values that are very high (i.e., >100 international units) are more specific for RA

      • However, values over 1000 international units are not common

      • Should prompt consideration of other conditions like hepatitis C and cryoglobulinaemia as the cause

  • Anti-cyclic citrullinated peptide (anti-CCP) antibody

    • Positive in 70%-80% of RA patients

    • Helpful in RF-negative patients since it may be positive in these patients

    • If the RF is positive, anti-CCP does not seem to add any valuable information, although it is helpful in early and very early disease.

  • X-rays

    • Erosions start at the margins of the joint and parts of the bone not covered by cartilage

    • Affect the subchondral bone first and later progress to cause joint space narrowing

    • Radiographs are done at baseline and then annually to monitor progress of disease#

    • Even though they are the most pathognomonic signs of RA, erosions are seldom useful for treatment decisions since they are seen in late disease

    • Erosions signify a worse prognosis.

  • Disease activity score(s)

    • On diagnosis it is useful to determine the level of disease activity

    • Composite disease measures are derived from the ACR (American College of Rheumatology) core data set

    • Includes:

      • tender joint count

      • swollen joint count

      • functional status measured by a health assessment questionnaire (HAQ)

      • multidimensional HAQ (MDHAQ) or its derivatives

      • pain

      • patients and physician global assessment of disease activity

      • either an ESR or CRP as a marker of inflammation.

    • Any three or more of these combined into a composite index can be used for disease activity monitoring

    • Each disease activity measure has its own thresholds of disease activity

    • For consistency the same disease activity measure is used throughout the patient's management

Management

a) conservative

  • The current approach to treatment can be summarised as early and aggressive

b) medical

  • Patients with mild to moderate disease are usually started on a single DMARD

    • Methotrexate is the most common DMARD used first line

    • Other commonly used first-line DMARDs include leflunomide, sulphasalazine, and hydroxychloroquine

    • Hydroxychloroquine is thought to be a less effective DMARD compared to the others

  • If the patient has severe disease with poor prognostic factors a more aggressive approach to initial therapy may be needed

    • Methotrexate plus biological agents, such as a tumour necrosis factor (TNF)-alpha inhibitor or abatacept

    • Occasionally, a biological agents may be started as monotherapy.

  • If a patient has not reached a level of low disease activity after 3 months of a DMARD being started, another DMARD should be added to the treatment regimen

    • A small minority of patients may respond to triple therapy (methotrexate with sulphasalazine and hydroxychloroquine)

  • If a combination of the more conventional DMARDs fails to control the disease adequately, combination therapy with a biological agent can be tried

  • TNF-alpha inhibitors used for the treatment of RA include etanercept, infliximab and adalimumab.

    • Etanercept is a soluble receptor that binds TNF-alpha

    • Infliximab and adalimumab are monoclonal antibodies to TNF-alpha

      • Adalimumab is the fully humanised version of the two

    • Abatacept is a T-cell modulator considered to be at the same level as a TNF-alpha inhibitor.

  • If a patient still does not improve, a combination of a DMARD with the B-cell inhibitor rituximab or the interleukin 6 inhibitor (IL-6) tocilizumab is used

  • The role of corticosteroids in the treatment of RA is controversial

    • They can be used as an adjunct to the first-line DMARDs in the case of disease flare

    • In addition to working faster than methotrexate and most other DMARDs, corticosteroids also have some disease-modifying effect

    • If corticosteroids are given daily, calcium and vitamin D supplementation and yearly to biannual bone density assessment are recommended

c) surgical

Prognosis

  • factors suggesting poor prognosis (functional limitation, extra-articular disease, positive rheumatoid factor, positive anti-CCP, bony erosions on radiograph)