Rheumatoid Arthritis

Introduction

Rheumatoid arthritis is a chronic auto-immune inflammatory arthritis. In rheumatoid arthritis, the body’s immune system attacks its own tissue, including joints. In severe cases, it attacks internal organs.

  • Autoantibodies that are characteristic of RA, including rheumatoid factor (RF) and anti-citrulluninated protein antibodies (ACPA), are present before clinical disease onset.
  • It typically affects females more than males.
  • It affects all age groups but especially 40yrs and above.
  • If untreated or badly managed, it could result in deformities, cardiovascular morbidities and decreased life expectancy
  • It is characterized by affectation of small and medium sized joints in a symmetric fashion
  • The synovium is the primary site of the inflammatory process, which if untreated leads to irreversible damage to the adjacent cartilage and bone.
  • Once RA synovitis is established, a number of amplification mechanisms serve to sustain the process leading to the persistence of the disease.
  • Risk factors of RA are genetic such as Shared Epitope of HLA DRBI; environmental such as infective agent parvovirus, Epstein Barr virus, mycoplasma, smoking

Clinical features

  • It diagnosis based on the American College of Rheumatology criteria (ACR)
  • Lately the ACR and European League Against Rheumatism (EULAR) criteria
  • Symptoms include constitutional features such as fever, loss of weight, loss of appetite, fatigue, nausea, anaemia
  • Polyarthritis involving especially joints of the hands, elbows, shoulders, feet, knees, hip and temporo-mandibular
  • It hardly ever affects joints of the spine except Atlanto-axial joint
  • Dryness of the mouth and eyes
  • Subcutaneous nodules especially the elbow
  • Internal organ involvement may include pleural effusion, interstitial pneumonitis, pericarditis, pericardial effusion, ischemic heart disease, conjunctivitis, hepatoslenomegaly

Differential Diagnosis

  • Polyarticular osteoarthritis
  • Polyarticular gout
  • Systemic Lupus Erythematosus
  • Spondyloarthropathy
  • Reactive Arthritis

Investigations

  • Haematocrit, white blood cell count, ESR, CRP
  • Liver function tests (as most of drugs used could be hepatotoxic)
  • Cholesterol, triglycerides
  • Rheumatoid factors
  • Anti Cyclic Citrullinated Peptide
  • Imaging
    • Plain radiographs especially of the hands and feet to demonstrate erosions
    • Ultrasound of the joints to demonstrate synovitis and erosions
    • CT scan
    • MRI
    • Radioisotope

Treatment of Objectives

  • To reduce pain and swelling
  • To prevent joint destruction and deformities
  • To prevent cardiovascular morbidities

Management

  • Non-pharmacologic treatment as in osteoarthritis.
  • Disease modifying Antirheumatic drugs (DMARDS) are the mainstay and must be started immediately
  • NSAIDs are supportive and should be stopped if there is no pain or if any adverse effects

Synthetic DMARDS:

Methotrexate
This is gold standard

  • 7.5mg – 25mg orally or SC once weekly
  • Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions
  • Methotrexate is strongly recommended over hydroxychloroquine or sulfasalazine for DMARD naive patients with moderate-to-high disease activity

Sulfasalazine tablets

  • 1gm – 3gm daily in divided doses

Hydroxychloroquine sulphate

  • 400-600 mg/day orally daily in divided doses

Leflunomide

  • 20mg – 30mg daily after loading dose

Azathioprine

  • 2-3mg/kg body weight daily.

Cyclophosphamide
In some cases, combination therapy is used:

  1. Methotrexate+ Sulfasalazine + Hydroxychloroquine or
  2. Methotrexate + Leflunomide

Biologic DMARD

  • This is used according to guidelines if disease activity is still high after synthetic DMARDs has been used

These include

  1. Anti TNF-
    • Etanercept
    • 50 mg SC once weekly
    • if necessary, methotrexate, glucocorticoids, salicylates, NSAIDs,  or analgesics can be continued during treatment with Etanercept
  2. B Lymphocyte Depletor
    • Rituximab
    • 1000 mg IV infusion, repeat after 2 week (one course)
    • Repeat course q24weeks or based on clinical evaluation (but no sooner than 16 weeks)
    • Use in combination with methotrexate
    • Premedicate with glucocorticoids 30 minutes before infusion to reduce infusion reaction
    • Do not to exceed 1000 mg/dose
  3. Corticosteroids
    • Prednisolone at low doses,
      less than 15mg eventually phased out within 6 months; intra-articular steroid
  4. NSAIDs
    • used only in exacerbation of pain.

Adverse Effects

NSAIDs

  • Dyspepsia,
  • Peptic ulceration,
  • Gastro intestinal bleeding,
  • hepatotoxicity,
  • fixed drug eruptions.

DMARDS

  • Susceptibility to infections,
  • Hepatotoxicity,
  • Elevated blood lipids,
  • Pancytopenia,
  • Bone marrow suppression,
  • Malignancy,
  • Teratogenicity

2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis