Rheumatoid Arthritis

 

• Background

  Pathophysiology

  • Autoimmune disease, in which IgG forms against cartilage, and rheumatoid factor (RF) – an IgM antibody – forms against that IgG, leading to synovitis.
  • This eventually leads to pannus (deposits in the synovial membrane) and joint destruction.

  Epidemiology

  • 1% prevalence.
  • 3:1 female:male ratio.
  • Peak onset around 50 years, but any age can be affected.

• Presentation

  Patterns

  • Typical: onset of symmetrical polyarthritis over weeks to months, then relapsing-remitting course.
  • Rarer: persistent large joint monoarthropathy, or palindromic RA, a recurrent acute monoarthritis.

  Articular manifestations

  Inflammatory features:

  • Swollen, painful, and stiff small joints of the hands and feet inc. MCP, PIP, wrist, and MTP.
  • Flexor tenosynovitis.
  • Worse in the morning, with stiffness >30 minutes.
  • Often spares thumb and 1st MTP, unlike osteoarthritis.

  In longstanding disease, deformities may develop:

  • Ulnar deviation, dorsal wrist subluxation, boutonniere and swan neck deformities, muscle wasting, Baker's cysts (from joint rupture).
  • However, these are less common in the age of effective treatments.

  Extra-articular manifestations

  Systemic symptoms:

  • Fatigue
  • Fever
  • Weight loss.

  Dermatological and mucosal:

  • Sjogren's
  • Raynaud's
  • Rheumatoid nodules on elbows and sometimes lungs and eyes.
  • Pyoderma gangrenosum.
  • Erythema nodosum.

  Anaemia:

  • Anaemia of chronic disease.
  • Methotrexate or sulfasalazine induced folate-deficiency anaemia.

  Neurological:

  • Nerve entrapment, especially carpal tunnel syndrome, which may be the presenting complaint. Tarsal tunnel syndrome also seen.
  • Cervical myelopathy/radiculopathy (inc. from atlantoaxial subluxation).

  Rheumatoid lung disease:

  • Pulmonary fibrosis.
  • Obliterative bronchiolitis: fibrotic and inflammatory narrowing of bronchioles.
  • Pleural effusion.
  • Methotrexate pneumonitis.
  • Lung nodules.

  Cardiovascular:

  • Atherosclerosis.
  • Pericardial effusion.
  • Mitral regurgitation.

  Eyes:

  • Kerato-conjunctivitis sicca.
  • Scleritis and episcleritis, which may lead to scleromalacia.

  Kidney:

  • Amyloidosis
  • Glomerulonephritis.

  Others:

  • Osteoporosis.
  • Lymphadenopathy and hepatosplenomegaly.
  • Felty's syndrome: RF +ve, splenomegaly, and neutropenia.
  • Vasculitis: nail fold infarcts, glomerulonephritis.
  • Hypothyroidism.
  • Cancer: lymphoma, lung if smoker.

• Risk factors

  • Family history.
  • Genes, including several variants of HLA-DR1B.
  • Smoking

• Investigations

  Diagnosis is usually made clinically by a rheumatologist, with investigations used to support the diagnosis and provide prognostic information.

  Bloods:

  • ↑ESR, ↑CRP. Can be normal.
  • FBC: anaemia.
  • Auto-antibodies (both 70% sensitive): rheumatoid factor, anti-CCP (more specific and prognostic).
  • LFT and U+E for baseline before DMARDs. U+E may also show signs of renal involvement.

  X-ray of hands and feet if there is synovitis, LESS:

  • Loss of joint space (symmetrical).
  • Erosions (high risk of progression).
  • Soft tissue swelling.
  • See-through bones: juxta-articular osteopenia.

  Other investigations:

  • Joint aspirate if diagnostic uncertainty or septic arthritis suspected.
  • Urine: may contain blood and/or protein.
  • CXR to exclude lung disease.

  DAS-28 score to assess severity:

  • Based on number of joints affected, CRP/ESR, and overall wellbeing.
  • Remission < 2.6 < Low activity < 3.2 < High activity < 5.1 < Biological treatment indicated.

• Management

  General

  Analgesia:

  • Paracetamol
  • Weak opioids.

  Anti-inflammatories:

  • NSAIDs. Avoid long-term.
  • Glucocorticoids: IM, intra-articular, or PO during flares. Avoid long-term.

  Physio and exercise, but rest during exacerbations.

  Disease modifying anti-rheumatic drugs (DMARDs)

  Drugs:

  • Conventional DMARDs (cDMARDs), all PO: methotrexate (MTX), sulfasalazine, leflunomide, hydroxychloroquine.
  • Biological DMARDs (bDMARDs): anti-TNFα (all SC except infliximab IV), rituximab (IV; anti CD20 → B-cell inhibition), abatacept (IV; anti CD80 and CD86 → T-cell inhibition), tocilizumab (IV; anti IL-6 → widespread anti-inflammatory effects).

  Treatment algorithm:

  • Start as soon as possible to minimize complications: MTX (with rapid dose escalation) plus glucocorticoids (short term).
  • Escalation if failure to control disease: MTX plus 2nd cDMARD (some guidelines skip this step in severe disease), then MTX plus bDMARD if still refractory.

  Consider dose reduction and trial of treatment withdrawal when in sustained remission.

  Surgical

  • Joint replacement if symptoms are severe.
  • Arthrodesis and osteotomy are other options.

• Methotrexate

  Indications

  • RA
  • Psoriasis
  • Crohn's
  • Chemotherapy
  • Ectopic pregnancy and abortion.

  Side effects

  • Pneumonitis and pulmonary fibrosis.
  • Pancytopenia and immunosuppression.
  • Nausea, vomiting, and diarrhoea.
  • Sore mouth due to ulcerative stomatitis, glossitis, and gingivitis.
  • Headache
  • Rash
  • Hair loss
  • Dizziness
  • Deranged LFTs and cirrhosis.

  Contraindications

  • Pregnancy. Stop 3 months before starting trying to conceive.
  • ASA or NSAIDs.
  • Caution: trimethoprim and co-trimoxazole.

  Management

  • Once-weekly PO in RA.
  • Keep taking if starting a biologic i.e. take both.
  • FBC, LFT, and U+E weekly until dose stabilised, then 3-monthly.
  • Baseline lung function tests and CXR, especially in smokers.
  • Take with folate.
  • Give flu vaccine.
  • Take week off if on antibiotics.

• Aminosalicylates

  Sulfasalazine and mesalazine (aka 5-aminosalicylic acid, 5-ASA).

  Mechanism

  Anti-inflammatory and immune modulating.

  Side effects

  Class effects:

  • Hypersensitivity: rash, urticaria. Other rashes may also occur e.g. SJS.
  • Headache
  • GI: diarrhoea, nausea, vomiting.
  • Renal impairment: interstitial nephritis, nephrotic syndrome.
  • Cytopaenia: neutropenia, aplastic anaemia, thrombocytopenia.

  Sulfasalazine:

  • Cough
  • Insomnia
  • Stomatitis and taste disturbance.
  • Pruritus
  • Macrocytosis due to impaired folate metabolism.
  • Rare: orange urine, ↓sperm count.

  Management

  • Check kidney function before starting then at 3 months then annually.
  • Any signs of cytopaenia – bleeding, bruising, soar throat, fever – stop drug and check FBC.

• Anti-TNF alpha monoclonal antibodies

  Drugs

  • Infliximab
  • Adalimumab
  • Etanercept
  • Certolizumab pegol.
  • Golimumab

  Side effects

  • Infection, including TB reactivation, so investigate and treat TB first.
  • GI: nausea, abdo pain.
  • Heart failure.
  • Hypersensitivity
  • Systemic: fever, depression.
  • Cytopaenia

• Joint injection

  Background

  • Usually a corticosteroid e.g. cortisone, methylprednisolone, or triamcinolone (aka Kenalog, also given IM). Non-steroid options: lidocaine, infliximab.
  • Effective for 2 weeks.

  Indications

  • RA: relapses or as a bridge until DMARDs.
  • Crystal arthritis.
  • Advanced OA.
  • Soft tissue inflammation: bursitis, tendinopathy, nerve entrapment.

  Contraindications

  • Infection: septic arthritis (or a past history of it in that joint), adjacent cellulitis or osteomyelitis, sepsis.
  • Prosthetic joint.
  • Fractured joint.
  • Immunosuppressed
  • Uncontrolled diabetes.
  • Coagulopathy
  • >4 injections per year in the same joint.

  Side effects

  • Post-injection pain flare, up to 48 hours.
  • Infection: 1/10,000.
  • Trauma, including to nerves or tendon.
  • Dimple at injection site (subcutaneous fat atrophy), especially in elbow, wrist, or hip.