Rheumatoid Arthritis Flashcards
Prevalence/ Natural History of RA
-Systemic (as immune response generated in lymphoid organs so symmetrical involvement) autoimmune disease affecting 1% of population (most common chronic inflammatory arthritis)
-Women 3:1 more common. Middle age
-Incurable, progressive and presents initially with synovial joint inflammation (stretching of tendons, bone and cartilage erosions)
-75% have an erosion within 2 yrs
Pathogenesis of RA
-Genetic component HLA region or regulation of immune response
-Environmental: infection/smoking triggers autoimmunity in genetically susceptible host by modifying proteins
-Infiltration of synovium with immune cells
-Lymphoid follicles form
-T cell activation producing cytokines and B cells activate to produce autoantibodies (RF and ACPA)
-Synovial fibroblasts proliferate= hypertrophy= matrix metalloproteinases and ADAMTS-5= degrade soft tissue and cartilage
-Prostaglandins and NO= vasodilation
-Inflamed synovium directly invades bone and cartilage at joint margin to cause erosions (osteoclast activation), angiogenesis
=Neutrophils in synovial fluid, macrophages and T-cells in synovial membrane
Main presenting symptoms of RA
-Swelling of the joints (symmetrical distribution affecting wrists, MCP and PIP joints of the hands and MTP joints of the feet so periphery to proximal, large joints may also be affected as gets worse)
-Joint tenderness
-Systemic malaise (low grade fever, depression, weight loss, fatigue)
-Loss of energy
-Severe early morning stiffness (typically >30 minutes and stiffness after a period of inactivity)
Examination findings of RA
-Soft tissue swelling and tenderness of affected joints
-Pain on squeezing MCP and MTP joints, warmth
=Psoriasis (skin) and pitting nails
=Wasted muscles
=Bruising (chronic steroid use)
=Nodules
=Consider lupus in young women
Investigations of RA
-FBC (anaemia- chronic disease, high platelet, WCC) , ESR, LFT (DMARD rx difficult in cirrhosis, coeliac screen, viral titres of HIV, Hep B/C, Parvovirus -ve, Rubella, Lipids (inflammation= accelerated cardiac disease)= associated with arthritis)
-Anti-CCP antibodies, RF (IgM, reacts with Fc portion of IgG, Rose-Waaler test), ANA-ve
-X-ray of the hands (periarticular osteoporosis, erosions, usually normal)
RA Scoring system (2010 ACR Classification Criteria)
-Synovitis plus score of >-6/10 needed for definite RA
-Joint involvement
=One large joint: 0
=2-10 large joints: 1
=1-3 small joints: 2
=4-10 small joints: 3
=>10 joints (at least one small joint): 5
-Serology
=RF-, ACPA-: 0
=Low RF+ or low ACPA+: 2
=High RF+ or high ACPA+: 3
-Acute-phase reactants
=Normal CRP and normal ESR: 0
=Abnormal CRP or abnormal ESR: 1
-Duration of symptoms
-<6 weeks: 0
->6 weeks: 1
Differential Diagnosis of RA
-Spondyloarthropathy
=Psoriatic arthritis (different distribution, CCP -ve)
=Reactive Arthritis
=IBD associated arthritis
-Viral arthritis= presents similarly but resolves 4-6 weeks
-Osteoarthritis= different distribution (DIP, PIP, 1st CMC joints of hand), due to osteophytes, CCP-ve, ESR and CRP normal
-SLE
-Viral arthritis
-Vasculitis
-Coeliac disease
-Lymphoma
-Still’s disease
Risks of RA
-Joint damage, chronic pain, disability
-Reduced work capacity -Forced ‘early retirement’, depression and anxiety
-Risk of earlier death (< 7 years)
=x2 MI (like Type 2 Diabetes)
=70% increased risk stroke
=70% increased risk infection
=Up to 26-fold higher risk of lymphoma
=Extra articular systemic complications
Complications of RA
-Tenosynovitis induced deformity (altered joint alignment by stretched tendons and ligaments)
=Swan neck (MCP joint flexion, PIP hyperextension, DIP flexion)
=Boutonniere (flexed PIP, DIP hyperextension)
-Ulnar deviation reduces hand function
=Cannot oppose thumbs
-Bone erosions cause permanent disability
=Orthopedic surgery
-Rheumatoid nodules
Extra-articular manifestations of RA
-Neurologic
=Neuritis, stroke
-Lungs
=Pulmonary nodules, effusions
-Ocular
=Episcleritis
-Heart
=Pericarditis
-Vascular
=Vasculitis, treat with steroids and cyclophosphamide
-Skin
=Nodules
Goals of RA Management
-Relieve pain, Normalize function, Prevent damage
=Prednisolone (oral, short course 30mg daily tapered over 12 weeks)
-Patient education about the disease-smoking. Self efficacy
-Nurse Practitioners, Physiotherapy Occupational Therapy
What is involved in early aggressive treatment?
-DMARDs (takes 8 weeks to be fully effective)
=Methotrexate (FBC and LFT monitoring for myelosuppression and liver cirrhosis, pneumonitis)
=Hydrocholoquine
=Sulphasalazine
=Leflunomide
-Short course oral steroids (prednisolone 30mg daily tapered over 12 weeks)
-Less able to tolerate DMARDs over time, indicated for biologics if high disease activity
Drug Management of Resistant RA-Biologics
-Interfere with cytokine function, indicated when inadequate response to at least 2 DMARDs including methotrexate (failed 3 and DAS28 5.1+)
=Anti-TNFa (Infliximab= IV monoclonal antibody, Etanercept= recombinant human protein, Adalimimab= subcutaneous monoclonal antibody)- risk reactiviating TB
=Anti IL-6 (Tocilizumab)
-Inhibit the second signal
=CTLA4-Ig-Abatacept (modulates T cell activation so less T cells) (5th line)
-Deplete B cells
=Rituximab (anti-CD20 monoclonal antibody IV)
-Oral small molecule inhibitors
=e.g. Baracitinib or Tofacitinib
Describe Tocilizumab
- Humanized Monoclonal antibody against the IL-6-Receptor.
-Administered by hour-long intravenous infusions or by SC injection.
Disadvantages of Tocilizumab
-Serious infections with upper respiratory tract infections being most common
-Long term safety not assessed
