Rheumatoid Arthritis Flashcards
How is inflammatory arthritis characterised
Joint Pain
Stiffness- after rest and in the morning (lasts several hours)
When does rheumatoid arthritis normally occur in which patient groups
Pre-Menopausal women (3 times more like than men)
30 to 50 years of age
Normochromic and normocytic anaemia is normally associated with rheumatoid arthritis, what does it mean
Reduced number of normal sized erythrocytes with normal haemoglobin content associated with chronic disease
What is rheumatoid arthritis
Non specific inflammatory response:
Localised tissue damage and release of neo-autoantigens
What is the mechanism of action of rheumatoid arthritis
- Local tissue damage leads to activation of synovial T cells
- B cells activated and produce autoantibodies and rheumatoid factors which form immune complexes
- Bind to complement and stimulate neutrophils- produces pro inflammatory cytokines (IL-1 and TNF-alpha) and chemokine
- Chronic inflammation- maintained by rheumatoid factors and continuous stimulation of macrophages by pro-inflammatory cytokines and chemokines
How is the chronic inflammation of rheumatoid arthritis maintained
Rheumatoid factors and continuous stimulation of macrophages by pro-inflammatory cytokines and chemokines
Describe the pathology of rheumatoid arthritis
Chronic Synovitis characterisation
Inflammation of synovial lining of joints, tendons sheaths or bursae
New synovial blood vessels made are induced by angiogenic cytokines and endothelial cell activation- expedites leucocyte extravasion
Synovium proliferates and grows out over cartilage surface- forms pannus
Pannus destroys articular cartilage and subchondral bone- bony erosions
What are the symptoms and features of Rheumatoid arthritis
Insidious onset of pain
Early- morning stiffness that lasts more than 30 minutes
Swelling in small joints of hands and feet (symmetrical)
Joint capsules weakened- instability and deformity
Multiple joints involved: wrists, elbows, shoulders, cervical spine, knees, ankles, feet
Affects one side then the other
What can rheumatoid arthritis increase the risk of
Atherosclerosis
Infection
Osteoporosis
What is Sjorgens syndrome
Dry eyes and mouth due to destruction of epithelial endocrine glands- auto immune disease
How do you diagnose rheumatoid arthritis
Blood count: anaemia- nromochromic and normocytic
Thrombocytosis- over production of platelets
Raised ESR and CRP
Presence of serum autoantibodies: Rheumatoid factor, anti-nuclear factor
Presence of Anti-citrulline containing peptide (CCP)
Radiology: presence of soft tissue swelling, joint narrowing, erosion of joint margins
Sterile synovial fluid- high neutrophil count
What is the treatment goals for rheumatoid arthritis
Remission of symptoms- return to full function and maintenance of remission
What treatment options are available for Rheumatoid Arthritis
NSAIDs- relieving pain and stiffness
Disease Modifying Anti-rheumatic drugs (DMARD):
Penicillamine
Gold Salts
Antimalarials- chloroquine, hydrochloroquine
Sulfasalazine
Methotrexate
Cytokine inhibitors- adalimumab, anakinra, entanercept, infliximab
Corticosteroids: short term
Others: Paracetamol, codeine
What NSAID should be used in rheumatoid arthritis?
Ibuprofen:
200 to 400mg THREE times a day
Allows for rapid pain relief (1 week) Inflammatory effect (3 week)
When should intra-articular injections be used in corticosteroids?
Used only if no response to drug therapies
Relieve symptoms in one or two joints- limitation on number of injections into joint (no more than 3 a year)
When can DMARDS be used and how are they used
Used only under consultant supervision alongside methotrexate
Can be used individually if combination not tolerated
What is the first choice in DMARD therapy in Rheumatoid Arthritis and its MoA
SULFASALAZINE
Immunosuppressant action by scavenging toxic oxygen metabolites produced by neutrophils
What are the common side effects of sulfasalazine
First 3-6 months
GI disturbances Malaise Headache Rashes Blood disorders
What are the testing required for sulfasalazine and the drug that must be used alongside it
Blood counts and liver function tests for first 3-6 months
Folic acid supplements
What is the common antimalarial drug used in modern rheumatoid arthritis
Hydroxychloroquine
What are the problems that may occur from using antimalarials
Ocular toxicity or progressive loss of vision with long term treatment
What is the mechanism of action with Methotrexate
Folic acid antagonist that inhibits dihydrofolate reductase
Reduces availability of tetrahydrofolic acid needed for purine production and DNA synthesis
Suppresses cell division in immune cells, suppresses cell mediated immunity
What are the monitoring requirements required for methotrexate
Full blood count for blood disorders
Liver function tests for liver cirrhosis
What is the dose of methotrexate for rheumatoid arthritis
Take ONE 7.5mg tablet everyweek
What is usually given alongside methotrexate to prevent adverse side effects
Folic acid supplement
What are the common side effects associated with methotrexate
Stomatitis GI disturbance Alopecia Mild drug induced hepatitis Pneumonitis Blood disorders/Rash
What adverse effects must patient report for methotrexate
Bone marrow suppression/blood dyscarasias
Pulmonary Toxicity-SOB
Liver toxicity- nausea, vomiting, abdominal discomfort, dark urine
What is the gold salt called used in rheumatoid arthritis and its role
Aurothiomalate
Believed to suppress cell mediated immune reactions
What is the mechanism of action of penicilliamine
Altering synthesis and maturation and cross linking of COLLAGEN (anti collagen antibodies)
Altered production of immunoglobulins
Reduction in circulating immune complexes
Decrease generation of IL-1 and suppression of lymphocyte secretion
What are the common side effects of peniclliamine
Nausea Loss of taste Rashes Blood disorders- report this Proteinuria hair loss
What should you monitor in patients taking penicillimine
Monthly blood counts
Urine tests and renal function
When should you use Cytokine Modulator biologics
Used for highly active rheumatoid arthritis if it fails to respond to TWO STANDARD DMARDS
What are cytokine modulators normally used alongside with
Used with methotrexate
What are the common side effects of Cytokine Modulators
Infections- TB, hepatitis B reactivation, septicaemia
Nausea
Vomiting
Abdominal pain
Worsening heart failure
Hypersensitivity reactions
Fever
Headache
Depression
Injection site reactions
Give examples of first line biologics used and when are they used
Etanercept, Adalimumab and Infliximab
When two standard DMARDS fail
What is the role of Infliximab, Golimumab and Etanercept
Infliximab (adalinumab as well) and Golimumab: Anti-TNF
Etanercept: recombinant fusion protein of TNF receptor fused to FC region of human IgG
What is the role of Rituximab and Abatacept
Rituximab: Anti-CD20 monoclonal antibody inhibitor that depletes B cells
Abatacept- recombinant fusion protein of IgG and CTLA-4 that inhibits T cell stimulation
What is the role of Tocilizumab and Anakinra
Tocilizumab- humanised monoclonal antibody to IL-6 receptor
Anakinra- IL-1 receptor antagonist- not recommend for rheumatoid arthritis
What activates TNF, IL-1, IL-6 and IL-8
TNF- macrophage
IL-1 - monocyte and macrophage
IL-8 synovial fibroblast
IL-6 Synovial fibroblast
What is the role of the new drug Leflunomide
Potent inhibitor of pyrimidine synthesis that affects T cell proliferation and is immunomodulatory
What are the severe adverse side effects associated with Leflunomide
Bone marrow toxicity
Hepatotoxicity
Infection
Malignancy
What is the role of Azathioprine and mechanism of action
Interferes with purine synthesis and is cytotoxic
MoA:
Represses both cell mediated and antibody immune reactions by preventing clonal expansion of T and B cells
What are the adverse effects of Azathioprine
Bone marrow toxicity Mild Hepatotoxicity Infections (herpes zoster) GI disturbances SKIN RASHES
What is cyclosporin licensed for and its mechanism of action
Severe rheumatoid arthritis
MoA:
Suppression of T cell mediated immune responses
Helps slow rate of joint erosion
What are the side effects associated with ciclosporin
Nephrotoxicity Hepatotoxicity Hypertension Anorexia Lethargy Tremor Gum hypertrophy GI disturbance
