Rheumatoid Arthritis Flashcards by Wing Vong

How is inflammatory arthritis characterised

Joint Pain

Stiffness- after rest and in the morning (lasts several hours)

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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

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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

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What is rheumatoid arthritis

Non specific inflammatory response:

Localised tissue damage and release of neo-autoantigens

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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

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How is the chronic inflammation of rheumatoid arthritis maintained

Rheumatoid factors and continuous stimulation of macrophages by pro-inflammatory cytokines and chemokines

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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

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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

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What can rheumatoid arthritis increase the risk of

Atherosclerosis

Infection

Osteoporosis

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What is Sjorgens syndrome

Dry eyes and mouth due to destruction of epithelial endocrine glands- auto immune disease

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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

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What is the treatment goals for rheumatoid arthritis

Remission of symptoms- return to full function and maintenance of remission

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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

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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)

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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)

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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

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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

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What are the common side effects of sulfasalazine

First 3-6 months

GI disturbances 
Malaise
Headache
Rashes
Blood disorders

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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 ```