This is a long term joint inflammation issue driven by autoimmunity cartilage and joint components
Presentation
This usually presents with pain and stiffness of the small joints of the hands and feet, which is worse in the morning and better in the evening. Fatigue is common. Deformity is common in advanced disease. It is often symmetrically distributed across body. (eg same joints on right and left side)
Pathology
Aetiology
We don’t really know how rheumatoid arthritis forms but we have some good guesses
ACPAS
Intolerances to Citrullinated protein builds in the lungs through stress smoking or infection which then react to
Symptoms
The articular symptoms are: swelling of joints, immobility, tenderness and pain, erythema. these are usually worse in the morning and better throughout the day.
we also see the accompanying signs of chronic inflammation
Pathological identification
we often see development of a Pannus, effusion into joint as well as erosion of the cartilage.
Treatment
we do not have a cure but we are able to use a number of treatments for symptoms
NSAIDS
NSAID stands for nonsteroidal anti inflammatory drugs, and they often act as a pain suppressant as well.
NSAIDS are prescribed to reduce pain, fever, and inflammation, and have Little side effects
They work by inhibitiing cycloxygenase (COX) which makes prostaglandins which trigger nociceptive and inflammatory resposes.
There are 2 COX enzymes which can be targeted:
- COX-1
- COX-2 (more important to target)
Examples are:
- aspirin (slightly selective for COX-1)
- ketoprofen
- ibuprofen (more potent than aspirin reversible and bind cox 1 and 2)
- indomethacin
- diclofenac (more potent thean ibuprofen and moderate selectivity for cox-2)
- naproxen
COX-2 specific inhibitors
Highly cox2 selective
no gastric problem but you do get increase in CV events
Examples - Celecoxib
- Etoricoxib
Glucocorticoids (Steroids)
These imitate cortisol, the chronic stress hormone. This has an anti-inflammatory and immunosuppressive effect, amongst others.
this is to stop the chronic immune system response
do not alter disease progression
prolonged use can cause reduction in bone healing
glucocorticoids can make lipocortin-1 which can inhibit phospholipase and inhibit cox-2 which synergises well with NSAIDS
Dmards
Cause disease remission or stop progression.
all cause immunosupression
Examples
- methotrexate (cytotoxic)
folate antagonist so slows fast reproducing cells - cyclophosphamide (cytotoxic)
- gold salts
- D-penicillamine
- hydroxychloroquine
- sulfasalazine
metabolised into 5-aminosalicylic acid (5-ASA) and sulfapyridine
5-ASA helps reduce inflammation and sulfapyridine may help effects
colonic bacteria metabolically process sulfasalazine
Biological agents (proteins and such)
- Infliximab anti tnf monoclonal antibodies (mouse variable region)
- Anakinra
- Abatacept
- Rituximab depletes b cells
- Onercept
- Etanercept
Treatment of RA preferred drugs
NSAIDS
- Ibuprofen
- Diclofenac
COX-2 Inhibitors - Celecoxib
Glucocorticoids - Prednisone
Xenobiotics (often just kill quickly replicating cells) - Methotrexate
- Cyclosporin
Biological Agents (specific which is nice) - TNF inhibitors
- Adalimumab anti tnf antibody with human variable region
- Etanercept (soluble tnf receptor to sponge up tnf)
- IL-6 receptor inhibitor
- Tocilizumab
- CTLA-4 inhibitor
- Abatacept blocks signal between antigen presenting cell and t cell