Rheumatoid Arthritis Flashcards
Definition
Autoimmune condition = Chronic, systemic inflammatory disease of the synovial lining of joints, tendon sheaths and bursa. This leads to a deforming, symmetrical inflammatory arthritis of the small joints which progresses to involve larger joints and other organs of the body, e.g. skin and lungs
Epidemiology
30-50 years of age
WOMEN
Risk factors
Family history
- Genetic predisposition: HLA-DR1 and DR4
Smoking
Infections
Hormones = increased risk in pre menopause possibly oestrogen
Aetiology
Genetic and environmental factors, leading to an immune response against self-peptides, particularly those which are citrullinated:
Genetic factors:
- HLA-DR1 and DR4 = activate T-cells
* also PTPN22 *
Environmental triggers
- Cigarette smoking is a significant risk factor
- Various pathogens have been proposed as a trigger
Pathophysiology
Environmental factors can cause modification of our own antigens, such as IgG antibodies or other proteins like type II collagen or vimentin through a process called citrullination.
= arginine -> citrulline.
HLA- DR1 and HLA–DR4 = immune cells no longer recognize these proteins as self-antigens = inflammatory cascade with IL1,6, gamma and TNF a = stimulate synovial cells to proliferate
The increase in synovial cells and immune cells creates a pannus, which is a thick, swollen synovial membrane with granulation or scar tissue, made up of fibroblasts, myofibroblasts and inflammatory cells.
Over time, the pannus can damage cartilage and other soft tissues and also erode bone.
Activated synovial cells also secrete proteases which break down the proteins in the articular cartilage = the underlying bones are exposed and can directly rub against one another.
In addition, inflammatory cytokines increase RANKL= RANKL allows the T-cells to bind RANK, a protein on the surface of osteoclasts, to get them to start breaking down bone.
Antibodies also enter the joint space.
- Rheumatoid Factor (RF) is an autoantibody presenting in around 70% of RA patients = targets the Fc portion of the IgG antibody. All antibodies have an Fc portion = used to bind to cells of the immune system. This causes activation of the immune system against the patients own IgG causing systemic inflammation. Rheumatoid factor is most often IgM however they can be any class of immunoglobulin.
- Cyclic citrullinated peptide antibodies (anti-CCP antibodies) are autoantibodies that are more sensitive and specific to rheumatoid arthritis than rheumatoid factor. Anti-CCP antibodies often pre-date the development of rheumatoid arthritis and give an indication that a patient will go on to develop rheumatoid arthritis at some point.
Signs
symmetrical distal polyarthropathy
- painful, swollen, warm, tender joints of the hands and feet (MCP, PIP, MTP)
- progress to larger joints (shoulder, elbow, knees)
- worst on rest, improves on activity (opposite of OA)
Hand deformities:
- Boutonniere deformity: PIP flexion and DIP hyperextension
- Swan-neck deformity: PIP hyperextension and DIP flexion
- Z-thumb deformity: hyperextension of the thumb IP joint with flexion of the MCP joint.
- Ulnar deviation of the fingers
- Rheumatoid nodules
Knee:
- Bakers cyst: synovial sac pushes knee joint into popliteal fossa
Symptoms
Morning stiffness: > 30 mins and improves thoughout the day
Constitutional symptoms:
- Malaise
- Myalgia
- Low grade fever
FELTY SYNDROME
Triad of:
- Rheumatoid arthritis
- Granulocytopenia
- Splenomegaly
Life threatening risk of infection
Palindromic rheumatism
Self limiting short episodes of inflammatory arthritis with joint point, stiffness and swelling typically affecting only a few joints. Only last 1-2 days then completely resolves. Having positive RF - may indicate full RA progression in future
Diagnosis
Examination of someone’s hands:
- Palpitation of the synovium in around joints when the disease is active will give “boggy” feeling related to the inflammation of swelling
Diagnostic criteria: RF RISES
- Rheumatoid Factor positive
- Finger/hand/wrist involvement
- Rheumatoid nodules present
- Involvement of 3+ joints
- Stiffness in the morning for more than 1 hour
- Erosions seen on x-ray
- Symmetrical involvement
Check rheumatoid factor and Anti-CCP
Inflammatory markers = ESR + CRP
Bloods = normocytic normochromic anaemia
X-ray: LOSE
- Loss of joint space/ Joint destruction + deformity
- Osteopenia periarticular
- Soft tissue swelling
- Erosions of bone
USS:
- confirm synovitis
American College of Rheumatoid Arthritis (ACR) and European League Against Rheumatism (EULAR)
Score of >6 out of 10 required for a diagnosis of RA
A: Joint involvement
= 1 large joint: 0
= 2-10 large joint:
= 1-3 small joints: 2,
= 4-10 small joints: 3
= > 10 joints (w/ 1 small joint): 5
B: Serology
= Negative RF and anti-CCP: 0
= Low titres of RF or anti-CCP: 2
= High titres of RF or anti-CCP: 3
C: Acute phase reactants
= Normal CRP and ESR: 0
= Abnormal CRP or ESR: 1
D: Duration of symptoms
= < 6 weeks: 0
= > 6 weeks 1
Treatment
FIRST LINE: DMARD = METHOTREXATE + folate
SECOND LINE: Add another DMARD = SULFASALAZINE or HYDROXYCHLOROQUINE
GOLD STANDARD = DMARD + BIOLOGIC = METHOTREXATE + INFLIXIMAB (FL) or RITUXIMAB (SL)
Treat flares:
- NSAIDS
- Intra-articular therapy: glucocorticoids = IM Methylprednisolone
Complications
Skin: rheumatoid nodules
Ophthalmological: Scleritis, Episcleritis
Systemic: Felty’s syndrome
- Splenomegaly
- Neutropoenia
- Rheumatoid arthritis
What class is INFLIXIMAB
TNF-a Inhibitor
What class is RITUXIMAB
B cell inhibitor (CD20 target)
