Rheumatoid Arthritis Flashcards
At what age is the peak prevalence of RA?
30-50 years
What is rheumatoid arthritis?
A chronic systemic autoimmune disorder causing a symmetrical polyarthritis
Describe the aetiological role of gender in RA?
Women before the menopause are affected 3x more often than men. After menopause there is an equal sex incidence, suggesting an aetiological role for sex hormones
What antigens confer susceptibility to RA?
HLA-DR4 and HLA-DRB1*0404/0401. This human leukocyte antigens are associated with more severe disease
What is rheumatoid factor? How often is it present in patients with RA?
Rheumatoid factor is autoantibodies directed against the Fc portion of immunoglobulin. These autoantibodies are produced by B cells. It is positive in 70% of patients. It is not, however, specific for RA and occurs in connective tissue disease and some infections
What is citrullination?
The conversion of the amino acid arginine in a protein into the amino acid citrulline. The immune system often attacks citrullinated proteins, leading to autoimmune diseases such as rheumatoid arthritis
What is anti-CCP?
Anti-CCP (anti- cyclic citrullinated peptides) are autoantibodies that are directed against peptides and proteins that are citrullinated. Anti-CCP (also known as ACPA (anti-cirullinated protein antigen) is often present in patients with rheumatoid arthiritis.
What antibody class is most rheumatoid factor?
IgM
Why are anti-CCP antibodies important markers for diagnosis and prognosis of RA?
- They are as sensitive and more specific than IgM RF
- They may predict eventual development into RA when found in undifferentiated arthritis
- They are a marker of erosive disease in RA
- They may be detected in healthy individuals years before onset of clinical RA
- Anti-CCP rarely occurs in healthy people (while healthy people can also have RF)
- Combination of RF and anti-CCP positive results makes RA very likely
- These seropositive patients have a poorer prognosis and often need more aggressive treatment
What is the importance of TNF in RA?
Overproduction and overexpression of tumour necrosis factors is a key inflammatory element in RA, leading to synovitis and joint destruction. TNF-α stimulations overproduction of IL-6. Antibodies to TNF-α and IL-6 produce marked short-term improvements in synovitis demonstration the role of these cytokines in RA
What are the characteristic pathological features of RA?
- Synovitis (inflammation of the synovial lining of joints, tendon sheaths or bursae)
- Thickening of the syovial lining
- Infiltration of the synovial lining by inflammatory cells
Describe the normal synovium
Thin, comprising a lining layer a few cells thick containing fibroblast-like synoviocytes and macrophages overlying loose connective tissue
How do angiogenic cytokines contribute to the development of RA?
They induce generation of new synovial blood vessels
How do activated endothelial cells contribute to the development of RA?
They produce adhesion molecuels such as vascular cell adhesion molecule-1 (VCAM-1) which expedite extravasation of leucocytes into the synovium
What is a pannus?
Proliferation of the synovium causes it to grow out onto the cartilage surface producing a tumour like mass called a pannus.
Why is the development of a pannus damaging to the joint?
The pannus damages the underlying cartilage by blocking its normal route for nutrition and by the direct effects of cytokines on the chondrocytes. The cartilage then becomes thinned, exposing the underlying bone, producing the diagnostic juxta-articular bony ‘erosions’ seen on X-ray
What early damage is caused by fibroblasts in the first 3-6 months of RA?
Fibroblasts from the proleferating synovium grow along the course of blood vessels between the synovial margines and the epiphyseal bone cavity and damage the bone. This early damage justifies the use of DMARDs within 3-6 months of onset of arthritis
What is seronegative RA? How is it diagnosed?
The term ‘seronegative RA’ is used for patients in whom the standard tests for IgM rheumatoid factor are per- sistently negative. They tend to have a more limited pattern of synovitis.
Diagnosis is made based on symptoms and signs and confirmed by ultrasound of joints showing synovitis
What is the difference between seropositive and seronegative RA in terms of Hb and inflammatory markers?
In seropositive RA, inflammatory markers are high and Hb may be low
In seronegative RA inflammatory markers are lower and Hb is normal
IgM RF is neither diagnostic of RA, nor does its absence rule disease out. Why then is it still a useful test?
It is a useful predictor of prognosis. A persistently high titre in early disease implies more persistently active synovitis, more joint damage and great disability eventually, and justifies earlier use of DMARDs
What is the most typical presentation of RA, occuring in approx. 70% of cases?
A slowly progressive, symmetrical peripheral polyarthritis, evolving over a period of a few weeks or months
How does RA present less commonly, in approx 15% of cases?
Rapid onset occuring over a few days (or explosively overnight) with a severe symmetrical polyarticular involvement, especially in the elderly.
What factors indicate poor prognosis?
- Older age
- Female sex
- Symmetrical small joint involvement
- Morning stiffness lasting >30 mins
- > 4 swollen joints
- CRP >20
- Positive RF and ACPA
What are the differentials for early signs of RA?
- Post viral arthritis: rubella, hep. B or erythrovirus
- Seronegative spondyloarthopathies
- Polymyalgia rheumatica
- Acute nodal osteoarthritis (PIPs and DIPs involved)
What are the ACR/EULAR 2010 criteria for RA?
- Joint involvement: (0-5)
- 1 medium to large joint= 0
- 2-10 medium to large joints= 1
- 1-3 small joints = 2
- 4-10 small joints= 3
- >10 joints, at least one of which is small= 5 - Serology: (0-3)
- Negative RF and negative ACPA= 0
- Low positive RF or low positive ACPA= 2
- High positive RF or high positive ACPA= 3 - Acute-phase reactants: (0-1)
- Normal CRP and normal ESR= 0
- Raised CRP or raised ESR= 1 - Duration of symptoms: (0-1)
- <6 weeks= 0
- ≥6 weeks= 1
Cut off point for RA is 6 or more points
Why are the ACR/EULAR 2010 criteria more suitable for assessing RA than earlier criteria?
They do not rely on later changes such as erosions and extra-articular disease so are more suitable for assessing early arthritis
In early RA, what criteria identify a patient for earlier treatment to avoid joint damage?
The combination of:
- At least one swollen joint
- For more than 6 weeks
- No associated history or family history of spondyloarthritis or associated conditions such as psoriasis
- A positive ACPA
What is the common presenting complaints in patients with RA?
Pain and stiffness of the small joints of the hands (MCP, PIP, DOP) and feet (MTP).
Fatigue is also a common complaint as pain and stiffness is worst in the morning, disturbing sleep
In 10% of cases, RA patients do not present with polyarticular pain of small joints. Why else might these patients present?
10% present with a monoarthritis of the knee or shoulder or with carpal tunnel syndrome
What is a palindromic presentation of RA?
Unusual (5%). COnsists of short liver (24-72 hour) episodes of acute monoarthritis. The joint becomes acutely painful, swollen and red, but resolves completely. Further attacks occur in the same of other joints. About 50% go on to develop typical chornic rheumatoid synovitis after a delay of months or years. The rest remit or continue to have acute episodic arthritis. Detection of RF or ACPA predicts conversion to chronic destructive synovitis
What is a transient presentation of RA?
A self-limiting disease, lasting less than 12 months and leaving no permanent joint damage. Usually seronegative for IgM rheumatoid factor and ACPA. Some of these may be undetected post-viral arthritis.
What is a chronic persistent presentation of RA?
The most typical form, it may be seropositive or seronegative for IgM rheumatoid factor. The disease follows a relapsing and remitting course over many years. Seropositive (plus ACPA) patients tend to develop greater joint damage and long-term disability. They warrant earlier and more aggressive treatment with disease-modifying agents.
What is a rapidly progressive presentation of RA?
The disease progresses remorselessly over a few years and leads rapidly to severe joint damage and disability. It is usually seropositive (plus ACPA), has a high incidence of systemic complications and is difficult to treat.
How may seronegative RA present?
Typically affects the wrists more often than the fingers and has less symmetrical joint involvement. It has a better long-term prognosis but some cases progress to severe disability.
What condition may seronegative RA be confused with?
Psoriatic arthropathy, which has a similar distribution
What are the complications of RA?
Ruptured tendons Ruptured joints (Baker's cysts) Joint infection Septic arthritis Spinal cord compression Amyloidosis (rare)
How does septic arthritis present?
Affect joints are often painful, swollen, red and hot. Symptoms develop quickly over a few hours or days. May also present with fever. There is usually neutrophil leucocytosis. Any effusion in RA, particularly of sudden onset, should be aspirated
What is the most common causative agent of septic arthritis?
Staph. aureus
What deformities are seen on the hands of patients with RA?
Ulnar drift Palmar subluxation of the MCPs Boutonniere deformity Swan neck deformity Swelling and subluxation of the ulnar styloid causing wrist pain
