Common disorder of connective tissue and important cause of disability morbidity and mortality. Life expectant reduced by 4 years in men and 10 years in women. Western countries affect 1-3%. 3:1 female preponderance - greater in the young females, equal in the elderly. Disease is high during child bearing age but disease tend to go into remission during pregnancy High gravity (more children) adds protections against disease as does the pill.
1st degree relatives of a patient with RA will share diagnosis of RA 2-10 times
greater cf the general population ! Uncertainty remains about the extent to
which genetics play a role ! allelic variation in the HLA-DRB1 gene, which
encodes the MHC II β-chain molecule. ! Non-MHC loci may also contribute E.g.
tyrosine phosphate non-receptor 22 (regulates T & B cell function appears to be
associated exclusively with anti-CCP positive disease).
Environment
Smoking
Most reproducible risk factor, it confers an
increased risk of 1.5 – 3.5 greater than
non-smokers. ! Risk remains high up to 15
years after smoking cessation. ! Cessation isn’t
generally associated with reduced disease
activity. ! Smoking is almost exclusively related
to Rheumatoid factor (RF) and anti-citrullinated
protein antibody (anti-CCP) positive disease
EBV
IgG antibodies against EBV antigens are higher
in patients with RA 26/07/17 than the general
population. ! EBV DNA has also been found in
synovial fluid and synovial cells of RA patients.
! Unable to establish a causal link
Pathogenesis
CD4+ helper T cell activation appear to be involved in
co-ordinating the chronic inflammatory response.
Stimulate macrophages and fibroblast-like
synoviocytes to release inflammatory mediators
and proteases ! Help B cell to produce
autoantibodies ! Differentiate into Th1 and Th17
cells which secrete pro- inflammatory mediators !
Directly and indirectly increase osteoclast activity
B cells and Autoantigens
Autoantigens – Serum RF and anti-CCP antibodies are present in 75-80%
of patients with RA ! RF have not been identified as pathogenic, nor
does higher levels always mean higher disease activity. But RF positive
patients tend to have a more aggressive disease. ! Anti-CCP antibodies
maybe present long before they develop symptoms of RA, and those
with positive antibodies have a poorer prognosis ! Other autoantigens
identified with possible links to RA include: ! including type II collagen,
human cartilage gp-39, aggrecan, calpastatin, BiP (immunoglobulin
binding protein), and glucose-6-phosphate isomerase
Pathology
The pathologic hallmarks of RA are
synovial inflammation and proliferation,
focal bone erosions, and thinning of
articular cartilage.
Chronic inflammation leads to: ! synovial lining hyperplasia and the formation of pannus ! the
pannus contains fibroblast-like synoviocytes and granulation- reactive fibro-vascular tissue that
invades the underlying cartilage and bone ! the area under the pannus is heavily infiltrated with
inflammatory cells, including T and B lymphocytes, macrophages, mast cells, and mononuclear cells
that differentiate into multinucleated osteoclasts ! structural damage to the mineralized cartilage
and subchondral bone (osteoclast mediated). ! periarticular osteopenia and thinning of the bony
trabeculae ! bone marrow lesions ! generalized osteoporosis
The end results of chronic inflammation for joint structure are variable. ! Loss of cartilage may result
in a loss of the joint space. ! The formation of chronic granulation or scar tissue can lead to loss of
joint motion or bony fusion (called ankylosis). ! Laxity of tendon structures can result in a loss of
support to the affected joint, leading to instability or subluxation. ! Tendon contractures also may
occur, leading to chronic deformity.
Clinical features
Effects of RA on hands:
Ulnar deviation, carpal tunnel syndrome,
subcutaneous rheumatoid nodules, flexion
contractures (boutonniere deformity - flexion of PIP
joint, and hyperextension of DIP joint) and swan neck
deformity (hyperextension of PIP joint and flexion of
DIP joint)
Early diease is usually insidous and can be episodic or
acute and may develop over weeks to months -
Prodromal symptoms include; fatigue, weakness, low
grade fever, loss of appetite, myalgia, joiint stiffness/pain
and stiffness and myalgie may precede develop of joint
swelling (heat, functional loss)
Late disease features include: loss of
joint motion, joint weakness and
deformity, atrophy of muscle, occurs
espically in the hand
Extra-articular manifestations
Although joint involvement in RA is the 1˚ feature in RA,
its important recognise that, as a systemi disease, other
organ systems are often involved. Rheumatoid nodules -
occur in 20% of patients, 1˚ located on the extensor
surface of elbow, forearm, hand and fingers
Annotations:
erferg
Vasculitis - invasion of blood vessel walls by inflammatory cells resulting in an
obliteration of the vessel, producing infarction of tissue distal to the area of involvement
- finger/nail beds, lower limbs ulcers often a consequence, nerves and organs
Pulmonary - pleural effusion, pulmonary fibrosis and nodules
Cardiac: pericarditis, mitral valve disease ( obstruction (stenosis) , leakage (regurgitiation)
and bulging backward during valve closure (prolapse)), conduction defects
Skin: palmr erythema, cutaneous vasculitis
Eye complications: Sjogrens syndromes (dry gritty eyes with slight redness but
normal vision) and scleritis (sevre pain and occasionally reduces vision
Neurological complications: Entrapment of peripheral nerves - carpal tunnel, ulnar, peripheral
neuropathy (assoicated with the disease, compression of nerve roots) and compression of cervical
region of the spinal cord
Complication of RA: Feltys syndrome, depression, loss of independent liiving, increased risk
of infections, complications of medical and surgical treatment
Diagnosis
Symptoms duration of longer than 6 weeks, early morning stiffness for longer than 1 hour,
arthritis in three or more regions, bilateral compression tenderness of the metatarsophalangeal
joints, symmetry of the areas affecte, rheumatoid factor posivity, anti0cyclic citrullinated
peptide (anti-CCP) antibody positivty, bony erosions evident on Xrays of the hands or feet
(uncommon in early disease) and family hisotry of imflam anthritis
Treatment
Drug treatment
Annotations:
Goals of treatment:
- relief of symptoms
- preservation of function
- prevention of structural damage and deformity
- Prevention or reduction of co-morbidities
- Maintenance of patients normal life style
Simple Analgesia:
- paracetamol, dextroprppxyphene and codeine are used for simple pain relief, strong narcotic analgesics should be avoided
NSAIDs:
- use for symptomatic relief of RA but do not alter the course of disease
Corticosteroids
Annotations:
Intra-articular corticosteroids can help to settle a flare
Bolus IV or IM corticosteroids can be used as adjunct to slower acting second line drugs
Daily oral corticosteroids may be during the initial treatment of RA if the disease is moderate/severe. Regular dosing is controversial
Actions of inflam cells include
Decreased egress of neutrophils from bleed
vessels and reduced actiavtion of
neutrophils, macrophages and mast cells 2˚
to decreased transcription of the genes for
cell adhesion factors and cytokines
Decreased overall activation of T-helper (Th) cells,
reduced clonal proliferation of T cells, and a
'switch' form the Th1 to the Th2 immune
response
Decreased fibroblasts function, less
production of collagen and
glycosaminoglycans, and, under some
circumstances, reduced healing and
repair
Actions on the mediators of inflam and immune
responses include
decreased production of prostanoids through
reduced expression of cyclo-oxygenase-2. decreased
generation of many cytokines, including IL-1, IL-2,
IL-3, IL-4, IL-5, IL-6, IL-8, TNF- alpha, cell adhesion
factors and granulocyte-macrophage
coloby-stimulating factor. These are largelt 2˚ to
inhibition of gene transcription
Reduction in the [] of complement components in plasma
Physical therapy
Complementary therapy
Measure of disease activity
DAS28 is a composite outcome measure that asses
How many joints in the hands, wrists, elbows, shoulders, and
knees are swollen and/or tender? The erythrocye
sedimentation rate (ESR) or C reactive protein (CRP) in the
blood to mesausre the degree of inflammation. The patients
Visual analgoue score (a simple scale) to assess how they are
feelng on that day from 0 (very good_ to 10 (very bad)
The results are combined to produce the DAS28 score, which correlates with
the extent of disease activity: <2.6: disease remission, 2.6-3.2: low disease
activity, 3.2-5.1: moderate disease activity and >5.1: high disease activity
Laboratory findings
Annotations:
Presence of rheumatoid factor
Presence of anti-CCP antibodies
Raised erythrocyte sedimentation rate (ESR)
Raised C reactive protein concentration (CRP)
AnaemiaThrombocytosisRaised ferritin concentration as acute phase proteinRaised serum globulin concentrationsRaised serum alkaline phosphatase activityAntinuclear antibodies may be present in some patients
Rheumatoid factors are anti-immunoglobulins and anti-IgG
and anti-IgM especially is an immunological hallmark of
rheumatoid arthritis. It is found in sera of 75-80% of patients
with RA however as a diagnostic toll it lacks specificty: RF can
be found in 1-5% of heealthy population, RF can be found in
other connective tissue disease such as Sjogren syndrome and
systemic lupus erthematosus. The other patients are
persistently seronegative despite otherwise typical disease
Indicators of acute phase responses are a raised ESR and the presence of a
acute phase proteins such as CRP are commonly found in patients with RA -
reflects general acute inflammation, may give indication of effectiveness of
drug treatment, disease is likely to progress if a rasied ESR (or presence of C
reactive protein) persists and progression can still occur if they dont persists
Anemia of chronic disease is often present in inflam
conditions and is resistant to normalisation w/ iron
supplement (differential diagnosis is important. If other
causes of anaemia are ruled out this introduces a
therapeutic problem - iron deficiency (blood loss caused
by NSAIDs), suppression of bone marrow function -
caused by sulphasalzine, penicillamin, gold & cytotoxic
drugs, folate deficinecy - caused by methotrexate,
sulphasalazine and haemolysis (caused by sulphasalazine
and dapsone)
Thrombocytosis - platelets often counts rise and fall in direct
correlation with disease activity (can also be from toxicity of
immunosuppressive therapy and associated with felty's
syndrome. Leukopenia - is associated with Feltys syndrome
(can also be from toxicity of methotrexate, gold, sulfasalazine,
penicillamine and immunosuppressive drugs and leukocytosis
often a result of corticosteroid treatment
LFTs maybe give abnormal results - transaminases and ALP
may be moderaltey elevated when the disease is active.
Radiography - hands are normal at presentation or may
show swelling of the soft tissue, loss of joint space or
periarticular osteoporosis and erosions typical of RA
develop within 3 years of the start of the disease in over
90% of patients