| Rheumatoid
arthritis
(Read
and study the rheumatoid arthritis articles in the course manual)
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An inflammatory joint disorder primarily characterised by symmetrical
polyarticular synovitis.
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Affects 1-3% of population.
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F 2-3x > M.
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Onset any age – more common 25 to 50 years (peak age of onset
is 35-45 years).
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Associated with reduced life expectancy and increased disability.
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Generally considered as a systemic disease – but, in the early
stages it is only an articular disease, with the systemic extra-articular
manifestations not developing until late in the disease
Aetiology:
• Unknown – probably multifactorial - inappropriate
inflammatory response. Genetic predisposition (HLA-DR4 antigen increases
risk by 5x) – localised to a pentapeptide in HLA-DRB1. Environmental,
infectious (parvovirus), diet, trauma or psychological factors may
play a role in initiating immune response.
Pathogenesis
• Inciting agent activates immune system --> immunological
reactions --> immune complexes in synovial fluid activate complement
--> inflammatory response --> joint destruction.
• Earliest change is inflammation and oedema of synovium with
increased vascularity and increased production of synovial fluid
– shows evidence of CD4+ T helper cells migrating into the
joint.
• Next the synovial villi hypertrophy, synovial cells proliferation,
increased vascularisation (angiogenesis) and pannus form (granulation
tissue that grows across surface of articular cartilage from adjacent
synovium).
•
This is followed by destruction of cartilage by pannus – mediated
by pro-inflammatory cytokines (eg TNF-alpha, interleukin-1-beta,
interferon-gamma) and metalloproteases (eg collagenases). The muscles
waste around the joint, hyperaemia develops and the joint capsule
is distended. There is also destruction of unprotected bone at joint
margin and subchondral bone by pannus, later leading to marked joint
damage and capsular laxity, leading to deformity and fibrous ankylosis
and eventually bony ankylosis of the joint.
Clinical
features
• Onset insidious in 70% – sometimes abrupt with multiple
joint involvement.
• Often begins with insidious ache and morning stiffness (>30
mins) - gets better with motion; ‘Gel phenomenon’ –
stiffness/ache after rest. Most common presentation: polyarticular
and symmetric – especially of small joint of feet and hands.
Tenderness in all joints affected. Early afternoon fatigue and malaise
also occur.
• Forefoot is presenting sight of symptoms in up to 20% -
but initial symptoms in this area may be more common, but tolerated
by patients and they may not present until other symptoms (eg fingers)
occur.
• The early symptoms prior to diagnosis may be ‘normalised’
by the patients as being part of their age and activities and not
part of a disease – most also responded to their initial symptoms
by taking no action or using self-treatment.
X-ray
• Typical radiographic changes in synovial joints –
initially get soft tissue swelling and widening of joint space with
some osteoporosis. Later get periarticular (juxta-articular) osteoporosis
and uniform narrowing of joint space (as cartilage is destroyed),
marginal cortical bone erosions (due to pannus destruction), subchondral
bone erosions and cysts form, subluxations. In end stages may get
bony ankylosis. Changes often first seen in fifth metatarsophalangeal
joint.
• Evidence of erosive damage to bone is seen in 45% patients
on MRI within 4 months of symptom onset and 75% with 2 years
Later
extraarticular manifestations
• Weight loss; malaise and fever; lymphadenopathy
• skin (nodules – in 20%, at periarticular positions
subject to high external pressure; inflammatory granulomatous lesions;
vasculitis);
• eye (keratoconjunctitis, scleritis, episcleritis);
• respiratory (pleurisy, pleural effusions, interstitial fibrosis,
rheumatoid nodules, bronchiolitis);
• cardiac (pericarditis, myocarditis, endocarditis, valvular
heart disease);
• gastrointestinal (adverse effects from drugs);
•
renal (amyloidosis, drug induced nephropathy, renal tubular acidosis);
• neurologic (entrapment syndromes – especially carpal
tunnel, peripheral neuropathy from vasculitis – sensory and
motor, mononeuritis multiplex);
• haematologic (anaemia, leucopoenia, lymphoma, thrombocytosis).
Extra articular involvement is more likely in those who have RF
factor and/or are HLA-DR4 positive.
• Typical hand deformities (have significant impact on ADL’s)
- fusiform swelling (PIP joint synovitis --> spindle shape to
fingers); Boutonniere deformity (PIP flexion and DIP hyperextension);
Swan-neck deformity (flexion contracture of MCP with PIP hyperextension
and DIP flexion); ulnar/lateral deviation of fingers. All these
will affect foot hygiene and self-management ability.
• Typical cervical spine involvement – up to 40% get
atlantoaxial subluxation of C1-C2 with up to 20% having subaxial
involvement.
Lab tests are not diagnostic.
• Blood – increased ESR in 90%; normochromic normocytic
anaemia
• Synovial fluid – during active joint inflammation
--> cloudy, sterile, reduced viscosity, and increased white blood
cells.
• Rheumatoid factor – present in 75% of those with rheumatoid
arthritis – higher prevalence in those with extrarticular
manifestations – good prognostic test, as those who are positive
for rheumatoid factor have a poorer prognosis. Higher prevalence
of other autoantibodies are also seen (antikeratin antibodies, antiperinuclear
antibodies, anti-RA 33 antibodies)
ARA
Criteria for Diagnosis:
Any
four of the following criteria must be present to classify patients
as having RA:
• • morning stiffness (> 1 hr for more than 6 weeks)
• • arthritis of three or more joints for greater than
6 weeks
• • arthritis of hand joints for more than 6 weeks
• • symmetrical arthritis for more than 6 weeks
• • rheumatoid nodules
• • serum rheumatoid factor
• • radiographic changes (including erosions or bony
decalcification)
Rheumatoid
arthritis can follow several unpredictable and variable courses
– some have an acute rapid onset (10%) and up to 20% have
a single episode of polyarthritis and have no further symptoms –
for most the disease is progressive --> disability and morbidity,
but up to 20% respond well to disease modifying drug intervention.
Pregnancy is usually associated with some clinical remission.
Early
involvement of the foot
• •many cases start with symmetric involvement of metatarsophalangeal
joints – presents as “metatarsalgia” - often also
metacarpophalangeal joints.
• •more likely to be lateral MPJ’s in early stage
– can be tender to palpation - seen as MPJ oedema on dorsum
and widening of forefoot – may be painful on compression
• •plantar or interdigital bursitis and/or flexor tendonitis
may be initial presenting complaint – can be detected by ultrasound,
often before being symptomatic.This may present as ‘spreading’
of the toes. Three case reports on spreading of the toes as presenting
feature of rheumatoid arthritis
•
rearfoot and ankle can also be an initial presentation of disease
process
• •radiologically – juxta articular demineralisation
in affected joint; rarely get joint space enlargement at this stage;
cysts, bony erosions are prime feature – occur at margin not
covered by articular cartilage – usually on medial side of
joint, except in fifth MPJ in which lateral side is affected early
• •radiographic changes in the foot early in rheumatoid
arthritis is indicative of a more aggressive form of the disease
Late Involvement of the foot
• •progressive foot deformities are invariably
seen in all those with rheumatoid arthritis at later stages
• •generally most have either a predominant involvement
of forefoot or rearfoot
• •pre-existing biomechanical/pathomechanical foot disorders
will exacerbate foot symptoms
Forefoot:
• •lateral deviation of toes, clawing of toes, subluxation
of MPJ’s. MPJ deformities occur in almost all cases within
10 years --> reduced foot function. Digital lesions develop from
increased pressure
• •hallux valgus (may have pre-existed ? made worse
by rheumatoid arthritis). Incidence increases with increased duration
of disease.
•
•anterior displacement of plantar fat pad --> increased
risk for plantar lesions and pain
• •spread of forefoot (splaying) & plantar depression
of metatarsal heads.
• •plantar hyperkeratosis and bursitis
• •forefoot supinatus
Mid/rearfoot:
• •midfoot involvement --> collapse of midfoot arch
structure – can occur early with minimal symptomatic joint
involvement – may be reason for higher incidence of plantar
fasciitis in rheumatoid arthritis
• •rearfoot pain common (but less common than forefoot
involvement) – pain from involvement of joint or achilles
tendonitis or retrocalcaneal bursitis (may get erosions on x-ray
from bursitis)
• •subtalar involvement --> palpable swelling behind
malleoli
• •ankylosis of tarsal bones may occur late in the disease
•
•valgus rearfoot (can be very disabling) – initially
flexible, then limited range of motion at subtalar joint -->
later may progress to ankylosis. The rearfoot going into valgus
is most likely due to the disease process in the joint, a weakness
and laxity in supporting structures and an inability of the foot
to counter the normal early stance phase pronation.
• •impingement of the calcaneo-fibular ligament has
been suggested as the cause of lateral pain in the rearfoot
• •tendon sheaths around rearfoot may become affected
• •posterior tibial dysfunction. Tears of the posterior
tibial tendon are common in those with ‘flat feet’.
• •radiographically – talocalcaneal sclerosis;
loss of joint space, osteophytes, angular changes associated with
flat/pronated foot, erosions uncommon in midfoot & rearfoot
Other foot involvement:
• •plantar heel pain – in 2-3% - calcaneal
spurs more common. Fibrosis of the plantar heel fat pad has been
demonstrated
• •changes in composition of fatty acids of heel pad
have been shown ? increased fat viscosity --> decreased ability
of heel to absorb shock.
• •tarsal tunnel syndrome can occur at any stage –
sometimes it occurs in initial stages
• •subcutaneous nodules – most commonly plantar
to central 3 metatarsal heads
• •tenosynovitis of long flexors and extensors
• •bursitis --> Morton’s neuroma like symptoms
• •atrophy of subcutaneous tissues (as part of disease
process or secondary to corticosteroid use)
• •longitudinal nail beading late in disease (may be
due to vasculitis of nail bed)
• •vasculitis --> skin ulceration and digital ischaemia
• •stress fractures (due to osteoporosis)
• •gait changes --> ‘shuffling’; no heel
contact or propulsive phases of stance (due to avoidance of pain
and muscle changes). Knees and hips tend to be flexed.
• •ankle oedema (may be due to hypoalbuminaemia or lymphatic
blockage from knee joint effusions)
• •venous insufficiency
• •mild sensory neuropathy
• •wound healing difficulty (vasculitis affects wound
oxygenation; patient may be on corticosteroids or immunosuppressives)
• •leg and foot ulcers (most due to venous insufficiency
and vasculitis)
• •side effects of corticosteroids --> skin problems,
osteoporosis (may predispose to calcaneal stress fractures)
Radiographic
changes in foot
Bilateral and symmetrical distribution of changes; periarticular
osteoporosis (early) and generalised osteoporosis (late); uniform
joint space narrowing; synovial cyst formation; central and marginal
erosions; bony ankylosis; deformity; soft tissue swelling
Management of RA
• •Patient education and motivation (information on
disease, treatment and prognosis – include spouses/caregivers)
– many lay publications and organisations can help
• •Exercise (especially range of motion exercises and
aerobic fitness) – complete rest may be needed in acute phases
• •Physiotherapy (patient education, swelling reduction,
heat, cold, exercise, joint mobility, electrotherapeutic modalities)
• •Joint protection – splinting and braces (especially
during active phase)
• Occupational therapy – eg using alternative ways of
performing tasks to reduce strain on joints; household and personal
aids
• Good nutrition – especially for weight reduction if
indicated and increased intake of omega-3 fatty acids has been suggested
to be of benefit
• Complementary/alternative therapies – used by up to
80% of those with rheumatoid arthritis
• Surgical (eg fusion for cervical subluxation
Pharmacological
management
• As there is no cure for rheumatoid arthritis, the
goal of pharmacological management is to relieve symptoms, prevent
joint damage and put the disease into remission.
• NSAID’s are commonly used early, but disease-modifying
agents are now being used earlier.
• More aggressive approaches are now being used than in the
past – combination of drugs is common approach as many of
them are not as effective if used as monotherapy.
• Delay of treatment --> poorer outcome
NSAID’s:
• •do not appear change natural history of disease,
but are widely used as first line drug
• •control pain and inflammation --> better joint
function
• •patient’s vary in response
• •often only drug necessary in mild disease
Corticosteroids:
• • suppress inflammation and immune response
• •commonly used, especially as a continuous oral background
therapy
• •can use with anti-osteoporotic therapy
• •intra-articular injections may help settle a flare
DMARD’s:
• Pharmacological intervention with DMARD’s before joint
erosion and permanent damage ? prevents and/or retards joint damage
--> reduction in symptoms.
• DMARD’s are being used with increased frequency in
combination and in an earlier stage of the disease process.
Antimalarials:
• •Hydroxychloroquine is safe and effective in mild
disease
• •have suppressive effect on disease – shown
to be very effective
• •retinopathy is a common side effect ? need opthamology
screens every 6-12 months
Sulphasalazine:
• •anti-inflammatory and modulates immune response
• •common first choice drug – takes 6+ weeks for
benefits to show
• •has been shown to reduce joint erosions
• •may be more effective in the seronegative spondyloarthropathies
Gold:
• •suppresses activity in a number of patients ? prevents
disease progression
• •IM more effective than oral – usually weekly
injections
• •mechanism of action unclear
• • associated with large number of side effects
D-Pencillamine:
• •degradation product of penicillin
• •shown to reduce inflammatory synovitis in 50%
• •Not used much due to high toxicity (in 60% and can
trigger a number of rare autoimmune diseases) and slow onset of
action (often 6+ months to get effects)
Leflunomide:
• •shown to be as effective at methotrexate and more
effective than sulfasalazine
• •suppresses disease activity and delays radiological
progression
• •rapid onset compared to methotrexate and sulfasalazine
• •well tolerated (given orally)
Methotrexate (MTX):
• •cytotoxic – shown to clearly control the inflammatory
response; most common first line agent – considered ‘gold-standard’
disease modifying agent
• • long term efficacy is well documented, but rarely
leads to a true/complete remission ? often used in combination
• •monotherapy with MTX is not often associated with
sustained disease remissions
• • only 50% of patients stay on it after 5 years due
to toxicity
Anti-tumour necrosis factor (TNF) drugs:
• •biological agents shown to reduce disease activity
and joint damage
• •the cytokine, TNF has a number of pro-inflammatory
effects ? plays a major role in inflammatory disease such as rheumatoid
arthritis and is a key element in its pathogenesis ? potential to
block TNF
• •eg Etanercept (subcutaneous injection); Infliximab
(given IV) ? block activity of TNF-alpha
• •shown to have rapid improvement in joint pain and
swelling – fast onset (1-2 weeks)
• used either alone or with methotrexate
Management
of the RA foot
• •patient education
• •hyperkeratosis and dystrophic nail debridement
• •skin hydration
• •infection may be more difficult to manage due to
use of immunosuppressants (may need to temporally come off these
if using antibiotics)
• •digital orthoses to maintain good digital alignment
or protect lesions/pressure areas. Silicone orthodigital devices
can be used serially to correct toe position – may also improve
gait.
• •footwear advice and prescription to accommodate foot
deformity (extra depth and width) – there are compliance issue
with the use of custom made footwear
•
- softer orthoses for accommodation of plantar lesions or painful
joints.
• - more rigid orthoses for realignment of rearfoot or prevention
of development of hallux valgus
• - rearfoot control may be vital to prevent calcaneus from
going in to valgus (especially early in rearfoot disease) and for
proper knee and hip function ? devices may need to be more rigid
to prevent the valgus rearfoot from developing (amount of rigidity
needed will depend on supination resistance testing and body weight)
• - ankle foot orthoses if valgus deformity is severe.
• - shock absorption
• - exercises to maximise range of motions
Functional foot orthoses to alter biomechanics have been shown to
prevent the progression of hallux valgus (Budiman-Mak et al, 1995)
but not in limiting pain and disability (Conrad et al, 1996). Accommodative
orthoses have been shown to reduce pain, reduce plantar pressures
and improve gait parameters (Hodge et al, 1999; MacSween et al,
1999; Li et al, 2000). More rigid orthoses in combination with supportive
shoes where more effective at reducing forefoot pain than softer
accommodative orthoses (Chalmers et al, 1999). Woodburn
et al (2002) showed that functional foot orthoses reduced pain
and disability in those with rheumatoid arthritis.
Increased use of knee replacement surgery --> increased mobility
--> increased importance to protect feet.
Surgical management:
• •indicated for severe pain, deformity and
functional incapacity – not indicated if conservative treatment
has a good chance
• •early prophylactic surgery for deformity may be indicated
if disease is not very destructive and involvement is localised
• •metatarsal head resections are common
• • rearfoot and midfoot joint fusions
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