Rheumatoid Arthritis

Aetiology

At present unknown trigger or triggers stimulate or activate a disturbed immunologic response in a genetically susceptible individual.
Immune response genes congregated on the short arm of chromosome 6 in the segment called the major histo-compatibility complex. HLA antigens are the result of expression of genes in this segment.

Class I

Consist of 3 related types of molecules - HLA-A, -B, -C .Antigens are identified on all cells (except RBC + early embryonic tissue) ® identification of self, development of tolerance and strong graft rejection responses.

Class II

Code for molecules termed HLA -DR, -DQ and -DP. These are involved in antigen presentation to T- helper cells and are present
on B cells, macrophages and activated T or killer cells.
Aberrant induction of Class II antigen expression on cells other than those normally evident ® inflammation in some auto immune diseases.

Class III

Antigens are coded from a locus between Class I and II regions ® soluble proteins primarily involved in the complement cascade.
Rheumatic diseases associated with Class I antigens include arthropathies of the axial skeleton eg Ank Spond B27
Reiters B27
Psoriatic arthropathy B27 and B38
Class II antigens have an association with
eg Rheumatoid arthritis DR1 and DR4
Sjogrens' Syndrome DR2 and DR3
JCA
SLE DR2
The reason that more than one group of alleles can increase susceptibility to a disease is due to shared epitopes bw the molecules of each group.
eg the DR4 subgroup has 5 subtypes - of these only two - Dw4 and Dw14 promote susceptibility to RA - they share a common epitope in their beta chain
Rheumatoid arthritis is associated with HLA Dw4 locus and the HLA DR4 allotype in 60-80% of cases compared to only about 20-25% in the general population
Sero-negative patients account for 24% of those with the HLA DR4 allotype and sero-positive patients 55% indicating that they may be separate disease processes
The immune response triggers production of auto antibodies which form immune complexes and trigger synovial proliferation and inflammation resulting in the typical pathological features of Rheumatoid Arthritis.

Incidence

Affects 3% of the population
Approximately 300,000 RA sufferers in Australia
Usually presents in the 4th decade of life
M:F incidence 1:3
May affect any synovial joint and less commonly also cartilaginous joints and enthesies
Increased incidence in first degree relatives of RA patients

Pathogenesis

An at present unknown stimulus ® activation of immune system ® antibody / complement initiation of synovial inflammation and extra-articular manifestations in genetically susceptible individuals.
? viral (EB virus implicated), bacterial (component of bacterial cell wall may be stimulus), environmental, endogenous collagen or perhaps an emotional stimulus.
? stimulus ® formation of anti IgG Ab (Rh factor)
Activation of immune system ® release of proteolytic enzymes and digestion of tissue.
Immune reaction ® complement fixation and release of interleukin 1, phosphorylase A2, prostaglandin E2 and plasminogen ® degradation of matrix proteoglycan, induces synthesis of collagenase® chondrocyte death, cartilage breakdown augmenting the process of irreversible joint destruction.
It is postulated that cartilage is a necessary factor for the chronic process to begin and be maintained due to the fact that little recurrence is seen in artificial joint replacements.
Process blocked by early administration of cortisone ® proteoglycan synthesis is inhibited and existing proteoglycans are degraded.

Pathology

Begins as non specific inflammatory synovitis
® Non specific increase in capillaries
® Proliferation of synoviocytes
® Hypertrophy of synovium ® villi formation
® Lymphocytic and plasma cell infiltrate mainly peri vascular and formation of lymphocytic nodules
® Focal fibrinoid deposition
® Cellular necrosis
Highly vascular reduplicated synovium covers articular surface ® pannus formation
At the cartilage-pannus junction macrophages and fibroblasts are the predominant cell types
Presence of macrophages and collagenase markers within cells and the subsequent collagenolysis of the eroded bone matrix suggest that these cells may be responsible for a major portion of the bone erosion
These cells also secrete lysosomal enzymes such as proteases, cathepsin and elastase which are capable of degrading proteoglycan
RA artic cartilage specimens in a significant portion contain anti-collagen (Type II) antibodies
Pannus erodes the artic cartilage, Cartilage may fragment and ® intra-articular loose bodies
Subchondral bone is exposed and secondary osteoarthritis may result
There is associated local myositis

Rheumatoid Nodule

Central fibrinoid necrosis (fibrin, degraded collagen and cellular fragments) surrounded by a radially disposed palisades of local histiocytes and beyond that by inflammatory granulation tissue which is vascular and later becomes fibrotic. Peri vascular plasma cells and lymphocytes
Generally in Rh positive patients and usually implies more severe disease and vasculitis.
Seen on extensor surfaces, olecranon, lateral aspects of fingers, gluteal, Achilles, trochanters, ischial tuberosities, scapula, spine sacrum and occiput (if bedridden)
May become apparent before the actual onset of the arthritis
May persist indefinitely or regress at any time

Neuropathies

Vasculitic ® motor and sensory peripheral neuropathy or due to entrapment or compression
Affects median- wrist (carpal tunnel), ulnar- elbow, radial as the posterior interosseous nerve

Tendon Rupture: (Aetiology)

Proteolytic enzymes from the hypertrophic synovitis
Direct synovial invasion of the tendon
Intratendinous nodules (may prevent free gliding of a tendon)
Attrition where the tendon is abraded running over sharp bony prominences
Extensor tendon rupture is more common than flexor and ulnar tendons before radial tendons

Classification

Rheumatoid Factor

Immunoglobin that acts against the FC portion of IgG, usually multivalent IgM however many patients have both IgG and IgA rheumatoid factor in their sera. IgE Rh factor which act against different portions of the IgG structure have also been identified.
Sheep cell agglutination test looks for IgM.
Rheumatoid factor positive (~80%), generally more severe
Rheumatoid factor negative
Incidence of Rh factor in general population 1% - 5% (increases with increasing age ® 10-20% people more than 65 years) and it is associated with other chronic inflammatory conditions eg, SLE, chronic liver disease, Sarcoidosis, TB, Syphilis etc.
The Rose-Waaler IgG coated sheep red cell agglutination test is slightly more specific but is not done in most clinical laboratories as the use of IgG adsorbed onto inert particles of LATEX or Bentonite is technically easier and faster. All these methods look for IgM factors. Specific radioimmunoassays are available for Ig G, A & E factors.

Functional Classification: (ARA)

  1. No restriction in ability to perform normal activities
  2. Marked restriction but adequate normal activities
  3. Marked restriction in ability to perform most duties of the patients usual occupation and self care.
  4. ncapacitation or confinement to a bed or wheelchair

Douglas classification of cartilage degeneration (Inflammatory)

Classes:
  1. Fibrillation / softening in central area of articular cartilage
  2. Increased fibrillation with lipping of articular margins and hyperplasia of synovial membrane
  3. Exposure of subchondral bone and generalised changes in synovial membrane
  4. Extensive exposure of bone, often eburnated and grooved with destruction of intra-articular ligaments, deformity, shortening or subluxation of the jointM

Clinical Stages

Stage 1

Synovitis
Proliferation of synovium, infiltration of sub synovial layer with inflammatory cells, capsular thickening, villous formation of synovium, cell rich effusion ® painful swollen tender joints
Mobility is maintained
X-Ray
extra / juxta articular osteoporosis secondary to increased vascularity
Acute inflammation
1 - 3 days ® increases small blood vessels
3 - 7 days ® synovial cells proliferate
14 days ®focal accumulation of T lymphocytes etc & increased interstitial fluid
Chronic Inflammation
Increased synovial surface area, (villi)
Increased blood vessels, lymphocytes, tissue fluid
Radiologically apparent erosions after 8 weeks

Stage 2

Destruction
Persistent chronic inflammation and pannus formation ® peri articular erosions secondary to release of proteolytic enzymes, pannus and osteoclastic resorption of bone, similar changes occur around tendons.
X-Ray
Marginal bony erosions, reduced joint space, especially proximal joints of the hands, feet, wrists and AC joints

Stage 3

Deformity
Secondary to articular destruction, capsular laxity and ligament ruptures- joint instability and deformity.
Inflammation may have subsided.
Deal with mechanical and functional aspects of the joint
X-Ray
Articular destruction and joint deformity usually obvious. cervical spine affected may ® subluxation of Atlanto-Occipital or mid cervical levels.

Clinical Features

70% of patients have an insidious onset over wks- mths with episodes of pain and quiescence.
May be malaise, tiredness, weight loss, muscle pain and stiffness
Older people may have an explosive onset with systemic illness and severe joint pains
(~ 10 - 15% and has a good prognosis)
Intermediate onset in 15 - 20% of cases
80% develop the disease between the age of 35 and 50 years
30% monozygous twins concordant for RA, only 5% dizygous twins
Usually symmetrical involvement affecting proximal joints of the hands and feet, IPJ of thumbs, wrists, ankles, knees and shoulders. Changes most marked in 2nd and 3rd metacarpals
Joints are swollen, tender and warm with limited ROM and there is often a boggy swelling
May have palmar erythema
Deformities develop ® function problems
Subcutaneous nodules are evident in 20 - 25% of patients on extensor surfaces and indicate a more severe form of the disease
Decreased muscle power and wasting
Associated with anaemia

Cervical spine


43 - 85% exhibit subluxations, pain in 40 - 88% of patients and neuologic signs noted in 7 - 34%. Once myelopathy is established mortality is common

Atlanto Axial Subluxation

Seen in 11 - 46% at autopsy
If 10-12mm requires complete disruption of transverse and apical ligaments
Greater than 3.5mm abnormal in an adult

Upward Migration of Odontoid

Seen in 5 - 32% of patients
McGregors line: from tip of odontoid to line drawn from the hard palate to the occiput on the lateral view

Sub axial instability

Usually C2/C3/C4 in 10 - 20% of patients

Shoulder

Evaluation should include examination of:
Cervical spine
AC Joint
Rotator Cuff / impingement
Nerve / muscle defects
Pain 60 - 120o ® impingement
Pain 120 - 180o ® AC joint
X-Rays
Plain radiographs (AP, scapula lateral, axillary, bicipital groove
Arthrography, (rotator cuff pathology)
CT ® define glenoid and soft tissue status
U/S ® rotator cuff & impingement
Arthroscopy ® ? therapeutic

Elbow

Affects 50% RA patients
Synovitis, instability may have FFD, ulnar nerve irritation
Bone erosion ® destruction of radial head

Hip

May be extremely painful and require aspiration / arthrotomy to exclude sepsis

Knee

Quads wasting a frequent finding
Bakers cyst and FFD are both common

Foot & Ankle

~ 16% have initial involvement foot & ankle
Long standing RA ® 90% and usually bilateral
MTP joints involved in 75%
Subtalar joints in 35%
Ankle joint 30%
Hind-foot ® flattening of longitudinal arch and calcaneo valgus, often associated with rupture of Tib Post.

Extra-articular Manifestations

  1. Rheumatoid nodules (20 - 25%)
  2. Vasculitis
  3. Ocular inflammation (uveitis, iritis, conjunctivitis)
  4. Amyloidosis
  5. Nephropathy ® Renal Failure
  6. Heart (pericarditis, myocarditis, conduction defects, granulomatous aortitis)
  7. Lung (pneumonitis, pleuritis, interstitial fibrosis)
  8. Myositis and muscle atrophy ® muscle weakness
  9. Neuropathy
  10. Normochromic, microcytic anaemia (secondary to Fe depletion)
  11. GIT (salivary problems, peptic ulceration)
  12. Cerebral complications
  13. Felty's Syndrome:
    Rheumatoid arthritis, Splenomegaly, Leucopoenia (weight loss, skin pigmentation and ulceration, lymphadenopathy and anaemia)
  14. Sjogrens syndrome:
    Progressive destruction of exocrine glands ® mucosal and conjunctival dryness (sicca syndrome) accompanied by a variety of auto immune phenomena
    Usually affects women in 3rd & 4th decade
    Affects up to 30% patients with RhA, 10% patients with SLE and 1% patients with scleroderma
    Lymphocytic infiltration & immune complex deposition
    Interstitial nephritis in 40% ® CRF
    25% ® vasculitis
    Sensory neuropathy or mono-neuropathy multiplex may occur
    10% ® pseudo lymphoma
    50% ® biochemical hypothyroidism and 10% require treatment
    Corneal and conjunctival lesions along with dryness of the eyes.

Rheumatoid Hand

Aetiology of Ulnar Drift

Anatomical

  1. Direction of pull of extensor and flexor tendons
  2. Shape of head of metacarpal (relative ulnar deficiency)
  3. Ulna collateral stronger than the radial collateral
  4. Presence of extensor indicis and digiti minimi on ulnar side of the communis tendon

Physiological (Functional)

  1. Gravity
  2. Force of opposition from thumb onto fingers
  3. Turning taps and door handles etc
  4. Forces sustained when rising from a chair etc

Pathological

  1. Synovitis attrition of radial collaterals
  2. Articular cartilage erosions
  3. Extensor tendon subluxation
  4. Capsular, ligamentous and volar plate disruptions
  5. Intrinsic tendon shortening
  6. Radial deviation of wrist ® Z deformity and increased displacing force of extensor and flexor tendons
  7. Trigger finger releases ® distorted pull of flexors as well

Swan Neck Deformity

Extension of PIP, flexion of MCP and DIP
Results in a long finger pinch with inability to wrap the fingers around the handle of any implement
May originate from pathology at any joint but level of most severe deformity usually to site of origin
eg. Mallet finger pathology at DIP
Rupture of FDS or volar plate at PIP level
Intrinsic tightness
Palmar subluxation of the MCP joint
Malunion of fractured middle phalanx

Classification: (Nalebuff)
Type 1

No limitation of PIP motion in any position
Treatment is aimed at preventing or correcting PIP hyperextension, restoring DIP extension or both.
Options:
  1. Silver ring splint - allows motion while correcting PIP
  2. Surgery DIP fusion - in extension
    dermadesis - excise ellipse of skin volar to PIP
    Tenodesis of PIP jt FDS
    lateral band
FDS tenodesis technique- one slip of FDS is divided ~ 1.5 - 2 cm prox to PIP jt, the jt is flexed ~ 20-30 deg and the detached slip attached into the bone of the prox phalanx.
Postop: begin flexion at 3 wks, protect hyperextension for 6 wks

Type 2

Limitation of PIP flexion when MCP is extended or radially deviated - the problem is due to MCP lat deviation and intrinsic tightness. Thus it is not enough to prevent PIP hyperextension alone - the intrinsic tightness must be relieved and any MCP disorder that contributes ie subluxation or deviation must also be corrected
Thus need intrinsic release is pts with minimally involved MCP jts and combined MCP arthroplasty and intrinsic release in others
Bunnell test of intrinsic tightness (Passive test) - The MCP joint is held extended and the PIP joint will be found to have restricted flexion in the presence of intrinsic tightness

Type 3

Limitation of PIP movement in all positions of MCP ( but with well preserved jts)- the problem is of stiffness due to skin, collat ligs and capsule, and extensor tethering.
The first step in the surgical correction of the stiff swan neck deformity is restoration of passive PIP ROM by
  1. Manipulation - use minimal force- if manipulation difficult proceed to soft tissue release
  2. lateral band mobilisation - the lat bands are displaced dorsally - free lat band from central slip via 2 longitudinal incisions
  3. skin release- do distal to PIP jt - will heal secondarily
  4. may require flexor tenolysis

Type 4

Limitation of PIP motion associated with joint changes
Options: fusion or arthroplasty depending on
1. adjacent joints - if are in good condition
2. status of supporting ligs
3. status of flexor tendons
Fusion preferred at index as stability most important
position - 25 deg index to 45 deg little

Boutonniere Deformity

PIP flexion, DIP & MCP hyperextension
PIP deformity is the primary deformity due to inability of central slip to maintain full extension and the lateral bands displace volar-wards ® shortening of oblique retinacular ligaments ® hyperextension and limited active flexion of DIP. As the flexion deformity of the PIP increases, the pt compensates by hyperextending at the MCP jt
Functional loss from a Boutonniere is usually minimal until late - thus treatment of early deformity should be simple and low risk

Classification: (Nalebuff)
Stage 1

Mild deformity: 10-15o flexion lag at PIP, the DIP may or may not be hyperextended
PIP passively correctable but when this is done there is limited flexion of the DIP
Treatment: extensor tenotomy or lenthening ( dorsal longitudinal incision, the extensor is divided either transversely or obliquely - a lag usually does not develop as oblique retinacular ligs are intact and act to extend DIP) over middle phalanx to improve DIP flexion & dynamic splinting to stretch DIP into flexion

Stage 2

Moderate deformity: 30-40o flexion with MCP hyperextension ® correctable passively with lateral bands fixed in volar subluxated position
Treatment: Repair/ shorten central slip (adjust tension so that the PIP can be flexed passively ~ 70 deg after reattaching the central slip), repair the lateral bands back to cental slip (need to divide longitudinally volar to the lat band to enable it to be moved back) , and extensor tenotomy at DIP jt to enable flexion of the DIP

Stage 3

Severe deformity whichcannot be corrected passively
No attempt should be made to restore extensor function unless the PIP can be extended passively - thus aim to restore passive range by stretching, manipulation and splintage
If passive correction achievable - can reconstruct as for moderate deformity
If X-Ray changes ® arthrodesis of PIP (25o for index increasing to 45o for little fingers) and frequently require MCP arthroplasty

Thumb


Classification: (Nalebuff)
Type I

Boutonniere deformity most common due to synovitis of MCP joint ® stretch EPB tendon and extensor hood, with subluxation of the EPL tendon volarly and ulnarward. Hyperextension of IP joint occurs due to subluxation of the Prox phalanx on the MC and secondary increased pull of both EPL and intrinsics
In early stage the MCP and IP jts are correctable passively, later fixed deformities develop
Treat: Early (both jts correctable): synovectomy of MCP jt and reconstruction of the extensor mechanism
Later (MCP jt not passively correctable +/- jt destruction, IP jt correctable): mobilisation of MCP + extensor reconstruction
MCP arthrodesis if jt destruction
Latest ( Both MCP and IP jts not correctable):
IP jt - if not destroyed- dorsal capsulotomy to mobilise
- if destroyed - arthrodese
MCP jt - if IP jt fused try to preserve motion with - synovectomy, extensor reconstruction +/- arthroplasty
if unsalvageable - fuse

Type II

MCP joint flexion, IP joint hyperextension and dislocation or subluxation of CMC jt (fixed) - is a rare deformity- ie is a combination of types 1 and 3

Type III

Swan neck deformity: due to CMC disease allowing dorsal and radial subluxation. As the CMC jt subluxes, abduction forces are reduced and adduction contracture of the MC develops. Hyperextension of the MCP jt develops secondary to the MC adduction contracture
where there is laxity of the volar plate
Treat: Early ( painful CMC jt - minimal subluxation, no secondary MCP jt involvement): Conservative- splintage, steroid injection
- if fails CMC excision arthroplasty /suspensoplasty
Later ( varying degrees of CMC deformity and mild, passively correctable MCP jt hyperextension): CMC excision arthroplasty /suspensoplasty combined with volar tenodesis of the MCP jt
Latest ( complete CMC dislocation, fixed adduction of the MC, fixed MCP hyperextension): CMC excision arthroplasty
/ suspensoplasty with MCP fusion if severely destroyed

Type IV

Game Keepers thumb with the ulnar collateral ligament stretched
Treat by ligament repair or arthrodesis of MCP

Type V

MCP jt hyperextension with secondary flexion of the IP jt as the tension on the flexor tendon increases - due to volar plate stretching
NB: no CMC disease - thus no adduction contracture

Investigations

ESR increased (50 - 100), increased CRP acute phase
Rh Factor in 80% - persistently high ® worse prognosis
Normocytic, hypochromic anaemia secondary to reduced RBC life and Fe deficiency
Synovial fluid ® Mirror of inflammation occurring in the joint as no basement membrane separates the joint space from the cells that line it. Therefore once substances traverse capillaries ® equilibrate with the joint
Inflammatory mediators in synovial fluid enhance the generation of substances that stimulate their own generation ® amplification process ® normal inhibitory processes become saturated.
Low viscosity, due to less hyaluronate
More fibrinogen ® clots on standing
2,000 - 100,000 WBC with 50% PMN (normal less than 200 and septic fluid more than 100,000 and glucose less than 50% normal)
Glucose 25gm%
Mucin clot test: Formation of loose friable clot after addition of dilute acetic acid

Diagnostic Criteria (Rheumatoid Arthritis)

  1. Bilateral, symmetrical poly arthritis
  2. Involvement / swelling of wrist, MCP or PIP joints for at least 6/52
  3. Rheumatoid nodules
  4. Rheumatoid factor in serum
  5. X-Ray changes typical of RA (peri articular erosions & peri articular decalcification)
  6. Morning stiffness more than 60 mins and present for at least 6/52
  7. Swelling of at least 3 joints for at least 6/52
  8. Poor mucin clot formation
  9. Synovial histology consistent with RA
Need at least three of the above ® diagnosis

Differential Diagnosis

Heberdens arthropathy (DIPs)
Reiters' Syndrome (larger joints & SIJ)
Ankylosing Spondylitis
Poly-arthritic Gout (tophi large and small joints)
Sero-negative poly-arthritis
Sarcoidosis
Polymyalgia Rheumatica

Treatment

  1. Stop synovitis
  2. Prevent Deformity
  3. Reconstruct
  4. Rehabilitate

1. Stop Synovitis

Rest and splintage

More effective than medication

Non Specific Drugs (NSAIDs)

Not curative, do not promote remission, alter progress of erosions or lower the ESR but control pain and stiffness ® improve function.

Specific Drugs

Gold (presence of HLA DR3 gene highly associated with development of side effects to gold therapy)
Penicillamine
Chloroquine & hydroxy-chloroquine
Cyclophosphamide
Methotrexate
Modify the disease process and suppress early factors of the immune response.
This group of drugs all have unpredictable responses and potentially lethal side effects on the liver, kidney and haemopoetic systems. Need to monitor their effects with regular blood tests.

Corticosteroids

Suppress inflammation and production of proteases
Effectively reduce pain and stiffness but should resist use due to adverse effects on metabolism, adrenal function, bone and soft tissue integrity.
May use for severe exacerbations, when no other treatment works or in rare fulminating disease
Intra-articular cortisone ® relief

Synovectomy

Pain relief and retards cartilage and tendon destruction
(NB: Synovectomy is a palliative procedure)
Particularly useful for the extensor tendons of the wrist, and flexor teno-synovectomy performed at the wrist in association with median nerve decompression
Also useful in the knee and elbow joints but only before there is evidence of joint destruction.
Intra-articular radio colloids for medical synovectomy (Yttrium 90, Dysprosium 165) ® good results in 2/3 patients for 2 years. Works best in early stages of disease and treatment can be repeated. Leakage of radiation to adjacent tissues the major concern, linkage to large molecules and use of agents with a short half life ® limits this.
80% success with medical synovectomy but should not be used in women of child bearing age.
Surgical synovectomy, indicated in early disease. There is no difference after a few months between open and arthroscopic synovectomy. ROM often improves by 20o

2. Prevent Deformity

Physio and splintage:
Rest joints, full passive ROM daily and increase activity as disease subsides.
Splint to prevent deformity, (difficult to correct established deformity)
Tendon reconstruction ® repair, or replace ruptured tendons
Joint surgery (soft tissue stabilisation)

3. Reconstruction

Indicated for advanced joint destruction, instability or deformity.

Options are

Arthrodesis
Not used in joints where motion is strongly required
Wrist arthrodesis for bony destruction or mal-alignment, try to avoid arthrodesis of MCPs or CMC of the thumb. Good for IP joints and MCP joint of the thumb (fuse in 20o flexion and 20o pronation for pinch grip)
Excision arthroplasty
Radial head, metatarsal heads, patella, CMC of thumb
Joint replacement
Silicone implants good for MCP joints and perhaps IPJs ® improved appearance but power grip and function not great (bony erosion and plastic deformation occurs in 30%)
Shoulder, elbow, knee, hip, ankle, MCP joints & IP joints

Upper Limb

Silicone implants in the hand use a longitudinal cut in extensor hood and capsule on ulna side of the extensor tendon, divide ulnar collateral ligament.
Distal joints best treated by arthrodesis in extension or slight flexion (Infection rate 0.5%)
Wrist is the foundation for good hand function and deformities of the wrist may be extrinsic or intrinsic
Rupture of ECU ® radial deviation which may accentuate ulnar deviation of fingers (primary pathology ® treatment)
Extensor tendon ruptures ® flexion deformity
Erosive changes, synovitis and ligament laxity ® carpal translocation
Arthrodesis of the wrist may be limited or pan carpal depending on the disease process and its extent
Swanson TWR ® maintain motion, metal and polyethylene components now available ® better results (short term).
Distal radio-ulna joint ® Darrach procedure useful (excision of distal end of ulna leaving ulna styloid)

AC joint

Involvement ® excision of outer end clavicle before considering TSR

Rotator Cuff

® myopathy or cuff defect may ® humeral head rides up and may ® secondary impingement or true cuff arthropathy

TSR:

(1952) Neer replaced humeral head with vitalium prosthesis (+/- glenoid component)
Indicated for incongruous gleno-humeral joint unresponsive to conservative management.
Gain in ROM less predictable than pain relief therefore not indicated just for limited ROM
Contraindications to TSR
Active or recent infection
Paralysis of deltoid or cuff muscles
Neuropathic joint
Massive cuff tear not reconstructable
Young patient & high physical demands
Results: 73 patients ® 92% satisfactory results (pain relief)
Active abduction improved 44%

Elbow

Early prostheses ® hinged / constrained failed early
New semi constrained prostheses 50% loose at 5 years
Forces across elbow due to muscle action ® effectively a weight bearing joint with complex biomechanics
Indications
Loss of function and restriction of movement (there is no ideal position for elbow arthrodesis)
Functional arc
30-130o flexion 5o pronation and 50o supination
Contraindications
Poor hand function ® limit benefit
Recent / active infection
Soft tissue deficiency
Inability to flex the elbow (triceps weakness not a contraindication)
Options
Synovectomy if prior to significant joint destruction
Young patient with pain principally on pronation / supination ® excision of radial head (Kocher; between Anconeus and ECU) results in 80% ® good pain relief, 50% ® improved ROM, (20% reduced ROM)
Some advocate use of silicone spacer after excision

TER

Complications
Reduced useful ROM
Ulna nerve palsy
Humeral Fracture
Triceps disruption
Heterotopic bone formation
Loosening
Deep infection in up to 20% ? due to rheumatoid disease or due to Subcutaneous nature of the joint
Best Results
(3 year follow up)
90% satisfactory results
ROM 35-135o
Loosening rate 1% (unconstrained prosthesis)
Nerve palsy 2%
Subluxation / dislocation 5%

Hip

Synovectomy may be useful in juvenile forms
Arthroplasty is the procedure of choice with severe pain and limitation of movement
THRs have been performed on patients in their second decade
Customised prostheses required in over 50%
Cement fixation favoured by most surgeons
Where there is no prospect of ambulation ® Girdlestone
THR should be performed before TKR where both are required due to difficulty mobilising a patient with a stiff painful hip after TKR. Need to differentiate hip pain referred to the knee, may not need TKR after THR.
Results
Average 30o improvement in ROM
93% relief of pain
~ 7% revision rate in first 2 years
For first time hip surgery infection rate similar to that of non rheumatoid patients

Knee

Synovectomy if fail to respond to medical management and no evidence of joint destruction
Tibial osteotomy, many feel this is contraindicated due to bi-compartmental disease process
Arthrodesis, only if hip normal, usually reserve for failed TKR or when TKR can not be performed

TKR:
Loosening ~ 1.3%
Infection ~ 0.4%
Pain relief 95%
Cement fixation and replacement of all cartilaginous surfaces advocated by many surgeons

Foot & Ankle

Most common operation is excision arthroplasty of MTP joints. At least 1cm gap should be achieved between distal metatarsal and proximal part of phalanx
Should be accompanied with arthrodesis of the first MTP joint. The IP joint should be mobile to fuse the MTP.
Most common complication being recurrence of pain and callosities due to inadequate resection initially.
Hind-foot ® talo-navicular arthrodesis may be performed if able to correct hind-foot valgus
Triple arthrodesis if more extensive involvement or if unable to correct valgus adequately

TAR:
Not produced any significantly good results to date. May only be indicated in pan-talar OA in order to maintain some movement after a triple arthrodesis.
Poor wound healing is a problem
Infection rate between 2% and 5%
High loosening rate early.

Cx Spine

Indications for surgical intervention are pain and neurological abnormality (subluxation is not an indication as this is common)
Atlanto- axial instability ® Gallie fusion
Upward migration of odontoid or atlanto- occipital instability® occipito cervical fusion
Sub axial instability ® posterior fusion / wiring
Post operative mortality probably ~ 10% overall

4. Rehabilitate

Accompanies all stages of treatment
Function assessment ® aids, home modifications etc

Prognosis

Factors correlating with prognosis (Indicate worse prognosis)
  1. Medical therapy with corticosteroids
  2. Rh Positive
  3. Presence of Rh nodules
  4. Erosive and mutilating articular disease
  5. Male sex
NB: Prognosis usually evident within 2 years
80% acute RA ® early sustained remission and when it occurs it is usually in the first 2 years
Median life expectancy of patients with RA is shortened by 3-7 years

Anti-Rheumatic Drugs

Simple Analgesics

Limited value but of use for mild and limited intermittent pain where regular medication is not indicated or as a supplement to other drug therapy.

NSAIDs

Are weak acids therefore concentrate in acidic cells such as inflammed synovium, the renal medulla and gastric mucosa

Action

Inhibit cyclooxygenase which converts arachidonic acid to prostoglandins
Aspirin irreversibly blocks action, other NSAIDs reversibly block by varying mechanisms
Activity ® decreased release of inflammatory mediator substances

Effect on bone

Decreased ectopic bone formaton
Decreased bone ingrowth into porous implants
Delayed fracture healing in animal models ? due to impaired osteoblastic activity or reduced ability to form woven bone

Other concerns

Risk of developing a gastric or duodenal ulcer 2 x normal risk
Increases to 4 x normal for women more than 65 years
Peak risk at four months of therapy, then it declines
Risk of renal damage in elderly with pre-existing problems
NSAIDs may promote hypertension by fluid & sodium retention

Aspirin & Salicylates

As least 3-6gm per day is required to get good results in conditions such as RA
Doses of this size ® difficulties with side effects particularly GIT, tinnitus and deafness (tinnitus and deafness is dose dependant)
Aspirin may also aggravate allergic rhinitis and asthma in about 10% of sufferers (other NSAIDs may have the same effect)
Dangers for patients on anticoagulants
Inhibits uricosuric effect of probenecid
May enhance oral anti-diabetic medications

Other NSAIDs

Groups of NSAIDs:
Salicylates eg aspirin: 600 - 1,500mg qid
Indole series eg indomethicin: 25 - 50mg tds & 75 - 100mg nocte for morning stiffness (t1/2 2-3 hours)
Pyrazole series eg phenylbutazone
Propionic acid series eg Naprosyn: 500mg bd (t1/2 12-15 hours)
Phenyl acetic acid series eg Diclofenac - ie Voltaren: 25 - 50mg tds or bd
Oxicam series eg Piroxicam - ie Feldene: 10 - 20mg daily (t1/2 45 hours)
Compounds with short t1/2 often adequate anti-inflammatory action by twice daily administration. More frequent administration desirable only for analgesia.
All ® same efficacy but individual response and drug tolerance ® selection. May need to try a number of NSAIDs before finding the best one for the individual
Safety + tolerance- main factors in choice of medication, cost + convenience also important
About 20% of patients fail to benefit from any one NSAIDs
Of the rest some improve slightly, others moderately and some very well

Side effects

except for GIT are unusual
Peptic ulceration, tend to be near the pylorus and often heal spontaneously following withdrawal of therapy
Rashes occur occasionally and respond to drug withdrawal
Renal effects ® may aggravate oedema, antagonise diuretics, increase serum creatinine and ® reversible acute renal failure
May ® drug induced hepatitis, usually minor, unimportant and transient
All NSAIDs excreted by the kidney therefore decrease the dose in renal failure
Combination of one NSAIDS with another is usually pointless

Corticosteroids


Potent anti-inflammatory action
Multiple side effects limits applications
Toxicity ® weight gain, diabetes mellitis, osteoporosis, thin skin, features of Cushings
Useful to control systemic manifestations of disease eg vasculitis
Dose required to control symptoms ® Cushings syndrome as safe dose of 7.5mg per day usually not effective (systemic administration ® prednisone / prednisolone)
Also useful for local injection into joints (intra-articular injections ® triamcinolone hexacetamide ® increased duration of local action)

Dose

Prednisone / Prednisolone 5mg daily = nocturnal production
Celestone chronodose (betamethasone) 0.2 - 2ml (3mg/ml) IM or intra-artic injection
Kenacort (triamcinolone) 10mg/ml local joint / soft tissue injections

Specific Anti-Rheumatoid Drugs

Slow acting or remission inducing compound ®plateau after 4-6 months. Mode of action ?
Persistence of uncontrolled disease despite adequate anti-inflammatory therapy is the principal indication for their use.
Should be used in those patients with severe and progressive disease before irreversible joint changes appear.

Gold Containing Compounds

First used to treat RA in the 1920's
Should reserve for those where the disease is progressive and has been poorly controlled by NSAIDs and conservative management

Mechanism of action

not established, may reduce vascular permeability, reduce cell numbers at sites of inflammation, suppress phagocytosis, prevent protein denaturation and suppress both lysosomal and non lysosomal enzymes

Pharmacokinetics

Rapid absorption from IM site
t1/2 long (5-6 days)
Most excreted in urine

Side effects

Toxicity to injectable gold occurs in 30 - 50% of patients
Rash occurs in 30% ® temporary cessation of therapy
Proteinuria occurs later due to immune complex mediated membranous glomerulonephritis and may ® withdrawal of treatment
Agranulocytosis, aplastic anaemia or thrombocytopenia are rare but potentially fatal complications ® preclude further administration of gold containing compounds
Stomatitis, colitis, fibrosing alveolitis and cholestatic jaundice may occur
Oral preparations ® less side effects (currently under development)
Need blood count and urinalysis at least before each dose

Dose

Aurothioglucose (50% gold by weight) ® Injectable preparation
Test dose of 10mg ® 50mg weekly until response, usually takes 3 - 4 months then injections every 2 weeks and later every 3 - 4 weeks to maintain remission
Auranofin is an orally absorbed preparation (30% gold by weight)
Auranofin usually given in a dosage of 6mg per day (PO)
Response in 80% after 4 - 16 weeks, max effect after 4 - 6 months - thus need to give drug for long periods
Dose should not be reduced more than once in 3 months to prevent relapse
If relapse ® increased dose with weekly injections until controlled

Penicillamine: (Metabolite of penicillin)

Similar effects to gold containing compounds

Mechanism of action

in RA unknown- is an immunosuppressant- lowers IgM RhF

Pharmacokinetics

Absorbed orally and excreted in both urine and faeces
Slow action usually evident ~ 2nd month and max after 4 - 6 months
Effective in 80% of patients

Side effects

Toxicity occurs in 30 - 60% of patients
Urinalysis and CBE should be done at least monthly
Nausea and vomiting may be avoided by slow increase in dose
Acute febrile reactions ® may need to start with very low dose
Loss of taste after 6/52 improving after another 6/52
Rashes appear after 6/52 and are quite different, and resistant to treatment
Proteinuria secondary to immune complex deposition in glomeruli after ~ 4 months
Mouth ulcers may be a problem
Thrombocytopenia may develop at any time but is usually benign ® stop medication if less than 100,000 / mm3
Rarely ® gradual marrow suppression ® must stop treatment
Myasthenia gravis, Goodpastures' syndrome, pemphigus, polymyositis, drug related lupus are rare complications ® stop medication

Dose

Commence at 125 - 250mg per day initially increasing after 1 -2 months to 500mg per day with no further increase until response assessed. Occasionally need up to 1gm per day

Hydroxy-chloroquine: (Action similar to gold)

Mechanism of action

Inhibit DNA, RNA and protein synthesis, interfere with antigen- antibody reactions, suppress lymphocyte responses to mitogens, inhibit chemotaxis and phagocytosis by neutrophils, stabilises lysosomal membranes
Does not alter radiological progression of disease

Side effects

reversible corneal opacities
irreversible Retinopathy the major problem
Examine eyes at least every 6/12
Once established usually problems are irreversible and may in fact progress
May aggravate psoriasis yet some people with psoriatic arthritis benefit from its use

Dose

200 - 400mg per day

Methotrexate: (Immuno-suppressant)

Mechanism of Action

Blocks DNA synthesis by binding with and blocking the action of folic acid reductase
Has greatest effect on proliferating cells with little alteration to resting cells
Useful in RA, psoriasis, psoriatic arthropathy and polymyositis

Side effects

Due to toxicity and side effects reserved for patients who have failed other therapy
Rapidly dividing cells eg haemopoetic, gastrointestinal and reproductive most affected by toxicity
Effects most prominent 7 - 10 days after admin ® careful attention to blood counts
GIT ® nausea, vomiting, diarrhoea and abdominal pain
Teratogenic properties therefore should not be used in pregnancy
Depression of immune system ® opportunistic infections
Should only be used for severe systemic disease

Dose

5 - 30mg weekly frequently given in 3 divided doses separated by 12 hours
IV dose 15 - 50mg weekly