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Sero-negative and Spondylo-arthropathies
Aetiology
HLA
B27 found in 4 - 8% of the normal population and is a marker for a
specific haptotype of the Class 1 antigens of the major
histocompatability complex of antigens
Up to 20% of HLA B27 patients develop spondylo-arthropathy after
exposure to shigella or other environmental agents
HLA B27 is passed on to 50% of the offspring
Randomly selected individuals with HLA B27 may have only a 2 - 10%
chance of developing disease whereas the risk for HLA B27 positive
relatives of HLA B27 patients with spondylitis is 25 - 50%
The link between HLA B27 and spondylo-arthropathies remains
unknown but it may be that;
HLA B27 acts as a receptor site for infective agents
It may be a marker for immune response gene that determines
susceptibility to environmental triggers
HLA B27 may induce tolerance to foreign antigens with which it
cross reacts
HLA B27 also increased neutrophil motility (? significance)
HLA B27 is associated with;
Ankylosing Spondylitis 95%
Reiters 60 - 70%
Psoriatic Arthropathy 20% (60% if sacroiliitis)
JCA, (Pauciarticular Type II) 20% (50% if sacroiliitis)
Enteropathic Arthritis 5% (50 - 70% if sacroiliitis)
Definitions
Enthesopathies
Inflammation
with cellular infiltration by lymphocytes plasma cells and PMN is
associated with erosion and eburnation of sub-ligamentous bone
Syndesmophyte
Ossification
within the annulus fibrosus leading to thin vertical radio dense
areas. Predominantly in anterior and lateral aspects of the spine
Dagger Sign
Single
dense central line on frontal radiographs related to ossification
of supra spinous and inter spinous ligaments
Spondylodiscitis
Loss
of inter vertebral disk height and extensive new bone formation
resembling infection without clinical or laboratory evidence to
support the diagnosis
Ankylosing
Spondylitis
Definition
Chronic
inflammatory condition of the spine and sacro-iliac joints
characterised by osseous proliferation and associated with HLA B27
Bilateral and asymmetric involvement predominate PIP, DIP &
MCP joints may be involved. Osteoporosis, erosions and deformity
are less marked than in RA
Osseous proliferation may be exuberant
Incidence
Affects
1 per 1,000 people in Western Europe
Prevalence ~ 1% whites
Low incidence in black Americans and Negro's
Classic Ank Spond ®
Male : Female 3 or 4:1
May be the incidence is equal but female form less likely to have
progressive spinal deformity.
Onset usually aged 15 - 25 years ( less than 40 years)
Aetiology
Genetic
predisposition HLA B27 but only a relatively small percentage of
people with HLA B27 go on to have Ankylosing Spondylitis
Virtually all patients with Ank Spond have HLA B27.
50% of first degree relatives of spondylitic patients also HLA B27
and of this group 20% ®
spondylitis
Trigger ?, similar to Reiters, ulcerative colitis, ? lymphatic
drainage to SI and spinal region important.
? Environmental trigger
Pathology
Primary
process is enthesopathy, inflammation at fibro-osseous junctions
of syndesmotic joints (inter vertebral discs, sacroiliac
ligaments, symphysis pubis, manubrium sterni and bony insertions
of ligaments and tendons; entheses)
Three stages of the disease
- Inflammatory reaction with round cell infiltrate, granulation tissue
and bony erosion
- Replacement of granulation tissue with fibrous tissue
- Ossification of fibrous tissue ®
ankylosis
Also
see synovitis of diarthrodial joints
Fibroplasia ®
cartilaginous metaplasia ®
chondro-ossification and bony ankylosis which is typical of Ank
Spond (and psoriasis) but rare in RA
SI joints, facet joints ®
joint destruction, costo-vertebral joints also frequently involved
®
reduced respiratory excursion
Clinical
Features
Many
remain undiagnosed
Insidious onset ®
back-ache and stiffness
May have referred pain similar to sciatica
In woman diagnosis often delayed, progressive disease is less
common and there is likely to be more peripheral joint involvement
and less spinal involvement
Pain and swelling of other joints and at the point of tendon
insertions (enthesopic features)
10% start as an asymmetrical poly arthritis
Morning stiffness with improvement following exercise
20% have a peripheral arthropathy ®
up to 35% eventually
Loss of spinal mobility (extension first) with flattening of
lumbar lordosis
Wright
/ Schober
Mark
two points one 10cm above and one 5cm below the level of the iliac
crests and flex ® should lengthern 5cm
Wall
test ®
heels, buttock and scapulae all should be able to touch but if
decreased extension unable to do this
Chest expansion should be at least 5cm and is often markedly
reduced in this disease due to costo-chondral arthrosis (not a
reliable sign in the elderly or in those with COAD)
Ocular inflammation occurs in ~ 1/3 of patients (uveitis ~20% and
conjunctivitis in 25%)
Aortic valve disease rarely a clinical problem present in ~ 3% and
pericarditis and myocarditis may also be a feature
Occasionally pulmonary fibrosis
Associated with weight loss, fatigue, low grade fever
Spinal fractures (? stress #) often ®
pseudarthrosis at the disco-vertebral junction. Epidural
haematomas seen in ~ 20%
Cervical spine #'s heal well in halo
If neurological involvement 46% chance of being fixed and 29%
mortality
Risk of massive epidural haemorrhage may ®
ascending paralysis
Investigations
Rh
factor is negative
ESR increased during active phase
HLA B27 present in 95% of cases (present in 5 - 10% normals)
95% of whites with Ank Spond have HLA B27 but only 60% of blacks
ALP & CPK increased
X-Rays
Erosions / fuzziness of the SI joints often the earliest feature ®
bony ankylosis
Vertebral squaring due to flattening of the normal anterior
convexity secondary to inflammation at point of annulus insertion ®
ossification across the inter-vertebral discs ®
bamboo spine
Peripheral joints erosive arthritis and ankylosis
Protrusio Acetabulae may be a feature
Three types of disco-vertebral lesions
- Central intra osseous discal displacement (Schmorls' node)
- Enthesopathy, peripheral lesion
- Both peripheral and central
Diagnostic
Criteria
- Low back pain of more than 3/12 duration
- Pain & stiffness in the thorax
- Limited chest expansion
- Limited lumbar motion
- Past or present iritis
- Radiological sacroiliitis
- Radiological syndesmophytes
Need
4 of the five clinical criteria or the radiological criteria plus
one other
Differential
Diagnosis
Other
sero-negative spondylo-arthropathies ®
vertebral and SI joint disease (Reiters, psoriatic arthritis,
ulcerative colitis & Crohns disease, Whipples disease, Behcets
syndrome) all show some familial aggregation and are associated
with HLA B27
Forestiers
Disease
(Ankylosing
Hyperostosis) Common disorder predominantly in older men ®
widespread ossification of ligaments and tendon insertions (ALL in
the cervical spine and in the lumbar spine ®
pronounced but asymmetrical inter vertebral spur formation and
bridging) Not an inflammatory disease and spinal pain and
stiffness seldom severe. SI joints are not eroded and ESR normal.
Associated with obesity and diabetes
Treatment
Anti
inflammatory medication
Analgesics
Physiotherapy etc to preserve movement and prevent deformity
Rest and immobilisation contraindicated as ®
increased osteoporosis and ankylosis
Significant hip involvement ®
THR (often left with limited ROM)
Spinal osteotomy (lumbar or cervical) to "improve outlook on
life"
Prognosis
Age
of onset is the most important factor in determining prognosis and
outcome
Reiters Disease (Reactive arthropathy)
Definition
Sero
negative arthritis that follows urethritis, cervicitis or
dysentery
Triad; (described by H. Reiter (1916)
Poly arthritis, urethritis and iritis / conjunctivitis
Incidence
Male
: Female ratio 5:1
Probably the commonest type of large joint poly arthritis in young
men
Usually males aged 15 - 40 years, rare in women, children &
the elderly
Familial aggregation
Arthritis appears 2 - 6 weeks after initiating infection ®
acute onset with asymmetric poly or oligo arthritis
Aetiology
Sero
negative arthritis that follows urethritis, cervicitis or
dysentery
Associated
organisms
Lymphogranuloma
venereum
Chlamydia trachomatis
Campylobacter
Shigella
Salmonella
Yersinia enterocolitica
Clostridia difficile
Asymmetrical
changes are typical
Lack of osteoporosis and exuberant periostitis as in psoriatic
arthropathy and Ank Spond
Also used to describe reactive arthritis associated with
non-specific urogenital (urethritis, cystitis, prostatitis,
cervicitis, balanitis) or bowel infection
Pathology
Organisms
found in the joint (intracellular) ®
triggers of local rather than systemic immune response
Clinically
Normal
progression Urethritis ®
Uveitis ®
Arthritis
Urethritis not necessarily sexually transmitted and may occur in
children
Skeletal
Affects particularly the large joints (knee and ankle)
Severe swelling of entire fingers and toes may be associated
(sausage digits)
Involvement of DIP joints of toes think of Reiters or psoriasis
Backache and stiffness secondary to sacroiliitis and spondylitis
common
3% of patients with Reiters syndrome will develop Ank Spond
Entheses
Tenosynovitis
and plantar fasceitis common (enthesopathy)
Eyes
Unilateral
or bilateral non infectious conjunctivitis occurs in ~ 40% and
more disabling involvement includes iritis (~ 5%), uveitis,
episcleritis and corneal ulceration
Integument
May have buccal ulcers and skin lesions
Balanitis Circinata (small shallow painless ulcers on the glans
and urethral meatus)
Keratoderma Blenorrhagica (hyperkeratotic skin lesions,
predominantly on the soles of the feet occurs in 10%)
Amyloidosis and pleurisy may develop
80% have symptoms for many years
Investigations
HLA
B27 positive in 60 - 70% of cases
ESR may be high during the active phase
Cultures (urine, stool)
X-Rays
Initially
normal ® erosive arthropathy
eventually
Sacroiliitis in 25% of patients but more asymmetric than in Ank
Spond
Vertebral changes similar to Ank Spond
Periosteal changes in ischial tuberosity, greater trochanter or
site of insertion of Achilles tendon
Differential
Diagnosis
Gouty
arthritis
Other enteropathic arthritis
Gonococcal arthritis ®
septic arthritis or reactive sterile arthritis
Treatment
General
treatment for active bowel or urinary infection (Tetracyclines for
urethritis)
Rest, splintage, anti-inflammatories
Local or oral steroids
Resistant cases not responding to NSAIDs may try methotrexate or
azathiaprine
Generally today use tetracycline for 6 - 8 weeks to decrease the
incidence and severity of recurrent attacks (especially if
Chlamydia cultured in the urine)
Prognosis
Minority
® spontaneous remission and no
recurrent episodes
Majority ®
recurrent episodes of arthritis with the episodes lasting less
than 6 months usually
Smaller minority ®
continuous unremitting course
Psoriatic Arthropathy
Incidence
About
7% of patients with psoriasis ®
evidence of inflammatory arthritis
? More common in men and tends to run in families
Usually over 30 years of age and skin disease usually precedes
joint disease
Aetiology
~
4% of chronic poly-arthritis pts ®
have psoriasis but not all of these have psoriatic arthritis
Pathology
Similar
to RA but
Less cellular infiltrate and more fibrosis
Pannus mainly on the surface and not eroding underneath cartilage
More bony proliferation and often ankylosis
Clinically
Characteristically
involves distal joints of the hands and feet with 95% of patients
having peripheral joint involvement
Usually pauci-articular asymmetric arthritis
25% have poly articular arthritis indistinguishable from RA
Bone and cartilage destruction may be unusually severe (Arthritis
Mutilans)
Nail changes evident in 10% of psoriatics but 80% of those with
arthritis ( oil droplet
discoloration, subungal hyperkeratosis and onycholysis)
5% have exclusively spinal involvement
10% arthritis preceeds psoriasis
Large joints may be involved
Tendon involvement may ®
fixed deformities
40% develop spondylitis and 25% develop sacroiliitis and or Ank
Spond
Ocular inflammation (iritis, conjunctivitis, episcleritis and
keratoconjunctivitis sicca ) in 30%
Clinical
forms
70%
Asymmetric oligoarticular disease involving 2-3 joints,
involvement of distal joints of hands and feet
15% Systemic poly arthritis similar to RA but Rh factor negative
10% Predominantly distal IP joint involvement
5% Arthritis Mutilans
Investigations
Rheumatoid
factor negative
May have increased ESR
Mild normochromic normocytic anaemia
HLA B27 present in 20 - 60% of patients (especially those with
overt sacroiliitis)
X-Rays Destruction of DIP and or PIP joints with erosions ®
pencil in cup deformities
Fluffy periostitis of long bones
Changes in large joints similar to rheumatoid
SI joint involvement fairly common, bilateral more than unilateral
Spinal involvement similar to Ank Spond
Treatment
Control
skin disorder with topical preparations
Splintage to prevent or limit deformity
NSAIDs ®
relief of joint symptoms
Intra-articular steroid injections no more than 3/year/joint and
not for multiple joints
Gold ® improvement in more than
50% of patients
Immuno-suppressives for resistant cases eg methotrexate in 3
divided doses, 2.5mg increasing to a maximum of 15mg per week
Surgery: arthrodesis of distal joints may improve function
Care at surgery due to staph skin carriage ®
infection risk
Enteropathic Arthropathy
Arthritis
usually follows onset of colitis by at least 6 months to several
years. Uncommonly onset may coincide
HLA B27 found in 70% of patients with spondylitis
Incidence
Synovitis
seen in
11%
patients with Ulcerative colitis
21% patients with Crohns
Aetiology
Associated
with
Crohns
Ulcerative colitis
Bacillic dysentery
Whipples disease
Behcets disease
Clinically
Usually
mono-articular affecting larger joints (knees and ankles) and
resolves without residual defect
Treatment
Best
treatment is control of the bowel disease
Give NSAIDs in short courses due to side effects
In ulcerative colitis procto-colectomy ®
cure joint problems
In Crohns arthritis may appear before the bowel symptoms and
surgery often not effective possibly due to the difficulty
identifying the extent of the disease at the time of surgery.
Behcets'
Syndrome
Definition
Muco-cutaneous
ulceration of oral cavity and genitalia
Unknown aetiology
Clinically
Characterised
by uveitis, corneal ulceration, erythema nodosum, cutaneous
pustules, peripheral arthropathy
Arthritis is usually destructive and usually self limiting
Knees most commonly affected
SI joints sometimes involved
Whipples'
Disease
Definition
Rare
systemic disease which may affect any organ system
Incidence
Affects
predominantly middle aged males
Aetiology
Evidence
supports infectious aetiology
Strong association with Ank Spond
Pathology
Infiltration
of involved tissue with large glycoprotein laden macrophages with
small rod shaped bacilli is diagnostic of the condition
Clinically
Greater
than 70% have an associated peripheral arthropathy
Treatment
Responds
to antibiotics
Sarcoidosis
Definition
Granulomatous
disorder of unknown aetiology affecting multiple organ systems
especially in young adults
Incidence
Male = Female
Blacks more than whites
Usually aged 20 - 40 years
Pathology
Granulomata
are non caseating with predominantly epithelioid cells but also
lymphocytes, granulocytes and plasma cells.
Granulomas may occur in any organ- May increase in size, decrease
in size or remain static.
Lesions resolve by fibrosis
Involvement of bone in the absence of other clinical involvement
or X-Ray manifestations is highly unusual
Osteoporosis most common feature with cortical thinning and
striations, coarsened trabeculae along with lytic lesions
Clinically:
(highly variable)
Leads
principally to bilateral hilar adenopathy, pulmonary infiltrates
and skin or eye lesions
General: malaise, fever
Skeletal
Acute
poly arthritis (symetrical & peripheral) and tenosynovitis
May get osteosclerosis either nodular or generalised especially
affecting the axial skeleton (differentiate from Pagets)
Hand most commonly involved site - May be associated with
symmetrical small joint erosive poly-arthropathy affecting DIPJs
particularly
Chronic poly arthritis may develop with relapsing and remitting
caurse eventually ®
subchondral collapse and permanent disability
Myopathy
CNS
& PNS involvement
Skin
granulomas
(erythema nodosum)
Respiratory
Cough
and dyspnoea
Asymptomatic hilar lymphadenopathy
GIT
hepato-splenomegaly
Eye
granulomatous
uveitis
Symptoms usually resolve in 4-6/52
Investigations
ESR
usually increased
Kveim test positive ®
granulomatous reaction
Diagnosis
Diagnosis
historically by non-caseating epithelioid-cell granulomas
Differential
Diagnosis
Skull
abnormalities ®
EG or neoplasm
Spinal ® infection
Joints ® RA, gout, septic
arthritis
Cyst like lesions of MC and phalanges
Gout TB
Fungal disease RA
Metastasis Xanthomatosis
Myeloma Tubero sclerosis
Hyperparathyroidism Fibrous dysplasia
Haemangiomas Enchondromatosis (Olliers')
Polymyalga
Rheumatica
Usually
middle aged women ®
marked post inactivity stiffness
Pain most often around pelvic and pectoral girdles
Tenderness in muscles rather than joints
ESR almost always increased
Pathology
Form
of giant cell arteritis and associated with temporal arteritis,
therefore risk of ® blindness
Treatment
Corticosteroids
® rapid and dramatic relief
SLE
Definition:
Chronic
inflammatory condition characterised by the presence of
anti-nuclear antibodies.
Incidence
Prevalence
3-400 / 100,000
Occurs mainly in young women
Male : Female ®
1:9 increases to 1:30 in child bearing years
Probable viral trigger in genetically susceptible individual
Aetiology
Genetic
or environmental mediators may ®
triggers
Pathology
Fibrinoid
necrosis of small vessels ®
variety of inflammatory lesions in the kidney, spleen, lungs, and
other organs
Fibrinoid deposits in synovium ®
mild inflammation
Cartilage destruction is seldom severe
Clinically
Malaise,
anorexia, weight loss and fever
Non destructive, non deforming arthritis -Joint pain is usual but
not a salient feature
May be tenosynovitis rather than arthritis
May ® tendon ruptures
Severe cases may resemble rheumatoid
Aseptic necrosis of the hip and other joints is not uncommon (?
related entirely to steroid therapy)
Associated with skin rashes (butterfly rash) and ulceration
Raynauds syndrome
Hepatosplenomegaly
Associated
with
Nephritis
(50% of patients)
Pericarditis (30% patients)
Myocarditis (25% of patients)
Pleuritis (40-50% of patients)
Normochromic normocytic anaemia (common)
Thrombocytopenia (25% of patients)
Hepatitis, splenomegaly and chorea
Investigations
Anaemia,
leucopoenia and increased ESR are common
Anti-nuclear factor always positive
Rh factor also positive in 25%
Treatment
Steroids
both topical and systemically administered
NSAIDs for minor clinical manifestations of SLE
Antimalarials also used for mild systemic disease, cutaneous and
musculo-skeletal manifestations
Prognosis
Survival
85% at 5 years and 65% at 10 years
Death usually secondary to renal failure
Scleroderma
Definition
Uncommon generalised disorder of connective tissue affecting
primarily the skin, lungs, GIT, heart, kidneys and musculo-skeletal
system
Incidence
Female
: Male 4:1
Usually 30 - 50 years at onset
Aetiology:
Chromosomal
abnormalities have been noted in as many as 90% of patients
? significance
Pathogenesis
Abnormal
regulation of connective tissue synthesis
Primary event seems to be endothelial cell damage ®
narrowing, decreased distensibility ®
obliteration of vessels
Pathology
Target
organ oedema ®
fibrosis
Hyper-gammaglobulinaemia and ANF are frequent findings
Clinically
Raynauds
Skin ® firm, thickened and
leathery
Lower limbs relatively spared
Taut skin over fingers ®
limit extension and may ®
FFD
Resorption of bone of terminal phalanx may occur
Facial skin contracture ®
unable to open mouth fully
CREST syndrome: Subcutaneous calcinosis, Raynauds, oesophageal
abnormalities, sclerodactyly and telangiectasia
Greater than 50% ®
pain / stiffness of fingers and knees
Systemic poly arthritis similar to rheumatoid may occur
Associated with intestinal malabsorption
Pulmonary fibrosis and pulmonary hypertension may occur
Cardiac involvement ®
degree of heart block & arrhythmias
Acute and chronic pericarditis may occur ®cardiac
tamponade and accounts for 15% of deaths
Renal failure is the leading cause of death and is usually evident
within 3 years of the onset of the disease
Investigations
Increased ESR
Normochromic, normocytic anaemia
ANF evident in 40-90% of patients
Treatment
No
specific treatment effective
® use appropriate treatment for
the organ systems involved
Rheumatic
Fever
Systemic
non supperatve inflammatory disease often recurrent and most
likely related to prior infection with a group A b haemolytic
strep.
® auto-immune response
Affects joints, the heart, skin, serosa, lungs
Joints are involved most often but the most significant effects
are on the heart as the other effects are nearly always benign and
transient
4% ® bacterial endocarditis ®
prophylactic antibiotics
Peripheral arthropathy is also sometimes seen with
Serum
sickness
Haemochromatosis
Hyperthyroidism
Giant cell arteritis
Occult neoplasm
Self limited viral illness
Hypertrophic osteodystrophy
Tietzes' syndrome
Erythema nodosum
Erythema multiformae
Pigmented
Villo-nodular Synovitis
Usually
occurs in the knee as a mono-articular proliferative process
Incidence
2
per 1,000,000 population
Knee involved more frequently than other joints and in diffuse
rather than localised form
Male : Female ®
1:1 (Male may be slightly more than )
Pathogenesis
Inflammation
with haemosiderin laden macrophages
? triggering mechanism
May be a benign neoplastic condition
Pathology
Histological
lesion characterised by fibrous stroma, deposition of haemosiderin,
histiocyte infiltration and giant cells occurring in the synovial
membrane of tendon sheaths and large joints
Sub-synovial nodular proliferation of larger round polyhedral or
spindle cells with prominent cytoplasm and pale nuclei
Phagocytic, histiocytic cells are also present
Lipid laden foam cells and multi-nucleated giant cells are
interspersed with haemosiderin laden cells
Gross
Most
lesions are a single nodular outgrowth more likely pedunculated
than sessile with a firm elastic consistency
Clinically
Two
forms: Localised, nodular
Diffuse
Mon-articular arthritis affecting adults in the 3rd to 4th decade
Onset insidious
50% or less recall an episode of trauma
Associated with a joint effusion
No abnormality may be evident or only evidence of effusion
X-Rays
Soft tissue mass
Cysts or bony erosions in ~ 33%
Diffuse bony lesion in ~ 25%
Arthrography may identify the synovial mass
Arteriography ®
richly vascular soft tissue masses
MRI ® may give typical picture
due to haemosiderin
Treatment
Recurrence
more common in the diffuse form
Local excision acceptable for isolated lesions
Radiotherapy, wide excision arthrodesis and grafting have been
used for diffuse disease
No treatment has ®
universally good results
Radiotherapy best early or when lesions are vascular rather than
later when they become fibrosed
Most commonly reported technique is wide synovectomy but ®
high incidence of recurrence
Diffuse form associated
with significant morbidity but total synovectomy seems the
treatment of choice
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Fax: (231) 929-4356
Email: info@imei.com
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