Investigation Of Musculoskeletal

Disease

Group 3

1) Balkis Mohomed Abdi

2) Ilham Sa’eed Jirde
3) Mukhtar Muse Abokor
4) Safia Ahmed Yaasin Sh. Cali
 Outline
 Introduction
 Joint Aspiration
 Imaging (X-ray, MRI, CT scan,
Ultrasonography)
 Blood tests
 Tissue biopsy
 Reference
 Introduction

 Clinical history and examination usually provide

sufficient information for the diagnosis and
management of the many musculoskeletal diseases.

 Investigations are helpful in confirming the diagnosis,

assessing disease activity and indicating prognosis.
 Joint Aspiration
 Joint aspiration with examination of synovial fluid (SF) is
crucial in patients suspected of having septic arthritis, crystal
arthritis or intra-articular bleeding.

 It should be carried out in all individuals with acute

monoarthritis, and samples should be sent for microbiology
and clinical chemistry.

 It is possible to obtain SF by aspiration from most peripheral

joint and only a small amount is required for diagnostic
purposes. Normal SF is present in small volume, is clear and
either colorless or pale yellow and has a high viscosity. It
contains few cells.
 Cont…
 With inflammation, the volume increases, the cell count and the
proportion of neutrophils rise (causing turbidity), and the viscosity
reduces (due to enzymatic degradation of hyalurnon and aggrecan).

 Turbid fluid with a high neutrophil count occurs in sepsis, crystal arthritis
and reactive arthritis.

 High concentrations of urate crystals or cholesterol can make SF appear

white.

 Uniform blood-staining is most commonly due to a bleeding diathesis,

trauma or pigmented Villonodular synovitis.

 A lipid layer floating above blood-stained fluid is diagnostic of intra-

articular fracture and is caused by release of bone marrow fat into the
joint.
 Cont…

 Crystals can be identified by compensated polarized light

microscopy of fresh SF (to avoid crystal dissolution and post-
aspiration crystallization).

 Urate crystals are long and needle shaped, and show a strong
light intensity and negative birefringence.

 Calcium pyrophosphate crystals are smaller, rhomboid in shape

and usually less numerous then urate crystals; they have weak
intensity and positive birefringence.
Imaging
 Plain X-rays
 X-rays show structural changes that are of value in the differential diagnosis and
monitoring of many bone and joint disease;

 They are of diagnostic value in OA, where they demonstrated joint space narrowing
that tends to be focal rather than widespread, as in inflammatory arthritis.

 In peripheral joints, proliferative erosion, associated with new bone formation and
periosteal reaction, occurs in SpA.

 Calcification of cartilage, tendons and soft tissues or muscle occurs mainly in

chondrocalcinosis, calcium-containing crystal diseases, tumoral calcinosis and
autoimmune connective tissue diseases.

 X-ray are of limited value in the diagnosis of RA because feature such as erosion,
joint space narrowing and Periarticular osteoporosis may be detectable only after
several months or even years. The main indicator for X-ray in RA is in the assessment
of disease over time when structural damage to the joints is suspected.
 Radiographic abnormalities in selected rheumatic
diseases
Rheumatic arthritis
1. Periarticular Osteoporosis 3. Joint subluxation
2. Marginal joint erosion 4. Joint space narrowing

Paget’s disease
1. Bone expansion 3. Osteosclerosis and lysis
2. Abnormal trabecular pattern 4. Pseudo-fractures

Osteoarthritis
1. Joint space narrowing 4. Joint deformity
2. Osteophytes 5. Subchondral cysts
3. Subchondral Sclerosis
 Bone Scintigraphy
 Bone Scintigraph is useful in the diagnosis of metastatic bone
disease and Paget’s disease of bone.

 Abnormalities may also be observed in primary bone tumors,

complex region pain syndrome, osteoarthritis, inflammatory
arthritis, stress fractures and Osteomalacia (e.g. Looser’s
Zones ), Sclerosing bone disorders (e.g. hypertrophic
pulmonary osteoarthropathy and Sponydyloarthritides (e.g.
abnormalities at Sacroiliac joints and tendon/ligament
insertions).
 Cont…

 It involves gamma-camera imaging following an intravenous

injection of 99mTc-labelled bisphosphonates. Early post-injection
images reflect blood flow and can show increased perfusion of
inflamed synovium, Pagetic bone or primary or secondary bone
tumors.

 Delayed images taken a few hours later reflect bone remodeling as

the 99mTc-labelled bisphosphonates localizes to sites of active bone
turnover.

 Scintigraph has a high sensitivity for detecting important bone and

joint pathology that is not apparent on X-ray.
 Magnetic resonance imaging
 Magnetic resonance imaging (MRI) gives
detailed information on anatomy,
allowing three-dimensional
visualization of bone and soft tissues
that cannot be adequately assessed by
plain X-rays.

 T1-weighted sequences are useful for

defining anatomy, whereas T2-weighted
sequences are useful for assessing tissue
water content, which is often increased
in synovitis and other inflammatory
disorders

 Contrast agents, such as gadolinium, can

be administered to increase sensitivity
in detecting erosions and synovitis.
 Cont …
 The technique is valuable in the assessment and diagnosis of
many musculoskeletal diseases including:

- Osteonecrosis
- Intervertebral disc disease
- Nerve root entrapment
- Spinal cord compression
- Spinal stenosis
 Ultrasonography
 Ultrasonography is a useful
investigation for confirmation of
small joint synovitis and erosions, for
anatomical location of periarticular
Lesions and for guided injection of
joints and bursae.

 Ultrasound is more sensitive than

clinical examination for the detection
of early synovitis

 In addition to locating synovial

thickening and effusions, ultrasound
can detect increased blood flow
within synovium using power
Doppler imaging
 Computed tomography
 Computed tomography (CT) is used selectively for assessing
patients with bone and joint disease.

 CT may be used when skeletal configuration needs defining,

when calcific lesions are being assessed (crowned dens
syndrome), when MRI is contraindicated
Blood tests
 Hematology
 Abnormalities in the full blood count (FBC) often occur in
inflammatory rheumatic diseases but changes are usually nonspecific.

 Examples include neutrophilia in crystal arthritides and sepsis;

neutropenia in lupus; and lymphopenia in autoimmune rheumatic and
connective tissue diseases.

 Reduced levels of haemoglobin and raised platelets are a common and

important finding in active inflammatory rheumatological disorders.

 Many synthetic and biologic disease-modifying antirheumatic drugs

(DMARDs) can cause marrow toxicity and require regular monitoring
of the FBC
 Biochemistry
 Routine biochemistry is useful for assessing metabolic bone
disease, muscle diseases and gout, and is essential in monitoring
DMARDs and biologic drugs (renal and hepatic function).

 Levels of C-reactive protein (CRP) are a useful marker of

infection and inflammation, and are more specific than the
erythrocyte sedimentation rate (ESR).

 An exception is in autoimmune connective tissue diseases, such

as SLE and systemic sclerosis, where CRP may be normal but the
ESR raised in active disease
 Immunology
 Autoantibody tests are widely used in the diagnosis of rheumatic
diseases. Whatever test is used, the results must be interpreted
in light of the clinical picture and the different detection and
assay systems used in different hospitals.

1) Rheumatoid factor
 Rheumatoid factor (RF) is an antibody directed against the Fc
fragment of human immunoglobulin. In routine clinical practice,
immunoglobulin M (IgM) RF is usually measured, although
different methodologies allow measurement of IgG and IgA RFs
too.

 Although the specificity is poor, about 70% of patients with RA

test positive. High RF titres are associated with more severe
disease and extra-articular disease.
 Cont…
2) Anti-citrullinated peptide antibodies

 Anti-citrullinated peptide antibodies (ACPAs) recognise

peptides in which the amino acid arginine has been
converted to citrulline by peptidylarginine deiminase, an
enzyme abundant in inflamed synovium and in a variety of
mucosal structures.

 ACPAs have similar sensitivity to RF for RA (70%) but

much higher specificity (>95%), and should be used in
preference to RF in the diagnosis of RA.
 Cont…
3) Antinuclear antibodies

 Antinuclear antibodies (ANAs) are directed against one or more

components of the cell nucleus, including nucleic acids
themselves and the proteins concerned with the processing of
DNA or RNA.

 They occur in many inflammatory rheumatic diseases but are

also found at low titre in normal individuals and in other diseases.

 ANAs are not associated with disease severity or activity. The

most common indication for ANA testing is in patients suspected
of having SLE or other autoimmune connective tissue diseases.
 Cont…
 ANA has high sensitivity for SLE (100%) but low specificity (10–
40%).

 A negative ANA virtually excludes SLE but a positive result does

not confirm it.

 Anti-DNA antibodies bind to double-stranded DNA (dsDNA) and

are useful in SLE monitoring as very high titres are associated
with more severe disease, including renal or central nervous
system (CNS) involvement, and an increase in antibody titre may
precede relapse.
 Antiphospholipid antibodies

 These antibodies bind to a number of

phospholipid binding proteins but the most
clinically relevant are those that target beta2-
glycoprotein 1
 They are seen in autoimmune diseases like SLE.
 Antineutrophil cytoplasmic antibodies
 Antineutrophil cytoplasmic antibodies (ANCAs)
are IgG antibodies.
 They are directed against the cytoplasmic
constituents of granulocytes.
 They are useful in the diagnosis and monitoring of
systemic vasculitis.
 Cont.….
 Two common patterns which are described by
immunofluorescence are included:
 cytoplasmic fluorescence (c-ANCA):
 which is caused by antibodies to proteinase-3
(PR3)
 perinuclear fluorescence (p-ANCA):
 caused by antibodies to myeloperoxidase (MPO)
and other proteins, such as lactoferrin and elastase
 Cont.….
 These antibodies are not specific for vasculitis and
positive results may be found in:
 autoimmune liver disease
 malignancy
 infection (bacterial, virus e.g. HIV)
 inflammatory bowel disease
 pulmonary fibrosis.
 RA, SLE
 Pulmonary fibrosis
 Complement
 Low complement C3 is an indicator of active SLE.
 This is due to consumption of complement by the
immune complex.
 Low C4 is less specific for SLE activity
 Tissue biopsy
 Tissue biopsy is useful in confirming the diagnosis
in certain musculoskeletal diseases.
 Therefore tissue biopsy can be:
 Synovial biopsy: can be useful in patients with
chronic inflammatory monoarthritis or
tenosynovitis
 It is benefit is to rule out chronic infectious causes,
especially mycobacterial infections
 Cont..
 Temporal artery biopsy: is used in patients
suspected of having temporal arteritis, especially
when the presentation is atypical.
 Negative result do not role out the disease.

 Muscle biopsy: plays an important role in the

investigation of myopathy and inflammatory
myositis.
 Cont..
 Bone biopsy: is occasionally required where non-
invasive tests give inconclusive results, in the
diagnosis of infiltrative disorders, in patients with
renal bone disease.
 Bone is taken from the iliac crest using a large-
diameter trephine needle under local anaesthetic.
 Reference

Davidson textbook

Harrison textbook