Rematological Examination

CHAPTER 2
Evaluation of the Patient

A. History and Physical Examination
DAVID B. ROBINSON, MD, MSC, FRCPC
HANI S. EL-GABALAWY, MD, FRCPC
䊏 The patient history and physical examination form 䊏 The joint examination must include pattern, range of
the basis of diagnosis and monitoring the course of motion, signs of inflammation, stability, weakness,
rheumatic and musculoskeletal diseases. and deformity.
䊏 Attention is focused on signs and symptoms of both
joint and extra-articular features.
Musculoskeletal complaints are among the most Location and Symmetry

common problems in clinical medicine. It is therefore
important that all physicians are able to conduct The location of a musculoskeletal problem is often the
a basic screening evaluation that identifies the pres- most important clue in identifying the specific cause.
ence of pathology or dysfunction of musculoskeletal Musculoskeletal problems can broadly be categorized
structures. as regional or generalized, although there is often con-
siderable overlap between these two categories.
Regional syndromes typically affect a single joint or
RHEUMATOLOGICAL periarticular structure, or an entire extremity or body
region. A regional pain syndrome can be on a referred
HISTORY basis, and have little to do with the area where the pain
is experienced. Joints both immediately above and
A thoughtful and detailed history plays a critical role in below the painful area should be routinely examined for
determining the nature of the complaint and helps to pathology.
focus the clinical evaluation (1). The history should be Specific arthropathies have a predilection for involv-
structured to answer specific questions. ing specific joint areas (2). Involvement of the wrists and
the proximal small joints of the hands and feet is an
Questions for the Clinician important feature of rheumatoid arthritis (RA). In con-
trast, psoriatic arthritis (PsA) often involves the distal
to Address joints of the hands and feet. An acutely painful and
1. Is the problem regional or generalized, symmetric or swollen great toe is most likely caused by a gouty attack.
asymmetric, peripheral or central? An important aspect of the articular pattern of involve-
2. Is it an acute, subacute, or chronic problem? Is it ment is symmetry. Rheumatoid arthritis tends to involve
progressive? joint groups symmetrically, whereas the seronegative
3. Do the symptoms suggest inflammation or damage spondyloarthropathies and osteoarthritis (OA) tend to
to musculoskeletal structures? be asymmetrical in their articular patterns.
4. Is there evidence of a systemic process? Are there
associated extra-articular features?
5. Is there an underlying medical disorder which may
Onset and Chronology
predispose to a specific rheumatologic problem? The mode of onset and evolution of musculoskeletal
6. Has there been functional loss and disability? symptoms over time is very helpful in establishing a
7. Is there a family history of a similar or related diagnosis. For most chronic arthropathies such as RA,
problem? the onset is typically subacute, occurring over weeks to
6
CHAPTER 2 • EVALUATION OF THE PATIENT 7
months rather than hours to days. Attacks of gout and important diagnostic clue. In addition, systemic rheu-
septic arthritis, on the other hand, have an acute onset, matic diseases are commonly associated with nonarticu-
reaching a crescendo within hours. The pain of fibromy- lar features that are of value in diagnosis. For example,
algia is often reported as being present for years with a history of recent genitourinary symptoms in associa-
episodic exacerbations. A temporally associated trau- tion with lower extremity asymmetric oligoarthritis is
matic event or history of repetitive use of a joint can be highly suggestive of reactive arthritis, whereas this same
a particularly good clue to diagnosing a regional mus- articular pattern in association with recurrent abdomi-
culoskeletal syndrome. nal pain and bloody diarrhea is more suggestive of the 2
arthropathy of inflammatory bowel disease. It is thus
important that the clinician perform a complete review
Inflammation and Weakness of systems and directly question the patient regarding
Articular pain and swelling can be on an inflammatory the presence of specific symptoms, such as rashes or skin
or non-inflammatory basis. When intra-articular inflam- changes, photosensitivity, Raynaud’s phenomenon,
mation is present, the process involves the synovial mouth ulcers, and dryness in the eyes and mouth.
membrane, and is termed synovitis. The swelling is
usually due to accumulation of fluid in the articular Functional Losses
cavity and/or infiltration and enlargement of the
synovium. Pain and swelling associated with the pres- Questioning regarding functional loss is essential for
ence of synovitis often occur at rest, whereas in degen- understanding the impact of a musculoskeletal disorder
erative disorders such as OA, these symptoms become and, in turn, developing a plan of management. The
more evident with joint use. In the presence of synovitis, questioning should span the spectrum of activities, from
the patient may also complain of difficulty moving the simple activities of daily living such as dressing and
joints after a period of immobility, a symptom referred grooming to more physically demanding activities such
to as stiffness. In inflammatory disorders such as RA, as sports. In some cases, the functional loss may be quite
this stiffness is most evident in the early morning. severe, impairing basic activities such as stair climbing
Indeed, the duration of morning stiffness, typically and gripping, while in others it may be quite subtle,
established by asking the patient, “How long does it detectable only as a reduction in strenuous activities
take you before you are moving as well as you are going such as jogging.
to move for the day?” is a semiquantitative measure of
the degree of articular inflammation. Family History
Complaints of limitation in joint motion, deformity,
and joint instability are usually caused by damage to A number of rheumatic diseases have a strong genetic
articular and periarticular structures. The patient should basis. Disorders such as ankylosing spondylitis are much
be carefully questioned to establish the circumstances more common in HLA-B27–positive families than in
around which these symptoms were initiated, and the the general population. Questioning regarding family
types of movements that aggravate them. history should not be restricted only to ascertaining
Patients with musculoskeletal pathology often com- whether other family members have a similar arthritis,
plain of muscle weakness. This feeling of weakness may but should be as complete as possible regarding autoim-
be associated with pain, stiffness, and, in some cases, mune diseases, many of which (e.g., RA, thyroid disease,
parasthesia or other neurological symptoms. General- and diabetes) tend to cluster in families.
ized weakness may be in response to pain from articular
or periarticular inflammation, as in the case of RA and
polymyalgia rheumatica. Alternatively, weakness may PRINCIPLES OF
be caused by a primary neuropathic or myopathic RHEUMATOLOGICAL
process. In the case of myopathies, the weakness is typi-
cally symmetrical and involves proximal muscles most EXAMINATION
severely, whereas neuropathies more commonly affect
the distal musculature. Evaluation of musculoskeletal complaints involves
examination of the joints and their soft tissue support
structures, the bony skeleton, and the muscle groups that
Systemic and Extra-Articular move the skeletal structures (3). The joints, bones, and
muscles can be directly accessible to examination, as in
Features the extremities, or they may be inaccessible to direct
Constitutional symptoms of fatigue, weight loss, examination, as in the case of the spine and hip joints.
anorexia, and low grade fever can be associated with any All joint areas should be inspected from multiple
systemic inflammatory process, and their presence is an angles to assess for deformity (sometimes seen as loss
8 DAVID B. ROBINSON AND HANI S. EL-GABALAWY
of symmetry with the contralateral side), muscular A key part of the musculoskeletal evaluation involves
atrophy, swelling, erythema, or surgical scars. Extremity examination of the ligaments, tendons, menisci, and
joints should be palpated for warmth using the dorsum muscles. These structures may be the primary source of
of the hand. Superficial joints are normally slightly the pathology, or may be involved secondary to the
cooler than the surrounding soft tissue. The joint line articular pathology. Examination of individual muscle
and major bony and soft tissue structures should be groups requires a basic knowledge of the origin, inser-
palpated for tenderness. tion, and primary action of each muscle. Atrophy and
Functional joint motion should be tested both by weakness of the muscles surrounding a particular joint is
having the patient actively move the joint to its extremes an important indicator of chronic articular pathology.
and by having the examiner passively move the joint
through its range. Tenderness elicited by gentle stress A Screening Musculoskeletal
on the joint at its end range of motion (stress tender-
ness) is characteristic of joint pathology and may be
Exam
absent in pain syndromes such as fibromyalgia. Loss of The GALS (Gait, Arms, Leg, Spine) system has been
range of motion is seen both with acute articular inflam- devised to screen rapidly for musculoskeletal disease
mation and with chronic arthritis and damage. Joints (4). Initially, the patient is asked three basic questions:
should be assessed for the presence of swelling. The “Have you any pain or stiffness in your muscles, joints,
cardinal signs of articular inflammation are warmth, or back?”; “Can you dress yourself completely without
joint line tenderness, pain on motion (particularly at the any difficulty?”; “Can you walk up and down stairs
extremes of the range of motion), and intra-articular without any difficulty?”. Depending on the answers to
swelling or effusion. the questions, further questioning is undertaken to
Deformity caused by loss of alignment is a conse- explore specific areas.
quence of destructive arthropathies such as RA. The The examiner then systematically inspects the
damage is commonly associated with loosening of the patient’s gait, arms, legs, and spine, first with the patient
soft tissue support structures surrounding the joints. In standing still and then responding to instructions (Table
some cases, the joint may not exhibit any obvious defor- 2A-1). Abnormalities detected on this screening are fol-
mity, but may be unstable when put through its range lowed up with a more detailed regional or generalized
of motion or is mechanically stressed. musculoskeletal examination.
TABLE 2A-1. MAIN FEATURES OF THE GAIT, ARMS, LEG, SPINE (GALS) SCREENING INSPECTION.
POSITION/ACTIVITY NORMAL FINDINGS
Gait Symmetry, smoothness of movement; normal stride length; normal heel

strike, stance, toe-off, swing through; able to turn quickly
Inspection from behind Straight spine, normal symmetric paraspinal muscles, normal shoulder and
gluteal muscle bulk, level iliac crests, no popliteal cysts, no popliteal
swelling, no hindfoot swelling/deformity
Inspection from the side Normal cervical and lumbar lordosis, normal thoracic kyphosis
“Touch your toes.” Normal lumbar spine (and hip) flexion
Inspection from the front

Arms
“Place your hands behind your head, elbows out.” Normal glenohumeral, sternoclavicular, and acromioclavicular joint
movement
“Place your hands by your side, elbows straight.” Full elbow extension
“Place your hands in front, palms down.” No wrist/finger swelling or deformity, able to fully exend fingers
“Turn your hands over.” Normal supination/pronation, normal palms
“Make a fist.” Normal grip power
“Place the tip of each finger on the tip of the thumb.” Normal fine precision, pinch
Legs Normal quadriceps bulk/symmetry, no knee swelling or deformity, no
forefoot/midfoot deformity, normal arches, no abnormal callous
formation
Spine
“Place your ear on your shoulder.” Normal cervical lateral flexion
SOURCE: Modified from Doherty et al., Ann Rheum Dis 1992;51:1165–1169, with permission of Annals of Rheumatic Diseases.
EXAMINATION OF SPECIFIC and spread out the digits. Pincer function of the thumb
and fingers should be tested. The grip strength can be
JOINT AREAS estimated by having the patient squeeze two of the
examiner’s fingers. Individual hand joints should be pal-
The Hand and Wrist pated to determine the presence of joint line tenderness
and effusion, these being the most important indicators
A number of generalized arthropathies have distinctive of synovitis. The technique for palpating the DIP and
patterns of hand involvement, and the recognition of PIP joints is similar. The thumb and index finder of one 2
these patterns is highly valuable diagnostically. Exami- hand palpates in the vertical plane, while the thumb and
nation of the hands should be initiated with the patient index finder of the other hand palpates in the horizontal
sitting comfortably with the hands open and the palms plane (Figure 2A-1). Alternating gentle pressure
facing down. In this position, the examiner can inspect between the two planes will displace small amounts of
the alignment of the digits relative to the wrist and synovial fluid back and forth, allowing the examiner to
forearm. Atrophy of the intrinsic muscles of the hands detect effusions in these small joints. Likewise, tender-
can readily be appreciated as a hollowing out of the ness suggestive of synovitis can be elicited by this tech-
spaces between the metacarpals. The nails should be nique. The technique for palpating the MCP joints is
inspected for evidence of onycolysis or pitting sugges- somewhat modified because of the inability to directly
tive of psoriasis. Redness and telangiectasia of the nail palpate these joints from the horizontal plane. The
fold capillaries can by detected on close inspection, and thumbs are used to palpate the dorsolateral aspects of
is often indicative of a connective tissue disease such as the joint, while the index fingers palpate the palmar
systemic lupus erythematosus (SLE), scleroderma, or aspect.
dermatomyositis. Tightening of the skin around the Palpation of the wrist involves a similar technique to
digits, or sclerodactyly, is typical of scleroderma and is that used for the MCPs. The thumbs are used to palpate
usually both visible and palpable. The pulp of the digits the dorsum of the joint, while the index fingers palpate
should be examined for the presence of digital ulcers, the volar aspect (Figure 2A-2). Synovial thickening and
also seen most commonly in scleroderma. tenderness suggestive of wrist joint synovitis can usually
Articular swelling of the distal interphalangeal (DIP) be palpated on the dorsum of the joint. Particular atten-
and proximal interphalangeal (PIP) joints can represent tion should be paid to swelling and tenderness in the
bony osteophytes as in the case of Heberden’s and area just distal to the ulnar styloid, where the extensor
Bouchard’s nodes in the DIP and PIP joints, respec- and flexor carpi ulnaris tendons are directly palpable.
tively, or can represent an intra-articular effusion This area is very commonly involved in early RA. Pain
associated with synovitis in the joint. Palpation will and tenderness confined to the radial aspect of the wrist
help in differentiating these. Swelling and redness of are most commonly due to either OA of the first carpo-
an entire digit, termed dactylitis, is highly suggestive of
a spondylarthropathy such as psoriatic arthritis or reac-
tive arthritis.
Swelling of the metacarpophalangeal (MCP) joints
can be visually appreciated as a fullness in the valleys
normally found between the knuckles (heads of the
metacarpal bones). In cases of RA where the MCP
synovitis has been longstanding, it is often associated
with ulnar subluxation of the extensor tendons, result-
ing in the ulnar drift of the digits that is typical of this
diagnosis. Swelling on the dorsum of the wrist area can
result from synovitis of the wrist or tenosynovitis of the
extensor tendons. Getting the patients to gently wiggle
the fingers helps differentiate these two findings in that
the swelling will tend to move with the tendons if it is a
result of tenosynovitis. Inspection of the palmar aspect
of the hands is important for identifying atrophy of the
thenar or hypothenar eminences, which can result either
from disuse due to articular involvement of the wrist FIGURE 2A-1
or, in the case of the thenar eminence, carpal tunnel
Technique for examining the small joints of the hands and feet.
syndrome. The thumb and index finger of the examiner’s hands are used
Global function of the hand should be evaluated by to gently ballot small amounts of intra-articular fluid back and
asking the patient to make a full fist and to fully extend forth to elicit evidence of joint line tenderness.
tis. With this maneuver, the bulge in the lateral recess

will tend to enlarge, becoming more tense due the
reduction in the internal dimension of the elbow in the
position of extension.
The synovial cavity and joint line can best be pal-
pated for swelling and tenderness in the area of the
lateral recess. This is also the site where arthrocentensis
of the elbow is performed. It should be noted that pain
in the lateral aspect of the elbow area is a common clini-
cal problem, and is usually due to lateral epicondylitis
or tennis elbow rather than elbow joint pathology. Ten-
derness directly palpable over the lateral epicondyle
and with stressing the wrist and finger extensors is sug-
gestive of this diagnosis.
FIGURE 2A-2 The Shoulder

The dorsum of the wrist joint is palpated for tenderness and Proper examination of the shoulder should always begin
swelling using the examiner’s thumbs. The wrist should be with appropriate visualization of the entire shoulder
examined in slight flexion to allow the joint line of the radiocar- girdle area, both from the front and the back. This
pal, intercarpal, and carpometacarpal joints to be optimally includes the sternoclavicular, glenohumeral, and acro-
palpated.
mioclavicular joints as well as the scapulothoracic
articulation. Comparison should be made with the con-
tralateral shoulder. Any asymmetry between the two
metacarpal joint, or to DeQuervain’s tenosynovitis. All sides should be noted. For example, patients with rotator
the joints of the hand and wrist should be evaluated for cuff tears often hold the affected shoulder higher than
stress tenderness. the other side. Atrophy of the shoulder girdle muscula-
ture is an important sign of chronic glenohumeral joint
pathology, as occurs in RA. This is most evident as
The Elbow squaring of the shoulder due to deltoid atrophy and
Flexion and extension of the forearm occur exclusively scooping out of the upper scapular area due to super-
at the elbow joint and involve the hinge type of articula- spinatus atrophy. Effusions in the shoulder joint are
tion between the proximal ulna and distal humerus. In visible anteriorly just medial to the area of the bicipital
examining the elbow, a number of surface landmarks groove, and if large enough are also evident laterally
need to be identified. These are the olecranon process, below the acromion. It should be noted that large
the medial and lateral epicondyles of the humerus, and amounts of fluid can accumulate in the glenohumeral
the radial head. A triangular recess is formed in the joint space without much visible evidence due to con-
lateral aspect of the joint between the olecranon process, siderable redundancy in the joint capsule.
the lateral epicondyle, and the radial head. This recess After inspecting the shoulder area in the resting posi-
is the point where the synovial cavity of the elbow is tion, the patient is asked to demonstrate the active
most accessible to inspection and palpation. range of motion of the shoulder. Abduction is observed
Examination of the elbow should be undertaken with as the patient moves both outstretched arms from their
the patient sitting comfortably and the entire arm being side in the lateral plane until the palms meet overhead.
well supported in order to eliminate muscle tension. The movement is evaluated for discomfort, symmetry,
Initially the joint should be inspected with forearm and fluid scapulohumeral coordination. Patients with
flexed to 90°. Particular attention should be paid to the shoulder pathology will usually move the arm forward
lateral recess described above. Obvious bulging in this somewhat in order to complete the maneuver. External
area is highly suggestive of an effusion and synovitis. In rotation can then be tested by having the patient attempt
contrast, swelling directly over the olecranon process to touch the back of their head with the palm of the
is more suggestive of olecranon bursitis. Any process hand from the fully abducted position. If abduction is
that causes true synovitis of the elbow is typically associ- abnormal, active flexion should be tested by having the
ated with a reduction in the range of motion of the joint, patient lift the outstretched arm from their side directly
both in flexion–extension and in supination–pronation. up in front of them. Active internal rotation and exten-
Having the patient extend the forearm as much as pos- sion is observed by having the patient reach behind
sible will detect the presence of a flexion contracture, their back and attempt to have their fingertips touch the
this being an almost invariant feature of elbow synovi- highest point possible on their scapula.
Palpation should include the entire shoulder girdle shoulder. The predictive value of these maneuvers is
area. The sternoclavicular joint is palpated, then the modest (5). Forced supination of the hand with the
fingers are walked laterally over the clavicle to the acro- elbow flexed at 90° will cause pain in the area of the
mioclavicular joint, which is palpated for tenderness and long head of the biceps in patients with bicipital tendi-
swelling. The subacromial space, containing the supra- nitis. Impingement of the subacromial bursa or supra-
spinatus tendon and subacromial bursa, lies directly spinatus tendon is suggested by pain with forced internal
below the acromion. Immediately below the acromio- rotation and flexion of the glenohumeral joint from a
clavicular joint, the coracoid process should be identi- position of 90° flexion with the elbow flexed at 90°. 2
fied. The short head of the biceps inserts on this process. Supraspinatus tendinitis can be detected by having the
The long head of the biceps can be palpated lateral to patient position their outstretched arm at 90° of abduc-
this in the bicipital groove. The anterior aspect of the tion while maximally internally rotating the glenohu-
glenohumeral joint can be palpated between the cora- meral joint such that the thumb is pointing downward.
coid process and the long head of the biceps and follows The examiner then asks the patient to resist attempts to
the contour on the rounded anterior aspect of the push the arm down. In patients with superspinatus ten-
humeral head. Shoulder synovitis can be palpated in this dinitis, the maneuver will be associated with pain, and
area as joint line tenderness and/or boggy effusion. may result in the patient suddenly dropping the arm.
Passive range of shoulder motion is then evaluated.
The most informative parts of the range of motion are
internal/external rotation and abduction. When testing
The Hip
these movements it is very important to immobilize the Pain resulting from hip arthritis is typically experienced
scapula to prevent rotation at the scapulothoracic area. in the groin or, less commonly, the buttock. It tends to
In this way, glenohumeral motion can be isolated and radiate down the anteromedial aspect of the thigh, occa-
appropriately evaluated. One effective technique to sionally down to the knee. Pain in the lateral trochan-
achieve this is to firmly press down on the top of the teric area is most often indicative of bursitis involving
shoulder area with the palm of one hand, while the other the trochanteric bursa.
hand moves the arm through the range of motion (Figure Because the hip joint cannot be directly examined,
2A-3). Internal/external rotation should be tested with the examiner needs to glean important diagnostic clues
the arm by the patient’s side and with the arm abducted from observing the patient’s gait, buttock and thigh
to 90°. Examination of the patient in the supine position musculature, and from evaluating passive range of
may aid in relaxing musculature in patients who are motion of the hip joint. As with all load bearing joints,
unable to fully relax during this maneuver. evaluation of functional joint motion needs to be
A large number of special maneuvers have been assessed under load with the patient walking and stand-
described that suggest specific clinical syndromes in the ing. Subtle hip pathology may be detected by having
the patient perform a squat. The patient with true hip
disease often walks with a coxalgic gait, tending to
quickly swing the pelvis forward on the affected side in
order to avoid weight bearing on the hip affected by
arthritis. If the hip arthritis is prolonged and severe, the
buttock musculature tends to atrophy, as does the thigh
musculature. In severe cases, the abductor muscles are
unable to hold the pelvis in a horizontal position when
the patient is asked to stand only on the affected hip.
This forms the basis of the Trendelenburg test, where
the patient’s pelvis tends to sag down on the contralat-
eral side when the patient is asked to hold their entire
weight on the affected leg.
With the patient in the supine position, passive range
of motion should initially be screened by log rolling the
entire extended leg. The leg is then flexed maximally to
assess completeness of this motion. With the knee flexed
FIGURE 2A-3 to 90° and the hip flexed to 90°, internal and external
rotation of the hip are then tested. Care should be taken
Glenohumeral joint motion is best examined with the elbow that the hip movements are isolated, and that the
flexed to 90° and the upper arm in partial abduction. Internal
and external rotation of the shoulder are then examined in this
patient’s pelvis is not rotating to compensate for lost
position. Care should be taken to immobilize the scapula using a range of motion. Pain and loss of motion on internal
technique such as that shown. rotation are particularly sensitive indicators of hip
pathology. Flexion contracture of the hip tends to motion, the marks identifying this 10 cm segment nor-
accompany longstanding severe hip arthritis. mally expand to 15 cm or more, indicative of distraction
between the vertebrae. While reduction in this mea-
surement is not specific for any particular pathology, it
The Sacroiliac Joint can be used over time to follow disorders with progres-
Palpation of the sacroiliac (SI) joint is undertaken with sive loss of motion, such as ankylosing spondylitis.
the patient lying flat on their abdomen. With the palm Patients presenting with symptoms suggestive of a
of the examiner’s hand held around the iliac crest, the lumbar radiculopathy, such as pain and parasthesia
thumb tends to fall directly over the joint which extends shooting down the leg, need to undergo an examination
down below the dimples in the posterior pelvic area. To of the lumbosacral area and a detailed neurological
elicit tenderness in the SI joint, direct pressure is applied examination of the leg. Maneuvers that put traction on
with the thumb in this area. In addition to direct palpa- the lumbar spinal roots are used to provide further evi-
tion, the examiner can perform other maneuvers to dence of a radiculopathy. The most commonly used of
further establish the presence of sacroiliitis. Direct pres- these maneuvers is the straight leg raising test, where
sure over the sacrum will produce pain in an inflamed the patient lies in the supine position and the leg is pas-
SI joint. Gaenslen’s maneuver is performed by having sively raised by the examiner with the knee fully
the patient hyperextend their leg over the edge of the extended. A positive test requires that the patient expe-
examining table, thereby stressing the ipsilateral SI rience pain and parasthesia shooting down the leg to the
joint. level of the foot.
Cervical range of motion begins with the patient
upright and the examiner in front. The patient is asked
The Spine to flex, extend, laterally flex (patient attempts to touch
The spine should be examined initially with the patient their ear to their shoulder), and laterally rotate (patient
standing and the entire spine well visualized. The normal attempts to touch their chin to their shoulder) their
curvature of the spine, lumbar lordosis, thoracic kypho- head. Movements should be evaluated for symmetry,
sis, and cervical lordosis should be evaluated by observ- fullness of motion, and discomfort. Gentle passive range
ing the patient from the both the back and the side, and of motion may be attempted with the patient supine.
any loss or accentuation of these curves noted. If scolio- Spinous processes and surrounding musculature should
sis is noted with the patient standing upright, they should be palpated for spasm or tenderness. It should be noted
be asked to bend forward and flex the spine to evaluate that pain in the neck area often radiates down the arm,
the effects of this movement on the scoliosis. True sco- up the occiput, or down to the scapular area. The pain
liosis will be present irrespective of the state of spinal may be aggravated by particular parts of the range of
flexion, while a functional scoliosis due to leg length motion.
discrepancy will tend to decrease with spinal flexion.
The level of the iliac crests relative to the spine should
also be evaluated by observing the patient from the
The Knee
back, and the examiner sitting with their eyes at approxi- Examination of the knee starts with inspection of the
mately the level of the iliac crests. A tilted pelvis can be patient’s gait and with the patient standing. When
due to compensation for a primary scoliosis in the spine inspecting from the front, attention should first be paid
or, alternatively, due to a leg length discrepancy. to the areas above and below the knee. Atrophy of the
The range of motion of the entire spine should be quadriceps usually indicates chronic knee pathology.
examined in segments. The lumbar spine is assessed by Swelling due to synovial fluid accumulation or synovial
having the patient attempt to touch their toes and then infiltration and thickening is most readily appreciated
extend their back. Lateral flexion is assessed by having in the suprapatellar bursa. When a large effusion is
the patient reach their fingertips as far as possible down present, it can be seen to also cause bulging of both the
the lateral aspect of their leg. Lateral rotation, which lateral and medial compartments of the knee. Inspec-
involves both the lumbar and thoracic spine, is tested tion of the knee from the back with the patient standing
by having the patient turn their upper body with the up is the best way to evaluate the alignment of the
examiner holding the pelvis stable. femur relative to the tibia. Varus deformities of the
The Schober test is performed to specifically assess knee causing a bow-legged appearance most commonly
movement in the lumbar spine. With the patient stand- result from OA preferentially involving the medial
ing, a distance of 10 cm is measured up the lumbar spine compartment. Valgus deformities, causing a knock-
from the lumbosacral junction at the level of the sacral knee appearance are more commonly associated with
dimples. Marks are placed at both ends of this 10 cm RA. Posterior inspection is also important for detecting
segment. The patient is then asked to flex forward as far popliteal or Baker’s cysts, which can be large enough to
as possible, attempting to touch their toes. With this track down the calf.
the medial and collateral ligaments. The cruciate liga-

ments are tested using the drawer sign, where antero-
posterior stress is placed on the upper tibia with the
knee in flexion. Instability of the ligaments will result in
the tibia moving back and forth relative to the femur,
much as a drawer would if pushed back and forth.
2
The Ankle and Hindfoot
The ankle and hindfoot should be examined as a unit,
because arthropathies often involve several structures
in this area. Valgus deformities of the ankle and hind-
foot can best be seen by inspecting the area from behind
with the patient standing. Swelling in the ankle area
eliminates the normal contours associated with the
malleoli.
FIGURE 2A-4 The joint line of the ankle is palpated anteriorly
The joint line of the knee is palpated on the medial and lateral (Figure 2A-5). Boggy swelling and tenderness in this
aspects for tenderness suggestive of synovitis. Stability of the area are typical of ankle synovitis. Tenderness and
cruciate ligaments can also be assessed in this position. Using swelling posteriorly at the insertion of the Achilles
the bulge sign or patellar tap sign, an effusion can be detected tendon usually indicates enthesitis, although this can
in the knee with the joint fully extended (see text for details).
also result from bursitis of the retrocalcaneal bursa.
Tenderness in the heel region can indicate plantar fas-
ciitis, another enthesitis associated with spondylar-
After inspecting the patient in the standing position, thropathies but also common in overuse injuries and
the knee is evaluated with the patient in the supine arch abnormalities.
position, and the joint fully extended. Flexion contrac- The ankle and hindfoot unit should be put through
tures should be noted. Loss of normal contours may the range of motion, isolating parts of the range associ-
suggest swelling. The knee should be palpated for ated with specific joints. The ankle proper, or talotibial
warmth. Bony and soft tissue landmarks should be pal- joint, is only capable of dorsi and plantar flexion. Pain
pated for tenderness, including the anserine bursa—a and limitation in this part of the range is associated with
common nonarticular source of knee pain. The medial ankle synovitis. The subtalar joint, separating the talus
and lateral joint line are palpated for tenderness with and the calcaneus, can be tested by rocking the calca-
the knee in partial flexion (Figure 2A-4). neus laterally from side to side with one hand, while
Detection of synovial fluid in the knee is an impor-
tant diagnostic clue. Large amounts of fluid cause dis-
tention of the joint in the suprapatellar area, as well as
the medial and lateral compartment. The fluid can be
confirmed by firmly pushing the swelling in the supra-
patellar area down into the main compartment of the
knee with the palm of one hand. While maintaining
pressure over the suprapatellar area, the examiner’s
other hand is used to either ballot the fluid back and
forth between the medial and lateral compartments of
the knee, or alternatively to perform the patellar tap by
pushing the patella up and down against the femoral
condyles. Small amounts of fluid in the knee may be
detected using the bulge sign. The medial aspect of the
knee is stroked from the inferior aspect towards the
suprapatellar area in order to move the fluid into the
lateral compartment. The lateral aspect of the knee is
then stroked in a similar manner while the medial com-
partment is observed for the return of the fluid bulge. FIGURE 2A-5
While firmly supporting the joint with one hand (or Palpation for tenderness and swelling in the ankle is undertaken
by holding the foot in the examiner’s armpit area), varus medial and lateral to the extensor tendons on the anterior part
and valgus stress are gently applied to the joint to test of the joint below the malleoli.
holding the talus stable with the other. Talonavicular entire digit becomes swollen and inflamed, a process
motion is tested by stabilizing the talus and calcaneus termed dactylitis and referred to as a sausage digit.
and rotating the midfoot. Examining the plantar aspect of the forefoot is impor-
tant for identifying areas of callus formation. These
tend to occur in conjunction with subluxation of the
MTPJ, where the metatarsal head can be directly pal-
The Midfoot and Forefoot pated subcutaneously.
Observation of the patient in the standing position will
reveal abnormalities in the longitudinal arch and the
anterior part of the foot. Pes planus (flat foot, collapsed REFERENCES
arch) or pes cavus (high arch) will be most evident with
the patient standing. Hallux valgus deformities causing 1. Dieppe P, Sergent J. History. In: Klippel J, Dieppe P, eds.
bunions are some of the most commonly observed prob- Rheumatology. Mosby, London 1998:1.1–1.6.
lems in the joints. 2. Hubscher O. Pattern recognition in arthritis. In: Klippel J,
Swelling of the metatarsophalangeal joints (MTPJ) Dieppe P, eds. Rheumatology. Mosby, London 1998:3.1–
causes a visible spreading of the toes referred to as the 3.6.
daylight sign. Direct pressure over each of the metatar- 3. Grahame R. Examination of the patients. In: Klippel J,
Dieppe P, eds. Rheumatology. Mosby, London 1998:2.1–
sophalangeal joints will confirm the presence of tender-
2.16.
ness and swelling. In cases of advanced RA, subluxation 4. Doherty M, Dacre J, Dieppe P, Snaith M. The GALS
of the MTPJ results in a hammer toe deformity, which locomotor screen. Ann Rheum Dis 1992;51:1165–1169.
can cause skin breakdown on the dorsum of the toes 5. Calis M, Acgun K, Birtane M, Karacan I, Calis H, Fikret
from constant rubbing against the footwear. Inflamma- T. Diagnostic values of clinical diagnostic tests in subacro-
tion of the interphalangeal joints of the toes is more mial impingement syndrome. Ann Rheum Dis 2000;59:
common with spondylarthropathies. In some cases the 44–47.
CHAPTER 2

B. Laboratory Assessment
KERSTIN MOREHEAD, MD
䊏 Laboratory testing is often valuable for screening for indication for additional investigations directed at
disease, confirming diagnoses, establishing disease identifying the precise autoantibody leading to the
stage, determining prognosis, gauging disease ANA pattern.
activity, and following responses to therapy. 䊏 Among others, anti-Ro, -La, -Sm, and -RNP antibodies
䊏 The erythrocyte sedimentation rate (ESR) and C- may all result in a positive ANA. These autoantibod-
reactive protein (CRP) frequently correlate well with ies are associated with a range of different rheumatic
disease activity in inflammatory disorders. diseases.
䊏 Rheumatoid factor (RF) and anti-cyclic citrullinated 䊏 Positive immunofluorescence assays for antineutro-
peptide (anti-CCP) anti-bodies are helpful in diagnos- phil cytoplasmic antibodies (ANCA) should be
ing rheumatoid arthritis. The specificity of RF for confirmed by enzyme immunoassays for antibodies
rheumatoid arthritis is poor. directed specifically against two antigens: proteinase-
䊏 Antinuclear antibodies (ANA) are found in many 3 and myeloperoxidase.
patients with rheumatic diseases and in essentially all 䊏 Decreased serum complement levels usually indicate
patients with systemic lupus erythematosus (SLE) and a disease process mediated by immune complex
systemic sclerosis. Under the proper clinical condi- deposition within tissues.
tions, the finding of a positive ANA assay is an
Laboratory testing is an important part of the evalua- ERYTHROCYTE

tion for many patients with possible rheumatic diseases.
As the understanding of rheumatic disease progresses, SEDIMENTATION RATE
new biomarkers are developed and the utility of existing
ones is refined. Laboratory tests can be valuable guides Inflammatory stress alters hepatic synthesis of plasma
for screening, confirming diagnosis, establishing disease proteins. As a result, fibrinogen and immunoglobulin
stage, and prognosis, as well as for following disease levels increase during the acute phase response. When
activity and response to treatment. Because no single red blood cells (RBCs) interact with these proteins,
test can provide absolute certainty about diagnosis, they form clusters that sediment at a faster rate than
prognosis, or state of disease activity, however, results individual RBCs. In chronic states of inflammation,
must be interpreted in the context of the broader clini- decreased serum albumin and hematocrit levels also
cal picture. Sensitivity, specificity, positive and negative lead to increased rates of erythrocyte sedimentation.
predictive values, and likelihood ratios all warrant
careful consideration when interpreting the utility of
any test. Although laboratory testing has grown sub-
Method (Westergren)
stantially as an aid to clinical diagnosis and management Whole serum is anticoagulated with sodium citrate and
over the past several decades, treatment decisions are allowed to stand. After 1 hour, the distance in millime-
rarely based on the result of a single test alone. In addi- ters between the top of the tube and the erythrocyte
tion to appreciating the strengths and shortcomings of sediment is measured. The test is sensitive to handling
testing approaches, the clinician must also be aware of and temperature (1). Normal values are not adjusted for
the variability that often exists between different assay age or gender in most laboratories, yet these character-
methods and individual laboratories. In general, the istics have well-known (if erratic) influences on the ery-
most useful tests are those that are ordered to answer throcyte sedimentation rate (ESR). The ESR generally
well-defined questions. increases with age and is somewhat higher in women.
15
16 KERSTIN MOREHEAD
The upper limits of normal for a man is equal to the age does not exclude an inflammatory process. Moreover,
divided by 2; for a woman, add 10 to the age and divide other disease processes, including heart disease, infec-
by 2 (2). tion, and malignancy, can lead to CRP elevations, as can
obesity, diabetes, and cigarette smoking.
Interpretation
The ESR is sensitive for most types of inflammation,
but cannot distinguish if the underlying cause is infec- RHEUMATOID FACTOR
tious, inflammatory, or paraneoplastic (3). A normal
value may help to rule out inflammatory disease, but an Rheumatoid factor (RF) is an autoantibody that binds
increased ESR, especially if the increase is only moder- to the Fc region of human IgG. IgM is the most common
ate, can be confusing. In addition, the normalization of RF isotype, but IgG and IgA RF may also be detected
a high ESR often lags behind the resolution of inflam- in the serum (6).
mation, making it less than ideal for monitoring disease
activity. Along with normal elevation due to age and
gender, the ESR can be increased by any condition that Method
raises serum fibrinogen, such as diabetes, end-stage The latex fixation test measures only RF IgM by pre-
renal disease, and pregnancy. Conversely, the ESR can cipitating the antibody with IgG-coated latex particles
be lowered by congestive heart failure, sickled erythro- mixed with serial dilutions of serum. Titers greater than
cytes, and the presence of cryoglobulins. 1 : 20 are positive. Nephelometry and ELISA are able
to detect all three isotypes.
C-REACTIVE PROTEIN
The c-reactive protein (CRP) is an acute phase protein
Interpretation
synthesized in response to tissue injury. Serum CRP In established rheumatoid arthritis (RA), RF has a
levels change more quickly than the ESR; with sufficient sensitivity on the order of 70%. In early RA the sen-
stimulus, the CRP can increase within 4 to 6 hours and sitivity is somewhat lower, approximately 50%, as some
normalize within a week (4). The CRP is often measured patients seroconvert only after having clinical disease
simultaneously with (and sometimes in place of) the ESR for weeks or months. A positive RF assay, far from
as a general measure of inflammation. Although CRP specific for RA, can be found in many other autoim-
and ESR values tend to correspond with each other, mune diseases, mixed essential cryoglobulinemia (see
some patients’ disease processes appear to correlate cryoglobulinemia, below), chronic infections, sarcoid-
better with one measure or the other. osis, malignancy, and a small percentage of healthy
people. The IgA isotype has been linked to erosive
Method disease and to rheumatoid vasculitis, but its precise
clinical utility remains unclear. Higher titers of RF are
Specific antibodies to CRP allow direct quantification by
associated with more severe disease, but as a longitu-
a variety of means. Nephelometry uses antibodies to bind
dinal measure of disease activity RF fares poorly. CRP
target proteins and then measures the scatter of light by
values may be more reliable for monitoring disease
antigen–antibody complexes. The enzyme-linked immu-
activity (7).
nosorbant assay (ELISA) uses coated plates to form
antigen–antibody complexes. These complexes are
detected by addition of secondary antibodies labeled with
an enzyme that, when mixed with a substrate, produces ANTI-CYCLIC CITRULLINATED
color that is measured by spectrophotometry. Because PEPTIDE ANTIBODIES
the CRP is a stable serum protein and its measurement is
not affected by other serum components, it tends to be Anti-cyclic citrullinated peptide antibodies (ANTI-
less variable than the ESR. The CRP is affected by age CCP) are autoantibodies directed against the amino
and gender, as is the ESR (5). In general, levels <0.2 mg/ acids formed by the posttranslational modification of
dL are considered normal and levels >1 mg/dL are deemed arginine. Some investigators believe anti-CCP anti-
consistent with inflammation, but there is considerable bodies have a role in the pathogenesis of RA (8).
laboratory-to-laboratory variation.
Interpretation Method
Because a certain degree of injury is required before IgG anti-CCP are measured by ELISA using synthetic
CRP is synthesized, a normal or indeterminate value citrullinated peptides. Reference ranges vary (9).
Interpretation that is positive for staining and the pattern of the

stain.
Anti-cyclic citrullinated peptide antibodies have a sen-
sitivity for RA that is similar to that of RF, but anti-CCP
antibodies are much more specific. These test charac- Interpretation
teristics lend considerable usefulness to anti-CCP anti- Aninuclear antibody assays are nearly universally posi-
bodies in the setting of seronegative patients suspected tive in SLE, to the extent that ANA-negative lupus is
of having RA, patients with other forms of connective virtually nonexistent. Patients with systemic sclerosis 2
tissue disease who are RF positive, and patients with (scleroderma) and many other connective tissue dis-
hepatitis C or other infections that are often associated eases are also ANA positive with a very high frequency,
with RF positivity. Anti-CCP antibodies are often often in high titers. Depending on the exact technique
detectable in early RA and, in some cases, antedate the used, up to 30% of healthy people may have a positive
onset of inflammatory synovitis. Although anti-CCP titer (11). The prevalence of positive ANAs increases
antibodies may be a better predictor of erosive disease in women and older people. A positive ANA is not
than is RF, they do not correlate with extra-articular specific for SLE or autoimmune disease, especially if it
disease. A positive anti-CCP combined with a positive is transient or in low titer.
RF IgM correlates strongly with radiographic progres-
sion. Anti-CCP levels are not useful in the longitudinal
monitoring of disease activity (10). Specific Autoantibodies
Autoantibodies directed against individual antigens
have increased specificity for particular diseases. Some
ANTINUCLEAR ANTIBODIES of these autoantibodies also predict disease severity
(Table 2B-2) (12). These are ordered separately from
Antinuclear antibodies (ANA) are a diverse group of the ANA test.
autoantibodies that react with antigens in the cell
nucleus. Different patterns reflect different nuclear
components including nucleic acid, histones, and cen-
tromeres (Table 2B-1).
ANTINEUTROPHIL
CYTOPLASMIC ANTIBODY
Method Antineutrophil cytoplasmic antibodies (ANCA) are
Hep-2 cells (a human tumor cell line) are incubated autoantibodies that react with the cytoplasmic granules
with serial dilutions of serum. Using immunofluores- of neutrophils. Two general staining patterns, cyto-
cence microscopy, labeled antihuman IgG is used as plasmic (C-ANCA) or perinuclear (P-ANCA) can be
a stain. The result reflects the highest serum dilution detected by immunofluorescence. In forms of systemic
TABLE 2B-1. ANTINUCLEAR ANTIBODY PATTERNS.

PATTERN NUCLEAR ANTIGEN CLINICAL ASSOCIATIONS
Homogenous Double-stranded DNA Systemic lupus erythematosus
Diffuse Histone Drug reaction

Systemic lupus erythematosus
Topoisomerase I Systemic sclerosis
Speckled Extractable nuclear antigens (Sm, RNP) Mixed connective tissue disease
Systemic lupus erythematosus
Ro-SSA/La-SSB Sjögren’s syndrome
Other Poly/dermatomyositis
Various autoimmune diseases
Infection
Neoplasia
Nucleolar RNA-associated antigens Systemic sclerosis
Peripheral Double-stranded DNA Systemic lupus erythematosus
Centromere Centromere Limited systemic sclerosis

18 KERSTIN MOREHEAD
TABLE 2B-2. AUTOANTIBODIES IN RHEUMATIC DISEASES.

TYPE DESCRIPTION CLINICAL ASSOCIATION
Anti-dsDNA Antibodies to double-stranded DNA High specificity for SLE

Often correlates with more active, more severe disease
ELISA test is very sensitive and can be positive in other diseases,
normal people
Anti-histone Five major types exist SLE, drug-induced SLE, other autoimmune disease
SLE patients will likely be positive for other autoantibodies as well
Anti-ENA Sm (Smith) High specificity for SLE

RNP (ribonucleoprotein) Mixed connective tissue disease
RNA–protein complexes Higher prevalence in African American and Asian patients
Anti-SSA (Ro) Ribonucleoproteins SLE (especially subacute cutaneous lupus), neonatal lupus, Sjögren’s
syndrome
Anti-SSB (La) Ribonucleoproteins Sjögren’s syndrome, SLE, neonatal SLE
Anti-centromere Antibody to centromere/kinetochore region Limited scleroderma

of chromosome High rate of pulmonary hypertension
Primary biliary sclerosis
Anti-Scl 70 Antibodies to DNA topoisomerase 1 Diffuse scleroderma

Risk of pulmonary fibrosis
Anti-Jo-1 Antibody to histidyl tRNA synthetase Poly/dermatomyositis

Patients tend to have interstitial lung disease, Raynaud’s
phenomenon, mechanic’s hands, arthritis
Typically resistant to treatment
Anti-SRP Antibody to signal recognition protein Cardiomyopathy

Poor prognosis
Anti-PM-Scl Antibody to nucleolar granular component Polymyositis/scleroderma overlap syndrome
Anti-Mi-2 Antibodies to a nucleolar antigen of Dermatomyositis

unknown function Favorable prognosis
vasculitis, such as Wegener’s granulomatosis, micro- One common laboratory approach is to screen with
scopic polyangiitis, and the Churg–Strauss syndrome, ethanol-fixed cells and to perform assays on formalin-
these patterns reflect autoantibodies to two lyzosomal fixed cells if immunofluorescence is observed on screen-
granule enzymes: serine protease-3 (PR3) and myelo- ing. Increasingly reliable ELISA assays for the detection
peroxidase (MPO), respectively. Upon immunofluores- of both PR3 and MPO have been available since the
cence testing of sera, many patients with other forms early 1990s. For optimal clinical utility, any positive
of inflammatory disease (e.g., SLE, autoimmune hepa- immunofluorescence assay should be confirmed by the
titis, inflammatory bowel disease) have positive ANCA performance of anti-PR3 and -MPO ELISAs.
assays. ELISA testing in such patients, however, reveals
antibody specificities for antigens other than PR3 and
MPO. ANCA directed against PR3 and MPO are
Interpretation
termed PR3-ANCA and MPO-ANCA, respectively. The combination of C-ANCA and PR3-ANCA has a
high positive predictive value for ANCA-associated
vasculitis, particularly Wegener’s granulomatosis. Simi-
Method larly, the combination of P-ANCA and MPO-ANCA
To identify C- and P-ANCA patterns of immunofluo- has a high positive predictive value for microscopic
rescence, ethanol- or formalin-fixed human neutrophils polyangiitis. (For further discussion of the role of ANCA
are coated with the patient’s serum and stained with assays in these diseases and in the Churg–Strauss syn-
labeled anti-IgG. Formalin fixation is preferred because drome, please see Chapter 21C.)
the presence of antinuclear antibodies may cause a The more active and extensive the vasculitis, the
false-positive P-ANCA pattern on ethanol-fixed cells. more likely are ANCA assays to be positive. ANCA
titers often normalize with treatment but do not always indicate the presence of cryoglobulins. Unfortunately,
do so, even if clinical remissions are achieved. Some the correlations between changes in complement levels
data suggest that a persistent rise in ANCA titer or and disease activity are poor. In addition, hypocomple-
return of ANCA positivity heralds an increased risk of mentemia may also be secondary to nonrheumatic
recurrent disease, but neither persistently positive diseases, notably subacute bacterial endocarditis
ANCA tests nor rising ANCA titers provide reliable and poststreptococcal glomerulonephritis (15). Low or
information about the timing of a disease flare. Treat- undetectable CH50 may indicate a deficiency of one or
ment decisions in ANCA-associated vasculitis are never more complement components. Patients with genetic 2
based entirely ANCA assay result. Moreover, positive deficiencies of early complement components (C1–C4)
ANCA tests may be caused by infection, drugs (particu- are at increased risk for developing immune-complex
larly thyroid medications such as propylthiouracil), and, diseases (16), particularly some forms of SLE.
as noted, other autoimmune diseases. Thus, under most
clinical circumstances, tissue biopsy remains the gold
standard for diagnosis (13). CRYOGLOBULINS
Cryoglobulins are immunoglobulins that precipitate
COMPLEMENT reversibly at cold temperatures. In a variety of diseases,
cryoglobulins often bind with complement proteins and
The complement cascade is a tightly regulated complex other peptides to form immune complexes. Based on
of proenzymes, regulatory proteins, and cell-surface their composition, cryoglobulins are classified into three
receptors that mediate and augment both of comple- types. Type I cryoglobulins are monoclonal immuno-
ment the humoral and cellular immune response. Acti- globulins, frequently of the IgM isotype. Type II cryo-
vation by antigen–immune complexes, bacterial surface globulins are a mixture of polyclonal IgGs and
proteins, and polysaccharides begins a fixed sequence monoclonal IgM. Type III cryoglobulins are a combina-
of reactions that lead to increased vascular permeabil- tion of polyclonal IgGs and polyclonal IgMs. In both
ity, chemotaxis, cell lysis, antigen–immune complex type II and type III cryoglobulinemia, the IgM compo-
clearance, and opsonization. The classical pathway (C1, nent has RF activity (i.e., it binds to the Fc portion of
C4, C2), the alternative pathway (factors B, D, and IgG), accounting for the fact that essentially all patients
properdin), and the mannose-binding lectin pathway all with these disorders are RF positive (often creating
share the final step of cleaving C3. The released product confusion in diagnosis with RA) (17).
(C3b) then induces formation of the terminal mem-
brane attack complex (C5–C9) (14).
Method
For proper collection of cryoglobulins, careful attention
Method to detail and preparation in advance are required.
Serum levels of individual components such as C3 and Whole blood must be drawn and maintained at body
C4 are measured by ELISA and nephelometry. The temperature until it coagulates. The sample is then cen-
plasma total hemolytic complement assay, or CH50, trifuged and the clot removed. The remaining serum is
assesses the functional integrity of the classical pathway. allowed to stand at 4°C for up to several days until
Serum is diluted and added to sheep antibody–coated precipitation is observed. The sample is spun again and
RBCs. The value reported is the reciprocal of the highest the cryocrit is measure in a calibrated tube. Isotype and
dilution able to lyse 50% of the RBCs. clonality are established by various immunochemical
techniques.
Interpretation
Decreased serum levels of individual components, espe-
Interpretation
cially C3 and C4, correlate with the increased consump- Cryoglobulins are not specific for any one disease. Type
tion observed in active immune complex mediated I cryoglobulins do not activate the complement cascade
disease, for example, SLE. In contrast, most inflamma- and are therefore associated with normal complement
tory disorders that are not associated with immune levels. They are linked to lymphoproliferative disor-
complex deposition demonstrate elevated levels of ders, malignancies, and hyperviscosity syndromes, and
complement because these proteins are acute phase often associated with sludging in the small vasculature
reactants. Hypocomplementemia, though useful in nar- of the extremities, eye, or brain. Type II and type III
rowing the differential diagnosis, is generally not spe- cryoglobulins, able to bind complement, are associated
cific for any particular disease. C4 levels that are with hepatitis C virus infections and a syndrome of
disproportionately low compared to those of C3 may small vessel vasculitis (see Chapter 21D) (18).
20 KERSTIN MOREHEAD
REFERENCES 9. Zendman AJW, Van Venroij, Pruijn GJM. Use and sig-
nificance of anti-CCP autoantibodies in rheumatoid
arthritis. Rheumatology 2006;45:20–25.
1. Sox HC Jr, Liang MH. The erythrocyte sedimentation 10. Niewold TB, Harrison MJ, Paget SA. Anti-CCP antibody
rate: guidelines for rational use. Ann Intern Med 1986; testing as a diagnostic and prognostic tool in rheumatoid
104:515–523. arthritis. QJM 2007;100:193–201.
2. Miller A, Green M, Robinson D. Simple rule for calculat- 11. Tan E, Feltkamp TE, Smolen JS, et al. Range of antinu-
ing normal erythrocyte sedimentation rate. BMJ 1983; clear antibodies in “healthy” individuals. Arthritis Rheum
286:266. 1997;40:1612–1618.
3. Bridgen M. The erythrocyte sedimentation rate. Still a 12. Lyon R, Sonali N. Effective use of autoantibody tests in
helpful test when used judiciously. Postgrad Med 1998; the diagnosis of systemic lupus erythematosis. Ann N Y
103:257–262. Acad Sci 2005;1050:217–228.
4. Morley JJ, Kushner I. Serum C-reactive protein levels in 13. Bartunkova J, Tesar V, Sediva A. Diagnostic and patho-
disease. Ann N Y Acad Sci 1982;389:406–418. genic role of antineutrophil cytoplasmic autoantibodies.
5. Wener MH, Daum PR, McQuillan GM. The influence of Rheumatology (Oxford) 2003;106;73–82.
age, sex and race on the upper limit of serum C-reactive 14. Walport MJ. Advances in immunology: complement. N
protein concentration. J Rheumatol 2000;27:2351–2359. Engl J Med 2001;344:1058–1066, 1140–1144.
6. Johsson T, Valdimarsson H. Is measurement of rheuma- 15. Egner W. The use of laboratory tests in the diagnosis of
toid factor isotypes clinically useful? Ann Rheum Dis SLE. J Clin Pathol 2000;53:424–432.
1993;52:161–164. 16. Ratnoff WD. Inherited deficiencies of complement in
7. Witherington RH, Teitsson I, Valdimarsson H, et al. Pro- rheuamtologic diseases. Rheum Clin North Am 1996;22:
spective study of early rheumatoid arthritis. II Associa- 1–21.
tion of rheumatoid factor isotypes with fluctuations in 17. Brouet JC, Clauvel JP, Danon F, et al. Biological and
disease activity. Ann Rheum Dis 1984;43:679–685. clinical significance of cryoglobulins: a report of 86 cases.
8. Vossenaar ER, Smeets TJ, Kraan MC, et al. The presence Am J Med 1974;57:775–788.
of citrullinated proteins is not specific for rheumatoid 18. Ferri C, Zignego AL, Pileri SA. Cryoglobulins. J Clin
arthritis. Arthritis Rheum 2004;50:3485–3494. Pathol 2002;55:4–13.
CHAPTER 2

C. Arthrocentesis, Synovial Fluid
Analysis, and Synovial Biopsy
KENNETH H. FYE, MD
䊏 When the diagnosis of an inflammatory arthropathy otherwise, and should be treated empirically
is unclear, synovial fluid should be evaluated for the with antibiotics until the results of culture are
three Cs: cell count, culture, and crystals. available.
䊏 Removal of infected synovial fluid is often a critical 䊏 Microcrystalline disorders (gout and pseudogout)
adjunct to antibiotics in the treatment of a septic occasionally lead to synovial fluid neutrophil counts
joint. >100,000/mm3.
䊏 Careful preparation, appropriate assistance, and 䊏 Examination of synovial fluid under polarized
planning of the approach to the joint enhance the microscopy is the only way of securing the diagnosis
likelihood of success in performing arthrocentesis. of a microcrystalline disease.
䊏 Synovial fluid neutrophil counts in excess of
100,000/mm3 spells an infection until proven
Despite the development of increasingly sophisticated may be present. Analyzing SF may yield information
serologic tests and imaging techniques, synovial fluid invaluable in making the diagnosis, determining prog-
(SF) analysis remains one of the most important diagnosis, and formulating appropriate therapy in patients
nostic tools in rheumatology (1). Normal SF lubricates with arthritis (4).
the joint and, along with blood vessels in subchondral
bone, supplies nutrients to the avascular articular carti-
lage. The majority of SF constituents originate in the
subsynovial vasculature, diffusing through the synovium
ARTHROCENTESIS
into the joint space. However, certain important mac-
romolecules, such as hyaluronic acid and lubricin, are
Indications
synthesized and secreted by synoviocytes (which line An acute, inflammatory, monarticular arthritis should
the joint). Plasma proteins not found in SF include pro- be considered either infectious or crystal-induced until
thrombin, fibrinogen, factor V, factor VII, antithrom- proven otherwise. Arthrocentesis is the only method of
bin, large globulins, and some complement components identifying infection or crystal-induced disease unequiv-
(2). ocally. Because acute bacterial infections can lead
Synovial fluid protein concentrations reflect the rapidly to joint and bone destruction, arthrocentesis
interplay between plasma concentration, synovial fluid must be performed immediately if there is any suspicion
blood flow, endothelial cell permeability, and lymphatic of infection. If preliminary analysis of the SF is compat-
drainage. There are few cells in normal SF. In arthritis, ible with infection—that is, the white blood cell (WBC)
invading inflammatory cells produce additional proteins count is markedly elevated but no crystals are identi-
and release activated cytokines into SF. Elevated intra- fied—antibiotic therapy should be initiated pending
articular pressure due to increased amounts of SF leads definitive culture results. SF analysis can confirm the
to diminished perfusion of synovial microvasculature, presence of crystal-induced arthritis and enable the cli-
disrupting the process of diffusion that supplies synovial nician to identify the culprit crystal precisely. If a polar-
nutrients (3). In addition, offending substance such as ized microscope is used, the sensitivity of SF analysis for
microorganisms, foreign bodies, or abnormal crystals, identifying a crystal-induced arthropathy is 80% to 90%
21
22 KENNETH H. FYE
(4). Trauma can sometimes result in an acute monar- be used to swab the area to prevent an iodine burn.
ticular arthropathy. Analysis of joint fluid is the only Although it is wise to wear gloves during any procedure
way to distinguish posttraumatic hemarthrosis from involving exposure to potentially infected body fluids,
posttraumatic arthritis with bland synovial fluid. sterile gloves are generally not necessary. Sterile gloves
Arthrocentesis can also be useful in the evaluation should be used if the clinician anticipates having to
of chronic or polyarticular arthropathies. SF analysis palpate the target anatomy after preparation of the
enables the clinician to differentiate inflammatory arthrocentesis site using antiseptic technique.
and noninflammatory arthritides. The procedure is
often essential in distinguishing chronic crystal-induced
arthritide such as polyarticular gout or calcium pyro-
Local Anesthesia
phosphate dehydrate deposition disease from other Local anesthesia with 1% lidocaine without epineph-
arthropathies, such as rheumatoid arthritis (RA). rine significantly reduces discomfort associated with the
Although chronic mycobacterial or fungal infections procedure. One-quarter to 1 cc of lidocaine is usually
can sometimes be identified in SF, synovial biopsy is sufficient, depending on the joint being anesthetized.
frequently necessary to distinguish indolent infections A 25- or 27-gauge needle should be used to infiltrate
from other unusual chronic inflammatory processes, the skin, subcutaneous tissue, and pericapsular tissue.
such as pigmented villonodular synovitis. Because Larger caliber needles are more uncomfortable and can
people with chronic inflammatory arthropathies (e.g., lead to local trauma. Although many clinicians apply
RA) have an increased susceptibility to infection, acute ethyl chloride to the skin before injecting the anesthe-
monarticular arthritis in a patient whose disease is sia, others believe this practice is cumbersome and
otherwise well controlled is an indication for a diag- results in no clinically significant additional anesthesia.
nostic arthrocentesis. After the periarticular tissues have been anesthe-
The cellular and humoral components of inflamma- tized, a 20- or 22-gauge needle can be used to aspirate
tory SF can damage articular and periarticular tissues small- to medium-sized joints. An 18- or 19-gauge
(5). The activated enzymes in septic SF are highly needle should be used for aspirating large joints or
destructive to cartilage. Thus, in a septic joint, repeated joints suspected of infections, intra-articular blood, or
arthrocentesis may be necessary to minimize the accu- viscous, loculated fluid. Small syringes are easier to
mulation of purulent material (6). If purulent SF re- manipulate and provide greater suction than large
accumulates despite repeated arthrocenteses, surgical syringes, but must be changed frequently when aspirat-
arthroscopy with drain placement should be performed ing large joints with copious amounts of SF. When using
to ensure adequate drainage of the infected joint. For a large syringe to aspirate a significant amount of fluid,
joints that are noninfected but inflamed, drainage of as the suction in the syringe should be broken before use
much SF as possible removes inflammatory cells and and the plunger drawn. Excessive negative pressure can
other mediators, decreases intra-articular pressure, and suck synovial tissue into the needle and prevent an
reduces the likelihood of articular damage (7). Removal adequate joint aspiration. A Kelly clamp can stabilize
of inflamed fluid also increases the efficacy of intra- the hub of the needle while removing a full syringe.
articular corticosteroids. Finally, blood in a joint, Typical landmarks are often obscured around a
such as may occur in hemophilia, can lead quickly to swollen joint. Therefore, after a thorough physical
adhesions that inhibit joint mobility. When clinically examination and before sterilizing and anesthetizing the
indicated, therefore, therapeutic arthrocentesis may be skin, it is often helpful to mark the approach with a
prudent in a patient with hemarthrosis. When contem- ballpoint pen. If landmarks are still obscure, use sterile
plating such a procedure in a hemophiliac, careful con- gloves to maintain a clean field while using palpation to
sideration should be given to approaches to maximize identify an aspiration site for the target joint. Many
hemostasis (e.g., the use of clotting factor VIII concen- joints, such as the knee, ankle, and shoulder, are ame-
trate; see Chapter 25A) and prevent additional intra- nable to both medial or lateral approaches.
articular bleeding as a result of the procedure. In contrast to joint injection, aspiration is performed
most easily when a joint is in a position of maximum
intra-articular pressure. For example, injection of the
Techniques knee is best done with the knee in 90° flexion while the
patient is seated at an examining table with the foot
Sterile Procedures
dangling. This position allows gravity to open the joint
Infections caused by arthrocentesis are very rare. space, offering easy access to the intra-articular space
Nevertheless, preventive measures to minimize the from either side of the infrapatellar tendon. However,
likelihood of postarthrocentesis infection are prudent. this position decreases intra-articular pressure, thereby
Betadine or povidone–iodine should be applied to the decreasing the likelihood of a successful aspiration.
aspiration site and allowed to dry. Alcohol should then Conversely, therefore, the optimal positioning of the
TABLE 2C-1. ANATOMIC APPROACH TO ASPIRATION.

JOINT POSITION OF JOINT LOCATION OF APPROACH
Knee Extended Medial or lateral under the patella
Shoulder Neutral adduction, external Anterior: inferolateral to coracoid

rotation Posterior: under the acromion
Ankle Plantar flexion Anteromedial: medial to extensor hallucis longus

2
Anterolateral: lateral to extensor digiti minimi
Subtalar Dorsiflexion to 90° Inferior to tip of lateral malleolus
Wrist Midposition Dorsal into radiocarpal joint
First carpometacarpal Thumb abducted and flexed Proximal to base of metacarpal
Metacarpophalangeal Finger slightly flexed Just under extensor mechanism dorsomedial or dorsolateral
or interphalangeal
Metatarsophalangeal Toes slightly flexed Dorsomedial or dorsolateral

or interphalangeal
Elbow Flexed to 90° Lateral in triangle formed by lateral epicondyle, radial head, and
olecranon process
patient for aspiration of the knee is lying supine with the porting structures. If bone is encountered, slight with-
knee fully extended, thereby maximizing intra-articular drawal of the needle followed by redirection and another
pressure. Although most joints can be aspirated without attempt at aspiration is indicated. In unsuccessful aspi-
radiologic assistance, some joints, such as the hips, sac- ration attempts, the needle may be outside the joint
roiliac joints, or zygoapophyseal joints, should be aspi- space, blocked by synovium or SF debris, or too small
rated using computed tomography guidance. Aspirations for the degree of SF viscosity.
should generally not be done through areas of infection,
ulceration, or tumor, or obvious vascular structures.
Table 2C-1 lists suggestions for optimal anatomic
approaches for aspirating or injecting specific joints. SYNOVIAL FLUID ANALYSIS
If corticosteroids are to be injected after aspiration
is complete, the drug should be prepared in a separate The four general classes of SF, defined by differences in
syringe ahead of time so that the aspirating needle gross examination, total and differential WBC count,
already in the joint can be used for the injection. If dif- the presence or absence of blood, and the results of
ficulties arise during the procedure, the needle should culture are shown in Table 2C-2. SF characteristics of
not be manipulated aggressively because of the risk of arthritic conditions can be extremely variable and may
damaging the cartilage, capsule, or periarticular sup- change with therapy. Therefore, the classes of SF are
TABLE 2C-2. CLASSES OF SYNOVIAL FLUID.

CLASS I (NONINFLAMMATORY) CLASS II (INFLAMMATORY) CLASS III (SEPTIC) CLASS IV (HEMORRHAGIC)
Color Clear/yellow Yellow/white Yellow/white Red
Clarity Transparent Translucent/opaque Opaque Opaque
Viscosity High Variable Low NA
Mucin clot Firm Variable Friable NA
WBC count <2,000 2,000–100,000 >100,000 NA
Differential <25% PMNs >50% PMNs >95% PMNs NA
Culture Negative Negative Positive Variable
ABBREVIATIONS: PMN, polymorphonuclear leukocytes; NA, not applicable.

24 KENNETH H. FYE
TABLE 2C-3. DIAGNOSIS BY SYNOVIAL CLASS.

CLASS I CLASS II CLASS III CLASS IV
Osteoarthritis Rheumatoid arthritis Septic arthritis Trauma

Traumatic arthritis Systemic lupus erythematosus (bacterial) Pigmented
Osteonecrosis Poly/dermatomyositis villonodular
Charcot’s arthropathy Scleroderma synovitis
Systemic necrotizing vasculitides Tuberculosis
Polychondritis Neoplasia
Gout Coagulopathy
Calcium pyrophosphate deposition disease Charcot’s arthropathy
Hydroxyapatite deposition disease
Juvenile rheumatoid arthritis
Ankylosing spondylitis
Psoriatic arthritis
Reactive arthritis
Chronic inflammatory bowel disease
Hypogammaglobulinemia
Sarcoidosis
Rheumatic fever
Indolent/low virulence infections (viral, mycobacterial, fungal,
Whipple’s disease, Lyme disease)
intended only as a general guide in the diagnosis of break down hyaluronan. The string formed by inflam-
arthritis (Table 2C-3). matory SF may be only 5 cm or less. Extremely viscous
fluid with a very long string is suggestive of hypothy-
roidism (9). One can also determine the integrity of
Gross Examination hyaluronic acid by placing a few drops of SF into 2%
Certain characteristics of SF provide the clinician with acetic acid. Normal SF will form a stable clump of hyal-
valuable clues as to the nature of an arthropathy. Clarity uronate–protein complex called a mucin clot. Inflamma-
reflects the density of particulate matter in SF. Normal tory SF fluid forms a mucin clot that will fragment easily,
SF or that from patients with osteoarthritis is colorless reflecting the loss of integrity of hyaluronan.
and clear. In contrast, the SF of systemic lupus erythe-
matosus (SLE) or mild rheumatoid arthritis may be
translucent, and the SF from a septic joint will be
Cell Count
opaque. Generally, the number of WBCs determines The WBC count and differential are among the most
the opacity of inflammatory SF (8). The xanthochromia valuable diagnostic characteristics of SF. Normal SF
that sometimes characterizes SF from patients with contains fewer than 200 cells/mm3. SF from noninflam-
arthritis is caused by the breakdown of heme from red matory arthropathies may have WBC counts of up to
blood cells that leak into the joint space from diseased 2000 cells/mm3 (9). Noninfectious inflammatory arthrop-
synovium. Gross, fresh bleeding due to trauma, hemo- athies have WBC counts that vary widely, ranging from
philia, pigmented villonodular synovitis, or other patho- 2000 to 100,000 cells/mm3 (10). Although the autoim-
logic processes will result in red or bloody SF. Other mune arthropathies generally present with WBC counts
materials that can opacify SF include lipids, crystals of 2000 to 30,000 cells/mm3, cell counts of 50,000/mm3
(such as calcium pyrophosphate dehydrate, monoso- or higher are not unusual in RA. Patients with crystal-
dium urate, or hydroxyapatite), and debris that accumu- induced arthritis, such as acute gout, usually have WBC
lates in destructive forms of arthritis (such as severe RA counts of greater than 30,000 cells/mm3 and counts of
or Charcot’s arthropathy). 50,000 to 75,000 calls/mm3 are common. The closer the
Normal joint fluid is viscous due to the presence of WBC count gets to 100,000 cells/mm3, the greater the
hyaluronan. Enzymes present in inflammatory arthrop- likelihood of a septic arthritis. Although a rare patient
athies digest hyaluronic acid, resulting in a decrease in with crystal-induced arthropathy, RA, or even a sero-
fluid viscosity. When a single drop of normal SF is negative arthropathy may have a WBC count greater
expressed from a syringe, a tail or string of fluid should than 100,000 cells/mm3, such patients should be treated
stretch approximately 10 cm before surface tension is empirically for a septic joint until microbiologic data
broken. The greater the degree of inflammation within exclude infection.
a joint, the higher the number of inflammatory cells and A WBC count of less than 100,000 cells/mm3 does
the greater the concentration of activated enzymes that not preclude the possibility of infection. Patients with
chronic inflammatory arthritides due to RA, SLE, or pigmentation derives from hemosiderin accumulated
psoriatic arthritis have an increased risk of joint sepsis from recurrent hemorrhage. The SF from patients with
secondary to both the structural joint damage caused tuberculosis is often hemorrhagic, as is that associated
by chronic inflammation and the immunosuppressive with local or metastatic tumors. Patients with con-
effects of many of the drugs used to treat those diseases. genital, metastatic, or hemorrhagic disorders, such
Moreover, many disease modifying agents in such as Ehlers–Danlos syndrome, pseudoxanthoma elasti-
diseases, including methotrexate, cyclosporine, lefluno- cum, sickle cell disease, or scurvy, may also develop
mide, azathioprine, cyclophosphamide, or other cyto- hemarthrosis. 2
toxic agents, may blunt the WBC response to infection
and cause spuriously low WBC counts within the SF. In
comparison with bacterial infections, more indolent
Crystals
processes such as tuberculosis or fungal infection are Although crystals can be identified in SF that is a few
associated with lower WBC counts; SF counts <50,000/ days old, optimal examinations for crystals are per-
mm3 are typical. formed on fresh SF prepared immediately after aspira-
The differential WBC count can provide valuable tion (12). If the SF is to be anticoagulated before
information (11). SF from a septic joint usually contains examination, only sodium heparin and EDTA are
greater than 95% polymorphonuclear leukocytes acceptable; lithium heparin and calcium oxalate may
(PMNs). Frequently, more than 90% of the WBC in the both form birefringent crystals that can confound the
SF from patients with crystal-induced arthropathies or fluid examination. In addition, a clean slide and cover
RA will be PMNs, as well. On the other hand, the dif- slip should be used, because talc, dust, or other debris
ferential WBC count of noninflammatory SF character- may mimic crystalline materials.
istically contains less than 50% granulocytes. Although monosodium urate crystals can be seen
Examination of a wet preparation is particularly with ordinary light microscopy (13), an adequate crystal
helpful in assessing SF for its cellular and crystalline examination requires a polarized light microscope with
content. The wet preparation is best done on SF applied a red compensator (14). The lower polarizing plate (the
directly from the syringe to a slide, but SF anticoagu- polarizer), inserted between the light source and the
lated with sodium heparin or EDTA can also be used. study specimen, blocks all light waves except those that
Ragocytes, which are PMNs with refractile inclusions vibrate in a single direction. The second polarizing plate
containing immune complexes and complement, can be (the analyzer) is positioned between the study specimen
observed on wet-preparation examination of SF from and the observer and is oriented 90° from the polarizer.
patients with RA. SF from patients with SLE may No light passes through to the observer, who sees only
contain lupus erythematous (LE) cells. Cytologic exam- a dark field through the microscope. Birefringent mate-
ination may reveal malignant cells in the SF of patients rial will bend light waves that have passed through the
with synovial metastases. polarizer, so they can pass through the analyzer to the
observer, who now sees a white object against a dark
field. If a first order red compensator is placed between
Blood the polarizer and the analyzer, the background field
The presence of blood in a joint is usually the result of becomes red and a birefringent crystal becomes yellow
acute trauma. If arthocentesis reveals a hemarthrosis, or blue, depending on its identity and orientation to the
the bloody fluid should be evacuated to prevent syno- direction of the slow-vibration axis of the light passing
vial adhesions that could decrease the range of motion through the red compensator.
of the injured joint. Hemarthrosis is sometimes seen in Light passing through the red compensator is
Charcot’s arthropathy because of chronic trauma to the refracted into two vibration waves, a fast wave and a
affected joint. In the absence of a history of trauma, slow wave, which are perpendicular to each other. The
bloody SF could represent a traumatic aspiration. The identical phenomenon occurs with light passing through
blood seen in a traumatic aspiration is not homoge- a birefringent crystal. The fast-wave vibration of mono-
neous throughout the sample and usually appears only sodium urate, which is a birefringent crystal, is oriented
after the clinician encounters difficulty with the proce- along the long pole of the needle-shaped crystal. When
dure. If the procedure was not traumatic, the presence the long pole of a monosodium urate crystal is parallel
of bloody SF should alert the clinician to several possi- to the slow-wave axis marked on the red compensator,
bilities. Recurrent hemarthrosis is common in people a color-subtraction interference pattern of fast and slow
with severe coagulation disorders such as hemophilia, vibration occurs, resulting in a yellow color. A crystal
von Willebrand’s disease, and platelet disorders, and that is yellow when its long pole is parallel to the slow
in patients on anticoagulation therapy. The SF from axis of vibration of the red compensator is, by conven-
patients with pigmented villonodular synovitis is virtu- tion, considered to be negatively birefringent. If
ally always hemorrhagic or xanthochromic. In fact, the the slow wave of vibration of a birefringent crystal is
26 KENNETH H. FYE
parallel to its long pole when the long pole of the crystal use the air to blow the fluid in the needle onto a slide.
is parallel to the slow axis of the red compensator, This is a particularly valuable technique when looking
an addition pattern of slow-plus-slow vibration will for monosodium urate crystals in podagra.
result in a blue color. By convention, a birefringent
crystal that is blue when the long pole is parallel to the
slow axis of vibration of the red compensator is consid-
Culture
ered to be positively birefringent. Calcium pyrophos- An inflammatory monarticular arthritis should be con-
phate dehydrate crystals, for example, are positively sidered infectious until proven otherwise. In most bac-
birefringent. Birefringence can be strong, meaning the terial infections, Gram stain and culture and sensitivity
birefringent crystal is bright and easy to see, or weak, yield valuable diagnostic information and are crucial
meaning the birefringent crystal is muted and difficult components of analysis. Generally, SF need only be
to detect. collected in a sterile culture tube and transported to the
Crystals are identified by a combination of shape laboratory for routine analysis. Unfortunately, some
and birefringence characteristics. Monosodium urate important infectious agents are difficult to culture, so
crystals are needle shaped and have strong, negative negative Gram stains and cultures do not necessarily
birefringence (see Figure 12A-7). In contrast, calcium preclude an infection. For example, SF cultures are
pyrophosphate dehydrate crystals are short and rhom- negative in more than two-thirds of people with gono-
boid, and show weak, positive birefringence. Calcium coccal arthritis, even if chocolate agar is used as the
oxalate crystals, which can be seen in primary oxalosis culture medium. In addition, tuberculosis is often diffi-
or in chronic renal failure, are rod or tetrahedron shaped cult to culture from SF, and special techniques and
and positively birefringent. Cholesterol crystals are flat culture media are required for anaerobic or fungal
and boxlike, tend to stack up, and often have notched pathogens. Sometimes mycobacterial (17) or fungal
corners. Spherules with birefringence in the shape of a (18) infections can be detected only on synovial biopsy
Maltese cross generally represent lipid. However, it has material. Because bacterial infections can lead rapidly
been suggested that some forms of urate or apatite may to joint destruction, early antibiotic therapy is essential.
take this shape (15,16). Hydroxyapatite is usually diffi- Antibiotic therapy should be initiated based on the
cult to recognize in SF, partly because it is not birefrin- results of WBC count, WBC differential, and Gram
gent. However, sometimes it forms clumps large enough stain, and adjusted later if necessary, based on the
to be seen when stained with alizarin red S. Finally, results of culture and sensitivity.
glucocorticoid crystals injected into the joint as a thera-
peutic measure are birefringent and may be misinter-
preted by the unwary observer. SYNOVIAL BIOPSY
The presence of intracellular crystals is virtually
diagnostic of a crystal-induced arthropathy. However, Arthroscopy has greatly facilitated the clinician’s ability
a superimposed infection must be excluded even if to obtain synovial tissue for analysis. At one time,
crystals are identified. In addition, a patient may have synovial tissue could only be obtained by open arthrot-
more than one crystal-induced disorder. For example, omy or blind needle biopsy (19). Advances in the tech-
up to 15% of patients with gout also have calcium nology of arthroscopy have led to the development of
pyrophosphate dihydrate deposition disease. It is small, flexible instruments that allow direct visualiza-
important to make that determination, because it will tion and biopsy of synovium (20). In certain clinical
affect therapy. A patient with chronic gout may require settings, synovial biopsy can add significant diagnostic
only ongoing hypouricemic therapy (and perhaps pro- information.
phylactic colchicine). In contrast, a patient with both The granulomatous diseases are frequently difficult
gout and calcium pyrophosphate dihydrate deposition to diagnose by SF analysis alone. SF acid-fast smears
disease may require continued nonsteroidal anti- and cultures are negative in a significant number of
inflammatory therapy in addition to ongoing hypouri- patients with tuberculosis. The diagnosis of tuberculous
cemic therapy. arthritis is often based on histologic demonstration of
Attempts to aspirate inflammatory joints are not caseating granulomata and acid-fast stain or culture evi-
always successful. For example, aspiration of an inflamed dence of Mycobacterium tuberculosis in synovial tissue.
first metatarsophalangeal joint is difficult. However, if Atypical mycobacterial and fungal arthropathies can be
the clinician keeps negative pressure on the syringe as indolent, inflammatory, oligoarticular infections that
the needle is withdrawn from articular or periarticular cannot be diagnosed without obtaining synovial tissue
tissues, there is almost always enough interstitial fluid for histologic and microbiologic analysis (18). In patients
in the needle to allow adequate polarized-light exami- without pulmonary involvement, the diagnosis of sarcoid
nation for crystals. Simply remove the needle from the arthropathy may rest on the demonstration of noncase-
syringe, fill the syringe with air, reattach the needle, and ating granulomata in synovial tissue.
Malignant infiltrations of the synovium can be seen 3. Gaffney K, Williams RB, Jolliffe VA, Blake DR. Intra-
in synovial sarcomas, lymphomas, metastatic disease, articular pressure changes in rheumatoid and normal
and leukemias. The diagnosis of synovial osteochon- peripheral joints. Ann Rheum Dis 1995;54:670–673.
dromatosis can be made based on the presence of foci 4. Shmerling RH. Synovial fluid analysis. A critical appraisal.
Rheum Dis Clin North Am 1994;20:503–512.
of osteometaplasia or chondrometaplasia on synovial
5. Chapman PT, Yarwood H, Harrison AA, et al. Endo-
biopsy. Sometimes cytologic examination of SF reveals
thelial activation in monosodium urate monohydrate
a malignancy. However, the diagnosis of a malignant
arthropathy is generally based upon histologic demon-
crystal-induced inflammation. Arthritis Rheum 1997;40: 2
955–965.
stration of malignant cells in synovial tissue. Therefore, 6. Sack KE. Joint aspiration and injection: a how-to guide.
synovial biopsy is indicated if there is a suspicion of J Musculoskel Med 1999;16:419–427.
articular malignancy. 7. Zuber TJ. Knee joint aspiration and injection. Am Fam
The diagnosis of some infiltrative nonmalignant Physician 2002;66:1497–1507.
processes depends on the histologic or microscopic 8. Pasqual E, Jovani V. Synovial fluid analysis. Best Pract
evaluation of synovial material. A diagnosis of amyloid Res Clin Rheumatol 2005;19:371–386.
arthropathy can be made if apple green birefringence is 9. Dorwart BB, Schumacher HR. Joint effusions, chondro-
calcinosis and other rheumatic manifestations in hypothy-
observed in Congo red–stained synovial biopsy material
roidism. A clinicopathologic study. Am J Med 1975;
examined under polarized light. Hemochromatosis is
59:780–790.
characterized by the deposition of golden brown hemo- 10. Krey PR, Bailen DA. Synovial fluid leukocytosis. A study
siderin in synovial lining cells. Hydroxyapatite deposits of extremes. Am J Med 1979;67:436–442.
in synovial tissue appear as clumps of material that stain 11. Trampuz A, Hanssen AD, Osmon DR, et al. Synovial
with alizarin red S and have a typical appearance on fluid leukocyte count and differential for the diagnosis
electron micrography. The synovium of patients with of prosthetic knee infection. Am J Med 2004;117:556–
multicentric reticulohistiocytosis is filled with multinu- 562.
cleated giant cells and histiocytes with a granular 12. Kerolus G, Clayburne G, Schumacher HR. Is it manda-
ground-glass appearance. The SF from patients with tory to examine synovial fluids promptly after arthrocen-
ochronosis has a ground-pepper appearance due to pig- tesis? Arthritis Rheum 1989;32:271–278.
13. Gordon C, Swan A, Dieppe A. Detection of crystals in
mented debris. The synovial biopsy from these patients
synovial fluid by light microscopy: sensitivity and reliabil-
contains shards of ochronotic pigment that is diagnostic.
ity. Ann Rheum Dis 1989;48:737–742.
In Whipple’s disease, foamy macrophages containing 14. Joseph J, McGrath H. Gout or “pseudogout”: how to dif-
periodic acid-Schiff (PAS)–positive material can be ferentiate crystal-induced arthropathies. Geriatrics 1995;
seen on synovial biopsy. Pigmented villonodular syno- 50:33–39.
vitis is defined by the presence of giant cells, foamy 15. McCarty DJ, Halverson PB, Carrera GF, Brewer BJ,
cells, and hemosiderin deposits in synovial tissue. Kozin F. “Milwaukee shoulder”—association of micro-
The ease of direct biopsy of target tissues that has spheroids containing hydroxyapatite crystals, active col-
resulted from advances in arthroscopic techniques has lagenase, and neutral protease with rotator cuff defects.
not changed the clinical indications for synovial biopsy. Arthritis Rheum 1981;24:464–473.
Biopsy should be done only if the diagnosis cannot be 16. Beaudet F, de Medicis R, Magny P, Lussier A. Acute
apatite podagra with negatively birefringent spherulites in
made using traditional, less invasive procedures.
the synovial fluid. J Rheumatol 1993;20:1975–1978.
17. Sequeira W, Co H, Block JA. Osteoarticular tuberculosis:
current diagnosis and treatment. Am J Ther 2000;7:393–
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18. Kohli R, Hadley S. Fungal arthritis and osteomyelitis.
1. Swan A, Amer H, Dieppe P. The value of synovial fluid Infect Dis Clin North Am 2005;19:831–851.
assays in the diagnosis of joint disease: a literature survey. 19. Schumacher HR, Kulka JP. Needle biopsy of the synovial
Ann Rheum Dis 2002;61:493–498. membrane—experience with the Parker-Pearson technic.
2. Gatter RA, Schumacher HR Jr. A practical handbook of N Engl J Med 1972;286:416–419.
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1991. Rheumatol 2005;19:387–400.
CHAPTER 2

D. Imaging of Rheumatologic
Diseases
WILLIAM W. SCOTT, JR., MD
WILLIAM J. DIDIE, MD
LAURA M. FAYAD, MD
䊏 Conventional radiographs are the initial imaging 䊏 High resolution CT of the lungs is an essential
agent of choice for most rheumatic conditions. For adjunct to the evaluation of many inflammatory
most forms of arthritis, no additional imaging studies rheumatic diseases, for example, systemic sclerosis,
are required. systemic vasculitis, and other disorders associated
䊏 Trabecular bone and small bone erosions are with signs of interstitial lung disease.
visualized well by conventional radiography. 䊏 Magnetic resonance imaging (MRI), which has
䊏 Weight-bearing views of the knees are important in superior imaging capabilities of soft tissue and bone
the evaluation of significant knee osteoarthritis. marrow lesions, is the study of choice for a host of
䊏 Computed tomography (CT) is superior to conven- musculoskeletal diagnoses, including meniscal tears
tional radiographs in the assessment of certain joint of the knee, spinal disc herniations, osteonecrosis,
conditions, including many cases of tarsal coalition, osteomyelitis, skeletal neoplasms, and others.
sacroiliitis, osteonecrosis, and sternoclavicular joint 䊏 Bone densitometry plays a crucial role in the diagno-
disease. sis and treatment of osteopenia and osteoporosis.
Imaging techniques may aid in making diagnoses, permit which individual structures are visualized), radiation
objective assessments of disease severity and response dose to the patient, availability, and specific uses in
to treatment, and promote new understandings of assessing musculoskeletal signs and symptoms.
disease processes. Imaging modalities that are valuable
in rheumatology include conventional radiography,
computed tomography (CT), magnetic resonance
imaging (MRI), ultrasound, radionuclide imaging, CONVENTIONAL RADIOGRAPHY
arthrography, bone densitometry, and angiography.
A basic knowledge of the merits and limitations of Conventional radiographs are the starting point for
these techniques is essential in selecting the most appro- most imaging evaluations in rheumatic disorders, even
priate and cost-effective imaging. In the discussion to when studies such as MRI are expected to follow. The
follow, high spatial resolution will indicate excellent cost is low and spatial resolution is very high, permitting
ability of an imaging modality to demonstrate fine bone good visualization of trabecular detail and tiny bone
detail and to detect small calcifications. High contrast erosions. When necessary, resolution can be enhanced
resolution will indicate excellent ability to distinguish further by magnification techniques and film–screen
different soft tissue structures. Techniques such as combinations optimized for detail. However, contrast
conventional radiography have good spatial resolution. resolution is poor compared to that obtainable with CT
MRI generally has best contrast resolution among and MRI. This limitation is especially noticeable when
current imaging techniques. This chapter reviews the trying to evaluate soft tissues. Although plain radiogra-
basic imaging techniques with regard to their spatial phy is a useful tool to assess the effect of a soft tissue
and contrast resolution (which determine the degree to mass on nearby bone and to detect calcification within
28
soft tissue, other techniques should be employed if atrophy, and evaluate the state of the biceps tendon and
optimal soft tissue imaging is required. articular cartilage in such cases.
Examination of peripheral structures, such as the Knee radiographs are useful in cases of advanced
hands and feet, delivers a low radiation dose to the arthritis, when they may demonstrate complete loss of
patient. Serial studies of the extremities can be per- knee joint cartilage and bone-on-bone contact. This
formed without concern about excessive radiation marks the end point for useful arthroscopic and medical
exposure. Studies of central structures, however, such treatment of knee arthritis and time to consider joint
as the lumbar spine and pelvis, expose patients to high replacement. Weight-bearing views are necessary 2
radiation doses. Close proximity to the gonads and to because hyaline cartilage loss is deduced from the
bone marrow increases the potentially detrimental degree of apposition of the bony surfaces. In this
effects to the patient. Whenever possible, the pelvic regard, the flexed posterior–anterior (PA) standing
region of pregnant or potentially pregnant women radiograph is often more useful than an anterior–
should not be exposed to x-rays, and radiation to posterior (AP) view in full extension, as the flexed
children should be minimized stringently. When such view images the portion of the articular surface subject
studies are necessary in these patients, radiation physi- to the greatest wear (Figure 2D-5). However, for earlier
cists can calculate the minimum radiation dose required stages of arthritis, MRI is important for detection of
for the imaging study. These same basic principles apply small focal articular cartilage defects that may poten-
to all other x-ray imaging techniques. tially be treated with recently developed surgical
Conventional radiography is widely available and techniques.
convenient. Moreover, a vast fund of knowledge about
plain radiographic findings in various rheumatic dis-
eases is available (Figures 2D-1–2D-3). In many cases, DIGITAL RADIOGRAPHY
simple, low cost imaging may provide all the informa-
tion necessary to make clinical decisions. If the plain Computed radiography uses a photosensitive phosphor
radiograph of the shoulder shows upward subluxation plate to create a digital image, rather than the analog
of the humeral head so that it contacts the undersurface image of conventional radiography. At present, com-
of the acromion, one can be quite certain that the rotator puted radiography images are utilized at most centers.
cuff is torn with atrophic musculature, and likely very The resolution is adequate for many routine joint
difficult to repair (Figure 2D-4). This may argue against evaluations and can be improved by magnification,
a decision to undertake surgery. If surgery is contem- if necessary for special tasks. The radiation dose is
plated, however, then MRI can confirm the large size of approximately the same as for conventional radiogra-
the rotator cuff tendon tear, the extent of muscle phy. Soft tissue is better visualized than on conven-
tional radiographs.
Direct radiography is a technique whereby digital
images are created at the time of x-ray exposure. The
advantages of digital images, whether digitized con-
ventional radiographs, computed radiography, or direct
radiography, include the ability to manipulate images
electronically and to display images simultaneously in
several remote areas. Image manipulation permits
technically excellent final images to be obtained under
adverse circumstances. For this reason, computed radi-
ography is currently popular in emergency departments
and intensive care units, locations where it is often
difficult to obtain optimal radiographic exposures.
The ability to manipulate digital data is also useful to
researchers wishing to make automated measurements
on radiographs and to clinicians wishing to send images
via the Internet.
The resolution of computed radiography can be
improved and conventional high resolution radiographs
FIGURE 2D-1 can be converted into digital format. CT, MRI, and
ultrasound images are also acquired in digital form, and
Typical radiographic findings in osteoarthritis of the hand
showing asymmetric joint narrowing with osteophyte formation.
are easily transported and manipulated. Digital imaging,
The distal interphalangeal joints, proximal interphalangeal joints, now widely utilized, has the advantages of rapid trans-
and first carpometacarpal joint are most commonly involved. mission, cost-effective storage, and easy retrieval.
30 WILLIAM W. SCOTT, JR., WILLIAM J. DIDIE, AND LAURA M. FAYAD
C D
FIGURE 2D-2
(A) Severe rheumatoid arthritis in an elderly woman showing erosive changes and marked
cartilage narrowing of wrist, intercarpal, metacarpophalangeal, and proximal interphalangeal
joints. The joints involved are typical for rheumatoid arthritis. Alignment abnormalities with ulnar
deviation of the metacarpals and osteoporosis are also typical. (B) Coronal short time inversion
recovery (STIR) image of the wrist in a different patient showing multiple osseous erosions and
synovial thickening, characteristic findings of rheumatoid arthritis. (C) T1 weighted coronal image
showing more extensive erosions (arrows) with areas of synovial thickening. (D) Axial postcon-
trast fat-saturated image depicting tenosynovitis, with fluid distention of the tendon sheaths
(arrow).
FIGURE 2D-3
A 57-year-old woman with systemic lupus erythematosus (SLE)

shows striking alignment abnormalities without erosions as well as
periarticular osteoporosis. Similar changes are seen in the arthropa-
thy associated with rheumatic fever (Jaccoud’s arthropathy). The
cartilage destruction and synovial proliferation of rheumatoid
arthritis is lacking. Early in the disorder, the alignment abnormalities
can be corrected by passive positioning.
A B
FIGURE 2D-4
(A) An 80-year-old woman with weakness and pain in the

right shoulder. Radiograph shows superior subluxation of
the humeral head and markedly decreased space
between humeral head and acromion. (B) Oblique–
coronal STIR MRI image shows similar decreased distance
between the acromion and humeral head, as well as a
complete rotator cuff tendon tear. (C) Sagittal oblique T1
weighted image demonstrating a significant degree of
atrophy of the supraspinatus, infraspinatus, and subscapu-
laris muscles. MRI findings could have been predicted
from the plain radiograph and the clinical history.
However, in this case the MRI provides an accurate
estimation of the size of the rotator cuff tear, as well as
commonly associated findings such as the status of the
long head of the biceps tendon and articular cartilage.
These soft tissue abnormalities cannot be assessed by
plain radiography.
C
A B
FIGURE 2D-5
(A, B) Standing anteroposterior (A) and standing flexed posteroanterior (B) views of the right
knee. In (A), no significant narrowing of the joint is identified although osteophytes and subchon-
dral sclerosis, indicative of osteoarthritis, are evident. In (B), however, the standing flexed view
demonstrates complete articular cartilage loss in the lateral compartment.
COMPUTED TOMOGRAPHY myelography and CT with intravenous contrast enhance-

ment are used to evaluate disc disease and other spinal
Compared with radiography, CT offers superior con- processes. In general, MRI is preferred over CT for
trast resolution, but spatial resolution of CT remains investigating disc disease (following plain radiography).
inferior. CT is especially useful in specific locations dif- For cases in which MRI is contraindicated, CT is an
ficult to evaluate by radiography, such as the sacrum. acceptable alternative and may be useful in circum-
Although relatively expensive, CT is less costly than stances where additional information about osteophytes
MRI. With the advent of multidetector technology is important. Elsewhere in the musculoskeletal system,
capable of producing CT datasets with isotropic resolu- CT is useful for evaluating structures in areas of complex
tion, the spatial resolution of CT is comparable or supe- anatomy where overlying structures obscure the view
rior to that of MRI, but its contrast resolution is inferior. on conventional radiographs. Examples include tarsal
Consequently, CT is not as sensitive as MRI for defining coalitions not visible on plain radiographs (Figure
bone marrow or soft tissue abnormalities. 2D-6) (1); sacroiliitis, especially that of infectious origin
Computed tomography is an excellent technique for (Figure 2D-7); and articular collapse of the femoral
evaluating degenerative disc disease of the spine and head following osteonecrosis, indicating the need for
possible disc herniations in older patients, in whom joint replacement rather than a core procedure. The
radiation dose is less critical than in young patients. CT sternoclavicular joint, which is notoriously difficult to
see on conventional radiography, is quite visible with

CT.
The radiation dose from CT is relatively high com-
pared with a single plain radiograph of the same region,
but the radiation doses between these imaging tech-
niques are comparable when several conventional
radiographic views of the same area are required.
If the correct initial data are obtained by appropri-
2
ately adjusting the thickness of the collimation used and
the thickness of the reconstructed slice width, images
can be reconstructed satisfactorily in any plane,
especially with the advent of advanced multidetector
technology capable of isotropic resolution datasets.
In addition to multiplanar reconstructions, three-
dimensional images can be obtained, which may aid in
evaluating abnormalities of the pelvis and other areas
of complex anatomy. Using multidetector technology,
including multiplanar reformatting, better images of
joints affected by respiratory motion, such as the shoul-
der, can be acquired rapidly during a single breath,
minimizing motion artifact.
High resolution (thin cut) CT of the lung may reveal
details of disease not seen on thicker CT slices of the FIGURE 2D-7
thorax. Thin cut CT scans have the additional advan-
tage of not requiring intravenous contrast—often a Woman with left hip and back pain. Plain radiographs demon-
strated no abnormalities. CT scan shows marked erosion and
concern in patients with rheumatic disease who have widening of the left sacroiliac joint, consistent with sacroiliitis.
tenuous renal status. The interstitial lung disease that Note relative osteopenia on the adjacent sacral side, indicating
hyperemia.
occurs in many patients with a variety of rheumatic

conditions (systemic sclerosis, rheumatoid arthritis,
inflammatory myopathy, microscopic polyangiitis) is
characterized well by high resolution CT. The demon-
stration of “ground glass” infiltrates connotes an active
process that may respond to treatment, but unfortu-
nately this finding does not distinguish between infec-
tion, inflammation, and other conditions (2).
Multidetector spiral CT is now used increasingly as
a means of excluding pulmonary emboli, a complication
to which many patients with rheumatic disorders (sys-
temic lupus erythematosus, primary antiphospholipid
antibody syndrome, Wegener’s granulomatosis) are
susceptible. For pulmonary thromboembolism detec-
tion, the chest is scanned rapidly following a bolus intra-
venous injection of contrast medium, timed so that the
pulmonary arteries are opacified to optimal effect.
MAGNETIC RESONANCE
IMAGING
FIGURE 2D-6
A 50-year-old woman with suspected tarsal coalition. CT scan

Because of its ability to image soft tissue structures not
shows the non-osseous talocalcaneal coalition between the visible on conventional radiographs, MRI has brought
sustentaculum of the calcaneus and the talus above. significant advances to musculoskeletal imaging. The
technique derives structural information from the Magnetic resonance imaging is free of the hazards of
density of protons in tissue and the relationship of these ionizing radiation, a major advantage in examining
protons to their immediate surroundings. central portions of the body. The technique does pose
Magnetic resonance imaging involves changing the some unique potential hazards, however. For example,
strength and timing of magnetic field gradients, as well the strong magnetic field can move metal objects such
as altering radiofrequency pulses and sampling the as surgically implanted vascular clips and foreign metal
emitted energy. By altering these factors appropriately, in the eyes, cause pacemaker malfunction, heat metal
varying amounts of T1 and T2 weighting are imparted objects, and draw metal objects into the magnet. Metal-
to the images. T1 reflects the time constant for spins to lic objects in the vicinity of the magnetic field can also
align themselves with the main magnetic field of the compromise the quality of MRI images. Because of
equipment and T2 reflects the time constant for loss of these risks and the adverse effect on imaging quality,
coherence among spins, resulting in decay of the com- operators must screen patients and visitors carefully.
ponent of magnetization perpendicular to the main Patients suffering from claustrophobia may be unable
magnetic field. These relaxation times are different in to tolerate the procedure, which is performed with the
different tissues, permitting optimal imaging of differ- patient positioned in a hollow tube. More open configu-
ent tissues by selection of an appropriate mix of T1 and rations for the magnet can circumvent this problem, but
T2 weighting. the quality of images produced by these devices varies.
As a result, MRI highlights different types of tissue MRI c̄ gadolinium is contraindicated in patients with
and metabolic states. Altering these parameters can significant renal dysfunction, because of the risk of
produce radically different images of the same anatomic inducing nephrogenic systemic fibrosis (3). Finally,
site. CT images, which basically map the density of because MRI instruments can be noisy, hearing protec-
tissues in a manner similar to conventional radiographs, tion should be provided for the patient.
are intuitively easier to grasp than are MR images. Spatial resolution using the latest MRI equipment is
Magnetic resonance imaging is more expensive than similar to spiral CT, but contrast resolution in soft tissues
most other imaging approaches, largely because of the as well as bone marrow is superior among imaging
cost of equipment and the time required to perform the modalities. Intra-articular soft tissue structures, such as
studies. In the future, more attention will probably be the menisci and cruciate ligaments of the knee, are dem-
given to tailored, limited imaging sequences, which onstrated clearly by MRI (Figure 2D-8). In fact, tiny liga-
potentially could lower the cost. Newer, faster imaging mentous structures in the wrist or ankle can be assessed
sequences continue to be developed, which may reduce quite readily (4). The synovium can be imaged, espe-
the time and cost of MRI, as well as provide dynamic cially using intravenous gadolinium. Joint effusions,
studies of joint motion. popliteal cysts, ganglion cysts, meniscal cysts, and bursi-
FIGURE 2D-8
(A) Sagittal proton density images of the knee, depicting vertical tear of the posterior horn of the
medial meniscus. (B) Sagittal proton density images of the knee. Bucket-handle tear of the medial
meniscus, with “double Posterior Cruciate Ligament sign.”
A B
tis can be imaged clearly (Figure 2D-9), and the integrity

of tendons assessed accurately as well (5). One limitation
of MRI is in the detection of calcifications, which present
as signal voids and are therefore not as well seen by MRI
as by radiographic images. For example, chondrocal-
cinosis, important to the diagnosis of calcium pyro-
phosphate dehydrate deposition disease (CPPD), is
demonstrated more reliably by plain radiography (Figure 2
2D-10). Otherwise, MRI remains the modality of choice
for evaluating potential internal joint derangements.
Magnetic resonance imaging has specific utility in the
assessment of:
• Imaging Cartilage. MRI has a negative predictive

value close to 100% for the presence of meniscal
tears in the knee. MRI is also a sensitive method for
diagnosing labral tears of the shoulder and triangu-
lofibrocartilage tears in the wrist.
Alterations in articular hyaline cartilage are visible
on MRI. Although direct observation with arthros-
copy is more sensitive to small superficial changes,
refinements are being made that improve the ability FIGURE 2D-10
of MRI to detect small articular cartilage defects (6). Chondrocalcinosis in the hand: 58-year-old man with chondro-
With recent improvements in therapy for cartilage calcinosis in triangular fibrocartilage and lunotriquetral ligaments
defects, MRI provides a useful noninvasive method (arrows). Note MCP joint degenerative changes, a typical location
for CPPD arthropathy. First carpometacarpal (CMC) joint also
for quantifying cartilage loss as well as evaluating the
shows moderate degenerative change.
success of surgical repair. In addition, MRI is the
study of choice for evaluating osteochondritis disse-
cans when information is needed about whether the Recent studies have suggested that MRI may have
osteochondral fragment is loose or detached. a role in assessing responses to therapy in arthritis.
For example, in rheumatoid arthritis, MRI can quan-
tify the volume of enhancing inflammatory tissue (7).
In ankylosing spondylitis, MRI may be used to assess
changes over time in spinal inflammation (8). MRI
has been established as the most sensitive modality
for the detection of bony erosions (Figure 2D-11) (9),
although its specificity for early erosive changes has
been reported to be low. Healthy subjects can occa-
sionally demonstrate imaging findings suggestive of
mild synovitis or erosions, indistinguishable from
early rheumatoid arthritis (10). Finally, as bone
marrow edema and synovitis can precede frank ero-
sions, MRI may have a predictive role, and thus
affect patient management early in the disease course
(11).
• Detecting Bony Abnormalities. MRI is extremely
sensitive to subtle bony abnormalities. In fact, micro-
fractures due to trauma or stress—often referred to
as “bone bruises”—were essentially unknown before
MRI. Now, recognizing their presence is quite impor-
tant. The pattern of bone bruises is also closely
related to ligamentous injuries (12). Similarly, much
FIGURE 2D-9 of the pain accompanying some acute meniscal tears
Adolescent with knee pain. Coronal proton density fat-saturated
may be caused by associated bone marrow edema.
image shows horizontal cleavage tear of the lateral meniscus, When the edema subsides, the pain disappears,
with associated parameniscal cyst (arrow). despite the persistent meniscal tear. This finding
• Diagnosing Disc Herniation. Following plain radiog-

raphy, MRI is an excellent study of the spine and its
contents in cases of suspected disc herniation, par-
ticularly in young patients, because it does not employ
ionizing radiation.
• Localizing Muscle Abnormalities, Including
Inflammation-Associated Edema in Inflammatory
Muscle Disease. MRI is indicated in the assessment
of muscle abnormalities for detection of potential
tears and contusions. The activity of different muscles
during joint motion can also be studied by noting
signal changes that occur with muscle activity. In
inflammatory myopathies (polymyositis, dermato-
myositis, inclusion body myositis), MRI demonstrates
characteristic (albeit not diagnostic) edema, and may
be useful in identifying sites to biopsy and following
disease activity.
FIGURE 2D-11
SCINTIGRAPHIC TECHNIQUES
MRI images of a patient treated with corticosteroids. T1 Scintigraphy following intravenous administration of
weighted image of hips demonstrates characteristic serpentine agents such as 99m technetium methylene diphospho-
foci of low signal intensity within the femoral heads bilaterally,
consistent with osteonecrosis.
nate (99mTc MDP) for bone scans, 99mTc sulphur colloid
for bone marrow scans, 67 gallium citrate (67Ga citrate),
and leukocytes labeled with 111 indium [111In-labeled
white blood cells (WBCs)] are useful for evaluating a
variety of musculoskeletal disorders (Figure 2D-12).
could have important implications for therapy. One These studies, similar in cost to CT, deliver a radiation
should possibly wait for the edema to resolve before dose similar to a CT scan of the abdomen. Scintigraphy
attempting surgical intervention to repair or remove is quite sensitive for detecting many disease processes,
the meniscus. In some cases intervention might be and has the advantage of imaging the entire body at
unnecessary. MRI studies of the knee in older people once. The technique is nonspecific, however, because
often reveal asymptomatic meniscal tears. These a number of processes may cause radionuclide accumu-
individuals may have had pain at the time of the tear lation. When areas of increased uptake are detected,
which resolved with the edema and did not cause additional studies such as radiography are often neces-
them long-term disability. sary to define the type of abnormality further. In clini-
• Diagnosing Osteonecrosis. MRI is the study of choice cal situations where the presence of skeletal disease is
for diagnosing osteonecrosis (Figure 2D-11). Early uncertain, a bone scan can be useful in excluding
in the course of disease, plain radiographs show no disease.
abnormalities.
• Evaluating Musculoskeletal Neoplasms. MRI is also
the best method for evaluating the extent of a mus-
culoskeletal neoplasm. Plain radiographs are still the Localization of Scintigraphic
mainstay for detecting bone neoplasms.
• Identifying Bone Infections. MRI is highly sensitive
Imaging Agents
to the presence of bone infection because of altera- 99m Technetium methylene diphosphonate, the most
tions in the marrow signal. Osteomyelitis cannot be commonly used radionuclide, accumulates in areas of
detected on radiography until approximately 30% to bone formation, calcium deposition, and high blood
40% bone destruction has occurred. Thus, MRI is the flow. 99mTC sulphur colloid localizes in the reticuloen-
study of choice for the early detection of osteomyeli- dothelial system (liver, spleen, and bone marrow).
67
tis (13). Small studies have shown variable results for Gallium citrate accumulates in inflammatory and
MRI in differentiating osteomyelitis and neuropathic certain neoplastic processes, and 111In-labeled WBCs
arthropathy, which is very difficult with other imaging localize in inflammatory sites, especially acute inflam-
techniques. matory processes.
A B
FIGURE 2D-12
(A) An 82-year-old woman with a history of breast cancer and recent onset of lower back pain.
Metastases were suspected. 99mTc MDP bone scan shows increased uptake in the sacrum and
right pubic ramus, typical of insufficiency fractures rather than metastatic cancer. (B) Computed
tomography scan in the same 82-year-old woman. This test demonstrates the linear nature of
the healing fracture in the sacrum, adjacent to the right sacroiliac joint, lending specificity to the
diagnosis suggested by the radionuclide scan.
Using Radionuclide Imaging to Other Uses of Radionuclide Imaging

Diagnose Osteomyelitis Bone scans are a reasonable alternative for early detec-
tion of osteonecrosis if MRI is not available. Bone scans
The 99mTc MDP triple-phase bone scan is commonly used can also detect stress injuries such as shin splints, tendon
for early detection of osteomyelitis. Images are obtained avulsions, insufficiency fractures, and stress fractures,
in the early vascular phase (during bolus injection of the which sometimes mimic arthritis symptome (Figure
radionuclide), intermediate blood pool phase (5 minutes 2D-12).
postinjection), and late bone phase (3 hours postinjec-
tion). A fourth phase (24 hours postinjection) can be
added to accentuate areas of increased bone uptake, ULTRASOUND
during which time soft tissue background is decreased,
although delayed imaging is not widely used because of Ultrasound provides unique information by creating
its inconvenience. If necessary, the specificity of scanning images based on the location of acoustic interfaces in
can be increased by also using 67gallium citrate or 111In- tissue. It is relatively inexpensive, widely available, and
labeled WBCs. The 111In-labeled WBC scan is especially free of the hazards of ionizing radiation. Spatial resolu-
useful when osteomyelitis is suspected to be superim- tion is similar to CT and MRI, but this depends on the
posed on a healing fracture or surgical incision because transducer. However, resolution is limited by the depth
uptake of 99mTc MDP is increased at these sites even in of tissue being studied; resolution is much higher for
the absence of infections. 111In-labeled WBC scans may superficial structures.
also be useful in diagnosing osteomyelitis of the foot in One limitation of ultrasound is dependence on the
people with diabetes. In suspected osteomyelitis of the operator. It is not always possible for one investigator
hematopoietic bone marrow, the combination of 99mTc to reproduce the results of another. Furthermore,
MDP and 111In-labeled WBC appears to be an effective because ultrasound has no cross-sectional orientation,
diagnostic technique. Spatial localization of bone scans it may be difficult for individuals who were not actually
can be improved with single-photon emission computed present during the study to interpret the images later.
tomography (SPECT), and radiographs of scan-positive In some centers, ultrasound has proved accurate
areas can be used to increase specificity. in detecting rotator cuff tears. It is also excellent for
assessing fluid collections, such as joint effusions, pop- containing contrast medium and sometimes air. The
liteal cysts, and ganglion cysts, and can therefore be cost is less than that of CT or MRI, and the procedure
used to guide aspiration of fluid. Superficially located can be performed wherever fluoroscopy is available.
tendons, such as the Achilles tendon and patellar The possibility of introducing bacteria into a joint or
tendon, can be studied for tears. encountering reactions to the local anesthetic or con-
Ultrasound is excellent for differentiating thrombo- trast medium must be considered, but these complica-
phlebitis from pseudothrombophlebitis. With real-time tions are very rare.
compression ultrasonography, venous thrombosis and One of the major reasons for developing arthrogra-
popliteal cysts can be identified. phy was to examine structures within the joint, such as
Ultrasound, similar to MRI, has been shown to be the menisci of the knee, which were not visible on con-
much more sensitive than radiography in detection of ventional radiographs. Now these structures can be
erosions in rheumatoid arthritis (14). With amplitude imaged noninvasively by MRI. However, certain impor-
color Doppler (ACD), it can demonstrate synovial hyper- tant roles remain for arthrography.
emia in active disease. The technique requires a skilled Conventional arthrography, using iodine-containing
operator and is more effective in the examination of the contrast medium either alone or combined with air,
metacarpophalangeal (MCP) and interphalangeal (IP) accurately detects full-thickness rotator cuff tears
joints than the intercarpal joints, but is relatively inex- (Figure 2D-13). CT scanning can be added to the air–
pensive and convenient. It avoids the potentially uncom- contrast arthrogram (CT arthrography), providing an
fortable positioning that may be necessary with MRI. excellent study of the glenoid labrum that can be an
Finally, although ultrasound has been reported to be alternative to MRI in selected patients (15).
useful in the diagnosis of temporal arthritis, there is an Knee arthrography can confirm the diagnosis of a
absence of blinded studies confirming its utility for this popliteal cyst, and permits injection of corticosteroids
purpose. at the same time. It is an alternative for evaluating the
menisci in patients who are claustrophobic or whose
size precludes MRI examination (Figure 2D-14).
ARTHROGRAPHY Wrist arthrography is excellent for evaluating the
integrity of the triangular fibrocartilage, ligaments
Arthrography involves injecting a contrast agent into between the scaphoid and lunate, and ligaments between
the joint followed by radiography. In conventional the lunate and triquetrum (16). Some clinicians prefer
arthrography, the joint cavity is filled with an iodine- arthrography to MRI in this situation.
FIGURE 2D-13
(A) Single contrast arthrogram of a normal shoulder. (B) Single contrast shoulder arthrogram of a
66-year-old man with a painful shoulder and history of injury in distant past. Contrast media fills
not only the shoulder joint [as in Figure 2D-11(A)] but has filled the subdeltoid–subacromial
bursa superiorly, a finding diagnostic of full-thickness rotator cuff tear.
A B
A B
FIGURE 2D-14
(A, B) A 40-year-old woman, too large to fit in the MRI scanner, was suspected of having a
popliteal cyst. Double contrast arthrogram demonstrated popliteal cyst and also a torn medial
meniscus. Ultrasonography would have been an appropriate alternative approach to making this
diagnosis.
Magnetic resonance arthrography is performed by are available for lumbar spine and proximal femur,
distending a joint with a dilute solution of a gadolinium- which are the most widely studied.
containing contrast medium. This technique, not widely Quantitative computed tomography scans several
studied, probably increases the diagnostic accuracy of lumbar vertebrae while simultaneously scanning a
glenoid and acetabular labral tears, as well as rotator phantom containing different concentrations of bone-
cuff tears (17). equivalent material. A standard curve is constructed
from the concentration values versus CT attenuation,
and then the bone density at any location scanned is
BONE DENSITOMETRY determined from the standard curve. The cost of this
study is moderate and the radiation dose fairly low,
Bone densitometry is used primarily for evaluating although not as low as that for DXA. One purported
osteoporosis. Two precise, accurate, and widely avail- advantage of this technique is that trabecular bone in
able techniques are dual-energy x-ray absorptiometry the middle of the vertebrae can be evaluated because
(DXA) and quantitative computed tomography overlying cortical bone and posterior elements of the
(QCT) (18). vertebrae are not measured. Trabecular bone, which
Dual-energy x-ray absorptiometry scans with a has tremendous surface area, is more rapidly affected
narrow x-ray beam that alternates energy (kilovoltage during bone loss than is cortical bone.
peak; KVP). A sensitive receptor detects the fraction of
the x-ray beam that traverses the body at each point
along the scan path. Because the absorption character- ANGIOGRAPHY
istics of bone and soft tissue vary at different x-ray
energies, the amount of radiation absorbed by bone Angiography is useful in the primary diagnosis of rheu-
can be calculated. From this, the amount of bone in the matologic disorders with vascular components. In poly-
path of the x-ray beam at any point along the scan is arteritis nodosa, for example, demonstration of multiple
determined. small aneurysms in medium-sized arteries may be
Dual-energy x-ray absorptiometry is relatively inex- diagnostic. Similarly, in Takayasu’s arteritis, the long,
pensive and delivers very little radiation to the patient. smooth tapering of involved vessels—most often the
It is thus a good choice for studies that must be repeated. subclavian arteries—is highly characteristic. Aortogra-
Any part of the body can be studied. Standard values phy with central aortic pressure measurement is also
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2
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Rematological Examination

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CHAPTER 2

Evaluation of the Patient

Musculoskeletal complaints are among the most Location and Symmetry

Gait Symmetry, smoothness of movement; normal stride length; normal heel

“Touch your toes.” Normal lumbar spine (and hip) flexion

Inspection from the front

tis. With this maneuver, the bulge in the lateral recess

FIGURE 2A-2 The Shoulder

the medial and collateral ligaments. The cruciate liga-

Evaluation of the Patient

Laboratory testing is an important part of the evalua- ERYTHROCYTE

Interpretation that is positive for staining and the pattern of the

TABLE 2B-1. ANTINUCLEAR ANTIBODY PATTERNS.

Homogenous Double-stranded DNA Systemic lupus erythematosus

Diffuse Histone Drug reaction

Nucleolar RNA-associated antigens Systemic sclerosis

Peripheral Double-stranded DNA Systemic lupus erythematosus

Centromere Centromere Limited systemic sclerosis

TABLE 2B-2. AUTOANTIBODIES IN RHEUMATIC DISEASES.

Anti-dsDNA Antibodies to double-stranded DNA High specificity for SLE

Anti-ENA Sm (Smith) High specificity for SLE

Anti-SSB (La) Ribonucleoproteins Sjögren’s syndrome, SLE, neonatal SLE

Anti-centromere Antibody to centromere/kinetochore region Limited scleroderma

Anti-Scl 70 Antibodies to DNA topoisomerase 1 Diffuse scleroderma

Anti-Jo-1 Antibody to histidyl tRNA synthetase Poly/dermatomyositis

Anti-SRP Antibody to signal recognition protein Cardiomyopathy

Anti-PM-Scl Antibody to nucleolar granular component Polymyositis/scleroderma overlap syndrome

Anti-Mi-2 Antibodies to a nucleolar antigen of Dermatomyositis

Evaluation of the Patient

TABLE 2C-1. ANATOMIC APPROACH TO ASPIRATION.

Knee Extended Medial or lateral under the patella

Shoulder Neutral adduction, external Anterior: inferolateral to coracoid

Ankle Plantar flexion Anteromedial: medial to extensor hallucis longus

Subtalar Dorsiflexion to 90° Inferior to tip of lateral malleolus

Wrist Midposition Dorsal into radiocarpal joint

First carpometacarpal Thumb abducted and flexed Proximal to base of metacarpal

Metatarsophalangeal Toes slightly flexed Dorsomedial or dorsolateral

TABLE 2C-2. CLASSES OF SYNOVIAL FLUID.

Color Clear/yellow Yellow/white Yellow/white Red

Clarity Transparent Translucent/opaque Opaque Opaque

Viscosity High Variable Low NA

Mucin clot Firm Variable Friable NA

WBC count <2,000 2,000–100,000 >100,000 NA

Differential <25% PMNs >50% PMNs >95% PMNs NA

Culture Negative Negative Positive Variable

ABBREVIATIONS: PMN, polymorphonuclear leukocytes; NA, not applicable.

TABLE 2C-3. DIAGNOSIS BY SYNOVIAL CLASS.

Osteoarthritis Rheumatoid arthritis Septic arthritis Trauma

Evaluation of the Patient

A 57-year-old woman with systemic lupus erythematosus (SLE)

(A) An 80-year-old woman with weakness and pain in the

COMPUTED TOMOGRAPHY myelography and CT with intravenous contrast enhance-

see on conventional radiography, is quite visible with

occurs in many patients with a variety of rheumatic

A 50-year-old woman with suspected tarsal coalition. CT scan

tis can be imaged clearly (Figure 2D-9), and the integrity

• Imaging Cartilage. MRI has a negative predictive

• Diagnosing Disc Herniation. Following plain radiog-

Using Radionuclide Imaging to Other Uses of Radionuclide Imaging