April 22

2007
Musculoskeletal
System
A complete history and physical examination are important in a patient with joint
symptoms, which may be part of localized or systemic disease. Laboratory and x-ray data
Laboratory
are usually of only supplementary help. Tests

Andina’s
Ruland Pakasi & Co

Contents
01.Rheumatoid Arthritis........................................................................................................................3
Hal. | 2
02.Osteoarthritis....................................................................................................................................6

03.Gout Arthritis....................................................................................................................................7

04.Systemic Lupus Erythematosus (SLE)................................................................................................9

05.Bell’s Palsy.......................................................................................................................................11

06.Mysthenia Gravis............................................................................................................................11

07.Bursitis............................................................................................................................................11

O8.Fibromyalgia...................................................................................................................................12

09.Acute Infectious Arthritis................................................................................................................12

10.Chronic Infectious Arthritis.............................................................................................................14

11.Osteomyelitis..................................................................................................................................14

12.Polymyositis and Dermatomyositis.................................................................................................15

13. Relapsing Polychondritis................................................................................................................16

14. Osteoporosis..................................................................................................................................17
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Laboratory Examinations
for Musculoskeletal Disoders
Hal. | 3

APPROACH TO THE PATIENT WITH JOINT DISEASE

Blood tests are useful in diagnosing some specific types of arthritis (for specific tests, see the chapters
for each disease). Elevated ESR or C-reactive protein suggests inflammatory disease. Serum uric acid
levels are elevated by diuretics, low doses of aspirin, other drugs, diet, or alcohol and in gout. Latex
fixation tests for rheumatoid factor are often highly positive in RA but may also be positive in hepatitis,
cirrhosis, sarcoidosis, subacute bacterial endocarditis, TB, and other infections and collagen diseases.
Antinuclear factors may be positive in RA, Sjögren's syndrome, progressive systemic sclerosis, SLE,
hepatitis, and other diseases. If SLE is suspected, anti–double-stranded DNA, anti-Sm, and complement
levels may also provide further support. Serum CK and AST are elevated in muscle disease, including
certain forms of muscular dystrophy, crush injury, and polymyositis or dermatomyositis. CK can also be
elevated in hypothyroidism.

01.Rheumatoid Arthritis
Rheumatoid arthritis is a chronic autoimmune disease, producing damage mediated by cytokines,
chemokines, and metalloproteases. Peripheral joints (eg, wrists, metacarpophalangeal joints) are
symmetrically inflamed, often resulting in progressive destruction of articular structures, usually
accompanied by systemic symptoms. Diagnosis requires specific clinical, laboratory, and radiologic
criteria. Treatment involves drugs, physical measures, and sometimes surgery. Drug therapy combines
NSAIDs, which help reduce symptoms, and disease-modifying antirheumatic drugs, which slow disease
progression.

Gambar 1 rheumatoid nodulus

Diagnosis
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RA should be suspected in patients with polyarticular, symmetric arthritis. Criteria for the diagnosis of RA
are as follows; presence of ≥ 4 criteria establishes the diagnosis. Patients should have a RF test, hand and
wrist x-rays, and baseline x-rays of affected joints to document future erosive changes.

Table 1
Hal. | 4
Diagnosing Rheumatoid Arthritis*
Any 4 criteria must be present to classify patients as having
rheumatoid arthritis:
Morning stiffness for ≥ 1 h†
Arthritis of ≥ 3 joints†
Arthritis of hand joints (wrist, metacar-  pophalangeal, or
proximal interpha-  langeal joints)†
Symmetric arthritis†
Rheumatoid nodules
Serum rheumatoid factor (positive in < 5% of normal
control subjects)
Radiographic changes (hand x-ray changes typical of rheumatoid arthritis
must include erosions or unequivocal bony decalcification)

*Based on criteria from the American Rheumatism Association

(now the American College of Rheumatology).
†Must be present for ≥ 6 wk.

Laboratoriuy Tests
 RFs, antibodies to human γ-globulin, are present in about 70% of RA patients. However,
RF, often in low titers, occurs in patients with other diseases, including other connective
tissue diseases (eg, SLE), granulomatous diseases, chronic infections (eg, viral hepatitis,
subacute bacterial endocarditis, TB), and malignancies. Low RF titers can also occur in
3% of the general population and 20% of the elderly. A RF titer measured by latex
agglutination of > 1:80 helps confirm RA. RF is now most often measured by
nephelometry, with normal ranges that vary according to laboratory.
 Anti-citrullinated peptide (anti-CCP) antibodies have high specificity (90%) and sensitivity
(96%) for RA. Anti-CCP antibodies are useful in the differential diagnosis of early
polyarthritis.
 X-rays show only soft-tissue swelling during the first months of disease. Subsequently,
periarticular osteoporosis, joint space (articular cartilage) narrowing, and marginal
erosions may become visible. Erosions often develop within the first year but may occur
any time. MRI appears to be more sensitive and detects earlier articular inflammation
and erosions.
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 If RA is diagnosed, additional tests help detect complications and unexpected

abnormalities. CBC with differential should be obtained. A normochromic (or slightly
Hal. | 5
hypochromic)-normocytic anemia occurs in 80%; Hb is usually > 10 g/dL. If Hb is ≤ 10
g/dL, superimposed iron deficiency or other causes of anemia should be considered.
Neutropenia occurs in 1 to 2% of cases, often with splenomegaly (Felty's syndrome).
Acute-phase reactants (eg, thrombocytosis, elevated ESR, elevated C-reactive protein)
reflect disease activity. A mild polyclonal hypergammaglobulinemia often occurs. ESR is
elevated in 90% of patients with active disease. Serum complement is normal or
elevated.
 Synovial fluid examination is necessary in any new onset arthritis or synovial effusion to
rule out other disorders and differentiate RA from other inflammatory arthritides (eg,
septic and crystal-induced arthritis). In RA, during active joint inflammation, synovial
fluid is turbid, yellow, and sterile, with reduced viscosity and usually 10,000 to 50,000
WBCs/μL; PMNs typically predominate, but > 50% may be lymphocytes and other
mononuclear cells. WBC cytoplasmic inclusions may be seen on a wet smear but are also
present in other inflammatory effusions. Crystals are absent.

Differential diagnosis: Many disorders can simulate RA. Some patients with crystal-induced arthritis may
even meet criteria for RA; however, synovial fluid examination should clarify the diagnosis. The presence
of crystals makes RA unlikely. Joint involvement and subcutaneous nodules can result from gout,
cholesterol, and amyloidosis as well as RA; aspiration or biopsy of the nodules may be needed.

 SLE usually can be distinguished if there are skin lesions on light-exposed areas, hair loss,
oral and nasal mucosal lesions, absence of joint erosions in even long-standing arthritis,
joint fluid that often has < 2000 WBCs/μL (predominantly mononuclear cells), antibodies
to double-stranded DNA, renal disease, and low serum complement levels. Arthritis
similar to RA can also occur in other connective tissue disorders (eg, polyarteritis,
scleroderma, dermatomyositis, or polymyositis), or there can be features of more than
one disease, which suggests an overlapping syndrome or mixed connective tissue
disease.
 Sarcoidosis, Whipple's disease, multicentric reticulohistiocytosis, and other systemic
diseases may involve joints; other clinical features and tissue biopsy sometimes help
differentiate these conditions. Acute rheumatic fever has a migratory pattern of joint
involvement and evidence of antecedent streptococcal infection (culture or changing
antistreptolysin-O titer); in contrast, RA has an additive arthritis.
 Reactive arthritis can be differentiated by antecedent GI or GU symptoms; asymmetric
involvement of the heel, sacroiliac joints, and large joints of the leg; conjunctivitis; iritis;
painless buccal ulcers; balanitis circinata; or keratoderma blennorrhagicum on the soles
and elsewhere. Also, serum and joint fluid complement levels are often elevated.
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 Psoriatic arthritis tends to be asymmetric and is not usually associated with RF, but
differentiation may be difficult in the absence of nail or skin lesions. Distal
interphalangeal (DIP) joint involvement and severely mutilating arthritis (arthritis
mutilans) can be suggestive. Ankylosing spondylitis may be differentiated by spinal and
axial joint involvement, absence of subcutaneous nodules, and negative RF test.
 Osteoarthritis can be differentiated by the joints involved; the absence of rheumatoid Hal. | 6
nodules, systemic manifestations, or significant amounts of RF; and synovial fluid WBC
counts < 2000/μL.

02.Osteoarthritis

(Degenerative Joint Disease; Osteoarthrosis; Hypertrophic Osteoarthritis)

Osteoarthritis is a chronic arthropathy of an entire joint characterized by disruption and potential loss of
joint cartilage along with other joint changes, including bone hypertrophy (osteophyte formation).
Symptoms include gradually developing pain ag-gravated or triggered by activity, stiffness relieved < 30
min after activity, and occasional joint swelling. Diagnosis is confirmed by x-rays. Treatment involves
physical measures (including rehabilitation), drugs, and surgery.

Diagnosis

OA should be suspected in patients with gradual onset of symptoms and signs, particularly in older
adults. If OA is suspected, plain x-rays should be obtained of the most symptomatic joints. X-rays
generally reveal marginal osteophytes, narrowing of the joint space, increased density of the
subchondral bone, subchondral cyst formation, bony remodeling, and joint effusions. Standing x-rays of
knees are more sensitive to joint space narrowing.

 Laboratory studies are normal in OA but may be required to rule out other disorders (eg,
RA) or to diagnose an underlying disorder causing secondary OA. If OA causes joint
effusions, synovial fluid analysis can sometimes differentiate it from inflammatory
arthritides; in OA, synovial fluid is usually clear, viscous, and has ≤ 2000 WBC/μL.

 OA involvement outside the usual joints suggests secondary OA; further evaluation may
be required to determine the underlying primary disorder (eg, endocrine, metabolic,
neoplastic, biomechanical disorders).
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Tabel 1 CLASSIFICATION OF SYNOVIAL EFFUSIONS

Hal. | 7
Normal Non- Inflammatory Septic
inflammatory

Gross examination

Viscosity High High Low Variable

Color Colorless Yellow Yellow Variable

Clarity* Transparent Transparent Translucent Opaque

Routine laboratory examination

WBC count < 200/µL 200–2,000/µL 2,000– > 100,000/µL

100,000/µL

PMN % < 25 < 25 > 50 > 75

Culture Negative Negative Negative Often positive

03.Gout Arthritis
Gout is precipitation of monosodium urate crystals into tissue, usually in and around joints, most often
causing recurrent acute or chronic arthritis. Acute arthritis is initially monarticular and often involves the
first metatarsophalangeal joint; symptoms include acute pain, tenderness, warmth, redness, and
swelling. Diagnosis requires identification of crystals in synovial fluid. Treatment of acute attacks is with
anti-inflammatory drugs. Attacks are prevented with NSAIDs and/or colchicine, and, for persistent
hyperuricemia, allopurinol or uricosuric drugs
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Podagra, or acute pain in the 1st metatarso phalangeal

joint accompanied by redness, tender ness, and swelling
(as seen in this image), is a common manifestation of
acute gout.

Diagnosis
Hal. | 8
Acute gouty arthritis has such distinctive clinical features that it can usually be tentatively diagnosed by
history and physical examination.

Laboratory tests

 Elevated serum urate (> 7 mg/dL [> 0.41 mmol/L]) supports the diagnosis but is not
specific. About 30% of patients have a normal serum urate at the time of the acute
attack.
 Demonstration in tissue or synovial fluid of needle-shaped urate crystals that are free in
the fluid or engulfed by phagocytes is pathognomonic. The appearance of MSU crystals
on compensated polarized light microscopy is described in the following table.

MICROSCOPIC EXAMINATION OF CRYSTALS

Crystal Type Birefringence Elongation* Shape Length
Monosodium Strong Negative Needle- or rod- 2 –15 µm
urate crystals
shaped
Calcium Weak Positive Rhomboid, 2 –15 µm
pyrophosphate square, or rod-
dihydrate shaped
crystals
Calcium oxalate Weak or strong Positive or inde Bipyramidal 5 – 30 µm
crystals† terminate
*Crystals that have negative elongation are yellow parallel to the axis of slow vibration marked
on the compensator; positive elongation appears blue in the same direction.
† Occur primarily in patients with renal failure.
‡ Can be stained with alizarin red S to confirm that they contain calcium.

Differential Diagnosis

In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, weakly positively birefringent
CPPD crystals cause acute synovitis; in addition, radiopaque deposits are present in fibrocartilage or in
hyaline articular cartilage (particularly the knee), and the clinical course is usually milder than in gout. An
acute septic joint may be confused with an acute gouty joint, but culture of the synovial fluid
demonstrates bacteria. Acute rheumatic fever with joint involvement and juvenile RA may simulate gout
but occurs mostly in young persons, who rarely get gout. Palindromic rheumatism (ie, acute attacks of
inflammation in one or more joints) is common, especially in middle-aged or elderly men; onset is often
even more sudden than in gout, and the pain can be as severe. Attacks spontaneously subside
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completely after 1 to 3 days. Such attacks may herald the onset of RA, and rheumatoid factor tests are
often positive (these tests are positive in 10% of gouty patients also). Such attacks are associated with
local fibrin deposition. Joint fluid is rarely obtainable because the attacks generally involve extra-articular
tissues. Osteoarthritic Heberden's nodes may be the site of gouty tophi, especially in elderly women
taking diuretics.
Hal. | 9

04.Systemic Lupus Erythematosus (SLE)

Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of probable autoimmune
etiology, occurring predominantly in young women. Common manifestations include arthralgias and
arthritis; malar and other skin rashes; pleuritis or pericarditis; renal or CNS involvement; and
hematologic cytopenia. Diagnosis requires clinical and serologic criteria.

Laboratory testing differentiates SLE from other connective tissue disorders:

 Antinuclear antibodies (ANA), CBC, urinalysis, and chemistry profile including renal and
liver function tests should be obtained. The diagnosis is especially likely if ≥ 4 of the
criteria in Table 1are present at any time but is still possible if < 4 criteria are present. If
the diagnosis is suspected but not established, additional testing for autoantibodies can
be useful. Establishing the diagnosis may require repeated evaluations over months or
years.
 The fluorescent test for ANA is the best screen for SLE; positive ANA tests (usually in high
titer: > 1:80) occur in > 98%. However, positive ANA tests can also occur in RA, other
connective tissue diseases, malignancies, and even in 1% of normal individuals. Drugs
such as, β-blockers, and tumor necrosis factor (TNF)-α antagonists can produce positive
ANA results as well as a lupus-like syndrome; the ANA eventually becomes negative if
the drug is discontinued. Positive ANA should prompt testing for anti-double-stranded
DNA antibodies; high titers are highly specific for SLE but occur in only 25 to 30% of
people with SLE.
 Other ANA and anticytoplasmic antibodies (eg, Ro [SSA], La [SSB], Sm, RNP, Jo-1) should
be obtained if the diagnosis of SLE is not otherwise clear. Ro is predominantly
cytoplasmic; anti-Ro antibodies are occasionally present in ANA-negative SLE patients
presenting with chronic cutaneous lupus. Anti-Ro is the causal antibody for neonatal
lupus and congenital heart block. Anti-Sm is highly specific for SLE but, like anti-double-
stranded DNA, is not sensitive.
 Leukopenia is common, and lymphopenia occurs if the disorder is active. Hemolytic
anemia may occur. Thrombocytopenia in SLE may be difficult or impossible to
differentiate from idiopathic thrombocytopenic purpura except that patients will be
ANA-positive. False-positive serologic tests for syphilis occur in 5 to 10% of SLE patients.
They may be associated with the lupus anticoagulant and a prolonged PTT. Abnormal
values in one or more of these assays indicate the presence of antiphospholipid
antibodies (eg, anticardiolipin antibodies), which should then be measured directly by
ELISA (enzyme-linked immunosorbent assay). Antibodies to β2-glycoprotein I are
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possibly more sensitive. Antiphospholipid antibodies predict arterial or venous

thrombosis, thrombocytopenia, and, during pregnancy, spontaneous abortion or late
fetal death.

Other tests help monitor disease severity and determine the need for treatment:
Hal. | 10
 Serum complement levels (C3, C4) are often depressed in active disease and are usually
lowest in patients with active nephritis. ESR is elevated almost uniformly during active
disease. C-reactive protein levels are not necessary: they may be strikingly low in SLE,
even with ESR > 100 mm/h.
 Screening for renal involvement begins with urinalysis. RBC and granular casts suggest
active nephritis. Urinalysis should be performed at regular intervals, perhaps every 6 mo,
even for patients in apparent remission. However, urinalysis may be repeatedly normal
despite biopsy-documented renal involvement. Renal biopsy is usually not necessary for
diagnosis of SLE or to confirm renal involvement but may help evaluate the status of
renal disease (ie, active inflammation vs
Table 1 postinflammatory scarring) and guide
therapy. Patients with chronic renal
Criteria for the Classification of SLE* insufficiency and mostly sclerotic
glomeruli are not likely to benefit from
At least 4 of the following are required to aggressive immunosuppressive therapy.
classify patients as having SLE in reports of
clinical research.

 Malar rash
 Discoid rash
 Photosensitivity 05.Bell’s Palsy
 Oral ulcers Bell's palsy is sudden weakness or paralysis of the
 Arthritis
muscles on one side of the face due to malfunction of
 Serositis
 Renal disorder cranial nerve VII (facial nerve), which stimulates the facial
 Leukopenia (< 4000/μL), muscles.
lymphopenia (<
1500/μL), hemolytic A blood test may be performed to check for Lyme disease
anemia, or or sarcoidosis. There is no specific test for Bell's palsy.
thrombocytopenia (<
100,000/μL)
 Neurologic disorder 06.Bursitis
 Positive anti-DNA or Bursitis is acute or chronic inflammation of a bursa. The
anti-Sm antibody, or cause is usually unknown, but trauma, either repetitive or
positive test for acute, may play a role, as may infection and crystal-
antiphospholipid
induced disease. Symptoms include pain, particularly with
antibodies
 Antinuclear antibodies motion, swelling, and tenderness. Diagnosis is usually
in raised titer clinical; however, diagnosis of infection and crystal-
induced disease requires analysis of bursal fluid.
*These 11 criteria are from the American
College of Rheumatology and are also
often used as aids in diagnosis. Although
at least 4 criteria are not needed to make
a diagnosis of SLE, the criteria help in
recognizing manifestations of SLE.
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Treatment includes splinting, NSAIDs, sometimes corticosteroid injections, and treatment of any
underlying cause.

Diagnosis

Bursitis should be suspected in patients with swelling or signs of inflammation over bursae. It can Hal. | 11
generally be diagnosed clinically. If the swelling is particularly painful, red, or warm, or if bursitis involves
the olecranon or prepatellar bursa, then infection and crystal-induced disease should be excluded by
bursal puncture.

Laboratory tests

Using local anesthesia and sterile technique, fluid is withdrawn from the bursa and analyzed for cell
count, gram stain and culture, and microscopic search for crystals.

 Gram stain is not sensitive, and WBC counts in infection can be lower than in septic
joints.
 Urate crystals are easily seen with polarized light, but the apatite crystals typical of
calcific tendinitis appear only as shiny, non-birefringent chunks.
 X-rays should be obtained if the bursitis is persistent or if infection or calcification is
suspected.

Hemorrhage into a bursa can cause manifestations similar to acute bursitis, as blood is inflammatory.
Cellulitis can cause signs of inflammation but does not normally cause bursal effusion; cellulitis overlying
the bursa is a relative contraindication to bursal puncture through the cellulitis, but aspiration must
occasionally be done if septic bursitis is strongly suspected.

O8.Fibromyalgia
(Myofascial Pain Syndrome; Fibrositis; Fibromyositis)

Fibromyalgia is a common nonarticular disorder of unknown cause characterized by achy pain,

tenderness, and stiffness of muscles, areas of tendon insertions, and adjacent soft tissues. Diagnosis is
clinical. Treatment includes exercise, local heat, and drugs for pain and sleep

Stiffness and pain in fibromyalgia frequently begin gradually, diffusely, and with an achy quality.
Symptoms can be exacerbated by environmental or emotional stress, poor sleep, trauma, exposure to
dampness or cold, or by a physician who gives the patient the incorrect message that it is “all in the
head.” Patients tend to be stressed, tense, anxious, fatigued, striving, and sometimes depressed. Many
patients also have irritable bowel symptoms or tension headaches.

Diagnosis

Fibromyalgia is suspected in patients with generalized pain and tenderness, especially disproportionate
to the physical findings; with negative laboratory results despite widespread symptoms; or when fatigue
is the predominant symptom.
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Laboratory tests

Tests should include ESR or C-reactive protein, CK, and probably screens for hypothyroidism and hepatitis
C (which can cause similar symptoms). The diagnosis is supported by explicit tender points and other
findings, which comprise diagnostic criteria (see Fig. 1: Bursitis, Tendinitis, and Fibromyalgia: Diagnosing
fibromyalgia. ). Patients meeting some, but not all, criteria may still have fibromyalgia. Chronic fatigueHal. | 12
syndrome (see Syndromes of Uncertain Origin: Chronic Fatigue Syndrome) can cause similar generalized
myalgias. Polymyalgia rheumatica (see Vasculitis: Polymyalgia Rheumatica (PMR)) can cause generalized
myalgias, particularly in older adults but tends to affect proximal muscles selectively and produce a high
ESR.

09.Acute Infectious Arthritis

Acute infectious arthritis is a joint infection that evolves over hours or days. The infection resides in
synovial or periarticular tissues and is usually bacterial—in younger adults, typically Neisseria
gonorrhoeae. However, nongonococcal bacterial infections can also occur and can rapidly destroy joint
structures. Symptoms include rapid onset of pain, effusion, and restriction of both active and passive
range of motion, usually within a single joint. Diagnosis requires synovial fluid analysis and culture.
Treatment is IV antibiotics and drainage of pus from joints

Diagnosis

Infectious arthritis is suspected in patients with acute monarticular arthritis and in patients with other
combinations of symptoms characteristic of particular infectious arthritis syndromes (eg, migratory
polyarthritis, tenosynovitis and skin lesions typical of disseminated gonococcal infection; erythema
migrans or other symptoms and signs of Lyme disease). Even mild joint symptoms should arouse
suspicion in patients with risk factors, such as RA, a prosthetic joint, or an extra-articular infection
capable of spreading to a joint (eg, genital gonococcal infection, bacteremia, any anaerobic infection).

Laboratory Tests

Patients suspected of having acute infectious arthritis should have arthrocentesis with synovial fluid
examination and culture and usually imaging and blood studies.

 Synovial fluid examination is the cornerstone of diagnosis. Fluid is examined grossly and
sent for cell count and differential, Gram stain, aerobic and anaerobic culture, and
crystals.
 Foul-smelling synovial fluid suggests anaerobic infection.
 Fluid from an acutely infected joint usually reveals a WBC count > 20,000/μL (often >
100,000/μL) consisting of > 95% PMNs. WBC counts tend to be higher in nongonococcal
bacterial than in gonococcal infectious arthritis. WBC counts may also be lower in early
or partially treated infections.
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 Gram stain reveals organisms in 50 to 75% of joints with acute bacterial arthritis, most
often with staphylococci. If positive, Gram stain can be virtually diagnostic, but cultures
are definitive.
 The presence of crystals does not exclude infectious arthritis. Sometimes synovial fluid
analysis cannot differentiate between infectious and other inflammatory synovial fluid. If
differentiation is impossible by clinical means or synovial fluid, infectious arthritis is Hal. | 13
assumed, pending culture results.
 Plain x-rays of the involved joint are not diagnostic but can exclude other conditions
(eg, fractures, chondrocalcinosis). Abnormalities in early acute bacterial arthritis are
limited to soft-tissue swelling and signs of synovial effusions. After 10 to 14 days of
untreated bacterial infection, destructive changes of joint space narrowing (reflecting
cartilage destruction) and erosions or foci of subchondral osteomyelitis may appear. Gas
visible within the joints suggests infection with Escherichia coli or anaerobes.
 MRI is considered if the joint is not easily accessible for examination and aspiration (eg,
an axial joint). MRI or ultrasound can identify sites of effusion or abscess that can be
aspirated or drained for both diagnosis and therapy. MRI can provide early suggestion of
associated osteomyelitis. Bone scans using technetium-99m can be falsely negative in
infectious arthritis. Also, because they show increased uptake with increased blood flow
in inflamed synovial membranes and in metabolically active bone, they can be falsely
positive in noninfectious inflammatory arthritis.
 Blood cultures, CBC, and ESR (or C-reactive protein) are usually obtained. However,
normal results do not exclude infection.
 If gonococcal arthritis is suspected, blood and synovial fluid samples should be
immediately plated on nonselective chocolate agar, and specimens from the urethra,
endocervix, rectum, and pharynx on selective Thayer Martin medium. Genital chlamydial
cultures are also obtained. Blood cultures are positive in 60 to 75% of cases during the
first week and may be the only method by which to identify the organism; cultures from
joints with early tenosynovitis or arthritis are often negative. Synovial fluid cultures from
joints with frank purulent arthritis are usually positive, and fluid from skin lesions may
be positive. If disseminated gonococcal infection is suspected based on clinical criteria, it
is assumed to be present even if all gonococcal cultures are negative.

10.Chronic Infectious Arthritis

Chronic infectious arthritis develops over weeks and is usually caused by mycobacteria, fungi, or bacteria
with low pathogenicity

Laboratory tests

 Patients should have fungal and mycobacterial cultures of synovial fluid or synovial
tissue, as well as routine studies.
 Plain x-ray findings may differ from acute infectious arthritis in that joint space is
preserved longer, and marginal erosions and bony sclerosis may occur.
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Mycobacterial and fungal joint infections require prolonged treatment, usually with multiple antibiotics,
depending on sensitivity testing results.

11.Osteomyelitis
Hal. | 14

Osteomyelitis is inflammation and destruction of bone caused by bacteria, mycobacteria, or fungi.

Common symptoms are localized bone pain and tenderness with constitutional symptoms (in acute
osteomyelitis) or without constitutional symptoms (in chronic osteomyelitis). Diagnosis is by radiography
and cultures. Treatment is with antibiotics and sometimes surgery.

Diagnosis

Acute osteomyelitis is suspected in patients with localized peripheral bone pain, fever, and
malaise; or localized refractory vertebral pain. Chronic osteomyelitis is suspected in patients
with persistent localized bone pain, particularly if they have risk factors.

Laboratory tests

If osteomyelitis is suspected, CBC and ESR or C-reactive protein, as well as plain x-rays of the
affected bone, are obtained.

 The WBC count may not be elevated, but the ESR and C-reactive protein usually are.
X-rays become abnormal after 2 to 4 wk, showing periosteal elevation, bone destruction,
soft-tissue swelling, and, in the vertebrae, loss of vertebral body height or narrowing of
the adjacent infected intervertebral disk space and destruction of the end plates above
and below the disk.

If x-rays are equivocal or symptoms are acute, CT or MRI can define abnormalities and reveal
abscesses (eg, paravertebral abscesses). Alternatively, a radioisotope bone scan can be
performed. It is abnormal earlier than plain x-rays but does not distinguish among infection,
fractures, and tumors.

 Bacteriologic diagnosis is necessary for optimal therapy of osteomyelitis; bone biopsy

with a needle or surgical excision and aspiration or debridement of abscesses provides
tissue for culture and antibiotic sensitivity testing.
 Culture of sinus drainage does not necessarily reveal the bone pathogen

12.Polymyositis and Dermatomyositis

Polymyositis and dermatomyositis are uncommon systemic rheumatic diseases characterized by
inflammatory and degenerative changes in the muscles (polymyositis) and in the skin and muscles
Ruland Pakasi & Co

(dermatomyositis). The most specific skin sign is a heliotropic rash. Manifestations include symmetric
weakness, some tenderness, and later atrophy, principally of the proximal limb girdle muscles.
Complications can include visceral involvement and malignancy. Diagnosis is by clinical findings and
abnormalities on muscle tests, which may include muscle enzymes, MRI, electromyography, and muscle
biopsy. Treatment is with corticosteroids, sometimes combined with immunosuppressants or IV
Hal. | 15
immunoglobulin.

Diagnosis

Polymyositis should be suspected in patients with proximal muscle weakness with or without muscle
tenderness. Dermatomyositis should be suspected in patients with a heliotropic rash or Gottron's
papules and in patients with symptoms of polymyositis and any skin findings compatible with
dermatomyositis. Polymyositis and dermatomyositis share certain clinical findings with systemic sclerosis
or, less frequently, with SLE or vasculitis. Establishing the diagnosis requires as many as possible of the
following 5 criteria: (1) proximal muscle weakness; (2) characteristic skin rash; (3) elevated serum muscle
enzymes (CK, or if this is not elevated, aminotransferases or aldolase); (4) characteristic
electromyographic or MRI abnormalities; and (5) muscle biopsy changes (the definitive test).

Muscle biopsy excludes some similar conditions such as inclusion body myositis and postviral
rhabdomyolysis. Biopsy findings can be variable, but chronic inflammation and muscle degeneration and
regeneration are typical. A definitive (usually tissue) diagnosis is needed to justify potentially toxic
treatments. By identifying regions of muscle edema and inflammation, MRI can help select a biopsy site.

Laboratory tests

Laboratory studies can increase or decrease suspicion for the disorder, assess its severity, identify
overlaps, and help detect complications.

 Antinuclear antibodies are positive in a few patients, most often those with another
connective tissue disorder. About 60% of patients have antibodies to thymic nuclear
antigen (PM-1) or whole thymus and Jo-1. The relationship between these
autoantibodies and disease pathogenesis remains unclear, although antibody to Jo-1 is a
significant marker for fibrosing alveolitis, pulmonary fibrosis, arthritis, and Raynaud's
phenomenon.
 Periodic measurement of CK is helpful in monitoring treatment. However, in patients
with widespread muscle atrophy, levels are occasionally normal despite chronic, active
myositis. Muscle biopsy, MRI, or high CK levels can often differentiate a relapse of
polymyositis from corticosteroid-induced myopathy.

Because patients often have unsuspected malignancies, some authorities recommend screening any
adult who has dermatomyositis or those ≥ 60 who have polymyositis with the following: physical
examination that includes breast, pelvis, and rectum (with occult blood testing); CBC; biochemical
profile; mammogram; carcinoembryonic antigen; urinalysis; and chest x-ray. Younger patients without
symptoms of malignancy need not undergo screening.
Ruland Pakasi & Co

13. Relapsing Polychondritis

Relapsing polychondritis is an episodic, inflammatory, and destructive disorder involving primarily
cartilage of the ear and nose but also potentially affecting the eyes, tracheobronchial tree, heart valves,
kidneys, joints, skin, and blood vessels. Diagnosis is clinical. Treatment requires prednisone and
sometimes immunosuppressants. Relapsing polychondritis is an episodic, inflammatory, and destructive
Hal. | 16
disorder involving primarily cartilage of the ear and nose but also potentially affecting the eyes,
tracheobronchial tree, heart valves, kidneys, joints, skin, and blood vessels. Diagnosis is clinical.
Treatment requires prednisone and sometimes immunosuppressants .

Diagnosis

Diagnosis is established if the patient develops at least 3 of the following: bilateral chondritis of the
external ears, inflammatory polyarthritis, nasal chondritis, ocular inflammation, respiratory tract
chondritis, or auditory or vestibular dysfunction. Biopsy of involved cartilage is helpful if clinical diagnosis
is not clear-cut.

Laboratory tests

Laboratory tests are not necessary but may help decrease the likelihood of other disorders. Synovial fluid
is usually mildly inflammatory, if at all.

 Blood tests may show normocytic-normochromic anemia, leukocytosis, elevated ESR or

γ-globulin levels, and occasionally positive rheumatoid factor, antinuclear antibodies
(ANA), or in up to 25%, antineutrophil cytoplasmic antibodies (ANCA).
 Abnormal renal function may indicate an associated vasculitis. A positive c-ANCA test
(ANCA that are reactive mainly to proteinase-3) suggests Wegener's granulomatosis,
which can cause similar findings

14. Osteoporosis
Osteoporosis is a progressive metabolic bone disease that decreases bone density (bone mass per unit
volume), with deterioration of bone structure. Skeletal weakness leads to fractures with minor or
inapparent trauma, particularly in the thoracic and lumbar spine, wrist, and hip. Acute or chronic back
pain is common. Diagnosis is by dual-energy x-ray absorptiometry. Prevention and treatment involve Ca
and vitamin D supplements, exercises to maximize bone and muscle strength and minimize the risk of
falls, and drug therapy to preserve bone mass or stimulate new bone formation.

Screening and Diagnosis

Dual-energy x-ray absorptiometry (DEXA) screening is recommended for all women > 65. Bone density
should also be measured in women between 50 and 65 who have risk factors, including a family history
of osteoporosis, a history of fragility fractures, and low body weight. Screening is also recommended for
both men and women who have had fragility fractures, even at younger ages.
Ruland Pakasi & Co

Osteoporosis should be suspected in patients who sustain fractures after only mild or trivial trauma;
older adults, particularly those with risk factors and unexplained back pain; patients with decreased
bone density that is incidentally noted on radiographic studies; and patients at risk of secondary
osteoporosis. If radiographic studies have been obtained or are necessary to evaluate symptoms (eg,
back pain), osteoporosis may be obvious. However, radiographic studies are often equivocal, and the
Hal. | 17
diagnosis should be established by DEXA.

Plain x- rays: Bones show decreased radiodensity and loss of trabecular structure, but not until about
30% of bone has been lost. A loss of horizontally oriented trabeculae increases the prominence of the
cortical end plates and of vertically oriented, weight-bearing trabeculae. Loss of height and increased
biconcavity characterize vertebral compression fractures. Thoracic vertebral fractures may produce
anterior wedging. In long bones, although the cortices may be thin, the periosteal surface remains
smooth. Vertebral fractures at T4 or above suggest malignancy rather than osteoporosis.

Corticosteroid-induced osteoporosis is likely to produce rib fractures and exuberant callus formation at
sites of healing fractures. Osteomalacia may produce x-ray and DEXA abnormalities similar to those of
osteoporosis . Hyperparathyroidism can be differentiated when it produces subperiosteal resorption or
cystic bone lesions, but these are uncommon.

Other testing: Once osteoporosis is diagnosed, patients should be checked for causes of secondary
osteoporosis. Serum Ca should be measured to rule out asymptomatic hyperparathyroidism. PTH levels
may be increased in type II patients with decreased Ca absorption or hypercalciuria. Other tests such as
thyroid-stimulating hormone or free thyroxine to check for hyperthyroidism, vitamin D levels,
measurements of urinary free cortisol, and blood counts and other tests to rule out malignancy,
especially myeloma (eg, serum protein electrophoresis), should be considered depending on the clinical
presentation. Serum alkaline phosphatase is usually normal but may be elevated by recent fracture.

Patients with weight loss should be screened for GI disorders as well as malignancy. Bone biopsy is
reserved for unusual cases (eg, young patients with pathologic fractures and no apparent cause). Levels
of serum or urine N-telopeptide crosslinks (NTX) or free deoxypyridinoline (DPYR) may reflect increased
breakdown of collagen. These tests are not sufficiently accurate for routine clinical use but may be used
to assess the effectiveness of therapy.

MICROSCOPIC EXAMINATION FOR CRYSTALS IN SYNOVIAL FLUID

PRINCIPLE:

A preparation of clinical material is used to facilitate the observation of uric acid crystals and/or
other crystals.

MATERIAL NEEDED:

 Clean glass slide and cover slip.

Ruland Pakasi & Co

 Polarized light
 Red compensator (if available).

PROCEDURE:
Hal. | 18
1. Place a drop of synovial fluid on a clean glass slide. Apply cover slip to make a thin
mount.
2. The wet prep should be examined immediately to demonstrate intracellular crystals.
3. Scan microscopically under low power with reduced light looking for cells. When cells
found, switch to polarized light. Adjust the light flow accordingly. Look for intracellular
and extracellular crystals.
4. Identification of urate and/or calcium pyrophosphate dehydrate requires the addition of a
first class-order red compensator. Insert the compensator between the polarizer and the
analyzer.

INTERPRETATION:

The types of crystals that may be seen in synovial fluid include: monosodium urate, calcium
pyrophosphate dehydrate, cholesterol, steroid, and apatite.

The presence of monosodium urate crystals is usually diagnostic of gout. The crystals may be
intracellular, extracellular, or both. They are needle-like with pointed ends and measure 1-30 μl
in length. The presence of intracellular crystals indicates the acute stage of gout.

Monosodium urate crystals grow in elongated prisms that have a negative optical sign of
birefringence, which generates a yellow (subtraction) interference color when the long axis of the
crystal is oriented parallel to the slow axis of the first order retardation plate (Figure 6(a)).
Rotating the crystals through 90 degrees changes the interference color to blue (addition color;
Figure 6(b)).

Calcium pyrophosphate dehydrate (CPPD) crystals is associated with pseudo-gout and

chondrocalcinosis. These crystals are most commonly seen in synovial fluid samples from
patients with degenerative arthritis but may also be seen in hereditary forms of pseudogout, in
arthritides associated with metabolic diseases, such as hyper-parathyroidism, hypothyroidism,
Ruland Pakasi & Co

diabetes mellitus, and hemochromatosis, and occasionally together with monosodium urate
crystals in gout.

In contrast to Monosodium urate crystals, pseudo-gout pyrophosphate crystals, which have

similar elongated growth characteristics, exhibit a blue interference color (Figure 6(c)) when
oriented parallel to the slow axis of the retardation plate and a yellow color (Figure 6(d)) when Hal. | 19
perpendicular. The sign of birefringence can be employed to differentiate between gout crystals
and those consisting of pyrophosphate.

Cholesterol crystals appear as strongly birefringent plates, often with notched margins. They
may occasionally have the appearance of needles or rhomboids.

Other birefringent materials:

Fragments of cartilage may also appear birefringent under polarized light but have irregular
margins.

Dirt from unclean glassware, and talcum crystals, talcum crystal has a Maltese-cross appearance.
Ruland Pakasi & Co

Lyme Disease

Medical Author: William C. Shiel Jr., MD, FACP, FACR Lyme Disease
Medical Author: William C. Shiel Jr., MD, FACP, FACR
Hal. | 20
What is Lyme disease?

Lyme disease is a bacterial illness caused by a bacterium called a "spirochete." In the United States, the
actual name of the bacterium is Borrelia burgdorferi. In Europe, another bacterium, Borrelia afzelii, also
causes Lyme disease. Certain ticks found on deer harbor the bacterium in their stomachs. Lyme disease
is spread by these ticks when they bite the skin permitting the bacterium to infect the body. Lyme disease
can cause abnormalities in the skin, joints, heart and nervous system.
Interestingly, the disease only became apparent in 1975 when mothers of a group of children who lived
near each other in Lyme, Connecticut made researchers aware that their children all were diagnosed with
rheumatoid arthritis. This unusual grouping of illness that appeared "rheumatoid" eventually led
researchers to the identification of the bacterial cause of the children's condition, what was then called
"Lyme disease" in 1982. The number of cases of the disease in an area depends on the amount of ticks in
an area and how often the ticks are infected with the bacteria. In certain areas of New York, where Lyme
disease is common, over half of the ticks are infected. Lyme disease has been reported most often in the
Northeastern United States, but has been reported in all 50 states as well as China, Europe, Japan,
Australia and the parts of the former Soviet Union. In the United States, it is primarily contracted in the
Northeast from the state of Maine to Maryland, in the Midwest in Minnesota and Wisconsin, and in the
West in Oregon and Northern California.
What is Lyme disease?

Lyme disease is a bacterial illness caused by a bacterium called a "spirochete." In the United States, the
actual name of the bacterium is Borrelia burgdorferi. In Europe, another bacterium, Borrelia afzelii, also
causes Lyme disease. Certain ticks found on deer harbor the bacterium in their stomachs. Lyme disease
is spread by these ticks when they bite the skin permitting the bacterium to infect the body. Lyme disease
can cause abnormalities in the skin, joints, heart and nervous system.
Interestingly, the disease only became apparent in 1975 when mothers of a group of children who lived
near each other in Lyme, Connecticut made researchers aware that their children all were diagnosed with
rheumatoid arthritis. This unusual grouping of illness that appeared "rheumatoid" eventually led
researchers to the identification of the bacterial cause of the children's condition, what was then called
"Lyme disease" in 1982. The number of cases of the disease in an area depends on the amount of ticks in
an area and how often the ticks are infected with the bacteria. In certain areas of New York, where Lyme
disease is common, over half of the ticks are infected. Lyme disease has been reported most often in the
Northeastern United States, but has been reported in all 50 states as well as China, Europe, Japan,
Australia and the parts of the former Soviet Union. In the United States, it is primarily contracted in the
Northeast from the state of Maine to Maryland, in the Midwest in Minnesota and Wisconsin, and in the
West in Oregon and Northern California.