Introduction to Clinical Medicine

(ICM)
Diseases of the Musculoskeletal System
and Joints

Prepared by:
Robert W. Wilhoite M.D.
Edited by Patrice Thibodeau, M.D.
 Case # 1
• A 38 year old woman has noted progressive morning
stiffness (now lasts for >2hrs) and pain in both hands
and her R knee over the past two years. This pain
had initially responded to aspirin and ibuprofen but
she now describes a lessening effect of these drugs.
• Physical exam shows her PIP and MCP joints and R
knee to be warm and swollen. She also has some
nodular lesions around her elbows.
• An x-ray of her hands was obtained and a biopsy
of the skin lesion was performed.
 Problem List
• Progressive morning stiffness and pain (>2
hrs)
• Stiffness and Pain in PIP and MCP joints
of hands and R knee.
• Warm and swollen PIP, MCP and R knee
joints (signs of arthritis)
• Nodular lesions around the elbows
Characteristics of pt’s arthritis?
• Joint pattern
– Inflammatory (vs noninflammatory)
– Symmetric (except knee) (vs asymmetric)
– Number of joints involved
• Polyarthritis >5 joints involved
• Types of joints involved
– Small joints with one large joint
• Presence of extraarticular manifestations: skin
nodules
 General signs of Inflammation
• Joint swelling
• Morning stiffness
• Joint pain better with movement;
Tenderness when the joint is “squeezed”
• Mild redness over the joint
• Warmth of the joint
• Limited movement of the joint
• Fatigue and low grade fever
 Differential Dx for
inflammatory arthritis?
• Rheumatoid arthritis
• SLE
• Psoriatic arthritis
• Gout
• Septic arthritis
• Lyme Disease
• Not Osteoarthritis – not inflammatory
What is your differential dx for
the symmetric polyarthritis?
• Rheumatoid Arthritis
• SLE
• Symmetric Psoriatic Polyarthritis
• Osteoarthritis (symmetric hand involvement
but asymmetric for larger joints like knees)

• Give evidence for and against each of the above

diagnoses on this and last slide (see next slide)
• Rheumatoid arthritis
What is Ddx?
– Symmetric and inflammatory
– Involves >3 sm joints; small joints then
progresses to large joints; MCP>PIP>
wrist>knee (not DIP)
• SLE
– Symmetric and inflammatory
– Usually involves small joints but can
involve large joints;
PIP>MCP>wrist>knee
• Psoriatic arthritis
– Inflammatory and usually asymmetrical •
– Multiple patterns of presentation*: distal
arthritis, symmetric polyarthritis, axial
disease, enthesitis, dactylitis; skin and
nail dz
• Gout
– Inflammatory monoarthropathy
– First MTP most common (podagra)
• Pseudogout
– Inflammatory monoarthropathy
• Septic arthritis
– Inflammatory, infectious
monoarthropathy
• Lyme disease
– Inflammatory, infectious monoarthritis
Osteoarthritis
– Symmetric/asymmetric and
noninflammatory
– Hands, knees, hips > shoulders and
ankles (DIPs are affected)

Onycholysis (early nail

separation), swelling
and erythema of index
and pinky DIPs
 What are your top
differentials?
• Rheumatoid arthritis
• SLE
RA vs SLE
 Thought Question
• What do you expect to see on the plain
film?
Hand Plain Film
 Common Xray findings in this
disease
• PIP joint narrowing
• Periarticular osteopenia and erosions at the
MCP joints
• Bone loss is primarily juxta-articular.
Describe the histologic changes
seen in the synovial biopsy.
• Synovial lining shows villous-like and frond-like
folds that fill the joint space
– Villous proliferation of the synovial membrane
– Hyperplasia of synovial lining with multi-nucleated
giant cells
• Leukocytic infiltration with lymphoid nodules
• Perivascular inflammatory changes with fibrinoid
necrosis
• Formation of a pannus which causes erosion of the
articular cartilage
What do you think the elbow
nodules are? Are they tender?
 Thoughts Questions
• What is the Rheumatoid factor?
– An IgM autoantibody directed against the Fc portion of
IgG.
• Activated CD4 lymphocyte helper B cells produce the IgM
antibodies
• Is it specific for rheumatoid arthritis?
– No! Also can be positive in SLE and Sjogrens, etc
• Which antibody is specific for rheumatoid
arthritis?
– Anti-cyclic citrullinated peptide antibodies (Anti-CCP
antibody); 95% specificity
 2010 RA Criteria
A) Swollen and tender joints – can start
asymmetrically
B) Serology (RF and anti-CCP antibodies)
C) Acute phase reactants (CRP, ESR)
D) Duration of joint sxs ( > 6 weeks)

• See Table 13 in handout and note below.

 What are the extra-articular
manifestations of RA (see pics next)
• Constitutional : fatigue, wt loss
• Derm: rheumatoid nodules, leg ulcers (seen in Felty’s
syndrome), rheumatoid vasculitis
• Eyes: episcleritis, scleritis, keratoconjunctivitis sicca
• Heme: anemia of chronic disease, thrombocytosis,
pancytopenia and splenomegaly (Felty’s syndrome)
• CV: Premature CAD, heart failure, pericarditis
• Lung: exudative pleural effusions, interstitial fibrosis,
pulmonary nodules, BOOP, bronchiectasis
• GI: dry mouth
• Renal: secondary amyloidosis
• Neuro: C1-C2 subluxation
Derm Manifestations
Eye findings
Lung Findings
Associated Syndromes:

+ neutropenia
Caplan’s Syndrome
 Treatment
• Begin with nonbiologic DMARD monotherapy-usually
start with methotrexate (MTX) if patient not pregnant.
• F/U every 2-3 months to assess if goals are being met (ie
reduce dz activity initially then remission eventually).
Also look for evidence of drug toxicity.
• Add another nonbiologic DMARD if MTX is not enough.
• If no better, add or switch to anti-TNF biologics
– Adalinmumab, certolizumab pegol, etanercept,
infliximab, golimumab
• Can also try non-TNF biologics
– Abatacept, rituximab or tocilizumab
 Case # 1

Final diagnosis

Rheumatoid arthritis
 Case # 2
• This 36 year old woman consults her doctor
because of worsening pain in her joints for
the last several months. Pain is located in
the joints of the fingers and wrists. She also
has felt feverish off and on along with
malaise.
• More recently she gives a history of pain in
her chest with deep inspiration.
• There is a past history of hypertension with
recent commencement of a new drug which
she can not recall the name of.
 Problem List
• Worsening pain in fingers and wrists
• Occasional fevers
• Pleurisy
• Hx of HTN with starting of new drug
 Thought questions
• What do you think is going on? And why?
• What is your differential diagnosis at this
point?
 Differential Dx?
• Idiopathic SLE
• Drug induced SLE
• Rheumatoid arthritis
• Mixed connective tissue disease
• Fibromyalgia
• Sjogren’s syndrome
• Systemic sclerosis
 Thought questions
• What do you make of the pain with
inspiration? What do you call this?
• What other information would you like
from the history/PE?
 More Hx and PE information
• Hand joints involved are PIPs>MCPs.
• Symmetrical involvement of joints is noted.
• There is mild swelling and warmth over the
involved joints.
• Patient was started on Hydrochlorothiazide
2 months ago for new onset hypertension.
• Skin exam is noted on next page
Skin Exam
 Updated Problem List
• Symmetric pain, swelling, and warmth in
PIPs > MCPs
• Pleurisy
• Occasional fevers
• History of hypertension with recent
commencement of HCTZ.
• Butterfly rash on the face
Refine your differential diagnosis
(will discuss in detail below)
• Idiopathic SLE
• Drug induced SLE
• Rheumatoid arthritis
• Mixed connective tissue disease
• Fibromyalgia
• Sjogren’s syndrome
• Systemic sclerosis
What are the various criteria used in
making a diagnosis of SLE?

– Malar rash – Renal disease protein >

– Discoid rash
– Photosensitivity
– Oral ulcers (painless)
– Arthritis, symmetrical
– Serositis
0.5 gm/24h; cellular casts
– Neurologic do
– Hematologic do
– Immunologic do
– ANA

Need 4 or more of 11 criteria to make a diagnosis

Differential Dx
Discussion
Drug-Induced Lupus Erythematosus
DILE
• Certain drugs may trigger an autoimmune response,
which may result in a clinical syndrome with features
similar to systemic (idiopathic) lupus, but there are some
differences in clinical and immunologic features and in
the frequency of such features.

• Drugs associated with the highest risk of inducing lupus

are procainamide, hydralazine and penicillamine.

• Minocycline, isoniazid, diltiazem and anti-TNF drugs as

well as many others are other causative agents, but at lower
frequency.
 Systemic Manifestations of
DILE
• Patients with drug-induced lupus can develop a
variety of systemic manifestations.
• The most common include fever, malaise,
myalgias, arthralgias, arthritis, and serositis.
• The frequency of these manifestations may vary
with the drug.
• Hematologic abnormalities, kidney disease and
central nervous system involvement are
uncommon, although they may occur.
Idiopathic vs Drug
Induced Lupus (DILE)
 Idiopathic vs Drug-Induced
Lupus
• Features more suggestive of idiopathic SLE,
and less common in drug-induced lupus,
include
– renal, neurologic, cutaneous, and severe
hematologic involvement.
• Antihistone antibodies may be seen in
both idiopathic and drug-induced lupus.
 Risk Factors for
Drug-Induced Lupus
• Multiple risk factors may be involved for a given agent.
• Risk factors for hydralazine-induced lupus
– drug dose (especially doses greater than 200 mg/day and/or a
cumulative dose of more than 100 g)
– female sex
– slow hepatic acetylation*
– and immunogenetic factors (i.e. HLA-DR4 genotype)
• Risk factors for procainamide–induced lupus
– Slow acetylators – genetically determined effect on drug metabolism
– HLA-DR6Y but not DR4 or DR3
 FYI
• There are several ways in which drugs may
potentially influence lupus
– they might exacerbate underlying idiopathic lupus
– or induce idiopathic lupus in a predisposed patient
– or cause the separate syndrome of drug-induced
lupus (DILE)
 Diagnosis of Drug-Induced
Lupus
• No definitive tests or criteria for the diagnosis of drug-induced lupus
• However, the diagnosis of drug-induced lupus is highly likely if there is:
– a history of taking one or more of the drugs known to be associated with this
condition for at least one month, and often much longer
– development of at least one clinical feature characteristic of SLE but the
diagnosis of drug-induced lupus does not require usual number of
manifestations as for idiopathic SLE
– a positive test for antinuclear antibodies (ANA) and anti-histone antibodies
(Note: Anti-dsDNA antibodies are not found in most forms of drug-induced lupus.)
– spontaneous resolution of the clinical manifestations of the disease, typically
within several weeks but sometimes up to several months after the offending
drug has been discontinued. The ANA often persist for a greater duration than
the symptoms and physical findings, and in some patients autoantibodies may
persist for a year or longer.
 Treatment of Drug-Induced
Lupus
• The initial step in treatment is to stop the
offending medication.
• Specific manifestations should then be
treated temporarily until they resolve using
the same approaches used in patients with
idiopathic systemic lupus erythematosus
(SLE).
 Treatment of Drug-Induced
Lupus
• Treat arthralgia, arthritis, and serositis initially
with nonsteroidal anti-inflammatory drugs
(NSAIDs)
• Cutaneous eruptions are treated with topical
therapies, including topical corticosteroids.
• Medications that are effective in idiopathic SLE
are also effective in patients with drug-induced
illness if patient needs further relief
– Glucocorticoids, Hydroxychloroquine
 Prognosis of Drug-Induced
Lupus
• Generally quite favorable in most cases,
with disease typically resolving after drug
withdrawal, even though treatment may be
needed for up to several months in some
patients
• Occasional patients require glucocorticoid
therapy, but life-threatening disease is
infrequent
 Rheumatoid Arthritis
RA vs Idiopathic SLE
• Early RA may be difficult to distinguish from the arthritis
of SLE since both conditions cause joint tenderness and
swelling (see table on next slide for comparisons).

• Features such as swan neck deformities, ulnar deviation,

and soft tissue laxity, which are observed in later stages of
RA in patients with more destructive disease, can also be
seen in some patients with SLE.

• However, important distinguishing features are that the

joint deformities in SLE are often reducible, and
infrequently erosive on plain radiographs.
RA vs SLE
Swan Neck Deformities in Lupus
 Rheumatoid Arthritis
RA vs Idiopathic SLE
• Some extraarticular RA manifestations, including serositis,
sicca symptoms, subcutaneous nodules, anemia, and
fatigue, are features that may also be observed in SLE.
These features are more common in RA patients with more
severe or advanced disease.

• Serologic abnormalities such as the presence of anti-cyclic

citrullinated peptides (CCP) are more supportive of the
diagnosis of RA, and can help distinguish the diseases.

• It should be recognized that the antinuclear antibodies

(ANA) may be positive in up to one-half of patients with
RA. Conversely, rheumatoid factor (RF) may be present
in approximately one-third of SLE patients.
Mixed connective tissue disease
MCTD vs Idiopathic SLE
• MCTD is characterized by overlapping features of SLE,
systemic sclerosis (SSc), and polymyositis (PM).

• High titers of antibodies against U1 ribonucleoprotein

(RNP) is seen with MCTD.

• The diagnosis of MCTD is often complicated since many

of its characteristic features occur sequentially, often over a
period of years.

• Some patients with MCTD may evolve into another

connective tissue disease, including SLE, during the
clinical course.
Fibromyalgia vs Idiopathic SLE
• Patients with SLE may present with generalized
arthralgias, myalgias, and fatigue, much like patients
with fibromyalgia.

• Other characteristic features of SLE such as a

photosensitive rash, arthritis, and multisystem organ
involvement are absent in patients with fibromyalgia.

• However, fibromyalgia occurs more commonly in patients

with systemic rheumatic diseases than in the general
population; thus, patients with SLE may have
concomitant fibromyalgia.
 Systemic sclerosis
SSc vs Idiopathic SLE
• The coexistence of Raynaud phenomenon and gastroesophageal reflux is
typically observed in Ssc but may be seen in patients with SLE or healthy
individuals.

• Sclerodactyly, telangiectasias, calcinosis, and malignant hypertension

with acute renal failure are more consistent with SSc rather than SLE.
 Systemic sclerosis
SSc vs Idiopathic SLE
• Further, a positive ANA is present in most patients with SSc, while other
serologies such as anti-double-stranded DNA (dsDNA) and anti-Smith
(Sm) antibodies which are more specific for SLE, are not commonly
observed in SSc.

• Patients with SSc commonly express antibodies to an antigen called Scl-70

(topoisomerase I) or antibodies to centromere proteins.

• Distinguishing SSc from SLE can be particularly difficult in cases where

there is overlap of these diseases, such as in MCTD.
 Sjögren’s syndrome
vs Idiopathic SLE
• Patients with Sjögren’s syndrome may have extraglandular
manifestations that can be observed in SLE, such as
neurologic, MSK, and pulmonary abnormalities.
• The arthropathy in Sjogren’s is usually symmetric,
intermittent, nonerosive on plain radiographs, and
nondeforming. The hands, wrists, and knees are preferentially
affected.
• Patients with Sjögren’s syndrome should have objective signs of
keratoconjunctivitis sicca and xerostomia, and characteristic
findings on salivary gland biopsy which are not typical of SLE.
• Also, patients with Sjögren’s syndrome commonly express
antibodies to Ro and La antigens.
• Back to our patient……
 Case # 2
• This 36 year old woman consults her doctor
because of worsening pain in her joints for
the last several months. Pain is located in
the joints of the fingers and wrists. She also
has felt feverish off and on along with
malaise.
• More recently she gives a history of pain in
her chest with deep inspiration.
• There is a past history of hypertension with
recent commencement of a new drug.
 Problem List
• Symmetric pain in small joints
• Pleurisy
• History of Hypertension with
commencement of HCTZ.
• Butterfly rash on the face
 Initial Lab testing
• Hgb 9.0 (L)
• WBC 2,300 (L)
• Platelet count 100,000 (L)
• Sed rate 53 (H)
• Urinalysis RBC’s, 3+ protein
• Urine Microscopy: Red blood cell casts

• Summarize labs in medical terms

What are the various hematologic
manifestatons of SLE?
– Hemolytic anemia
– Thrombocytopenia
– Lymphopenia
– Leukopenia
 Thoughts Questions
• What additional tests would you order?
– Antibody profile to include…. what?
• Is a positive ANA specific for any
diagnosis?
– No! can be elevated in the following:
• SLE, systemic sclerosis, RA, Sjogrens, drug induced
lupus, MCTD
 Antibody profile
• Idiopathic SLE
– ANA – 95 % sensitive but poor specificity
– Anti Sm (25 % of patients are positive)-specific for SLE
– Anti double stranded DNA – specific for SLE
• Drug induced Lupus
– Antihistone – 95% sensitivity
• Rheumatoid Arthritis
– Anti-CCP – 95% specificity
• MCTD
– anti-U1-RNP
• Systemic sclerosis-DcSSc (diffuse cutaneous systemic sclerosis)
– Anti-Sc1-70 (40 % of patients are positive)
• Sjogren’s
– Anti-Ro / SSA; anti-La / SSB (70% sensitivity)
Summary of Diagnostic Evaluation
of patient with possible SLE
• CBC
• CMP
• UA
• Antibody tests
– ANA, dsDNA, Anti-Sm, Anti-RNP, Anto-
Ro/SSA, Anti-La/SSB, antihistone antibody (if
suspect drug-induced lupus)
 Case # 2

Final diagnosis:

Idiopathic SLE
Joint pain and systemic disorders
Can you guess the disorder?
• Butterfly rash (malar) on cheeks • Red, burning, itching eyes
• Scaly plagues, especially on (conjunctivitis), eye pain and
extensor surfaces and pitted nails blurred vision (uveitis)
• Heliotrope rash on upper eyelid
• Scleritis
• Papules, pustules, vesicles with
reddened bases on the distal ext • Oral ulcerations
• Expanding erythematous “target” • Pneumonitis; interstitial lung
or “bulls eye” patch early in an disease
illness
• Diarrhea, abdominal pain,
• Painful subcutaneous nodules
cramping
especially in pretibial area
• Palpable purpura • Urethritis
• Hives • Mental status change, facial or
• Erosions or scaling of the penis and other weakness, stiff neck
crusted scaling papules on the soles
and palms
• Nailfold capillary changes
 Case # 3
• This 58 year old woman presents with progressive R knee
stiffness which has been periodic in nature but now has
become more prominent. Stiffness is now happening daily,
but lasts less than 30 minutes. She has gained 30 pounds
over the past year. Knee pain is worse with activity and
better with rest. Knee stiffness is made worse by rest and
improves with activity. More recently these symptoms
tend to limit the range of motion of her knee. She denies
any trauma.
• PE reveals knee swelling and deformity of the medial
compartment, but no erythema or warmth.
• X-ray of her knee is illustrated in upcoming slide.
 Problem List
• R knee stiffness worse with rest, better with
activity lasting less than 30 min
• R knee pain worse with activity, better with
rest
• 30 pound weight gain
• Limited knee ROM
• Noninflammatory knee swelling and
deformity
Joint space marrowing
 Thought Questions
• What is the pattern of joint involvement?
• Number of joints involved?
• Inflammatory or non-inflammatory?
• Symmetrical or asymmetrical?
 Differential Dx for
monoarticular involvement?
– Osteoarthritis
– Gout
– Pseudogout
– Trauma related

• DDx for noninflammatory arthritis?

– OA, Trauma, Avascular necrosis,
Hemochromatosis

• What is your final diagnosis and why?

– Osteoarthritis
 Osteoarthritis
• Primary or idiopathic type
– Evident around age of 55
– A wear and tear arthritis – degenerative joint disease
• Secondary type
– Indicates joint degeneration in the setting of preexisting
joint abnormality
• Due to trauma or congenital abnormalities (hip dysplasia)
• May follow inflammatory arthritis such as: RA, Gout, CPPD
• Associated with avascular necrosis, infectious arthritis etc
• Due to metabolic or systemic diseases (ochronosis,
hemochromatosis, Ehlers-Danlos syndrome)
 Osteoarthritis
• A degenerative noninflammatory disease
• Most common form of arthritis
• Characterized by loss of articular cartilage, and reactive bony
changes (osteophytes, subchondral bony sclerosis,
subchondral cysts)
• No systemic manifestations
• Asymmetric involvement with localization to only a few
joints . Hands are usually symmetrical and bilateral, though.
• Most commonly affects weight bearing joints (knees, hips,
spine). Also affects the hands, especially the 1st
carpometacarpal joint. Less commonly affects shoulder
elbow, wrist, ankle.
• Pain worsens with activity, relieved by rest; stiffness worse
with rest and better with activity
• Morning stiffness less than 30 min
 Physical Exam
• Joints are tender when put thru ROM
• Joint effusions may be present, but usually no warmth or
erythema and actually may be cool to touch.
• Joint abnormality: bony enlargement or change in
alignment
– i.e. Knock kneed or bow legged –misalignment
• First carpometacarpal joint; DIPs and PIPs of hands;
knees, hips, spine are most commonly affected
• Heberden’s nodes (DIP) Bouchard’s nodes (PIP)
• MCP’s relatively spared
• Joint line tenderness and crepitus is felt on palpation of
knee; reduced ROM.
 X ray
• Joint space narrowing (articular cartilage
loss)
• Subchondral sclerosis (increased bone
density subjacent to joint space narrowing)
• Osteophyte formation
• Degenerative changes to the 1st
carpometacarpal joint
OA clinical manifestations
summary slide
 Joint Mice
Due to small fractures with dislodged pieces
of cartilage into joint space
Femoral Neck Fracture Osteoarthritis
 Management
• Nonpharmacologic
– Exercise program, PT, nutritional counseling (for wt
loss), appropriate footwear, splint, canes and walkers
• Pharmacologic
– No disease modifying drugs available, so treat
symptoms of pain and stiffness
– Glucosamine chondroitin –may work
– Start with acetaminophen < 4gm/day
– Next try NSAIDs (oral and topical forms)
– Consider tramadol (less addictive the narcs)
– Duloxetine (Cymbalta) for chronic MSK pain
 Management
If previous measures fail:
• Intra-articular injections
– Used when single joint involved
– Glucocorticoid
– Hyaluronic acid injections
• Surgical
– For knee and hip: total joint arthroplasty
 Case # 3

Final diagnosis

Osteoarthritis
 Case # 4
• A 56 year old male executive presents
complaining of severe right toe pain. Pain is sharp.
Started overnight awakening him from sleep. Even
the bed sheet on his toe caused intense pain.
Tylenol did not help. Denies trauma to the toe.
Spends most of his time behind his desk or wining
and dining his clients at restaurants.
• PMHx: GERD, HTN, Calcium Kidney stones
• Meds: omeprazole and HCTZ
• SH: drinks 3-4 beers a day
• On PE patient is afebrile and in discomfort
from the toe pain. The first MTP joint on the
right is swollen, tender, and warm. No
lesions or ulcers are seen.
• Labs: WBC 14,000(H), HCT 44, Plts 400
ESR 70 (H), Uric acid 10 (H)
• Xray was obtained and was normal
• Joint aspiration done
 Problem List
• Acute right toe pain with swelling and
warmth
• Patient with HTN on thiazides
• History of calcium kidney stones
• Elevated WBC, uric acid level and ESR
 Thought questions
• What is your working diagnosis?
• How are thiazides affecting this patient?
– Ie how is it affecting new symptom of toe pain?
– Ie how is it affecting him with regards to hx of
calcium kidney stones?
 Arthrocentesis results
Synovial fluid analysis
– Yellow fluid
– WBC: 26,000 with neutrophil predominance
– Gram stain negative
– Culture negative
– Polarized light evaluation was done.
 Differential Dx?
• Gout
• Pseudogout
• Cellulitis of surrounding skin
• Septic arthritis
• Trauma
• Bunion
 What are the causes of
hyperuricemia ?
• Primary renal uric acid under excretion
• Chronic kidney disease (secondary uric acid under
excretion)
• Excessive uric acid production due to primary defect
in purine metabolism.
• Conditions with high cell turnover (lympho- and
myeloproliferative disorders(leukemia/lymphoma)
• Drug induced (thiazides, loop diuretics, etc)
• Diet induced (high purines-alcohol, shell fish, red
meat)
 Gout’s Clinical Spectrum
1. Asymptomatic hyperuricemia
2. Acute gouty arthritis
– Classic presentation is podagra- like our patient had
– First gout attacks are typically monoarticular and
begin at night.
– Recurrent attacks can occur in any joint and can occur
in mono or poly-articular presentation
– Systemic inflammation is common (fever, peripheral
leukocytosis, elevated inflammatory markers)
– Adjacent soft tissues can become red, painful and
edematous and may mimic cellulitis
 Gout’s Clinical Spectrum
3. Intercritical gout – asymptomatic intervals
between attacks
4. Chronic tophaceous gout
– Frequent flares with eventual gouty arthropathy in
which synovitis persists between acute attacks
– Usually the consequence of undertreatment, med
noncompliance or ineffective therapy
– Tophi (stone like deposits of monosodium urate
surrounded by a fibrous and inflammatory rind) may
form in joints and soft tissues. Tophi lead to bone
erosion, chronic joint damage, skin ulceration,
infection, disability and impaired quality of life.
Gouty Tophus
Gouty Arthritis
Destruction of 1 st MTP by tophi
 Complications of Gout
• Tophi:
– Chalky, cheesy, yellow white pasty deposits of
mono-sodium urate crystals
• Renal colic
– deposition of uric acid stones
• Chronic renal failure
– common cause of death (20 %)
• Hypertension
How would you treat the patient?
• Acute treatment of gout flare
– Colchicine or NSAIDs (ie Indomethicin) or glucocorticoids (po or
intraarticular)
• Continue colchicine or NSAID for 1-2 days after symptoms have resolved; typical
duration is 5-7 days of colchicine or NSAID therapy.
• Can give patient refill and tell patient to take the colchicine in the future within first
48 hours (preferably, first 24 hours) of symptoms. If recurs too often will need urate
lowering med)
– Ice
• Urate lowering therapy
– Life style modifications (weight loss; decrease intake of shell fish, red
meats, foods containing high fructose (soda and processed foods),
ETOH (esp beer); increase low-fat dairy products
– Switch thiazides to CaCh B, or losartan -both can lower serum urate
– Urate lowering therapy med ie allopurinol
 Pseudogout
(Acute calcium pyrophosphate crystal arthritis)
• Calcium pyrophosphate crystal deposition
• Present a lot like acute gout –painful
inflammatory arthritis
• However, the knees, wrist, shoulders are more
often affected. Podagra is uncommon
• Occurs most commonly in patients > 65 yo
• Polarized light: positively birefringent
rhomboid shaped crystals.
 Pseudogout
(Acute calcium pyrophosphate crystal arthritis)

• If occurs in the young, should look for associated

– Hyperparathyroidism, hemochromatosis, hypothyroidism,
hypomagnesemia
• Treatment
– Local treatment
• Joint aspiration
• Intra-articular glucocorticoid injection
• Ice packs
• Joint immobilization
– Systemic
• NSAIDs, colchicine, oral or parental glucocorticoids
• If recurrent attackslow dose colchicine or daily NSAIDS (with GI
protection)
 Case # 4

Final diagnosis

Gouty arthritis
 Case # 5
• This 70 year old post-menopausal woman
with steroid dependent COPD presents with
acute onset of back pain.
• On PE she was found to have tenderness on
percussion of her upper low back.
• An x-ray of her spine was taken.
What do you see?
 Case # 5
• This 70 year old women was diagnosed
with an L1 compression fracture.
• The following laboratory studies were
obtained with corresponding results:
– Serum calcium, phosphorous, alkaline
phosphatase and PTH are all normal.
 Problem List
• Post-menopausal female
• Steroid dependent COPD
• L 1 Compression fracture
• Calcium, phosphorous, Alk Phos and PTH
are normal
 Differential Dx of bone pain and
fracture?
– Osteoporosis (quantity of bone)
• Primary cause : Hormone deficiency ( lack of estrogen)
• Secondary causes
– Exogenous glucocorticoid use Drug induced (prednisone)
– Hyperparathyroidism
– Thyrotoxicosis
– Cushing’s syndrome (cortisol excess)
– Immobilization
– Anorexia nervosa
– Rheumatoid arthritis
– Hyperprolactinemia
– Multiple Myeloma
– Vit D Deficiency

– Osteomalacia (quality of the bone)

• softening of the bone
• most common cause is Vit D def
– Malignancy, Paget’s disease
What additional tests would
you order?
• 25 OH vitamin D level
• Bone density/Bone densitometry (DEXA)
 WHO definition
DEXA scan
• Osteoporosis - spinal or hip bone mineral density
(BMD) that is 2.5 standard deviations or more
below the mean bone mineral density for healthy,
young women, measured by dual energy x-ray
absorptiometry (DEXA). ( The T score is less
than -2.5.)
• Osteopenia - a spinal or hip bone mineral density
between 1 and 2.5 standard deviations below the
mean for healthy, young women. (The T score is
–1 to -2.5)
Which is the osteoporotic hip?
Osteoporosis
 Vertebra

Normal Bone Osteoporotic bone

 Osteoporosis
• Peak bone mass – 30 years of age
• Average loss 0.7 %/ year
 Microscopic view of
Osteoporosis
• Porous bone and reduced bone mass 
predisposing to fracture
• Increased osteoclastic activity
• Loss of bone but normal mineralization
• Trabeculae thinner & more widely spread out
with Haversian canal widening
• Micro-fractures and bony collapse
• Subperisoteal and endosteal resorption
Normal bone just less of it
 Treatment for Osteoporosis
• Lifestyle recommendations
– Balanced diet with adequate calcium and Vit D
– Regular weight-bearing and muscle strengthening
exercises
– Smoking cessation
• 1st line medication treatment
– Bisphosphonates (alendronate, ibandronate, Risedronate etc)
• inhibit bone resorption via actions on osteoclasts or on
osteoclast precursors; decreases the rate of bone resorption,
leading to an indirect increase in bone mineral density.
• Other medication treatment options
– Parathyroid hormone (teriparatide) 20 mcg SQ
– Estrogen receptor modulators (ie raloxifene)
– Denosumab (Prolia)
 Case # 5

Final diagnosis

Osteoporosis
 Case # 6
• An 18 year old man complains of severe pain in
his right knee that began a few days ago and has
worsened to the point where he is in unable to
weight bear. He is the captain of the local high
school soccer team and is sexually active.
• Patient tried ibuprofen 600mg, but that only took
the edge off the pain.
• Physical exam reveals a swollen knee which is
warm to the touch. There is limited extension and
flexion due to the pain and swelling.
 Thought Questions
• What else do you want to know?
• What are you thinking?
• What do you want to do next?
 Imaging
• A magnification of the x-ray of the femur reveals
destruction of the cortical bone as well as an
adjacent soft tissue mass. (sunburst pattern)
 Biopsy / Resection
• A resection was performed and the microscopic
slide is representative of the lesion.
 New bone formation

Malignant spindle cells

 Problem List
• Sexually active 18 year old athlete with pain
and swelling in the right knee
• X-ray – cortical bone destruction with
sunburst pattern
What is your diagnosis?
 Osteosarcoma
• Most common primary malignant bone tumor
• Most arise in the first two decades of life
• Male>female
• More than half occur around the knee
• First clinical manifestation is often pain as the
tumor breaks through the bone cortex and lifts
off the periosteum, forming an angle with the
cortex called codman’s triangle
• Associated with retinoblastoma-often
patient will have hx of RB before diagnosis
with osteosarcoma.
 Case # 6
Final diagnosis

Osteogenic sarcoma
 Case # 7
• This 58 year old white woman has noted pain in several
bones of her body including pelvis, spine and skull. Only
recently has she developed severe pain in her left hip and
an x-ray revealed a “chalk stick” fracture of her femur.
• Laboratory studies revealed an elevated alkaline
phosphatase level.
• A skeletal survey was done and a biopsy was performed.
• The following x-ray is of her femur and the following
slide of the bone biopsy is representative of her lesion.
Chalk stick fracture
Bone Biopsy
 Problem List
• Multiple areas of bone pain
• Elevated alkaline phosphatase level
• Chalk stick femur fracture on Xray
• Mosaic pattern of lamellar bone on biopsy
What are you thinking?
 Differential Diagnosis?
• Paget’s disease of bone
• Osteomalacia
• Multiple osteoporotic fractures
• Metastatic bone disease
• Osteogenic sarcoma
Transverse fx
Spiral bone fx
 Define Paget’s disease
• A chronic disease of bone characterized by
excessive osteoclastic destruction and
resorption of bone, followed by the
unregulated disorganized osteoblastic
formation of new bone leading to bony
deformity,. (Matrix madness!)
• Leads to bone pain and pathologic fractures
• Commonly involves spine, pelvis, skull,
femur and tibia
 What are the clinical manifestations of
Paget’s disease of bone?
• Many are asymptomatic and only get discovered based
on high alk phos or incidental finding on Xray
• Bone pain due to fracture or lytic activity
• Fracture of vertebrae or long bones
• Bony deformity – skull enlargement
• High output failure - due to hypervascularity of
pagetoid bone there is increased blood flow (AV shunt)
and high output failure
 Stages of progression
• “Hot” or osteoclastic bone resorption stage
• Mixed osteoblastic and osteoclastic stage in
which there is seen thickening of the cortex due to
new bone formation
• “Cold” or burnt out stage (quiescent phase)

• Net result is an increased bone mass with disordered and

architecturally unsound bone
 Other Complications?
• leontiasis ossea (Lion Face Syndrome) – over
growth of cranial-facial skeleton

• platybasia - invagination of base of skull with

compression of posterior fossa structures
• osteogenic sarcoma or giant cell tumor
 Comments
• The osteoclast is
the pathologic cell
seen in Paget’s
disease and
contrary to normal
osteoclasts,
Pagetoid
osteooclasts will
contain multiple
nuclei (up to 100)
 Case # 7

Final diagnosis

Paget’s disease of bone

(Osteogenesis deformans)
 OSCE
• No index cards needed
• Timing (25 minute doctor; 10 min presenter); No
feedback given
• Will have clipboard and blank sheets of paper available
• Can not write anything on the blank sheets (except vitals
and patient name) until get into the room.
• Presenter should leave paperwork with attending in the
room
• Remember recapping will help you AND your partner
• Please do not share information with others
• No SOAP notes will be written that day