Case 3 - Acute L Ankle
COMPLAINT
56 yr. old white woman
complains of new onset left
ankle pain and swelling for 6
days.
Case 3 - Acute L Ankle
HISTORY
Complains of difficulty walking and warmth
over the ankle.
Self-treated with rest, elevation and taking "6
aspirins daily".
Denies trauma, fever, or prior episodes joint
swelling.
Past history: NIDDM, coronary artery disease,
and CHF.
Medications: Digoxin, furosemide, KCL,
glyburide and aspirin.
Case 3 - Acute L Ankle
EXAMINATION
All joints were normal, except the left
ankle.
Left ankle - moderate warmth,
erythema, tenderness and swelling
present.
Case 3 - Acute L Ankle
INVESTIGATIONS
Glucose = 244 mg/dl
Creatinine = 2.4 mg/dl
Uric acid = 6.7 mg/dl
WBC = 13,000/mm3
ESR = 88 mm/hr.
Case 3 - Acute L Ankle
What diagnostic test(s) are warranted?
Joint aspiration
Radiographs of ankles and feet
MR image of the lumbosacral spine
Rheumatoid factor
Repeat serum uric acid
None of the above
Case 3 - Acute L Ankle
ADDITIONAL
INVESTIGATIONS
Synovial Fluid Analysis
Amount aspirated:
10 ml
Appearance:
Cloudy, yellow
WBC count:
34,000 cells/mm3 (89%
PMNs)
Gram stain/Culture: negative
Crystals: negatively birefringent MSU crystals
Gout
Disorder of urate metabolism, results in
deposition of monosodium urate (MSU) crystals
in joints and soft tissues.
1st described 5th century BC – Hippocrates
described gout as “the king of diseases and the
disease of kings”
Burden: In 1981, 37 million lost work days in US*
2003 Kim et al estimates the annual cost of Acute
Gout is $27,378,494 in the USA (underestimate:
women excluded & not all indirect and intangible
costs included)
* Roubenoff et al
Gout
Primary gout: from purine metabolism
abnormalities (HGPRT defic. or PRPP
synthetase) or from idiopathic decreased renal
excretion of urate.
Secondary gout: neoplasms, Alcohol,
lymphoproliferative disease, chronic renal
failure, psoriasis, or drug therapy (eg, diuretics,
ethanol, cytotoxics).
Most patients are Underexcreters rather than
Overproducers
Gout Epidemiology
Men: onset is 40-50 yrs (most common
inflammatory arthritis in men)
Women: peak onset is post-menopausal
Less than have 15% onset prior to menopause
Prevalence influenced by hormonal, geographic,
racial, genetic, dietary, background conditions:
Males > Females. Estrogen is uricosuric
Populations: Maori, Tokelauan migrants, Filipinos,
Taiwan males, etc (genetics or dietary)
renal transplant (2-13%); HTN (RR 2.7+)
Seasonal:Gout more often in spring (possibly summer)
Is the frequency of gout increasing over time?
Is the Frequency Increasing?
Author
NHIS
Population
Self-report
(prevalence)
Rochester
Arromdee
MN
Wallace
Wortmann
USA
Managed
Care
1st Era
Incidence rate
2nd Era
Incidence rate
1969
5/1000
1996
9.4/1000
1977-78
45/100,000
1995-96
62.3/100,00
1990
2.9/1000
1999
5.2/1000
Testing? Increasing life-span? Insulin resistance? Obesity?
Prevalence of Gout
Age (years)
20-29
Men 3.4 Million
Population %
0.2
Women 1.7 Mill
Population %
0.6
30-39
2.1
0.1
40-49
2.2
0.6
50-59
5.7
2.3
60-69
9.1
3.5
70-79
10.8
4.7
>80
8.6
5.6
•NHANES
III 1988-94
Serum Uric Acid & Incidence of Gout*
Serum Urate
mg/dl
Gout
Incidence/yr/1000
5 year
cummulative
< 7.0
0.8
5
7.0 – 7.9
0.9
6
8.0 – 8.9
4.1
9.8
> 9.0
49 (4.9%)
220 (22%)
*Campion EW et al (1963-87) Am J Med 82:421-26, 1987
NHANES III 1988-94
(5.6%)
•National
(2.7%)
Health Intv Survey (&PE) = 17,030 men/women
Diet and Gout
Low Purine Diet
High Purine Diet
Cereals, bread, pasta
Milk, dairy products, eggs
Sugar, gelatin
Butter, margarine, fats
Fruit, peanut butter
Lettuce, tomato, greens
All Meats, Anchovies
Seafood, herring, sardines
Yeast, beer, alcohol, sweetbreads
Beans, peas, lentils, oatmeal,
spinach, asparagus, cauliflower,
mushrooms
Survey of 47150 males over 12 yrs. (w/ no hx Gout).
Identified 730 new cases of gout
Comparing highest and lowest quintiles: RR
• Meat intake
1.41 (1.07-1.86)
• Seafood intake
1.51 (1.17 – 1.95)
• Dairy products
0.56 (0.42-0.74)
• Purine Vegetables and protein intake were not associated with
increased risk of gout
Choy HK. NEJM 350:1093, 2004
Alcohol and Gout
Choy HK. Lancet 363:1277-81, 2004
Surveys of 47150 males over 12 yrs( w/ no hx Gout)
Identified 730 incident cases
RR
Relative Risk: 10-15 g/d
1.32
15-30 g/d
1.49
30-50g/d
1.96
>50g/d
2.53
Beer
1.49 per 12oz serving
Wine
1.04 per 4 oz serving
Gout Epidemiology
Associations:
Precipitants:
Hypertension
Alcohol
Obesity
Hospitalization (fever,Poly)
Diabetes
Surgery: joint replacement,
Renal insufficiency
carpal tunnel release
Diuretics/congestive heart Drugs: Diuretics, ASA, IV
failure
NTG, PZA, GCSF, CyA
Alcohol consumption
Total parenteral nutrition
Lead exposure
Septic arthritis, reactive
Family history
arthritis, lupus, elderly
Saturnine Gout
Saturnine gout: gout due to chronic lead
intoxication, either from occult or occupational
exposure or the ingestion of moonshine.
This account for <5% of cases and is due to
lead induced tubulointerstitial renal damage.
Saturnine gout should be expected when the
magnitude of hyperuricemia exceeds the
reduction in glomerular filtration.
Gout
Acute: intermittent/recurrent, LE, ascending,
inflammatory mono/oligoarthritis, “Podagra”
Atypical Gout: affects elderly women w/ OA
Intercritical (interval) gout: between attacks
Tophaceous gout: chronic, accumulation of
MSU crystals as “tophi” (may look like RA)
Asymptomatic hyperuricema: elevated uric
acid without evidence of gout, nephrolithiasis.
Higher levels increase risk of these diseases
Renal: nephrolithiasis, gouty nephropathy,
uric acid nephropathy
Acute (Classic) Gout
Precipitants: stress, trauma, excess alcohol, infection,
surgery, drugs
Acute, severe onset of pain, warmth, inflammation,
Limited motion  cant walk, cant put sheet on it.
Podagra (50-90%): pain, swelling warmth in 1st MTP
Joints: MTP, tarsus, ankle, knee
Assoc. w/ fever, leukocytosis, high ESR or CRP
Initially monarthritis (80-90%) and with repeated attacks
ascends from the lower extremity
(initially a polyarthritis: in elderly, women,
myeloproliferative disorders, CyA)
Chronology: untreated attacks last 7-14 days. Acute
gout risk of repeat attack estimated to be 78% w/in 2 yrs
Natural Hx of Acute Attack
Bellamy N, et al. Br J Clin Pharmacol 24:33-6, 1987
11 volunteers with acute podagra studied
2 withdrew on day 4 for severe pain
9 remaining showed improvement
• Pain by day 5
• Swelling by day 7
• Tenderness improved in 7/9 by day 7 (2 persisted)
• But only 3 noted resolution of pain during 7d study
Implications for clinical trial endpoints?
Pain improvement/resolution by day 3-5
Resolution of symptoms, return to normal activity
Comparison of Gout Forms
CLASSIC GOUT
Any age
Mostly Men
Acute onset
Monarthritis
Asymmetric
Lower extremity
Rarely tophi 1st seen
Mis-Dx cellulitis, Septic jt
ATYPICAL GOUT
Elderly patients
Women > Men
Insidious, chronic
Polyarthritis
Symmetric or
asymmetric
Upper and lower extrem.
Tophic common
Mis-Dx: RA, OA, infx
* Adapted from Rott KT, Agudelo CA. JAMA 289:2857, 2003
Gouty Tophi
Incidence has decreased over last few decades
Seen in 25-50% of untreated patients (after 10-20yrs)
Location: Olecranon, bursae, digits, helix of ear
Damages bone, periarticular structures and soft tissues
Palpable measure of total body urate load
Other: Renal manifestations
Uric acid calculi (seen in10-15% of gout pts)
Chronic urate nephropathy (in those with tophi)
Acute uric acid nephropathy (in pts undergoing chemotherapy)
Hypertensive renal disease is the most common cause of renal
disease in gout
Assessment of Gout
Laboratory Findings
Acute gout: 40-49% have normal uric acid levels
>90% will be hyperuricemic during intercritical period
Leukocytosis common
ESR and CRP elevated
No indices of chronic inflammatory disease (alb, Hgb)
Measureable elevations in IL-6 and IL-1
Radiographic findings
Soft tissue swelling (Opacities = tophi)
Normal Joint space and Normal ossification
Erosions: nonarticular, punched out, Sclerotic
margins, overhanging edge
Gout: Xray Changes
•Soft tissue swelling
•Opacities = tophi
•Nl Joint space
•Nl ossification
•Erosions: punched out
Sclerotic margins
Overhanging edge
Treatment
Acute Gout
NSAIDs Contraindicated?
 Renal insufficiency
 Peptic ulcer disease
 Congestive heart failure
 NSAID intolerance
1. NSAIDs
Antiinflamatory
doses
no
yes
Are Corticosteroids
Contraindicated?
no
2.Corticosteroids
yes
# Joints
Involved?
1
3.Oral Colchicine
Intraarticular
PO Steroid
Lipsky PE, Alarcon GS, Bombardier C, Cush JJ,
Ellrodt AG, Gibofsky A, Heudebert G, Kavanaugh
AF, et al. Am J Med 103(6A):49S-85S, 1997
>1
Oral or
Intraarticular
Steroid
NSAIDs in Acute Gout
FDA approval:indomethacin, naproxen, sulindac
Tested: etodolac, flurbiprofen, meclofenamic
acid, indoprofen, carprofen, phenylbutazone,
piroxicam, isoxicam, fentiazac, ketorolac,
etoricoxib
Benefits
Faster onset of relief (compared with colchcine)
• Within 2-4 hours for indomethacin
Less toxic (when prescribed appropriately); better
tolerated
Widespread use and familiarity
Cost
Colchicine Serious Toxicity, Suidice, & Death
Carr AA. Colchicine toxicity. Arch Int Med 115:29, 1965
Ellwood MG, Self poisoning with colchicine. Postgrad Med 47:129, 1971
Baum J, Colchicine use as a suicidal drug by females. J Rheumatol 7:124, 1980
Ferranini E, Marrow aplasia following colchicine in gout. Clin Exp Rheum 2:173,1984
Pasero G. Colchicine: should we still use it? Clin Exp Rheumatol 2:103-4, 1984
Roberts WN. Colchcine in acute gout: reasses risk/benefits. JAMA 257:1920-2, 1987
Wallace SL. Systemic toxicity assoc with the IV colchicine. J Rheum 15:495, 1988
Hoffman RS. Outpatient colchicine poisoning. Del Med J. 65: 257-60, 1993
Lee BI. Colchicine myopathy with cyclosporine. J Korean Med Sci 12:160, 1997
Dawson TM. Colchicine induced rhabdomyolysis. J Rheumatol 24:2045, 1997
Maldonado MA, IV colchicine:retro analysis hosp patient. Clin Exp Rheum 15:487, 1997
Mullins ME. Fatal CVS collapse after acute colchicine. J Toxicol Clin Tox 38:51, 2000
Goldbart A. Fatal colchicine intox in a child. Eur J Pediatr 159:895, 2000
Mullins ME. Troponin I cardiac toxicity w/ colchicine. Am J Emerg Med 18:743, 2000
Sanchez Munoz LA, Acute colchicine poisoning. An Med Intern 17:109, 2000
Dogukan A. Fatal colchicine intoxication w/ CAPD. Clin Nephrol 55:181, 2001
Dixon AJ. Colchicine neutropenia, not overdose. Ann Pharmacother 35:192, 2001
Bonnel RA. Deaths assoc w/ IV colchicine. J Emerg Med 22:385-7, 2002
Jones GR. LC-MS analysis of colchicine fatality. J Anal Toxicol 26:365-9, 2002
Maxwell MJ, Accidental colchicine overdose. Emerg Med J 19:265-7, 2002
Debie K, Colchcine induced rhatbomyolysis in CHF. Acta Cardiol 58: 561, 2003
Phanish MK, Colchicine induced rhabdomyolysis. Am J Med 114 (2) 2/1/03
Asuvdevan AR, Colchicine induced rhabdomyolysis. Am J Med 115 (3) 8/15/03
Deaths associated with IV Colchicine
Since 1990, AERS reports 90 deaths associated
with IV colchicine use (429 allopurinol)
Bonnel RA, et al. J Emerg Med 22:385-7, 2002
20 deaths 1983-2000 (13 AERS, 7 literature)
8F:11M; 17 gout pts (ages 50-91 yrs), 2 FMF(21,31)
All exceed rec. dose (2-4 mg). Range 5.5-19 mg
Adverse effects: thrombocytopenia (8), leukopenia (8),
pancytopenia (3), agranulocytosis (2), aplastic anemia
(2), acute renal failure (6), and DIC (4)
Death within 1-40 days; 80% showed BM depression
13 risk factors: age > 65 yrs, preexisting medical cond,
concomitant NSAIDs, recent oral colchicine use
Warnings, precautions, contraindications, dosing NOT
followed or were misinterpreted
Number of
<2
Gouty Attacks per Year
>2
yes
Treatment
of Interval
Gout
Can pt. Stop Alcohol,
Diuretics, Weight Loss?
no
Hx of nephrolithiasis?
yes
Tophi present?
Serum urate > 11?
Serum Creat > 2.0?
Uric acid >650mg/24h?
Lipsky PE, Alarcon GS, Bombardier C, Cush JJ,
Ellrodt AG, Gibofsky A, Heudebert G, Kavanaugh
AF, et al. Am J Med 103(6A):49S-85S, 1997
no
Uricosuric
(Probenecid)
Colchicine during
initiation
Observe
Educate
Rx Acute
Attack
yes
Allopurinol
Therapy
(colchicine during
Initiation)
Gout: management
Acute Rx: NSAIDs > steroids > colchicine (oral only)
Steroids: PO, IM, intraarticular
> 2-3 attacks/year > prophyllaxis?
Chronic Rx:colchicine,probenecid,allopurinol
Probenecid: uricosuric, promotes excretion
Don’t use with CRI, nephrolithiasis or Tophaceous gout
Colchicine: (diarrhea) decr. PMN motility
Allopurinol: decrease formation- use w/ CRF, renal
stones, Tophaceous gout, Uric acid > 11
*
* Adjust dose for renal insufficiency
Gout Review
Demographics: males and postmenopausal
females. Incidence rises when uric acid >9.0
Clinical: exquisite tenderness, red, warm, fever,
attacks last 7-14 days
Labs: High WBC, ESR, uric acid may be normal
in 40% of acute attacks.
Renal function? 24 hr. uric acid excretion
Dx: Hx Plus synovial fluid (inflammatory)
crystals (negatively birefringent) or ^uric acid or
Xray proof.
Differential Dx: septic arthritis, pseudogout,
Reiters
55 yr. old “dude” with
Oligoarthritis
Acute onset (3 wks) of Oligoarthritis: knee and ankle
Inflammatory Sxs? fever, 1 hr AM stiffness
PMHx: EtOH abuse
Exam: T=100.2F, Swollen/warm Left knee and
ankle. 2+ L knee effusion.
Differential Diagnosis?
Tests?
Procedures?
55 yr. old “dude” with
Oligoarthritis
Acute onset (3 wks) of Oligoarthritis: knee and ankle
Inflammatory Sxs? fever, 1 hr AM stiffness
PMHx: EtOH abuse
Exam: T=100.2F, Swollen/warm Left knee and ankle.
2+ L knee effusion.
ESR=112, Uric acid=7.5, negative RF & ANA
XRAY L Knee: STS, Ca++ of Menisci, -erosion
Procedures?
RED FLAG
CONDITIONS
FRACTURE
SEPTIC ARTHRITIS
GOUT/PSEUDOGOUT
CALCIUM PYROPHOSPHATE CRYSTAL
DEPOSITION DISEASE (CPPD)
Synonyms: Pseudogout, chondrocalcinosis,
pyrophosphate arthropathy
Chondrocalcinosis: calcification of articular
cartilage.
Chronic CPPD: damage associated with intraarticular deposition of CPPD crystals.
Pseudogout: acute synovitis with intra-articular
CPPD crystal deposition. Pseudogout is the most
common form of CPPD.
CALCIUM PYROPHOSPHATE CRYSTAL
DEPOSITION DISEASE (CPPD)
OA and aging.
hyperparathyroidism
hypophosphatasia
hypomagnesemia
hypothyroidism
hypocalciuric
hypercalcemia
hemochromatosis
hemosiderosis
CPPD - Dx & Rx
Pseudogout: self-limited acute monarticular attacks w/
swelling lasting from 1 day to 4 weeks . Knee>wrist >
shoulder >ankle. Fever may occur
Chronic CPPD: women. symmetric polyarthritis affecting
the knees or hands
Chondrocalcinosis:usually incidental radiographic finding.
Labs: normal uric acid, high ESR & + WBC
Diagnostic Tests: Synovial fluid inflammatory w/
intracellular crystals, weakly positive birefringence.
Rx: NSAIDs
Intraarticular steroids
Colchicine prophyllaxis
Synovial Fluid Analysis
Visual inspection (color, clarity, hemorrhagic)
Viscosity
- incr w/ normal (noninflam) SF (long “string sign”)
- decreased with inflammatory SF (loss of string sign)
Place in tubes: EDTA (purple)-cell count.;
Na heparin (green)-Crystals
Cell Count and Differential
noninflammatory: WBC < 2000/mm3 (PMNs < 75%)
inflammatory: WBC = 2000 - 75,000/mm3 (PMNs >
75%)
septic: WBC > 60,000/mm3 (PMNs >80%)
• GC may have WBC from 30K - 75K
Synovial Fluid Analysis
Analyze SF immediately by “wet prep”
• If cannot, refrigerate @ 4oC.
• Delay will lower WBC counts and increase
artifacts
• MSU crystals will persist for days/weeks. CPPD
crystals will decrease over time (days/weeks)
Do not do protein or glucose - no predictive value
No value to SF urate, RF, ANA, LE cells, complement, LDH
Gram stain, c/s, Tbc, fungal, cryptococcal Ag as indicated
Use Thayer-Martin media if gonococcal infx is suspected
Low Yield Tap
Visually inspect, assess viscosity, perform SF
culture, do “wet prep” to assess the # and type of cell
Indications for Arthrocentesis and Joint
Injection
Monarthritis
(acute/chronic)
Suspected infection or
crystal-induced arthritis
New monarthritis in old
polyarthritis
Joint effusion and
trauma
Intrarticular therapy
Arthrography
Uncertain diagnosis
Osteoarthritis with pain
RA - focal pain/swelling
Acute gouty attack
Acute bursitis (r/o
septic)
Tendinitis
Early adhesive
capsulitis
Reflex sympathetic
dystrophy
Contraindications to Corticosteroid Injections
Suspicion of infected joints or bursae
Overlying cellulitis
Neuropathic (Charcot) joints
Referred pain
Known bacteremia
Thrombocytopenia (platelets < 50K)
Coagulopathy - anticoagulant therapy
Uncontrolled diabetes (?)
Lack of response to previous injection
Prosthetic joints
Inaccessible joints (SI, hip, etc)
Synovial Fluid Analysis
Type I
Type II
Type III
Type IV
Noninflamatory
Inflammatory
Septic
Hemorrhagic
Appearance
Straw
Yellow
Purulent
Bloody
Clarity
Clear
Cloudy
Opaque
Opaque
Normal
Decreased
Decreased
Variable
Cell #
200 –2000
2000-75,000
> 60,000
RBC > WBC
PMN%
< 25%
> 60%
> 80%
OA, Trauma,
AVN, SLE
RA, Gout, viral
Reiters, Tbc
Bacterial
Crystal
Viscosity
Examples
Trauma, FX,
Hemophilia,
PVS
Leave needle in place, change
syringes
Knee Joint Injection
A Moran – Cush Video Exclusive
“I’ve seen the needle and the
damage done...”
- Neil Young “Harvest” 1972
Complications
Allergic reactions: iodine, lidocaine adhesives
Vasovagal episodes
Local ecchymosis
Corticosteroid crystal-induced synovitis
Depigmentation of overlying skin
Subcutaneous atrophy at injection site
Rare: skin/joint infection, hemarthrosis,
calcification or rupture of periarticular structures