1. GOUT
By: Sunit tolia, PGY III

2. Gout Affects > 5 million people in the United States alone
MCC of inflammatory arthritis in men.
Is caused by monosodium urate (MSU) crystals formed in joints and tissues when serum urate levels exceed 6.8 mg/dL.
Gout usually occurs only after many years of hyperuricemia. It is not currently recommended to treat asymptomatic hyperuricemia to prevent the disease.
Needle-shaped, Negatively birefringent crystals on polarized microscopy.

3. Risk Factors Hyperuricemia (MOST IMPORTANT RF)
Medications (i.e. thiazides or cyclosporine)
Male sex if younger than 60 years
Renal insufficiency
Obesity
Lead exposure
Diet high in purines (i.e. red meat, shellfish)
Organ transplantation
Specific diseases increase the risk for gout (i.e. HTN, DM, HLD, metabolic syndrome, hematologic malignant conditions)
Consumption of alcohol (i.e. beer and spirits) and high fructose drinks (i.e. sodas, some juices)
Genetic risk factors
Common diseases that increase risk for gout include diabetes, the metabolic syndrome, hyperlipidemia, hypothyroidism, and hypertension.

4. Symptoms Episodic self-limited joint pain, swelling, and erythema
Recent trauma which may have triggered the pain
Attacks often begin in the middle of the night or early morning.

5. Physical Examination Joint involved may be: Warm Swollen Red
Severe joint pain is common complaint
Joints that are usually involved are either previously diseased joints or more distal joints (i.e. midfoot, first metatarsophalangeal joint, ankle, or knee)
First attacks are monoarticular and chronic gout can present w/ involvement of various joints.

6. DDX of Gout RA Calcium Pyrophosphate Deposition Disease (Pseudogout)
Septic Arthritis
Cellulitis
Reactive Arthritis
Fracture / Trauma OA
Psoriatic Arthritis
Sarcoidosis

7. DDX of Gout Pseudogout Septic Arthritis RA Cellulitis
Reactive Arthritis
Fracture / Trauma OA
Psoriatic Arthritis
Sarcoidosis

8. Pseudogout Chondrocalcinosis (calcium deposits in cartilage)
Parameter
Pseudogout
Risk factors
Hypothyroidism
Hemochromatosis
Renal osteodystrophy
Hyperparathyroidism and/or recent parathyroidectomy
Wilson's disease
Affected joints
Knee (most common)
Wrist
Hip
Synovial fluid
Positively birefringent crystals, linear or rhomboidal
Calcium pyrophosphate crystals
50, ,000/mm3 WBC
Chondrocalcinosis (calcium deposits in cartilage)
Dx of CPPD is suggested radiographically by
showing chondrocalcinosis and/or synovial fluid showing positively birefringent crystals under polarized light microscopy.

9. Septic Arthritis Fever, arthritis, great tenderness.
Joint sepsis most commonly occurs in previously abnormal joints.
Radiography generally shows swelling and effusion.
If not treated promptly it causes diffuse joint-space narrowing and joint destruction.
Diagnosis is usually suggested by synovial fluid showing elevated leukocytes (50, ,000 cells/µL), positive Gram stain, and positive fluid culture.
However, synovial fluid Gram stain can be negative in 20-30% of septic arthritis cases, especially with gram-negative bacteria.
Blood cultures are positive in 50% of patients and must always be obtained prior to antibiotic therapy.
Treatment consists of IV antibiotics and joint drainage. This patient should be monitored clinically and started on IV antibiotics until culture results return.

10. What tests can diagnose gout?
Serum urate level
CBC with differential (if considering septic arthritis)
Serum creatinine
Examination of synovial fluid or tophus aspirate
Radiography (to rule out other causes)

11. What are the components of the synovial fluid…
Gross appearance: (clarity, color, viscosity)
Microscopic examination:
WBC and differential
Crystals
Gram stain
Culture
Synovial fluid tubes:  From left to right,
 normal
noninflammatory (e.g., osteoarthritis)
inflammatory (e.g., rheumatoid arthritis)
septic (e.g., gonococcal septic arthritis)
hemorrhage (e.g., trauma, hemophilia A)

12. Joint Fluid Characteristic…

13. CRYSTALS…
Gout crystals (left) and pseudogout crystals (right) under the microscope. Urate crystals have sharp, needle-like ends, while CPPD crystals are shaped more like rods or rhombuses.

14. Treatment of Gout

15. Xanthine Oxidase Inhibitors
Tx for Gout
Acute Tx
NSAIDS
Colchicine
Corticosteroids
Oral
Intra-articular
Corticotropin
Chronic Tx
Xanthine Oxidase Inhibitors
Uricase
Rasburicase
Pegloticase
Uricosuric

16. Treatment of Acute Gout
Will usually last about 1 week w/o any medical intervention.
NSAIDS
usually the first-line therapy because of combined analgesic and anti-inflammatory effects. Two to 10 days of NSAIDS is usually enough to treat a gout attack.
Ibuprofen and naproxen seem to be as effective as indomethacin but better tolerated.
To hasten the antiinflammatory action, start the NSAID at a higher dose and taper over about 1 week.
Gastrointestinal toxicity from NSAIDs is an important concern.
PPIs can reduce NSAID ulcers by more than 50%

17. Treatment of Acute Gout
Colchicine:
a mainstay treatment of acute gout
Oral colchicine treatment is most effective when initiated 12 to 36 hours after the start of an acute gouty attack
Doses should be reduced for renal or hepatic dysfunction.
It should be avoided in elderly persons, and should not be administered with other strong CYP3A4 inhibitors.
Regularly check CBC, CK, AST/ALT in patient w/ CKD on colchicine on any dose.
Avoided in patient who are on hemodialysis as this drug is not removed by dialysis or by exchange transfusion.

18. Treatment of Acute Gout
Corticosteroids
are the preferred treatment for acute gout in patients with renal insufficiency or other contraindications to NSAIDs
Use w/ caution in patient w/ hyperglycemia or CHF. May be used in moderate-to-severe renal impairment.
Prednisone 40mg q day until a day after the acute attack resolves and then taper over another 7-10days.
Intra-articular steroid injections:
Useful in tx of acute gout if limited to single joint or bursa.
One needs to confirm that the joint is not infected.

19. In Summary: Tx for Acute Gout
Treatment
Indications
Contraindications
Side Effects
NSAIDs
First-line therapy
Peptic ulcer disease CKD Heart failure
GI bleeding
Acute kidney injury
Sodium retention, edema
Colchicine
NSAID intolerance
CKD
Diarrhea, abdominal cramps
Neuromyopathy
Steroids Intra-articular:
1-2 inflamed joints
NSAID/colchicine contraindication
Drug hypersensitivity
No major systemic side effects
Steriods Systemic:
>2 joints involved
Risk of rebound attacks
Elevated blood pressure
Elevated blood sugar
Fluid retention

20. When do you recommend treatment for hyperuricemia…
At least 2 or 3 acute attacks of gout
Tophaceous gout
Severe attacks or polyarticular attacks
Radiographic evidence of joint damage from gout
Identifiable inborn metabolic deficiency causing hyperuricemia
Nephrolithiasis

21. Treatment for Chronic Gout
Uricosurics
Is warrented for underexcretion of uric acid (if they excrete less than mg/d while on low-purine diet).
Probenecid is the only uricosuric durg available in the US.
Contraindicated in patient with nephrolithiasis and a CrCl <30mL/min.

22. Treatment for Chronic Gout …
Xanthine Oxidase Inhibitors…
Avoid if the patient is on azathioprine or 6-mercaptopurine because these drug metabolized by xanthine oxidase.
Allopurinol:
Can be used in patient w/ urea overproduction or underexcretion.
Monitor LFTs, CMP, CBC, and uric acid level before and after starting tx.
Reduce the dose of allopurinol in patients with renal insufficiency
Adverse Effect: rash
Febuxostat
For those who have CI or an inadequate response to allopurinol or uricosuric therapy.
Does not require dose adjustment for mild-to-moderate renal impairment. But limited data on the use of this drug if the CrCl<30mL/min
When starting these medications the acute episode of gout should be resolved.

23. Start low, go slow to avoid a flare…
In patient w/ normal kidney function the FDA recommend slow upward titration of allopurinol , starting at mg/day anddose is increased by increments of 100mg/day at intervals of 1 week until the serum urate level is lower than 6mg/dL.
Concurrent colchicine prophylaxis may help decrease flares.

24. Flare prophylaxis during initiation of urate-lowering therapy…
Colchicine:
Should be combined with allopurinol or probenecid
Dosing is based on renal function
Not to be used in patients with severe renal insufficiency or hepatobiliary dysfunction.
Tx is continued for atleast 6 months after the serum urate level is less than 6 mg/dL or until tophi disappear.

25. How can patients reduce their risk for gout?
Weight Loss
Decrease the intake of high-purine foods such as:
Red meat (beef, pork, lamb)
Meat extracts (broth, gravy)
Organ meats (such as sweetbreads, liver, and kidney)
Seafood (shrimp, anchovies, mussels, scallops, sardines, herring, fish roe, canned tuna, shrimp, and lobster)
Yeast products (beer and baked goods)
Reduce the intake of high fructose foods & drinks
Reduce the alcohol intake
Avoid medications like:
Thiazide
Low – to – moderate levels of aspirin
Pyrazinadmine, Ethambutol, Pyrazinoate.
Cyclosporine.
Staying hydrated

26. When to consult a Rheumatologist?
Joint sepsis
Poorly controlled gout
Gout along w/ other forms of arthritis

27. QUESTIONS…