GOUT, Diet, and Insulin Resistance Syndrome

Crystal Arthopathy
Case studies in GOUT, CPPD, Diet, and
other Management strategies
Pearls you might not have previously known
David Regule MD
Rheumatologist
Internal Medicine Faculty SEHC
Note No finacial disclosures
Distinguish etiologies of acute
monoarthritis
2. Understand treatment options for acute
treatment and chronic prophylaxis of
crystal arthropathies
3. Educate patients on recent studies and
the revised dietary management
strategies for control of gout
1.
Objectives
Don’t let this happen to
your patient!
Urate crystal arthropathy can cause
erosive damage to joints
This can be prevented with appropriate urate
lowering strategies
First attack Monoarticular Arthritis
History

Traumatic
◦ Noted swells post trauma
 Hemarthrosis (>100,000 RBC)
 Noninflammatory (<2000 wbc)
◦ Nursing home transfer of dementia patient sent in with
swollen knee – consider ordering Xray first

Atraumatic
◦ ―Chronic‖, recurring by end of day swells
Noninflammatory DJD (<2000 WBC)
◦ Inflammatory synovial fluid >5000 WBC
 Crystal Deposition
◦ Gout
◦ Pseudogout CPPD
◦ Basic Calcium crystals
 R/O Septic Arthritis—check for breaks in skin
Recurring Attacks…
Gout vs CPPD?
◦ Gout--Very tender, duration few days
 MASSAGE not tolerated,
ice (not heat) works best
◦ CPPD -- Less tender lasting days/weeks
◦ EARLY Family History suggests early onset gout
◦ Middle age male then likely Gout, cppd usually elderly

ASK WHERE on body previous attacks were:
◦ Early gout 1st MTP
◦ Early CPPD wrists, shoulders
◦ Both crystal diseases affect knees / ankles only
 unusual for RA / SLE to spare hands think crystal if acute
flares of swollen knees/ankles only
◦ Chronic tophaceous Gout (dips and pips)—similar to OA
◦ CPPD can affect wrists/MCPs --similar to RA
Chronic Tophaceous Gout
elderly female >male frequently presents without
preceeding history of acute attacks

Chronic tophaceous gout can present as a
smoldering low grade inflammatory OA mimicker
 DIPs, PIPs chronic daily joint swelling with small tophi which
can be confused with djd changes
◦
◦
◦
◦
tophi more yellow than heberdens nodes
Xrays may show marginal erosions
Low dose steroids help
Consider colchicine trial?

Bouchards Nodes vs Tophi?
Bouchards Nodes? Gouty
Tophus?
XRAYs

Chondrocalcinosis on XRAY only
supportive for CPPD (not diagnostic)
◦ Ulnar side wrist, knees, pubic symphysis

Gout may show erosion (like RA)
◦ Gout in classic distribution severe 1st MTP feet
predominant sparing hands mild dip/pip.
First attack of One hot swollen
joint ATRAUMATIC, then TAP

Tests synovial fluid sent for?
◦ 1. Crystal exam:
 sensitive in gout, less sensitive CPPD
◦ 2. Cell count with Dif
◦ 3. Gram Stain and culture
◦ If subacute/chronic course consider adding
mycobacterium and fungal stains/culture

Intracellular crystals ―swallowed‖ by WBC,
absence of infection, Inflammatory fluid
>5000 WBC, neutrophil predominant
Serum Uric Acid

Generally NOT helpful for diagnosis, but
useful for following treatment
◦ Falsely suppressed during acute flare

Serum Uric Acid Level helpful if >10 or <5

Urine Crystals may also be suggestive
◦ Very high serum uric acid >11 that gouty attacks
likely at some point now or in future
◦ Uric acid in urine or CPPD crystals

―Sandy Naples‖ a not quite so young Italian doctor
with known recurring swollen 1st MTP and ankles 2
times in past year presents with 2 days of warm,
red, tender MTP synovitis.
◦ Today uric acid level 5.5 now
 2 months ago UA level 8
◦ Creatinine 1.4 stable for years
◦ Chronically for years allopurinol 200mg daily
◦ Also Hx or hypertrig and HTN
 81mg ASA, HCTZ, Lopid, Lisinopril


Recommendations to treat acutely?
Recommendations to treat chronically?
ACUTE treatment for either Gout
or Pseudo Gout Attack

Short approx 10 day course
 Steroids systemic (caution uncontrolled BS)
◦ Preferred if multiple joints affected
 IA steroids – avoid if septic arthritis concerns, If
not purulent inject steroids and fu culture
 Oral Nsaids, IV/IM Toradol, high dose
colchicine are adjunctive or abortive options
 ―Steroid allergy‖? Trial cosyntropin stim q6 hrs IV
◦ What if RENAL Patient? Cr. >1.5
 avoid NSAIDs or multiple doses >4 colchicine/day
 Steroids best option for acute treatment
Chronic gout prophylaxis

Indications:

Start uric acid lowering medication like Allopurinol
shortly after acute attack (3-14 days)
◦
◦
◦
◦
Start if >1 attack per year
Evidence of urate nephropathy, uric acid kidney stones
Erosive changes on XRAY in young person
Tophaceous nodules and skin changes
◦ Once chronically on allopurinol don’t stop during
acute attacks

Uric Acid Goal <6 titrate monthly to achieve goal

―Bridge‖ therapy

Identify dietary triggers or provocative medications
◦ calm down for next few months after starting urate
lowering therapy with Low dose steroids, NSAIDs,
colchicine
What medications increase
risk of gout flare or inc UA?

Aggressive Diuresis and dehydration (post
op) puts patient at risk for gout and CPPD flares

Drugs that specifically increase risk for gout
◦ 12.5 mg HCTZ small risk
◦ Low dose ASA (insigificant risk)
 not high dose ASA>500mg/day
◦ Niacin
◦ TB treatment
◦ Renal transplant Cyclosporin/Tacrimulos very high
risk
Crystal negative exam?


Pt s/p hospitalization when diuresis initated for chf.
4 days later onset of swollen knee and wrist

Knee tapped and injected with steroid
 20cc fluid slightly cloudy aspirated

Medrol dose pack results in resolution of both knee
and wrist synovitis

2 weeks later (s/p medrol dose finished) and
continued diuresis now a new swelling in opposite
knee noted

Labs and Prior knee aspiration results:
 10,000 wbc in synovial fluid, no crystals seen, gram
stain/culture negative
 Uric acid 8.0 cr. 0.9
Home medications include low dose aspirin and niacin, lasix
PMhx of ―observed‖ untreated primary hyperparathyroidism


What are the prophylactic treatment options?
CPPD Diagnosis,

Diagnosis is by Aspiration joint fluid
◦ Inflammatory fluid and + intracellular ―box‖ crystal
◦ If noninflammatory joint fluid = ―bystander crystal‖
 Incidentally 1/3 of specimens noted s/p TKA
◦ Frequently these crystals are missed
 patient may be labeled culture negative septic arthritis or
seronegative RA


affects wrists, knees in the elderly
Diagnosis of CPPD in young person screen:
◦ Hemochromatois
◦ Hyperparathyroidism
CPPD treatment

Acute Tx similiar to gout
◦ NSAIDS vs Colchicine unless renal failure then IA
steroid if one joint or systemic steroids if polyarticular

As opposed to GOUT no dietary
recommendations
◦ Avoid dehydration, no need to stop Calcium tabs

Chronic NSAID or low dose colchicine prophylaxis

Methotrexate or chronic low dose prednisone in
more severe refractory cases
Colchicine

―Anti-Inflammatory‖
◦ GI distress, loose stools common
◦ Less common side effects noted in CKD:
 Painless Myopathy like polymyositis
 Aplastic Anemia (noted with IV infusions)

Crystal synovitis or recurrent inflammatory
serositis
◦ can bolus as ‖diagnostic trial treatment‖
◦ must be used in first 48 hours to abort
 Chronic prophylactic Dosing based on renal function:
◦ GFR >60 0.6mg BID
◦ GFR 30-60 0.6mg QD
◦ GFR <30 0.6mg M,W,F or after dialysis

―expensive‖ Colcrys only available formulation now
◦ Colchicine isolated from OTC herb: Autumn crocus

Pt s/p hospitalization when diuresis initated for
chf. Days later develops swollen knee and wrist.
Knee tapped with 20cc fluid with 10,000 WBC no
crystal or infection

Treatment with injection and medrol dose pack
results in resolution of both joint synovitis

2 weeks s/p medrol dose and continued diuresis
swelling in opposite knee noted. UA 8. cr. 0.9 on
low dose aspirin and niacin, lasix, patient also
has hx of primary hyperparathyroidism

All of above are prophylactic treatment options,
except:
◦
◦
◦
◦
◦
1.
2.
3.
4.
5.
chronic nsaid
OTC autumn crocus herbal
Low dose 2.5 to 5mg pred daily
Allopurinol 100mg daily
Methotrexate 7.5mg / week
Xanthine Oxidase inhibitor

Start Allopurinol 100-300mg QD
 If inpatient and recent flare D/C patient on 100mg QD
while tapering steroids
 titrate up to 600 (divided doses not needed)
 If CKD then start at 100mg qd max dose 300

Febuxostat Uloric 40-80mg QD
◦ possibly preferred in CKD with very high UA
Initiate with ―bridge therapy‖
 Titrate to goal <6.0

 In one month Check CMP (liver) and UA, ask about
flaring, side effects such as rash, fevers, adenopathy
 Special care interaction azathioprine (renal trans)
◦ 1-25 dihydroxy Vit D levels increase with UA lowering
Probenecid

Only used if Allopurinol NOT tolerated

Patient Must be Underexcretor of UA
preferred <400/day on 24hr urine
◦ Feboxustat may be better alternative if Allopurinol
NOT tolerated
◦ Most (80-90%) gout patients are underexcretors

Precautions:
◦ Renal Insufficiency
◦ Interaction with Multiple Medications
◦ Hx of URIC ACID kidney stones
 Risk if UA excretion >800/day in urine
URIC acid lowering medications

Losartan – lowers UA 20-25%
◦ Uncertain if beneficial effect mitigated by
concommiant use of allopurinol

Fenofibrate – lower UA 15%
Vitamin C 1000-1500mg / day
 Unsweetend Cherry juice or extract?
 Low Fat milk?
 Coffee?



High doses of Aspirin >500mg/day can be helpful but not
recommended
Any NEW biologic type medication available?

Krystexxa = peguricase IV enzyme
infusion breaks down formed uric acid
◦ (not found in humans)
◦ q 2weeks for 3-6 months works immediately
in most everybody – stops working in ½
patients
 ―DEBULKING agent‖-- breaks down uric acid
 Uric acid levels plummet <2 after first infusion
◦ Tophi shrink within weeks
◦ However Various reactions common
 G6PD precaution
◦ Loss of efficacy in half
 UA levels increase bc antibody formation

―Sandy Naples‖ recurring swollen 1st MTP and
ankles 2 times in past year presents with 2 days
of warm, red, tender MTP synovitis.
◦ Today uric acid level 5.5 now
 2 months ago UA level 8
◦ Creatinine 1.4 stable for years
◦ Chronically for years allopurinol 200mg daily
◦ Also Hx or hypertrig and HTN
 81mg ASA, HCTZ, Lopid, Lisinopril






1. Stop ASA and HCTZ
2. Hold Allopurinol for now during acute flare
3. Colchicine 0.6mg Q 1 hr till pain relief or
diarrhea
4. Toradol one dose and Medrol dose pack
5. Indocin 50mg TID x 7 days
6. Switch to Losartan and Fenobribate/Tricor
Break Time

Sandy now asks you how to prevent his
recurring acute gout attacks. He feels he
has gained weight in past few years may
be borderline diabetic… best dietary
advice .. He admits he likes his wine and
asks how should he change his diet?
◦ 1. Give list of purine rich foods to avoid
◦ 2. Tell him to stop drinking alcohol
◦ 3. Increase protein intake, limit simple sugars
and saturated fats
◦ 4. Avoid high protein intake and dehydration
Acute attacks and diet

Uric Acid accumulates in synovium over
20+years
◦ Therefore risk reducing diet should lower UA over years

UA is 1/3 what you eat in purine rich
foods, but 2/3 of the level related to renal
excretion
◦ ONLY 10% of hyperuricemia is due to Primarily to
endogenous overproduction usually a genetic defect

Occasionally patient sensitive to trigger
which fluctuates their UA levels
 FEW patients note consistent Dietary TRIGGER
 —binge fatty meal, fast with beer/whiskey binge
◦ Most people do NOT note a dietary trigger
DO NOT perpetuate
misinformation– what does the
evidence suggest we advise
patients?

Websites and patient information telling
patients to avoid eating these foods:
◦ Coffee, tea, cocoa, chocolate, mussels, sardines,
anchoview, veal, salmon, turkey, trout, pork, beef,
cauliflower, mushrooms, peas, scallops, etc…
◦ What’s left to eat?

Note that a lot of these foods are high in
protein, is high protein diets bad?
◦ Protein rich, low saturated fat, low sugar diet
which promotes weight loss has been shown to be
helpful why?
Weight loss versus Purine
Restriction

Weight loss of 8kg associated with 11%
reduction in uric acid

Whereas a strict purine free diet will
reduce SU by 15-20%
◦ Moderation in dietary purines rather then strict
purine free diet may be helpful
◦ Cooking purine foods worse than boiling b/c of
increased bioavailability of nucleic acids
IRS and hyperuricemia

Basic defect is insulin resistance
◦ Onset years before type 2 DM
◦ Hyper-insulinemia reduces renal excretion of urate
 Hyperinsulinemia 95% incidence inc UA
 IRS 76% incidence in UA

Weight gain and centripetal obesity increases
endogenous insulin
◦ Gout is now thought to be a manifestation of
Metabolic Syndrome and centripetal obesity
Effect
High 1-2
vs Low
 Small of
transient
mg/dlPurine
rise withDiet
diet
rich in purines—red meats, sea food
 Purine-rich diet may exacerbate a
significant rise is serum uric acid in
minority of the general population
◦ underlying renal genetic defect
◦ Genetic predisposition of recently emigrated
Filipinos with a North American diet

Isocaloric purine FREE diet only decreases
serum uric acid 1-2 mg/dl
◦ VERY STRICT GOUT DIET in most patients
lowers blood urate level 15-20%

…weight loss assoc. with calorie/carb
restriction and increased intake of protein
and unsaturated fats on…gout
◦ Dessein, Shipton, Stanwix, Joffe, Ramokgadi
 Annals of Rheumatic Diseases 2000;59:539-543
Small Pilot Study

13 middle aged men with gout
◦ Confirmed by polarizing microscopy
◦ Gout duration 7 years
◦ 77% were alcohol users
◦ Ave BMI 30.5 kg/m2

No patient taking urate lowering therapy

Patients must have had >1 attack in
preceeding 4 months
◦ Ave attacks per month 2.1
Small Case Series Study

Calorie restricted 1600 kcal/day

Carbohydrates 40% of energy kcal/day

Increase proportional intake of protein
◦ 30% energy kcal/day
◦ 120 grams of protein/day
 USDA recommends 80-90 grams

Alcohol intake remain unaltered
Diet

Replacement of Saturated fat by
Unsaturated fat 30% of kcal/day
◦ Unsaturated fats included both
monounsaturated nuts, olive and canola oils
and polyunsaturated fats in fish

Purine rich foods were NOT restricted

Encouraged to LIMIT whole DAIRY
◦ b/c high in saturated fats
Diet continued

Mean weight loss 5.4 kg

Follow up 4,10,16 weeks after enrolment

Significant reductions in serum urate
◦ Urate level 0.57 to 0.47 mmol/L (p=0.001)

Significant decrease in Gouty attacks
◦ 2.2 decreased to 0.6 attacks/month (p=0.002)
16 week trial results
Alcohol



Beer greatest risk
Liquor next greatest risk
MODERATE wine intake did NOT increase risk

8/9 patients with prior gout given Whiskey
while FASTING experience one or more
acute episodes of gout
◦ Moderate BEER consumption results in RR of 1.49 per 12 0z
◦ Spirits associated with RR 1.15 per shot
◦ Moderate wine of 1-2 glasses / day yielded NO increased
risk
◦ Acetoacetic and ketoacids assoc. with fasting results in
inhibition of renal urate excretion-- sharp rise in serum
urate
Dairy products

Ingestion of milk proteins (casein and
lactalbumin) has been shown to reduce SU
because of uricosuric effect
◦ 12 year cohort study: 2 glasses of milk daily
assoc. 50% REDUCTION in gout attacks
◦ 4 week randomized trial showed an INCREASE
in UA with dairy-FREE diet

Low fat milk recommended

227 grams of cherry products
daily reduced urate levels to
normal over days to months

Randomized control trial

◦ significant decrease in
plasma urate over 5 hours
post dose
◦ Other fruits yeilded no
change
Tart Cherry Juice

◦
The juice contains anthocyanins
and antioxidants.
Mix 4 to 6 oz. tart cherry juice
with equal amount of water
◦ BID during acute attack
◦ QD prophylactically
Beverages Review

Drinks to avoid
◦ Beer and Spirits
◦ High fructose beverages
 shown to increase risk for gout flares significant
over time in nurses health study
 Sucose pop, OJ and other sweetened juices
Neutral drinks– diet pop, tea, wine
 Beneficial Drinks

◦ Coffee, tea, low fat milk
◦ Drink lots of water to avoid dehydration
◦ Cherry juice (tart) unsweetened
Diet Review

Calorie Restriction diet, few pounds of weight
loss helpful
◦ Encourage High protein, don’t worry if purine rich
◦
◦ Reduce refined simple sugars
 Avoid sucrose rich pop
◦ Replace saturated fats with unsaturated fats
◦ Low fat dairy products recommended, coffee?


Modest alcohol without fasting, wine preferred
Cherrys, Vegetables, grains encouraged,
 Avoid excess fruit juice OJ, beer, spirits, sugary pop etc…
Preferred treatment?
78 yo female
 20 yrs Chronic
tophaceous gout
 taking Autumn crocus
b/c can’t afford
colchicine
 Vit C 1000mg/daily
and cherry juice
extract BID
 Uloric started 10
weeks ago…now UA<6
Preferred treatment?


Questions

Supplemental question

material and references related to gout
and dietary management also included
Thank you
Chronic steroid therapy--bone




Chronic steroids 7.5 mg pred daily
GFR 35. Oral Fosamax for 7 years. Calcium 500mg
tid. DEXA average for her age.
Chonic GERD when takes alendronate
Which of the following would you NOT recommend:
◦ 1. dec calcium to qd
◦ 2. switch oral bisphoshonate to IV Reclast then when
patient declines the infusion b/c of the high copay add a
PPI bc of the possible fosamax induced gerd
◦ 3. Denusamab / Prolia
◦ 4. Nitropaste 1 inch qhs plus tylenol
◦ 5. Add HCTZ to build bone
◦ 6. Krystexxa infusion then wean prednisone soon
Answers, steroids and bone






1. Yes, >700mg calcium daily inc CV risk
2. No, GERD overimplicated with chronic
bisphosphonate, however CKD and >5 years
bisphosphonate may consider bisphos holiday
3. Yes, Rank ligand inhibitor denosumab preferred for
osteoporosis in CKD, also evidence slows joint erosion
in RA
4. Yes, nitroglycerin ointment qhs very potent in build
bone strength
5. Yes, HCTZ has been shown to be beneficial in
building bone density this patient – carefully monitor
known renal insufficiency
6. This would be an excellent candidate for Krystexa

High protein meals contain large
quantities of purines, however
◦ often increases urinary urate excretion
◦ Neutral net effect or may even lower serum
urate levels
◦ Large quantities of TOFU only small rise in
serum URATE in normal and gout sufferers
High protein meals

Weight reducing, calorie restricted,
moderate carbohydrate restricted, and
increased proportional intake of protein
and unsaturated fats
◦ Note that LOW PURINE foods are often rich in
both carbohydrates and saturated fats
 Resulting in decreased insulin sensitivity and
increased endogenous production
“Metabolic Syndrome Diet”

Taiwanese vegetarians diet high in purines
◦ Low gout frequency
◦ Diets also rich in dietary fiber, folate, Vit C,
fruits and vegetables

Chinese vegetarian more insulin sensitive than
Chinese omnivores
◦ Degree of insulin sensitivity correlate with
years on a vegetarian diet

Diets high in vegetable protein (specifically
wheat gluten) lowers serum lipids and UA
Vegetables