DERM IE2 MATERIAL: Gout + Hyperuricemia

uric acid

• breakdown product of purines

• waste product

endogenous purines vs exogenous purines

• endogenous: manufactured by body

• exogenous: obtained from food

T or F: humans have uricase to break down UA

F: humans excrete UA renally

normal UA level

2.0 - 7.2 mg/dL

hyperuricemia levels

• males

• females

• males: > 7.2

• females: > 6.0

overproduction: primary hyperuricemia

idiopathic, or acclerated purine nucleotide synthesis

overproduction: secondary hyperuricemia

• excessive purine intake

• tissue catabolism

• accelerated ATP degradation

high purine foods to avoid

• liver, kidney

• anchovies

• trout

• sardines, codfish, mussels, scallops

• veal

• venison

• turkey

• EtOH (beer > liquor > wine)

undersecretion of UA

• impaired tubular secretion of UA

  • meds, renal impairment, excess EtOH, metabolic syndrome, HTN, CVD

where is UA excreted mostly in?

• 2/3 of UA excreted in urine

• 1/3 of UA excreted via GI tract

conditions associated w/ Hyperuricemia

• diet/lifestyle

  • obesity, excess alcohol, purine rich foods

• metabolic

  • metabolic syndorme, type 2 DM, hyperlipidemia

• CV

  • HTN, urolithiaisis

• Renal

  • CKD, renal disease

• genetic

• environmental

  • lead intoxication

• meds

  • serum urate-elevating meds

drugs that increase serum urate

• loop and thiazide diuretics (hydrochlorothiazide)

• low dose aspirin (< 1g/day)

medications that decrease serum urate

• SGLT2 inhibitors

• Losartan

• dihydropyridines (amlodipine)

• statins and fenofibrate

• estrogen

which med can help with HTN and gout?

Losartan = only ARB that decreases UA levels thru uricosuric effect

• increased serum UA is common, especially with

• effect can be minimized by concurrent treatment with

• switch patient to ACE or ARB if they have

• hydrochlorothiazide

• ACEi/ARB

• HTN

symptoms of acute gouty arthritis

• rapid onset of pain

• erythema

• warmth

• swelling

• tenderness

joint involvement of acute gouty arthritis

• monoarticular (affecting one joint)

• 1st MTP, big toe = Podagra

• MTP > insteps > ankles > heel > knees > wrists > fingers > elbows

• when do gouty attacks occur?

• what is elevated?

• aspiration of synovial fluid shows what?

• when to treat for best efficacy

• how long do attacks last if left untreated?

• night time

• UA levels and leukocytosis

• MSU crystals

• 24 hrs

• 3 - 14 days

interval gout

asymptomatic period between attacks

tophaceous gout

• deposits of MSU crystals (tophi) in soft tissues —> deformitym nerve compression

  • usually in long standing gout

atypical gout

polyarthritis affecting any joint

• confused with RA or OA

gout nephropathy

nephrolithiaisis (kidney stones), acute/chronic renal impairment

diagnosis of acute gouty arthritis

• identification of MSU crystals

• increased serum UA levels (may be normal during attack)

• imaging: X rays, MRIs, ultransonography, DECT

goals of therapy for

• acute gout

• chronic gout

• acute gouty attack

  • relieve pain and inflammation

  • treat within 23 hrs for best efficacy

• chronic gout

  • prevent attacks

  • decrease UA levels < 6 mg/dL

• prevent complications of gout

Nonpharmacologic Therapies

• cold compress/applications

• weight loss

• diet: avoid purine rich foods

• avoid/limit EtOH

acute gout treatment

• NSAIDs

• colchicine

• corticosteroids

• ACTH

urate lowering therapy initiation

• recommended during acute flare

• modifying UA concentrations during attacks may precipitate another attack

NSAIDs

• 1st choice

• meds

• timing

• ADRss

• CI

• Caution

• 1st choice

  • Indomethacin

  • any NSAID can be used tho

• meds

  • naproxen, sulindac, Celebrex

• timing

  • effective if initated within 24 - 48 hrs of attack

  • continue 5 - 7 days

• ADRs

  • bleeding, reduced CrCl, increased BP, HA

• CI

  • active PUD

  • uncompensated CHF, renal impairment, allergy to ASA

• Caution

  • pts on antiplatelet or anticoagulant therapy

• which NSAID is not used if CrCL is <30 ml/min?

• which NSAID is good option for patients with high GI risk?

• which is not used for managing gout?

• Naproxen

• Celecoxib

• aspirin → low dose for CV prevention OK

Colchicine (Colcrys)

• timing

• ADR

• DI

• timing

  • good response if started within 24 hrs of attack

  • guidelines: use only within 36 hrs

• ADR - dose dependent

  • n/v, diarrhea, abdominal pain

  • reversible peripheral neuropathy

  • rare: blood cytopenias, rhabod, liver failure

• DI

  • many

    • increases conc of statins (Rosuvastatin ok)

    • CYP3A4 inhibitors, P-glycoprotein inhibitors

• renal/hepatic impairment dosing needed

Corticosteroids

• use

• administration

• Avoid what

• ADRs (short term)

• use

  • when unable to use NSAIDs and colchicine

• administration

  • systemic (PO or IM) or IA

• Avoid what

  • long term use due to SEs

• ADRs (short term)

  • mood changes

  • hyperglcemia

  • increased BP

  • fluid retention

relationship between gout and hyperuricemia

hyperuricemia = risk factor for gout

• pts w/ gout have hyperuricemia

• pts w/ hyperuricemia do not develop gout

• hyperuricemia SHOULD NOT be used as diagnosis of gout

asymptomatic hyperuricemia

• latency period lasts for years

• do not treat

strong recs of who gets ULT

• frequent attacks (≥ 2 attacks/year)

• tophi

• evidence of radiographic damage of joints

conditional recs for who gets ULT

• gout w/ renal insufficiency (CKD Stage ≥3 = CrCl < 60 ml/min

• UA nephrolithiaisis/urolithiaisis

• serum urate concentration > 9mg/dL

• CVD

goal of ULT (urate-lowering therapy)

• reduce gout flare frequency

• prevent gout complications

• treat-to-target urate levels < 6 mg/dL

timing for intiation of ULT

during gout flare until resolved

meds for hyperuricemia in in gout

• Xanthine Oxidase Inhibitors (XOI)

  • allopurinol (Zyloprim)

  • Febuxostat (Uloric)

• uricosurics

  • Probenecid (Benemid)

  • Lesinurad (Zurampic)

which is first line option, XOI or uricosuric?

XOI

Allopurinol

• MOA

• dosing

• onset

• ADRs

• monitoring

• counseling

• MOA

  • XOI = decrease UA synthesis

  • 1st line for all pts including those with CKD

• dosing

  • start slow and low, titrate

  • desired: at least 300 mg

• onset

  • takes 2 -3 weeks for effect

• ADRs

  • rash, leukopenia, GI issues, HA, itching

• monitoring

  • LFTs, SCr

• counseling

  • drinks lots of water → prevent kidney stones

specific ADR of Allopurinol

• rash (SJS, TEN)

  • genetics in Asian populations (HLA-B*5801 positive)

• can switch to Febuxostat to avoid this for asian populations (Chinese, Thai, Korean)

Febuxostat

• MOA

• dosing

• ADRs

• BBW

• avoid in

• CI

• rash?

• MOA

  • XOI = decrease UA synthesis

• dosing

  • start low, slow, titrate

• ADRs

  • nausea, arthralgia, LFT elevations

• BBW

  • pts w/ CVD are at high risk of CV death

• avoid in

  • hx of CVD or CVD-related events

• CI

  • Azathiprine and Mercaptopurine → decreases their metabolism = bone marrow toxicity

• rash?

  • no

Probenecid

• MOA

• used for

• CI

• avoid

• DI

• counseling

• MOA

  • uricosuric = decrease renal reabsorption of UA = increase renal excretion of UA

  • competitively inhibit active reabsoprtion of urate at proximal renal tubule

• used for

  • underexcretors of UA

• CI

  • hx of urolithiasis

• avoid

  • salicylates, renal dysfunction

• DI

  • meds affecting kidneys

• counseling

  • drink lots of water

  • take w/ food

Lesinurad

• MOA

• indicated in

• renal considerations?

• ADRs

• DI

• counseling

• MOA

  • uricosuric

• indicated in

  • in combo w/ XOI

    • ex. + Allopurinol

• renal considerations?

  • yes

• BBW

  • acute renal failure

• ADRs

  • HA, influenza, GERD, CV events

• DI

  • decrease oral contraceptive effectiveness

  • may increase SCr

• counseling

  • stay hydrated

Pegloticase

• MOA

• 1st line or last resort?

• administration

• cost

• MOA

  • uricosuric

  • recombinant uricase → convert UA to Allantoin

• 1st line or last resort?

  • last line for refractory gout

• administration

  • IV

• cost

  • very expensive

recommendations for choice of ULT

• XOI (allopurinol mostly) as 1st line option for all pts

• start low, slow, titrate up

• pegloticase = last line option

duration of therapy for ULT

• mostly indefinitely

• need to be on it for at least a year → to see if effective

Monitoring and Management

• UA levels

  • check every 2 - 4 weeks

preventing acute gout attacks during initiation of ULT (prophylaxis)

• meds

• meds

  • colchicine 0.6 mg BID → favored

  • low dose NSAID (250 mg BID)

  • low dose CS (≤10 mg/day) → not rec due to SEs

duration of prophylaxis

• pts w/o tophi

• pts w/ tophi

• pts w/o tophi

  • d/c 3 - 6 months after achieving target UA levels

• pts w/ tophi

  • d/c 6 months after achieving target UA levels

misc agents (off label)

• fenofibrate

• losartan

• can be used w/ XOIs