Gout: An Update (Maniscalco, 5/6/26)

A recording of this presentation is available HERE.

Thanks to Dr. David Maniscalco, SMGR Endocrinologist, for an update on Management of Gout. 

1st MTP

Common signs/symptoms

• 80% of gout is monoarticular process (single ankle, knee, 1st MTP, wrist, olecranon bursa)

• significant pain ("cannot even let a bedsheet touch it")

• red/hot/swollen

• flares commonly overnight and early morning (pts may describe this)

polyarticular gout (<20%) becomes an issue in pts with longstanding gout that hasn't been treated, can be seen in hospitalized patients, can be associated with fever, can mimic sepsis
tophaceous gout: pts who haven't received care as outpatient, develop significant tophi, pain can hit critical point with severe pain

Diagnosis

• ideal: presence of uric acid crystals on synovial fluid analysis (crystal-proven gout)

• less ideal: often diagnosed on typical clinical presentation + hyperuricemia

NOTE: serum uric acid level can be erroneously low when a patient is in the midst of a gout flare, so don't be fooled (should recheck uric acid after flare resolves)

Management
Based on 2020 American College of Rheumatology Guidelines for Management of Gout
Indications for urate lowering therapy:

• 2 or more gout flares within a year

• no need to start after first attack>> monitor and see if repeated attacks

• tophaceous gout (rheum should manage)

• radiographic damage attributable to gout (erosions on x-ray)

• hx multiple flares over time (even if <2/year)

• first gout flare with CKD >3

• uric acid >9 (significantly high) or hx nephrolithiasis

no need to start with incidental elevation of uric acid in the absence of gout symptoms
Urate lowering therapy:

• Allopurinol is PREFERRED first-line agent

• recommended including for pts with CKD>3 (safe)

• allopurinol does not cause kidney injury (safe in AKI as well)>> decreased GFR can increase risk of side effects, e.g. severe cutaneous reactions (Stevens Johnson, DRESS), which are rare but do happen>> lower dose if rash develops

• in pts of southeast Asian descent (Han Chinese, Korean, Thai) and African American>> check for alelle HLA B5801 before starting allopurinol

• Feboxostat is used as an alternative to allopurinol

• previously concerned recommended for patients with CKD>> now no longer an indication

• used rarely

• per current guidelines, contraindicated in pts with hx CVD (increases risk of CV death, mixed data)

start lowest dose and titrate up monthly, need serial uric acid measurements to titrate
Goal uric acid <6mg/dl (for non-tophaceous) <5mg/dl (for tophaceous, managed by rheum)

• starting dose: allopurinol 100mg daily (lowest dose), feboxostat 40mg daily (lowest dose)

• decreases risk of hypersensitivity reactions, decreased risk of flares with initiation

• there is no inherent danger in increasing allopurinol>> max dose 800mg

• max dose of feboxostat is 80mg

• about 1/3 of patients will be at goal with 300mg allopurinol

• for pts with CKD3, start with 50mg allopurinol (titrate up by 50 mg/month until goal uric acid)

• There is NO need to stop allopurinol in AKI in hospitalized patients

• can lead to gout flares and do not worsen AKI

Acute flare management
Colchicine is first line most effective within first 36 hours of flare (doesn't work better if started after): 1.2mg, followed by 0.6 mg 1 hour later, then 0.6mg BID until flare resolves
If not resolving, transition to prednisone
If attack is going >48 hours, choose something other than colchicine (prednisone preferred)
Prednisone: 0.5mg/kg 2-5 days, then taper over 7-10 days
NSAID: naproxen 500mg BID, indomethacin okay (often cannot be used due to comorbidities)
ICE!!!!
Medication Prophylaxis

• Any time you are starting urate lowering therapy, you need prophylaxis at the same time!!

• Colchicine is preferred agent for ppx: 0.6mg daily, okay in CKD (CrCl<30, 0.3mg/daily or 0.6mg qod)

• If cannot do colchicine (diarrhea is common), NSAID, e.g. Naproxen 200 or 250mg BID (limited by CKD)

• Last option is prednisone  for those who cannot tolerate colchicine or NSAID: pred 2.5-7.5mg (usually start with 5mg), if worried about diabetes, try to get away with lower dose (e.g. 2.5mg daily)

• Titrate up q2-4 weeks (with uric acid via lab to direct)

Duration of prophylaxis: continue for 3-6 months AFTER target uric acid (longer for tophaceous gout)
Lots of crystal still in joint, take a long time to dissolve, people tend to have flares until treated for a long time

Medication monitoring
Allopurinol is safe (stop if rash), CBC/CMP after initiation, liver issues are not much of an issue, can monitor periodically q6-12 months (CBC, CMP), more frequently if renal impairment. Similar for colchicine.
Diet: low purine diet, low alcohol, reduce high fructose corn syrup, no concrete evidence on cherry juice, avoid red meats/organ meats/scallops, mussels, meaty fish
HCTZ increases uric acid>> change and may help uric acid improve
Losartan is gout-friendly-- evidence it decreases uric acid

Myth busters:

• No need to stop urate lowering therapy while having a gout flare

• No need to stop urate lowering therapy in AKI (can lead to bad flare)

• Okay to start urate lowering therapy DURING a gout flare (despite what UptoDate says)

• Colchicine is safe and NOT highly toxic and can be safely taken as long as adjusted for renal impairment, drug interactions

Refer to rheum:
polyarticular gout
tophaceous gout
unable to be treated with allopurinol/feboxostat

What a Pain! Tales of Adult Arthritides (Ramirez, 3/31/2021)

Thank you to Dr. Vanessa Ramirez for her review of two very important inflammatory arthritides at Grand Rounds this week: psoriatic arthritis and gout.  I gleaned so many important pearls from her presentation. For those of you interested in seeing the full recording, it is available here. My summary notes are below:

Inflammatory arthritides

• infectious (septic)
• crystal induced (gout, pseudogout)
• immune related (RA, SLE, psoriatic arthritis, dermatomyositis, Sjogren's)
• reactive

Psoriatic arthritis (PsA) 

• PsA affects about 20% of people with psoriasis 
• skin changes can precede arthritis sx for years-- even up to 12 years
• skin changes and PsA flares are not necessarily temporally related, nor is disease severity necessarily correlated
• typically asymmetric arthritis (in one, several or multiple joints), sacroiliitis (30-78%) 
• historic definition of PsA: serological negative (i.e. negative rheumatoid factor) polyarticular arthritis in someone with psoriasis skin manifestations
• classification Criteria for Psoriatic Arthritis (CASPAR) (2006) may be helpful in making this clinical diagnosis (see image below)
• early identification and treatment prevents joint destruction
• anti-CCP may be elevated (usually mild) in 12% of patients with PsA
• more likely in higher numbers of involved joints
• Risk factors for PsA
• scalp psoriasis 4x risk, intergluteal/perianal 2.3x risk, nail involvement
• earlier age at dx with psoriasis, >3 body sites affected, family hx of PsA (first degree)
• ESR is superior to CRP as a marker of damage progression and mortality
• Treatment for PSA includes lifestyle modification (diet, smoking cessation, exercise), followed by symptomatic treatments (NSAID, steroids, injections) and then TNF alphas
• see images below from the 2018 ACR Guidelines
• also see AAFP image, which includes cost of these treatments

2018 ACR Guidelines for Treatment of PsA

https://www.rheumatology.org/Portals/0/Files/PsA-Guideline-2018.pdf

https://www.rheumatology.org/Portals/0/Files/PsA-Guideline-2018.pdf

AAFP Psoriasis (Am Family Physician 2013)

https://www.aafp.org/afp/2013/0501/p626.html

Gout 

• Gout is caused by deposition of monosodium urate crystals in the joint space, periarticular structures and soft tissues
• associated with obesity, htn, hyperlipidemia, DM, CKD, heart failure, thiazide diuretic 
• ACR online tool Clinical prediction (see image)

• 

  https://www.aafp.org/afp/2020/1101/p533.html

  
  
  
• Treatment Acute
• 2020 ACR Guidelines for Treatment of Gout Flare
• Naproxen 500 mg BID OR indomethacin 50 mg TID, ibuprofen 800mg TID
• Colchicine (low dose) 1.2mg PO, then 0.6mg 1 hour later, then BID until flare resolves
• Oral prednisone 0.5mg/kg (5-10 days full dose then stop OR 2-5 days full dose and then taper over 7-10 days)
• Treatment Chronic
• all patients with tophi, radiographic evidence or damage or 2+ flares/year
• goal is symptom relief AND maintenance of urate levels (<6)
• we should be titrating allopurinol based on checking uric acid levels
• Allopurinol is treatment of choice, lower doses preferred to start
• if on thiazide for BP, switch to losartan