In acute gout flares, there's more than meets the eye!
A deep dive reveals a fascinating story of unusual pathophysiology and a number of unintuitive clinical pearls!
Read on for some surprising truths and practical tips for management!
- Gout 201, A Thread -
Check out these @pointofcaremed digital resources on Gout Flare for use at the point of care!
They include admission checklists, HPI intakes, differentials, sample dotphrases, and key clinical pearls, along with a podcast and YouTube video with accompanying slides.
If you're like me, when you think about gout, you see those negatively birefringent crystals in synovial fluid - STEP 1 stuff.
I thought that gout flares only happen when urate levels rapidly increase and crystals start to form in the synovium.
But there's more to it!
Gout is characterized by the chronic deposition of monosodium urate crystals into the synovium.
The "solubility threshold" for monosidum urate is ~6.8 mg/dL, above which circulating uric acid can turn into crystals.
This can constantly happen without causing a flare!
Hyperuricemia is necessary but not sufficient to cause gout.
Almost all UA is filtered at the glomerulus, but ~90% is reabsorbed.
Humans don't make uricase, so all formed UA must be excreted.
Hereditary underexcretion of UA is the most common cause of hyperuricemia.
Acute gout flares can happen when there is increased deposition OR mobilization of already present crystals within the joint.
The "free-floating" crystals are ingested by neutrophils which activate inflammatory pathways via the NLRP3 inflammasone and production of IL-1B.
A sudden increase OR decrease in uric acid levels in blood can lead to a flare!
A decreased uric acid level can lead to mobilization of deposits already present in the joint.
This is why starting allopurinol to lower uric acid levels can precipitate a flare!
A sudden increase in uric acid can also start a flare.
When consumed, purines are metabolized into uric acid.
Some of the most purine-rich culprits include:
- organ meat (liver)
- beer and other alcohol products
- seafood
- red meat
- high-fructose soft-drinks
Beer consumption is especially suited to provoke a gout flare because:
- Yeast cells contain high purine content
- Alcohol metabolites compete with uric acid to be excreted by the kidneys
- Alcohol is a diuretic, contributing to dehydration
Note the alcohol in the pic!
URAT1 (Urate Anion Transporter 1) is a protein transporter in the proximal tubule of the kidney.
Overactive URAT1 is commonly implicated as a genetic variant that can increase the risk of gout.
Diuretics lead to conditions that can increase the activity of URAT1!
Gout flares are more common at night.
Why? Because three things are more likely to happen at night that support the deposition of uric acid or lessen the body's ability to stave off inflammation.
1. Lower body temperature
2. Dehydration
3. Noctural dip in cortisol
Understanding all this key background pathophysiology can help inform how you approach the workup and management of acute flares!
Here's an admission checklist!
Key points:
- Determine if you need synovial fluid
- Rule out septic joint
- Start treatment ASAP!
Here is the most pertinent info to collect for your HPI!
Key things:
- Prior flares
- Onset of this flare
- Signs/symptoms - pain, swelling, warmth, erythema, reduced ROM
- Involved joints
- Allopurinol use and adherence
- Narrow in on possible trigger
Podagra is a painful/inflamed MTP joint at the base of the big toe.
It originates from Greek.
"Pous" means "foot" and "Agra" means "trap", aptly describing the sudden and severe pain of a gout flare, as if the foot has been caught in a trap!
Podagra is the first symptom in 50% of early gout flares.
But why this joint specifically?
In short, we don't know.
Possible reasons:
- MTP is coolest joint
- Big toe subject to repetitive trauma
- Synovial lining may be more susceptible
- Higher UA concentration
As gout progresses, it is more likely to involve other joints such as the knees or hands.
Tophi are aggregations of urate crystals and giant cells that are formed after repeated attacks and can cause deformities and arthritis of joints - commonly interphalangeal joints.
twitter.com/NEJM/status/1476885857239920640?s=20
Here's a relevant differential.
You can't miss a septic joint!
Be on the lookout in those with recent surgery or prosthetic joints.
Note that the presence of crystals does NOT rule out an infection! Always send cultures.
Calcium Pyrophosphate Deposition Disease (CPPD), or "pseudo-gout," is another crystalline arthropathy.
It's very common in patients over 80, but often asymptomatic.
CPPD flares more commonly involve the knees, wrists, and MCP joints.
CPPD is associated with hyperparathyroidism, hypothyroidism, hypomagnesemia, and hemochromatosis.
It more commonly involves the knees, wrists, and MCP joints.
You may see chondrocalcinosis on X-Ray due to deposition in cartilage.
Here's a sample plan for managing gout.
Key points:
- best to start therapy within 24 hours
- generally monotherapy
- colchicine reduces neutrophil activity
- NSAIDs and steroids reduce inflammation
- continue allopurinol if already on it
- ice packs
If left untreated, acute gout flares can last days to weeks, but they will always resolve on their own!
If gout is not treated early in its course, gout flares tend to become increasingly frequent and severe and are often polyarticular.
Uric acid levels at the time of a flare are rarely helpful.
Why?
- Uric acid may be actively forming crystals
- Inflammation lowers the level
- Acutely lower levels can also lead to the flare
Check ~2 weeks after the flare for a better sense of a patient's baseline.
Allopurinol should be started if:
- Greater than 2 attacks per year
- CKD3
- Baseline UA > 9
- Presence of tophi
- Radiographic evidence of joint damage
Make sure you are giving prophylatic anti-inflammatories when starting and uptitrating the doses to prevent a flare!
Start allopurinol at 50-100mg daily.
Titrate by 100mg weekly up to a max of 900mg daily.
Divide doses if giving >300mg daily.
The Goal UA is less than 6 (below the solubility threshold!)
Allopurinol is taken indefinitely.
Patients with the HLA-B*5801 allele have an increased risk of hypersensitivity to allopurinol
You should screen in Asian patients and black patients of African ancestry
It can cause serious adverse events like SJS/TLS, and DRESS.
Advise patients to look for skin changes
An excellent thread hot off the presses from kidney week on gout management in CKD!
twitter.com/NephroSeeker/status/1720859874383241512?s=20
A short and sweet summary of gout!
twitter.com/DrAmirKhanGP/status/1635332864874250240?s=20
If you remember nothing else:
- Gout flares are caused by more than increases in UA!
- Don't miss a septic joint
- Tap the joint if diagnosis uncertain - always send cultures
- Treat with early NSAIDs or colchicine
- Continue allopurinol during flares
- Goal UA <6
For making it this far, here's the checklist, differential, and sample EHR dotphrase for admitting a patient with an acute gout flare.
You can also find the downloadable PDF on the @pointofcaremed website.