Gout

Gout

Crystal arthritis

Two key forms of crystal arthritis: gout and pseudogout (now known as calcium pyrophosphate deposition disease (CPPD)).

Hyperuricemia

Gout stems from hyperuricemia and resultant deposition of monosodium urate crystals in the joints, which activate a painful inflammatory cascade.
Note that > 90% of the time the hyperuricemia in gout most often stems from underexcretion rather than overproduction of urate and that acute attacks are often triggered by alcohol (3-4 beers/day), certain foods (excess purines), certain medications (which we address below), radiation therapy, trauma, exercise, as well as certain underlying medical conditions.

Needle-shaped, negative birefringence

Polarized light microscopy reveals urate crystals that are needle-shaped and have negative birefringence.
We show two needle-shaped crystals: a yellow horizontally-oriented crystal (its color indicates that it is in parallel to the slow wave of the light (the axis of slow vibration)) and a blue vertically-oriented crystal (in perpendicular to the axis of the slow vibration).

Negative birefringence refers to the physics of optical light refraction that occurs when polarized light is shown through a crystal.
If the refractive index of the light in parallel to the long axis of the crystal is greater than that in perpendicular, then there is negative birefringence; whereas, if the opposite is true (if the index in parallel is less than the index in perpendicular), then there is positive birefringence.

Acute Attack: Podagra

Patients are typically asymptomatic with hyperuricemia for 20 years or so before they then have their first acute painful inflammatory attack.
This most commonly occurs (in ~ half of cases) at the first metatarsophalangeal (MTP joint), called podagra.

Chronic disease: Tophi

With chronic gout, tophi can form within synovial tissues and extrasynovial tissues (ie, the skin).
On a standard H&E slide we show a tophus – a deposit of monosodium urate crystals – surrounded by inflammatory cells.

Disease Course

Gouty attacks are self-limited – they last for ~ 10 days and resolve (as the proinflammatory attack converts to an anti-inflammatory response) but then subsequently return months to years later. Over time, the attacks occur with greater frequency and duration, less acuity, and with more joint involvement.

Treatment

Acute treatment involves the use of NSAIDs (eg, indomethacin), as well as glucocorticoids, and colchicine.
Chronic treatment involves mitigating risk factors for gouty flares and the use of urate-lowering therapies, namely xanthine oxidase inhibitors (allopurinol, mostly, as febuxostat), and other urate-lowering therapies (eg, probenecid).

Iatrogenic causes of gout attacks

We can use the acronym CAN'T LEAP to remember drugs that induce gout through decrease of urate excretion:

Image Sources

Urate and CPPD Histological Image References