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:
- Cyclosporine
- Alcohol
- Nicotinic acid
- Thiazide diuretics
- Loop diuretics (Lasix)
- Ethambutol
- Aspirin (at low dose)
- Pyrazinamide
Image Source
- e.roddy@cphc.keele.ac.uk, Arthritis Research UK Primary Care Centre, Primary Care Sciences, Keele University, Keele, UK. English: Tophaceous Gout Affecting the Right Great Toe and Finger Interphalangeal Joints. Note the Asymmetrical Swelling and Yellow-White Discolouration. May 22, 2014. http://openi.nlm.nih.gov/detailedresult.php?img=3117776_1757-1146-4-13-2&req=4. https://commons.wikimedia.org/wiki/File:Tophaceous_gout.jpg.