Gout Flashcards
Gout
an inflammatory disease resulting from the formation of urate crystals in joints and soft tissues.
Crystal formation is the consequence of improper handling of uric acid causing super saturated solution of urate precipitating crystals
Gout is associated with or aggravated by:
Genetics Obesity Age Adult males Postmenopausal women Hypertension Diet (high purine, high fructose)
Disease states associated with Gout
Lesch-Nyhan syndrome
End stage renal disease
Cancers with cell lysis
major organ transplant
Drugs that can induce Gout
Thiazides low dose ASA Niacin immune suppressants Cytotoxic agents that cause cell lysis
Lesch-Nyhan syndrome
AKA: juvenile gout
- rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphribosyltransferase (HGBRT)
- X-linked trait
Phases of Gout
Acute
Intermittent
Chronic (advanced)
Acute Gout
- Initial phase where crystals are starting to form, normally starts in a joint, like a toe or elbow.
- Normally see a low grade fever
- it is possible to only have one gout attack ever
- attack may only last 3-14 days, acute attack doesn’t mean you need chronic therapy
Intermittent Gout
Start having acute attack 2 times or more per year
And most often start seeing the attack in more than one joint
Chronic (Advanced) Gout
You can see changes in renal function.
Significant inflammation.
Hand and feet start to look like RA
pathway to making urate
IMP –> Inosine –> Hypoxanthine (xanthine oxidase) –> Xanthine (xanthine oxidase) –> Urate (Uricase)–> Allantoin (more soluble form)
Renal elimination of uric acid
Uric acid enters glomerulus , undergoes glomerular filtration.
Proximal convoluted tubule reabsorbs about 90% of uric acid, and excretes only about 8-10%
inflamasomes
are created due to high levels of uric acid in the blood
the inflammatory response from gout
stimulated by metabolic, exogenous, and endogenous stimuli that active caspase-1. once caspase-1 is activated it actives IL-1b, IL-18, and IL-1a.
These IL’s then further active an even bigger inflammatory response (TNF-a, IL-6, KC).
Chronic Sequelae of Gout
Renal: Nephrolithiasis (kidney stones), and interstitial nephritis
Arthritic: deposition of tophi; erosion of cartilage and bone; joint deformities and loss of function
Metabolic(?): increasingly it is thought to be associated with metabolic syndrome, stroke and other types of cardiovascular disease
Diagnosis of gout
aspiration of synovial fluid and visualization of crystals, differential diagnosis can sometimes be difficult
Treatment goals of Gout
Acute: resolve inflammatory process rapidly
Intermittent/chronic: limit crystal formation, tophi (deposit of crystals and other substances on the surface of joints) and tissue damage by lowering serum uric acid, especially if there are comorbid conditions.
Gout treatment guidelines
Treat to relieve symptoms not the level of uric acid in the blood.
Medications that can treat acute gout symptoms
-colchicine
-NSAIDs (non-ASA)
-Steroids
Il-1 antagonists
ACTH (?)
Opioids (?)- just for pain
A decision to initiate chronic therapy is made when:
Uric acid levels exceed 7 mg/dl AND
- greater than 2 acute flares occur within one year OR
- tophi are present OR
- significant kidney disease OR
- incidence of kidney stones
Xanthine oxidase inhibitors
Allopurinol ( a purine, uric acid analog inhbitor)
Febuxstat ( a non-purine inhibitor)
Neither are preferred over the other, except in certain disease states.
Allopurinol
Dosing: 100mg/d, can be slowly increase by 100mg/week. Maintenance dose: 300mg/day, can be pushed to 800mg/d (top of dosing curve.
Acute SE: Rash, fever, GI, malaise, itching
Excretion: 80% by the kidney (dose to be adjusted with decreased renal function)
-Allopurinol Hypersensitivity reaction
DI: Azathioprine, 6-mercaptopurine (both of these are degraded by xanthine oxidase)
-Has a lot of long term data for efficacy
Allopurinol Hypersensitivity Reaction
- SIGNIFICANT
- Similar to SJS
- Rash
- Can lead to kidney failure
- Would D/C therapy
- Can screen for patients with HLA-B 58:01 Allele. It is associated with developing this hypersensitivity reaction
- -> Asian populations generally have a high incidence of this allele
Febuxostat
- non-competitive inhibitor of xanthine oxidase
- Acute SE: rash, GI, fever, malaise, itching
- Hepatic metabolism- would want to monitor hepatic function
- Dosing: 40 mg/day up to 80mg/day
- no long term data for efficacy
Colchicine
MOA: decreases microtubule formation, which limits(inhibits) chemotaxis (inhibits the inflammatory response)
- Want to treat within 36 hours of flare up.
- Dosing: 1.2 mg, then 0.6mg 1 hour later. if treating a flare up over a few days: 1.2 mg/d x 14 days
NSAIDs
most common is Indomethacin, but naproxen is pretty common too.
Steroids
- Prednisolone 0.5 mg/kg (usually about 35 mg/day) and treat for about 5 days
- Oral steroids are very effective, and intrajoint injections are also effective
IL-1 antagonists
-Anakinda & Cankinumab
definitely not first line, mainly because to expensive
Probenecid
- Dosing: 250 mg BID up to 2000 mg daily
- SE: GI upset, rash
- CIearance: less than 50ml/min CrCl
- Counseling point: make sure patient knows to stay adequately hydraded
- DI: increase in concentrations of beta-lactam antibiotics, and methotrexate (this is bad)
- decrease in Glucose-6-phosphate dehydrogenase, which increases incidence of hemolytic anemia
Lisinurad
Just approved in December of 2015, by a SINGLE vote
-URAT-1 inhibitor
-Dosing: 200mg/d, can move up to 400mg/d but there is an increased risk of SE
SE: HA, malaise, GERD
-never used alone, always in conjunction with a xanthine oxidase inhibitor
–>when used alone it showed an increased risk of renal failure
