Gout

In medicine, gout is a "hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi."

Etiology /cause

Calcium channel blockers and losartan are associated with a lower risk of gout as compared to other medications for hypertension.

Diagnosis

Accuracy of diagnostic criteria for gout among patients who had synovial fluid analysis

	Criteria	Sensitivity	Specificity
ARA (ACR)	6 of 12 criteria	70%	79%
Rome	2 of 4 criteria: • Painful joint swelling, abrupt onset, Clearing in 1-2 weeks initially • Serum uric acid: >7 in males; >6 in females • Presence of tophi • Urate crystals in synovial fluid or tissues	70%	83%
New York	2 of 5 criteria: • 2 attacks of painful limb joint swelling • Abrupt onset and remission in 1—2 weeks initially • First MTP attack • Presence of a tophus • Response to colchicine-major reduction in inflammation within 48 h	67%	89%

Several sets of diagnostic criteria exit (see table).

The serum uric acid level during an attack of gout

	Sensitivity	Specificity
> 5.88 mg/dl	95%	53%
≥ 6 mg/dl	86%	?
≥ 8 mg/dl	68%	?

A clinical prediction rule (online link) found that the following predicted urate crystals by aspiration:

• Male
• Onset within one day
• Joint redness
• First metatarsaophalangeal joint
• Previous arthritis attack per patient
• History of hypertension or 1 or more cardiovascular diseases
• Serum uric acid level > 5.88 mg/dl

However, among patients with high scores, 20% did not have crystals. Only one of 381 patients had bacterial arthritis.

Treatment

Clinical practice guidelines address treatment. However, trials comparing glucocorticoids (steroids) and non-steroidal anti-inflammatory agents (NSAIDs) were not published till after the guidelines.

Regarding medications, if there are no mitigating factors in choosing a drug, glucocorticoids, non-steroidal anti-inflammatory agents (NSAIDs), and colchicine all work; however, colchicine consistently causes drug toxicity.

A combination treatment is ice four times a day with oral prednisone 30 mg orally tapered over 6 days (30 mg for two days, 20 mg for two days, 10 mg for two days) and colchicine 0.6 mg/day. An advantage of this regimen is the reduced toxicity from the low dose of colchicine and that the colchicine helps prevent flares if allopurinol is later started. Colchicine has been combined with NSAIDs that are not metabolized by the CYP3A4 isoenzyme of cytochrome P-450 (naproxen is not metabolized by CYP3A4). Combining glucocorticoids with NSAIDs increased the risk for gastrointestinal drug toxicity

Local ice

Ice packs, applied for 30 minutes 4 times per day, can help according to a randomized controlled trial without allocation concealment. In this trial, ice reduced the visual pain analog score by an additional 33 mm beyond the reduction provided by a combination of glucocorticoids and colchicine.

Non-steroidal anti-inflammatory agents

Non-steroidal anti-inflammatory agents (NSAIDs) are better than placebo according to a randomized controlled trial of 30 total patients. According to a summary of this trial, "the knee was affected in 14 cases and the great toe in only two cases. After 24 h, 67% of tenoxicam group had ≥50% reduction in pain compared with 26% of placebo group (P<0.05). However, at the end of the treatment (4 days), there was no significant difference between the groups."

Glucocorticoids

Comparison of NSAID and steroids for acute gout

	Patients	Interventions		Results
		Steroid	NSAID
Janssens et al 2008	120 total patients with uric acid crystals on arthrocentesis	Prednisolone 35 mg once daily for 5 days	Naproxen 500 mg twice daily for 5 days	NSAID trended better (88% versus 80% response; p=0.3) No differences in rates of drug toxicity.
Man et al 2007	90 total patients with clinical diagnosis of gout†	Initially prednisolone 30 mg Followed by prednisolone 30 mg daily for 5 days and as needed acetaminophen	Initially diclofenac 75 mg with indomethacin 50 mg Followed by indomethacin 50 mg every 8 hrs for 2 days then 25 mg every 8 hrs for 3 days and as needed acetaminophen.	Steroids faster reduction in pain. Steroids used more acetaminophen. More adverse effects from indomethacin. Indomethacin trended to more relapses at 2 weeks (11% vs 17%).
Notes: † Clinical diagnosis of gout was "pain and warmth in a joint, and presented within 3 days of the onset of pain and also had 1 or more of the following: metatarsal-phalangeal joint involvement; knee or ankle joint involvement and aspirate containing crystals; or typical gouty arthritis, with either gouty tophi present or previous joint aspiration confirming the diagnosis of gout." Seven patients allowed arthrocentesis and all were positive for gout.

Randomized controlled trials find similar benefit from non-steroidal anti-inflammatory agents and oral glucocorticoids. In the first trial the reduction in visual analog scale after 5 days was 44.7 with prednisolone and 46.0 with naproxen. Less drug-related side effects and adverse reactionss occurred in the glucocorticoids group; however, the NSAID group received a high dose (50 mg every 8 hours for 2 days, followed by 25 mg every 8 hours for 3 days).

In the second randomized controlled trial statistically equal effect resulted from prednisolone 35 mg orally per day or naproxen 500 mg orally twice per day; however there was an insignificant 8% improvement in the NSAID group. There were no significant differences in drug toxicity.

Colchicine

Colchicine is better than placebo according to a systematic review by the Cochrane Collaboration that found a single randomized controlled trial of 43 patients. In this study, colchicine 1 mg orally, followed by 0.5 mg every two hours led to a 50% reduction in pain in about 70% of patients compared to about 35% of patients who received placebo. However, all patients had drug toxicity from colchicine and in 90% of the patients toxicity occurred before 50% reduction in pain.

Regarding the best dose, 1.2 mg followed by 0.6 mg in 1 hour may be as effective as higher dose.

To avoid drug toxicity, lower doses of colchicine (0.6 per day) have been used in combination with glucocorticoids. The UK National Library for Health recommends 0.5 mg two to four times a day.

Anti-cytokines

The monoclonal antibody against interleukin-1 beta, canakinumab, may help according to a randomized controlled trial.

Prognosis

Acute flares

Without treatment, one third of flares improve within 2 days.

Prevention

Diet

Avoiding products with high fructose such as sugary soft drinks (sweetened with high fructose corn syrup), and other high-fructose products, such as fruit juice, apples, and oranges may help.

Medications

Xanthine oxidase inhibitors

Allopurinol can reduce frequency of attacks.:

• According to a small randomized controlled trial, allopurinol can be initiated at the time acute therapy is initiated for a flare without increasing complications among patients also started on indomethacin 50 mg 3 times per day for 10 days and colchicine 0.6 mg twice per day. Previously, allopurinol was delayed till resolution of the acute attack.
• Colchicine 0.6 mg twice daily should also be used to prevent a flare. In a randomized controlled trial, co-treatment with colchicine 0.6 mg twice daily while allopurinol was tapered up from 100 mg/day until 3 months after the serum urate concentration < 6.5 mg/dl, reduced flares of gout from 77% in the placebo broup to 33% with colchicine prophylaxis. Most of these patients had tophi. One third of the patients had diarrhea and many reduced the medication to once per day.
• Colchicine, or a non-steroidal anti-inflammatory agent, may be needed for six months.

Allopurinol should be increased as possible to achieve a goal serum urate of <6 mg/dl (360 micromoles/liter).

Febuxostat, a non-purine inhibitor, is equally effective as allopurinol when compared in a randomized controlled trial.

Famous persons with gout

Holy Roman Emperor Charles V had gout and Theodore Roosevelt may have had gout.