HIGH SERUM URIC ACID TREATMENT

HIGH URIC ACID TREATMENT, When should a high uric acid be treated. I have found that there is a great deal of confusion amongst physicians regarding this topic. In fact, there are consultants writing prescriptions for 2 weeks courses of uric acid lowering drugs citing generalized body aches only or asymptomatic hyperuricemia. These guidelines should sufficiently educate a physician regarding the appropriate approach towards uric acid in general and patients with Gout in particular.

• Asymptomatic hyperuricemia shouldn’t be treated even though some studies have demonstrated that urate crystals deposit in soft tissues.
• Patients with uric acid higher than 11 milligram per deciliter who over excrete uric acid are at an increased risk for renal stones / impairment. Renal function should be closely observed in such individuals.
•  In patients with gout + uric acid levels greater than 7 , with urate level lowering therapy, renal improvement was 37% more than if left untreated.
• In severe Gout where tophi are present and frequent attacks occur , the target for uric acid is lower than 5 milligram. In gout without tophi and less frequent attacks the Uric acid level target is less than 6.

Treatment Targets

• Uric acid level target
• Decrease tophi size and number
• Decreased flares/ acute attacks
• Decreased overall pain index

• Septic Arthritis should always be ruled out in a red hot and tender joint.
• With regards to Flare NSAIDS, steroids colchicine ACTH and intra articular steroids are mainly employed as treatment options.
• Uric acid lowering therapy should not be started in an acute flare unless the renal uric acid overload is profound.
• If allopurinol was already in use then it should be continued even in a flare.
• A single attack of gouty Arthritis does not indicate uric acid lowering therapy.

The indications are

•  Recurrent attacks / acute flares
• Tophaceous gout
• Renal dysfunction with gout
• NSAIDS should be given for a course of 5 days at full dose. They should be tapered off over the next two weeks.

• Gout symptoms should be absent for at least 2 days before therapy with non steroidal anti inflammatory drugs is stopped.

• It has a narrow therapeutic index and is only indicated in the first 36 hours of an acute flare in hourly regimens.
• It is given as a 1.2 mg dose orally followed by a 0.6 mg dose at an interval of 1 hour and then according to the symptomatic relief.
• It is contraindicated if the GFR is less than 10 ml per minute.
• One should decrease the dose to half if the GFR is less than 50 ml per minute.
•  It should be avoided in hepatobiliary dysfunction.
• IV colchicine should never be used as it is too toxic.

• Prednisolone at a dose of 40 m per day for a period of 3 days can be initiated.
• The dose should be tapered over the next two weeks.
• Rapid tapering can also lead to acute flare of Gout.
• If the treatment exceeds 2 weeks then osteoporosis cover should be given.

ACTH

• A good alternative to steroids is ACTH as a dose of 40 international units subcutaneously to increase the patients endogenous corticosteroid production via the adrenals.
• Such a regimen isn’t dependent on tapering of the steroid dose as is required with prednisolone.
• If a single option isn’t effective then the above methods can be combined for example colchicine and NSAIDs or corticosteroids can be combined for proper symptomatic relief.

• Lifestyle changes intended to help a patient with gout include losing weight , avoiding alcohol in every form,  avoiding purine rich foods.
• After an acute attack of Gout if the serum uric acid is greater than 9 then allopurinol should be considered for Urate lowering therapy.
• Patients with stage 2 CKD (chronic kidney disease) or a past history of urolithiasis should also be offered urate lowering therapy.
• Medications that need to be avoided in a patient with gout include thiazide diuretics and aspirin.
• If the Uric acid excretion is less than 800 mg over 24 hours on an unrestricted diet then it is termed as under excretion and is an indication for probenecid.
• Xanthine oxidase inhibitors (allopurinol or febuxostat) are first line medications in patients with renal impairment in addition to gout.
• This can be combined with probenecid if the Uric acid level isn’t being lowered sufficiently.
• Do not use probenecid if the GFR is less than 50 ml per minute.
•  In the process of lowering uric acid levels gouty arthritis can be precipitated so prophylactic prednisolone, NSAIDS,  prednisolone or colchicine at a dose of 0.6 milligram oral twice a day can be used for up to 6 months when starting.
•  Another approach is immediate colchicine with no prophylaxis at the onset of pain.
•  If the acute attack occurs after starting allopurinol then it should not be discontinued as it will cause a longer and even more intense attack.
•  Allopurinol starting dose should be 100 mg per day. In renal dysfunction the dose should be reduced to 50 mg per day. The dose should be adjusted upward over a period of 6 weeks if the Uric acid level is less than 6.
• Maximum dose of allopurinol is 800 mg per day. This should be lower in patients with renal dysfunction.
• Febuxostat is metabolized in liver so it can be used without any dose adjustment in patients with renal dysfunction. Its more expensive though. To be on the safe side the dose should be halved if the gfr is less than 30 ml per minute.
• Studies show that febuxostat achieved uric acid target quicker with minimal side effects as compared to allopurinol.
•  Alternative and second line treatment options are also available. Lesinurad (available as zurampic in the market ) is a selective uric acid absorption inhibitor. It is FDA approved but only used in combination with either allopurinol or febuxostat as if used alone can worsen renal function. It is used if the uric acid lowering isn’t achieved alone with the febuxostat or allopurinol.
• Uricase, Its main indication is prevention of tumor lysis syndrome
• Benzbromarone, is a uricosuric agent however it is associated with fulminant hepatotoxicity and is rarely used.
• Vitamin C at a dose of 500 mg per day for 2 months is also used for treatment. However it should be avoided in patients with history of cystinuria or urinary tract stones.
•  Anakinra is an interleukin 1 antagonist. It is used in cases of refractory gout.
• Fenofibrate achieve Lipid lowering + uric acid lowering effect so in patients with deranged lipid profile plus gout fenofibrate can be an option
• Canakinumab is an interleukin 1 beta antibody used in acute gout with good results however FDA approval  for this drug has not been given yet.
•  Uric acid is released from purines. So high purine containing diet should be avoided or consumed in moderation.
• Very high purine containing foods include organ meats like pancreas and thymus, sardines, smelt and sweetbreads. They should ideally be avoided completely.
• Moderately high content of purines is present in trout and Salmon fish, liver Kidneys ,mutton, bacon and Turkey.
• Purines are part of a lot of most protein rich foods and they should not be stopped or eliminated completely.
• Strict lowering of purines diet can reduce uric acid levels by maximum 1 milligram and majority of the diets that do not contain purines are not palatable.
• Tomatoes are low in purines and can be consumed. There is a misconception regarding tomatoes that they are high in uric acid.
• Fruits like avocado, apple, banana, pineapple, dates, figs , kiwi are also high in purines and should be consumed in moderation.
• But restriction can lead to lesser flares.
• High Fructose corn syrup , naturally sweet juices and table salt are to be avoided or limited at least. Good hydration should be maintained consuming at least 8 glasses of 250 ml liquid per day.
• Rheumatology consultation should be sought if the acute gout attack does not respond to NSAIDS within 2 days and colchicine within one day.
• DASH diet is more palatable then a low purine diet and can be helpful in lowering the symptoms associated with gout.