By Neda Amiri, MD, FRCPC, PGY5 (biography and disclosures); Kam Shojania, MD, FRCPC (biography and disclosures)
Part 1: Diagnosing Gout in Primary Care Settings: Do we have to tap?
Disclosures:
Kam Shojania: No conflict of interest. Has been involved with: Augurex, Pfizer, UCB, Abbvie, Janssen, Roche, and Celgene.
Mitigating Potential Bias:
- Recommendations are consistent with published guidelines.
- Recommendations are consistent with current practice patterns.
- Treatments or recommendations in this article are unrelated to products/services/treatments involved in disclosure statements.
Neda Amiri: No dislosures.
What care gaps/frequently asked questions I have noticed:
Despite being one of the most common forms of arthritis afflicting adults, optimal care of patients with gout including treatment of acute attacks as well as long-term management is not always achieved. I have noticed primary care providers are hesitant to initiate allopurinol or titrate to an optimal dose, especially in patients with chronic kidney disease.
We covered the diagnosis of gout in the acute setting in a previous “This Changed My Practice” article (https://thischangedmypractice.com/part-1-diagnosing-gout). In this article, we will specifically address the data supporting management of acute and chronic gout.
Data that answers these questions or gaps:
As per American College of Rheumatology (2012) guidelines for the management of gout, the self-reported prevalence of gout in adults is almost 4% (8.3 million people) in the United States. The rising rate has been attributed to the concomitant rise in comorbidities including hypertension, obesity, type 2 diabetes and chronic kidney disease.
In the setting of acute gouty arthritis, monotherapy with NSAIDs (Naproxen, and Indomethacin), Colchicine, or systemic corticosteroids is recommended, particularly if involving one or a few small joints. Guidelines emphasize that oral colchicine is particularly efficacious when started within the first 36 hours of the attack. In absence of renal impairment, the loading dose is 1.2 mg orally, followed by 0.6 mg one hour later. The colchicine is continued at 0.6 mg daily or twice daily until symptoms are resolved. Corticosteroids (oral or intra-articular) are often considered when either the initial therapy fails, or there are more than two joints involved. The dosing of intra-articular steroids depends on the size of the joint. However, for systemic steroids, Prednisone at 0.5 mg/kg per day for five to ten days is recommended. If the pain is severe or if there is polyarticular involvement, combination therapy can be considered. In cases of inadequate response (defined as less than 20% improvement in pain score within 24 hours or <50% improvement after 24 hours), switching to an alternate monotherapy or adding combination therapy is valid. Additional agents such as interleukin-1 inhibitors (anakinra) are available, but their use is limited by cost and access.
In management of hyperuricemia, the etiology and secondary causes should be considered. Patient education regarding lifestyle recommendations should specifically include avoidance of alcohol (particularly beer), meats (high in purine content), and sugar-containing sodas. If possible, urate-elevating medications such as thiazides or loop diuretic should be substituted with other agents.
Indications for initiating uric acid lowering therapy includes: ³2 gout attacks per year, evidence of tophus/tophi on exam or imaging, history of urolithiasis or CKD stage 2 (eGFR <90) or worse. Both allopurinol and febuxostat may be considered as first choice. However, given the higher cost of febuxostat and similar efficacy between the two, allopurinol is used preferentially in Canada. Initial dose is usually 100 mg and titrated every two to four weeks. If the patient has CKD stage 4 (eGFR <30) or worse, 50 mg is used as the initial dose. This approach has been found to be safe in recent trials in patients with CKD. Uric acid should be measured serially (every four weeks) along with creatinine to ensure patients achieve a target uric acid level of 360 umol/L or less. To prevent acute gout attacks at the initiation of therapy (Also referred to as “mobilization gout”), colchicine at a dose of 0.6 mg (daily or twice daily) can be used for the first three to six months.
What I recommend:
- Acute Treatment of Gout: In absence of contraindications or major comorbidities, I use mono or combination therapy with NSAIDs and colchicine in the acute treatment of gout. I use the “loading dose” of colchicine at 1.2 mg, followed by 0.6 mg an hour later, followed by 0.6 mg PO BID until the patient’s symptoms resolve (if no renal impairment).
- In absence of significant clinical improvement (or polyarticular involvement) I inject the active joints with methylprednisolone or I start the patient on prednisone 0.5 mg/kg for 5-10 days; alternatively if there are limited joints involved and they are accessible for injection, I consider glucocorticoid injection.
- Uric acid lowering treatment is indicated in patients who have a) history of renal stones; b) tophi (on exam or imaging); c) more than 2 attacks per year; d) CKD stage 2 or worse (eGFR <90).
- Allopurinol is my first uric acid lowering therapy of choice. I start Allopurinol at 100 mg PO daily and titrated by 100 mg every 2-4 weeks until the serum uric acid goes below 360 umol/L. If the patient has CKD stage 4 (eGFR <30) or worse, I start at 50 mg PO daily, and increase slowly.
- I consider HLA-B*5801 testing in patients who are of Han Chinese, Thai or Korean descent, given the increased risk of Allopurinol hypersensitivity syndrome in those with this HLA subtype.
- Patients who develop a rash with allopurinol can usually be switched to febuxostat 80mg daily.
- I obtain monthly uric acid, creatinine, and liver enzymes to ensure that the target uric acid (below 360 umol/l) is being reached.
- Patients who have an unclear etiology of hyperuricemia, have difficulty reaching their target uric acid levels (especially in the setting of renal impairment) or have adverse events with uric acid lowering therapy should be referred to rheumatology for further assessment and treatment.
- The most common cause of treatment failure in gout is medication non-adherence. Patient education is important to ensure adherence.
Remember that gout is the most common inflammatory arthritis in men and can be successfully managed in almost all patients.
References
American College of Rheumatology Guidelines for treatment of gout. 2012 http://www.rheumatology.org/Portals/0/Files/Gout_Part_2_ACR-12.pdf
Handouts for Patients:
- http://rheuminfo.com: helpful website designed and operated by Canadian Rheumatologists. They have handouts on Colchicine, Allopurinol, NSAIDs for review of side effects, as well as information on gout, and its treatment.“Gout Counseling Tool” for patients: http://rheuminfo.com/wp-content/uploads/2011/04/GOUT_PRESCRIPTION_2011.pdf.
- https://www.rheumatoidarthritis.org
Additional Reference:
- Becker MA,Fitz-Patrick D, Choi HK, Dalbeth N, Storgard C, Cravets M, Baumgartner S. An open-label, 6-month study of allopurinol safety in gout: The LASSO study. Semin Arthritis Rheum. 2015;45(2):174-83. (View with UBC) DOI: 10.1016/j.semarthrit.2015.05.005
- Stamp LK,O’Donnell JL, Zhang M, James J, Frampton C, Barclay ML, Chapman PT. Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment. Arthritis Rheum. 2011 Feb;63(2):412-21. (View with UBC) DOI: 10.1002/art.30119
Resources:
https://www.rheumatoidarthritis.org/
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This is a helpful article. Personally I like to inject acute joints with steroid when possible. I will certainly consider combination NSAID/colchicine in resistant episodes of gout.
I usually treat with Indocid but now will add Cochicine
Good summary of steps to treat gout.
I also encourage drinking of lots of water (lowers uric acid) and 1 or 2 Vitamin C 500 mg (folklore suggests ‘black cherry juice’) to also lower uric acid.
In addition I suggest avoiding soft drinks with fructose sweetener and gradual weight loss.
Patients appreciate the ‘non-medical’ interventions in addition to the very necessary treatment of acute inflammation.
I was unaware of testing for HLA-B*5801 status. Thanks for that tip!
Is there any role for splinting in acute gout?
some good tips, thanks – #9 especially is a good reminder
a few important points:
1) diet and lifestyle have been omitted from this article; there is very little evidence around this – only observational studies so far showing an association (http://www.cochrane.org/CD010039/MUSKEL_lifestyle-interventions-for-chronic-gout). Since that review, one paper https://www.ncbi.nlm.nih.gov/pubmed/26500085 suggests presentation with gout is correlated with a 9-fold increase in alcoholism. It is yet to be determined whether asking about alcohol intake (or any intervention) could decrease the number of gout flares an individual has.
2) there is some evidence to suggest that ongoing/high dose (4.8 mg total over 6 hours) treatment with colchine is not better than low dose (1.8mg over 1 hour) but may cause more harm for acute flares:
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0013795/ (Cochrane review)
http://www.ncbi.nlm.nih.gov/pubmed/query.fcgi?cmd=Retrieve&list_uids=20131255&dopt=Abstract (LOE = 1b, featured as an infoPOEM)
3) choice of NSAID
for some reason, indomethacin (indocid) keeps getting used for gout. ANY NSAID will do and some have fewer adverse events and/or lower costs. Naproxen is considered the safest with respect to cardiovascular risk profile though other considerations may apply
4) monthly uric acid levels may be excessive and are unlikely to change management; UpToDate suggests “Serum urate levels should be monitored to assure maintenance of concentrations in the goal range and to permit antihyperuricemic drug dose adjustment as needed. One approach is to determine serum urate concentration within two to four weeks of a dose adjustment, with confirmation three months later. Once goal values are confirmed, measurement every six months for the next year and then annually is usually adequate, unless drugs or lifestyle factors potentially altering urate levels have been introduced in the interim.”
5) RheumInfo is unfortunately has pharma-funding as does Dr S and so the advice offered must be viewed with these considerations in mind.
Hello,
Thank you for this helpful article.
Is HLA-B*5801 status testing covered by MSP?
How does a positive test for HLA-B*5801 change management? Would you suggest avoiding allopurinol completely or start at a lower dose and titrate more slowly?
How long we should keep the patient on ALLOPURINOL?
Thanks everyone for your comments and feedback.
Dietary changes should definitely be discussed with patients – alcohol, red meat, in addition to high fructose corn syrup containing foods/beverages. Hydration is important as mentioned above. Furthermore, cherries have been shown to be uricosuric, and a handful cherries once daily sound reasonable to us. However, these alone may not be sufficient to prevent further occurrences of gout in your patient.
There is currently no role for splinting/immobilization in acute management of gout. I called BC Bio Laboratories. It appears the HLA-B^5801 testing is covered by MSP (the blood gets sent to Vancouver General Hospital lab for testing). I would avoid starting Allopurinol in patients who test positive, given the high likelihood of adverse reactions.
Allopurinol is considered a “life long” treatment. Of course, if a patient has not had a flare in years, and is insistent to be taken off the medication, this can be attempted. But they should be warned they will likely have another flare.
I had always considered Indocid as the Go-To NSAID for gout, but will now use the others more readily. I don’t think Indocid is covered by Pharmacare without Special Authority – and I rarely request it – so there can be added cost to patient. I will more eagerly add Colchicine to acute therapy.
Thank you for excellent summary.
Very useful article especially about treatment of acute gout. The combination of NSAIDS and Colchicine sounds great and also the use of Allopurinol in ckd patients and the tips to prevent acute attacks.
My 47-yr old male patient has been on Allopurinol for circa 6 years.
2.5 years ago he suffered a concussion via a hit in the back of the head. He has since complained of brain fog and fatigue that has not improved. The brain fog did not intensify until 3-4 months post concussion.
The patient believes the allopurinol is driving the brain fog and making the concussion recovery slower as the fog seems to lessen when he takes Allopurinol less frequently.
Has anyone else dealt with this symptom presentation? Or seen brain fog as a side effect? Some patients in inline forums have also complained of intense brain fog and fatigue.