Primary Care Corner with Geoffrey Modest MD: Oral Steroids for Acute Gout?

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By Dr. Geoffrey Modest

A recent study from 4 EDs in Hong Kong looked at the relative efficacy of oral prednisolone vs indomethacin in the treatment of acute gout attacks (doi=10.7326/M14-2070​).

Details:

  • 416 adult patients (mean age 65, 75% male, mean duration of symptoms 2.8 days, mean pretreatment pain score using a visual analog scale VAS from 0-100 of 33mm at rest and 81mm with activity, 71% with recurrent gout, 83% with monoarthritis, lots of medical comorbidities, 43% with first MTP joint, 62% with knee, ankle, wrist, or elbow; tophi in 15%). Gout was not confirmed by joint aspiration
  • Randomized to indomethacin 50mg tid for 2 days, followed by 25mg tid for 3 days; vs prednisolone 30mg daily for 5 days.

Results:

  • No statistically significant difference between the meds either while in the ED at rest or with activity; or from days 1-14 afterwards
  • While in the ED: the VAS decreased from about 30 mm to about 20mm at rest  and from 80 to about 60mm with activity, with a very slow decrease over a 4 hour period
  • For the 1-14 day follow-up: the VAS decreased from about 35mm at rest to about 10mm by day 6 and leveled out thereafter; and from about 60mm with activity down to about 20mm by day 6 and leveled out thereafter. Of note, a VAS change of 13mm is considered clinically meaningful.
  • ​Adverse events: at least one adverse event in the first 2 hours in the ED in 18.8% on indomethacin and 6.3% on prednisolone; and at least one from days 1-14 in 37% on either indomethacin or prednisolone. Though no serious events, 8 patients required discontinuation of treatment (7 with indomethacin)

So, a few comments:

  • The latest Am College of Rheum guidelines recommend several approaches to the management of acute gouty attacks, including oral steroids along with nsaids and colchicine (with the comment to consider intraarticular steroids). These guidelines were in 2012 and predate the BMJ blogs, so will append my analysis of them below, including both the management of acute gout and
  • I personally do not think there is any role for indomethacin, since there seems to be equivalence with other nsaids in treating the acute attack, and indomethacin seems to tear up the stomach pretty effectively. (This data on nsaid equivalence has been around for a long time, and the Am College of Rheum guidelines comment that there are good data supporting naproxen and sulindac, and that others are probably fine. Ibuprofen has also been used a lot locally with good effect)
  • BUT, my drug of choice for many years has been injected steroids if there are only a few joints involved. And, the more I do it, the more impressed I am. basically, I inject a 50:50 combo of an intra-articular steroid (e.g. triamcinolone 40mg/cc) plus lidocaine 1%, mixed in a single syringe, then I put on a really small bore needle (no larger than 27 gauge). The size of the needle varies a bit (e.g. 30-gauge with first MTP joints, most others 27-gauge) and the volume varies (from about 0.5 cc in a first MTP and up to 3cc in a knee).

My results:

  • 100% effective, within minutes (from the lidocaine), and long-lasting. (i.e., the patient walks comfortably out of the office within 10 minutes of the injection, and returns smiling/dancing a week or 2 later)
  • And this is true for really small joints (first MTP) as well as the big ones. (And I’m sure I have done >30 injections over the years for gout, though almost all have been first MTPs or knees)
  • The injection seems to work even after the gout has been around a few days (i.e., unlike colchicine, which should be given right away)
  • And, though the gouty joint is very very tender, swollen, and often with indistinct landmarks, injections are really well-tolerated by the patients (even those needle phobic, given the underlying intensity of the gout pain). It is important to note that, especially with the first MTP joint, I only occasionally actually get into the joint (and I assume I get into the joint only because the needle seems to travel the expected distance in the joint). But the injection still works even when I pretty clearly do not get into the joint.
  • And, also, I have seen 0 (as in, zero) adverse effects from the shots. And no systemic effects of the steroids on diabetes, etc. (though, per blog https://stg-blogs.bmj.com/bmjebmspotlight/2014/11/19/primary-care-corner-with-geoffrey-modest-md-avoid-giving-steroids-with-ritonivir/ , I would not give any steroids, intra-articular, intranasal, or otherwise in patients on ritonivir).

Prior blog from 10/11/12:

Am college of rheum just published a new set of guidelines for managing hyperuricemia (see DOI 10.1002/acr.21772) and acute gouty arthritis (see DOI 10.1002/acr.21773 ). Several points:

  • Increasing prevalence of gout, now 3.9% in US, prob from increasing comorbidities which lead to high uric acid (obesity, htn, metab synd/dm, ckd), drugs which inc uric acid (thaizides/loop diuretics) and diet/alcohol.  More complex to treat, given pts are often older and have lots of these complex comorbidities/complex med regimens. They do note that low-dose asa can inc uric acid, but consider this to be likely a non-modifiable agent
  • This article not address asx hyperuricemia, since little data
  • Major clinical manifestations of hyperuricemia is acute gout; less commonly as chronic goutyarthritis,  tophi, urolithiasis. Urate nephropathy, in spite of older studies, seems to be very uncommon
  • This task force looked at different case scenarios, varying from mild to severe activity in pts with intermittent sx (from <=1 attack/yr up to >7/yr), with and without tophi, as well as those with chronic tophaceous goutand few or many joints involved. They noted specifically that the quality of supportive evidence was often low, so consensus opinion often prevailed
  • They suggest that urine uric acid be checked for uric acid overproduction in pts with clinical goutbefore age 25 or hx of urolithiasis
  • Dietary recommendations overall:avoid purine-rich meats (organ meats), high-fructose corn syrup (my experience is that uric acid does come down significantly with limiting this and should be a primary dietary target), alcohol overuse (>2/d for men and 1/d women), and avoiding all alcohol in those with frequent attacks or advanced gout not well-controlled (beer also may be worse than wine and spirits). Also limit red meats, high-purine seafoods (shellfish, sardines), naturally sweet fruit juices, table sugar and table salt/very salty foods). And encourage low fat dairy and vegies.
  • Meds: first-line rx of xanthine-oxid inhibs — XOIs  (allopurinol/febuxostat — they do not state preference, though note that lack of safety data of febuxostat in those with stage 4 or worse CKD. They also don’t deal with med costs). Probenecid ok in those intolerant of XOIs, but not in those with creat clear of <50. Okay to start XOIs in setting of acute attack, BUT ONLY if adequate anti-inflam management (these agents can precipitate attacks)– see below. When using these agents, check uric acid every 2-5 weeks during the titration and q6 months when appropriate uric acid level achieved  (target of at least <6mg/dl, often <5 esp if sx not controlled or if tophi present).
  • From their case scenarios, they suggest the following meds: single agent XOI in patients with any intermittent sx, with or without tophi, and any chronic goutpatient, with a +/- indication only for those with <= 1 flare/year. In their cases if not achieve target uric acid and sx persist, then add uricosuric agent to XOI. Then if serum urate continues too high and sx persist, and if patient has >7 flares/yr (with or without tophi), or if chronic gout, then consider using pegloticase (i.e., rheum referral)
  • Allopurinol dosing: (pretty complicated). Basically, don’t start at more than 100mg/d (to minimize goutflare and dec likelihood of AHS = allopurinol hypersensitivity syndrome, which is in about 1/1000 pts with stevens-johnson and toxic epid necrolysis, but also can present with systemic dz with eosinophilia, vasculitis, rash, end-organ dz — esp prevalent in those on thiazides and pre-existing renal dz). Start allopurinol at 50mg/d if pt has CKD stage 4 or worse. The AHS usually happens within first few months of therapy. Patients from Korea with stage 3 or worse ckd, or in any Chinese/Thai patients are genetically at high risk of HLA-B*5801 allele, which predisposes them to AHS, and should be screened for the allele prior to starting allopurinol. This consensus conference does not recommend more universal screening. Max dose of allopurinol is 800mg/d and for febuxostat can go to 120mg. They note that the generally held max of 300mg/d will fail to reach goal uric acid in the majority of cases, and that it is okay, with care, to increase to 800mg/d. They note, without a clear maximum, that it is okay to go >300mg/d even in pts with CKD, though they express some concern about long-term safety of >300mg/d esp in those with CKD.
  • For primary therapy with uricosuric: contraindicated if has urolithiasis (drug assoc with 10% development of urothiasis). Need to measure initial urine uric acid and not use if high. Probenecid and increased fluids is first line Rx. They do note that one can use losartan or fenofibrate, which are uricosuric (several months ago I sent out an interesting BMJ article which showed lower likelihood of developing goutin hypertensive pts on losartan — Not other ARBs — or calcium channel blockers — see  DOI: 10.1136/bmj.d8190).
  • In terms of imaging, the guidelines are a little unclear. Seems that there was some support in the group for using high-resolution ultrasound, CT or dual-energy CT to detect tophi, and note that plain x-rays looking for bone erosion suggestive of tophi might be useful in guiding therapy

For treatment of acute attacks:

  • Several case scenarios, with the attack (on scale 0-10) being mild (<4), moderate (5-6) or severe (>=7); duration of early (<12h), well-established (12-36 h) or late (>36h); and extent being one or few small joints, 1-2 large joints, or polyarticular.
  • They recommend treatment begin within 24 hours (though, as above, this is consensus guidelines with little clear data from randomized trials)
  • Continue urate lowering therapy during treatment of acute attack
  • In pts with mild attacks involving a few small or large joints, monotherapy with nsaid, systemic steroids or oral colchicine (colchicine only if started within 36 hrs of onset of attack). In pts with severe pain, esp if polyarticular or 1-2 large joints, they support combo therapy (colchicine + nsaids, oral steroids +colchicine, or intra-articular steroids with above.
  • NSAIDS — recommends full-dose. Best data for naprox, indomethacin, and sulindac. Others prob ok (many of us have used ibuprofen with good effect). Can use celecoxib. Use till attack completely resolved. Consider tapering off then, though no clear guideline on tapering.
  • colchicine — load with 1.2 mg, then 0.6mg once or twice daily (unless need to dose adjust, e.g. for renal insuff or if used with other drugs which inhib P-450, like clarithro, erytho, etc.)
  • Steroids — consider intra-articular injections if 1-2 large joints involved, otherwise oral steroids (my experience is really different: given toxicity of nsaids, other oral agents, etc. in my older patients with comorbid conditions, I mostly use intra-articular steroids if only 1-2 joints, and have had 100% success even in patients with only a small joint such as 1st MTP involved — even if I do not get the needle into the joint space, which happens probably 50% of the time). If giving oral steroids: 0.5 mg/kg for 5-10 days without taper, or 2-5 days fulldose with 7-10 day taper. can also give triamcinolone 60mg IM followed by pred)
  • If inadequate response (defined by the consensus group as <20% improvement in pain score within 24 hrs or <50% after 24 hrs), first consider an alternative dx (they do not mention it, but a joint deformed previously by a goutyattack is more susceptible to a septic arthritis, so this should always be in the differential). If still likely gout, consider a different monotherapy or just add another agent. In severe cases, consider IL-1 inhibitor… (i.e., refer to rheum)
  • Some utility to topical ice application as an adjuvant to above
  • As above, there is a significant incidence of acute goutassoc with starting uric acid lowering therapy: so, should prophyllax, preferably with colchicine 0.6mg 1-2x/d (dose adjust if CKD, though no consensus on exactly how — some suggest 50% lower dose if creat cl <50). Can also try lower dose nsaid (e.g. naprox 250bid) with PPI, though not much data on that. Also can try low dose pred (<=10mg/d), but also little data. Should continue prophyllaxis if there is any clinical evidence of gout or recent gout attack or chronic gouty arthritis for 6 months, or for 3 months after achieving target urate level if no tophi, 6 months if tophi
  • Again, as with the first guidelines, 70% of these guideline recommendations are NOT based on high quality trials, but on lesser trials and expert opinion.

One issue not addressed is the use of colchicine for gout prophyllaxis in patients with pretty frequent attacks and no tophi. This has fallen out of favor, since the uric acid level is not lowered (which may or may not be really important) and because of potential toxicity (e.g., myopathy or neuromyopathy). In the older literature, this was a very acceptible longterm prophyllactic regimen. I have used colchicine as prophyllaxis a lot (given the potential problems with allopurinol, I have had several patients on colchicine 0.6mg/d with excellent acute gout prevention and long-term tolerability — for many years in some cases. So, I’m not so convinced. No question about using allopurinol/XOI for pts with tophi.)

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