tophus

Last edited 01/2022 and last reviewed 05/2023

A tophus is a tissue deposit of sodium urate in patients with gout.

Tophi develop in untreated or uncontrolled gout:

Typically tophi form:

• in tendon sheaths
• around joints
• in the pinna

Rarely tophi may develop in:

• fingertips, palms & sole of feet
• eye
• tongue & larynx
• heart

Initially tophi contain soft creamy deposits which become hard with time. A chronic foreign-body inflammatory reaction is produced.

It has been said that gouty tophi were once used by hard up schoolmasters to write on blackboards in the absence of chalk. The story illustrates the relatively painless nature of the gouty tophus, in comparison to the agonising pain of acute gout.

• tophi can become infected, cause pain and lead to a decrease in function
• complications may occur when tophi develop in unusual sites, such as the heart valves, carpal tunnel, larynx and spine

A review (5 trials; n=1796) found that pegloticase is probably beneficial for resolution of tophi (1)

• lesinurad 400mg may be better than 200mg, in combination with febuxostat, but it is not known if this is better than placebo. Lesinurad plus allopurinol is probably not beneficial

Pegloticase is a recombinant pegylated uricase (2)

• is a mammalian recombinant uricase covalently conjugated to monomethoxypoly (ethylene glycol) in order to reduce immunogenicity and maximize solubility and serum half-life
• mean half-life of pegloticase is approximately 2 weeks, significantly longer than its nonpegylated uricase counterpart
• once administered intravenously, pegloticase remains in the circulation, where it degrades urate to allantoin, with the resulting urate concentration gradient drawing further extravascular urate into the circulation to be degraded by the recombinant enzyme
• ultimately leads to a marked decrease in the sUA (serum uric acid) concentration, relative resolution of tophi, and prevention of future gout flares

Reference:

• Sriranganathan MK, Vinik O, Pardo Pardo J, Bombardier C, Edwards CJ. Interventions for tophi in gout. Cochrane Database of Systematic Reviews 2021, Issue 8. Art. No.: CD010069. DOI: 10.1002/14651858.CD010069.pub3.
• Guttmann A, Krasnokutsky S, Pillinger MH, Berhanu A. Pegloticase in gout treatment - safety issues, latest evidence and clinical considerations. Ther Adv Drug Saf. 2017;8(12):379-388. doi:10.1177/2042098617727714