Pain in Your Big Toe?… Uric Acid Might Be the Culprit
“pearls of wisdom” by the late Dr. Gilbert
For your information re Uric Acid in MPN: Uric acid is a
by-product of the metabolism of nucleoproteins(opens in new tab). These are molecules
that arise from DNA and RNA released by cells when they die.
Patients with MPN turnover a lot of bone marrow cells when they are in a
proliferative phase and, thus, produce a lot of uric acid.
Uric acid is cleared from the blood by the kidney. When levels of uric
acid are high in the plasma there may be crystallization of uric acid
in the joints. This is what produces gout. When a lot of uric acid has
to be cleared by the kidney, uric acid may crystallize in the kidney
tubules, causing kidney stones or sludge that may damage the kidney.
In patients who have a lot of uric acid production it is advisable to
interrupt uric acid metabolism at the step before it is produced from
a precursor called hypoxanthine(opens in new tab). This is a more soluble molecule that
does not precipitate in joints or kidneys and is cleared more readily by the kidney.
Uric acid levels may be measured in the blood. If they are elevated
there is clear cut evidence that uric acid production is increased.
However, even if the plasma level is not increased, uric acid
production may still be increased. This can be detected by measuring
the total uric acid that appears in the urine.
Treatment
I generally use a drug – Allopurinol(opens in new tab) (Zyloprim) – that inhibits the
step that turns hypoxanthine into uric acid(opens in new tab). I use this
as a preventative in patients with MPN. Side effects are unusual and
occur early in its administration. If it is well tolerated, I suggest
that the patient take one pill/day throughout the course of their
disease.
You might want to ask your doctor about this medication. Once gout has
occurred, it must be treated with colchicine and anti-inflammatory
drugs, since uric acid is already crystallized in the joint.
For more information on Gout – click here
Publisher’s Note:
Updated July 2026 with the FDA’s Boxed Warning for Uloric (febuxostat) and current treatment guidance.
Gout is one of several classic symptoms of PV. I suffered from it for 2-3 years prior to diagnosis. The PAIN(opens in new tab) was so intense at times, it felt like a 9000-pound elephant had stepped on my big toe….ouch!! Once I started a daily regimen of allopurinol, the gout has been pretty well under control. As with all drugs, it is important to remember there can be side effects.
While conducting research on gout and allopurinol, I discovered this recent article (July 2015) – Reducing Life Theatening Allopurinol Hypersensitivity by Rachel Stern, MD. Dr. Stern’s commentary is based on a study conducted in Taiwan where 0.4% of new users experienced hypersensitivity reactions. 8.3% of whom died from the drug reaction. In the U.S., allopurinol hypersensitivity occurs one-fourth as often as the Taiwan study. This lower incidence is in part a matter of genetic epidemiology.
Uloric (febuxostat) was the first new FDA-approved gout drug in decades, getting the green light in 2009. While it is not associated with the same hypersensitivity reactions as allopurinol, it is no longer a first choice. In February 2019, the FDA added a Boxed Warning (its most serious warning) to Uloric after a large safety trial showed an increased risk of heart-related death compared to allopurinol. The FDA now reserves Uloric for patients who have failed or cannot tolerate allopurinol. If you are currently taking Uloric, do not stop on your own, as this can worsen your gout. Talk with your doctor about your heart health and whether it remains the right medication for you.
You may find this article helpful if you are suffering from bone and joint pain(opens in new tab).
References
- Stern RJ. Reducing Life-Threatening Allopurinol Hypersensitivity(opens in new tab). JAMA Internal Medicine. 2015;175(9):1558.
- Yang CY, et al. Allopurinol Use and Risk of Fatal Hypersensitivity Reactions: A Nationwide Population-Based Study in Taiwan(opens in new tab). JAMA Internal Medicine. 2015;175(9):1550-1557.
