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June 9, 2023 BlogGoutMedEvidence

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Gout has been called the “disease of kings.” This is in part because of its ancient association with lavish, relaxed lifestyles. It is also in part because the disease is old enough that kings were common. Gout was first identified around 4,600 years ago in Egypt as an affliction of the joints. Since then, it has moved from the disease of kings to that of the common man. Gout affects over nine million Americans. Its underlying partner in crime, elevated uric acid in the blood (hyperuricemia), affects over 32 million. The disease is most common in middle-aged men. There is a genetic component:   Mexican Americans have a lower risk than White or Black Americans. In this article, we’ll dig into the nitty gritty of what gout is, how it works, and what we can do about it.

On its surface, gout is straightforward. Uric acid forms crystals in the joints, causing arthritic inflammation. Uric acid is commonly and unfairly dismissed as a waste product. It is formed when the body breaks down purines – one of the building blocks of DNA. Purines are found in high levels in the meat and seafood we eat and are also normally produced in the body. Uric acid circulates in our bloodstream, acting as a powerful antioxidant. It cleans things up and is expelled in the urine. Unsurprisingly, urine is where uric acid gets its name. It is protective when it’s in the right places in the body – and at the proper concentrations. When we have too much uric acid, problems begin. At high concentrations, it condenses into sharp, needle-like crystals. These build up in our joints.

Let’s pivot for a moment. Why would uric acid concentrations be high? There are two major mechanisms: either we make too much uric acid, or we don’t get rid of it well enough. Creating too much uric acid is actually relatively rare, making up only 10% of cases. It may be influenced by consuming meat, seafood, and beer. Low exercise, high weight, and metabolic syndrome may contribute, as do some cancers and tumors. The vast majority of cases are from an underexcretion of uric acid. This could be from other medicines, kidney issues, alcohol consumption, or genetics. We can have high concentrations of uric acid in the blood and crystals in the joints without other symptoms. This is called asymptomatic hyperuricemia. A- at the front means “not,” so asymptomatic indicates that there are no symptoms. Hyper- indicates “too much,” uric refers to the uric acid, and -emia means “presence in blood.” Asymptomatic hyperuricemia means there is too much uric acid in the blood, but there are no symptoms.

The first stage of symptoms takes the form of acute gout attacks. This is where we can see intermittent periods of often very painful symptoms. Uric acid crystals accumulate in the joints, and the body needs to get rid of them. Unfortunately, the body can’t just delete things it doesn’t like and make them disappear forever. Instead, the body uses the immune system. Three major types of cells intervene. Macrophages, also called monocytes, are gigantic immune cells that eat things. Genetic and acquired differences between people can result in different skill levels of macrophages. For many people, the problems stop here; macrophages eat the uric acid crystals, and no problems emerge. Likely these people would have asymptomatic hyperuricemia. For an unlucky subset of people, their macrophages can’t deal with the crystals by themselves, so they call for help using powerful chemicals. These calls bring in mast cells, which sound an alert and release other potent chemicals. These chemicals include histamines, cytokines, and hormones which cause inflammation and sometimes destroy the crystals. With an acute gout attack, however, neutrophils are brought in. Neutrophils are big bad destructobots that follow the chemical trails released by macrophages and mast cells. They come in and smash everything rapidly. This leads to an acute or rapid onset gout attack. It hurts a lot, and they clear out some of the uric acid crystals.

After acute gout attacks, it may take a bit for crystals to form again or for an immune response to trigger. This is called the intercritical period and usually has few or no symptoms. Unfortunately, this intercritical period tends to shorten over time, meaning attacks become more frequent.

The fourth and final stage of gout is chronic gout. This is a very painful, destructive stage. Crystals form into big, visible deposits called tophi (plural for tophus). A tophus is a swollen area filled with white and chalky uric acid deposits—these form in cartilage, around joints and tendons, and occasionally in the kidneys. The kidneys are in charge of filtering uric acid from the blood, so this creates an accelerating feedback loop. Tophi formation is accompanied by constant joint inflammation. Inflammation chemicals and tophi formation together erode bone and degrade cartilage. This is very painful and gets worse over time.

So what can be done? The first and most important is diagnosis. Gout is common but can look like other types of arthritis, so getting accurate labs and imaging is vital. If gout is positively identified, a flare-up might be helped using medication. NSAIDs like aspirin or ibuprofen are widely used but may be dangerous if you have kidney failure, which may be a cause of gout. Colchicine is also contraindicated by kidney failure, as well as many other medications. Steroids work well but come with several side effects. Each of these, as well as off-label choices, can also seriously interact with other medications and should be discussed with your doctor before use.

Chronic gout must be treated at a systemic level. Education, such as this exact article you are currently reading, is a significant first step. Consider discussing uricosuric medications in detail with your doctor. Early treatment can be successful, so be vigilant! Lifestyle changes may also help. This includes limiting meat and seafood intake, cutting back on sugary soda and beer, and increasing exercise, vegetables, and possibly vitamin C. Urate-lowering drugs, such as allopurinol, are effective but may come with side effects. These reduce the formation of uric acid or reduce the absorption of it into the bloodstream. By lowering the amount of uric acid in the bloodstream, deposits in joints will start to break down, resulting in painful flare-ups as the uric acid is cleared away. This is painful enough that it is difficult for many patients to stay on their medicine. Hopefully, new medicines will help people break up this painful condition. Though the age of kings is mostly gone, gout can still be a royal pain.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA


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Sources:

Nuki, G., & Simkin, P. A. (2006). A concise history of gout and hyperuricemia and their treatment. Arthritis research & therapy, 8(1), 1-5. https://arthritis-research.biomedcentral.com/articles/10.1186/ar1906

Ragab, G., Elshahaly, M., & Bardin, T. (2017). Gout: An old disease in new perspective–A review. Journal of advanced research, 8(5), 495-511. https://doi.org/10.1016/j.jare.2017.04.008

Singh, G., Lingala, B., & Mithal, A. (2019). Gout and hyperuricemia in the USA: prevalence and trends. Rheumatology, 58(12), 2177-2180. https://doi.org/10.1093/rheumatology/kez196


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