Gout
Presented by Christoffer Cansicio
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Introduction
One of the most common causes of chronic inflammatory arthritis in the United States is gout, formerly known as the "disease of kings and king of diseases" and characterized by the deposition of monosodium urate (MSU) monohydrate crystals in the tissues. Since gout was originally identified before the common era, it is the rheumatic condition that is the easiest to understand and treat (Fenando et al. (2022).
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Given that hyperuricemia frequently manifests in people, humans are the only known mammal species can spontaneously acquire gout. The most common factor causing gout is hyperuricemia. Higher serum urate levels increase the risk of gout attacks and make attacks more likely to occur over time. In a study of more than 2000 older persons with gout, those with levels higher than 9 mg/dl had a threefold higher risk of experiencing a flare within the following 12 months than those with levels lower than 6 mg/dl. (Fenando et al. (2022).
Primary a small percentage of these people go on to develop gout, and hyperuricemia is not the only risk factor for the disease. The impact of nutrition on the uric acid levels in other non-uricase-producing species can be evaluated using the lower physiological uric acid range. Consuming animal products like red meat, organ meats like the liver and kidney, and shellfish like shrimp and lobster are dietary sources that can cause hyperuricemia and gout (pork, beef). Alcohol, sweetened beverages, sodas, and high-fructose corn syrup are a few beverages that may also exacerbate this condition.
Gout disease burden has increased according to epidemiological research, which can be largely attributed to sedentary lifestyles and changes in protein diet.
Older age, male sex, obesity, a purine diet, alcohol, drugs, concomitant conditions, and heredity are additional risk factors for gout and/or hyperuricemia. Diuretics, low-dose aspirin, ethambutol, pyrazinamide, and cyclosporine are among the offending drugs. Numerous genes have been linked to gout, according to genome-wide association studies (GWAS). SLC2A9, ABCG2, SLC22A12, GCKR, and PDZK1 are a few of these. (Fenando et al. (2022).
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Anatomy & Physiology
When monosodium urate (MSU) crystals form in joints, bones, and soft tissues, gout develops as a result (Merriman, 2022). Acute arthritis (a gout flare), chronic arthritis (chronic gouty arthritis), and tophi (tophaceous gout) may all occur from it. Although a common and necessary pathogenic factor in the development of gout, hyperuricemia is insufficient to explain the clinical manifestation of self-limited gout flare-ups, chronic gouty arthritis, or tophaceous gout. Hyperuricemia is typically defined as serum urate concentration >6.8 mg/dL. Additionally, MSU crystal formation, deposition in tissues, and acute and/or persistent inflammatory reactions to the presence of such crystals are necessary for these clinical symptoms (Merriman, 2022).
As the gene encoding the enzyme uricase is silenced by mutation, uric acid is the end result of purine metabolism in higher primate species like humans (Fenando et al. (2022). Urate is primarily produced endogenously by the liver, with a minor amount coming from the small intestines. Nearly all urate is filtered by the glomerulus, therefore in steady-state settings, renal excretion controls the body's urate pool. A hyperuremic state results in an expansion of the urate pool. The typical range for urate in men is 800–1000 mg, and for women it is 500–1000 mg. Between 500 and 1000 mg of urate are turned over each day. Children have lower serum urate concentrations, which rise to adult levels during male puberty.
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Gout Flares
Intensely painful and incapacitating inflammatory arthritis, gout flares often affect one joint but can also affect two or more. In a gout flare, therapy aims to quickly and safely end pain and incapacity. Without treatment, the gout flare typically goes away completely in a matter of days to weeks, especially in cases of early illness. However, symptoms improve more quickly when any of a wide range of anti-inflammatory medications is administered (Gafflo, 2022).
A patient is said to have entered a symptom-free (interval, intercritical, or between flares) period once a gout flare has subsided. The majority of patients, however, have flares again and again; with more frequent episodes, flares may be more severe and protracted, shortening asymptomatic times. In order to avoid repeated episodes of gout flare and chronic tophaceous disease, patients with recurrent flares, those who acquire chronic arthritis, or those who develop tophi, can benefit from long-term prophylactic therapy with a urate-lowering drug (Gafflo, 2022).
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Principle of Treatment
Colchicine, nonsteroidal anti-inflammatory medications (NSAIDs), intraarticular and systemic glucocorticoids, nonsteroidal anti-inflammatory drugs (IL-1 beta inhibitors), and biologics are all useful in the treatment of gout flares. Regardless of the specific anti-inflammatory drug utilized, a set of general guidelines are crucial for the efficient management of a gout flare. They consist of the following:
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Early Treatment
As soon as the patient notices the start of a flare, ideally within a few hours after the commencement of symptoms, treatment should begin. The earlier treatment is started, especially if treatment is started at the maximum recommended dose of the selected antiinflammatory drug, the more quickly and completely symptoms are resolved. Once a noticeable reduction in symptoms is attained, patients should continue medication for the length of the flare, usually at reduced doses. (Gafflo, 2022).
Duration of Therapy
With oral glucocorticoids, we occasionally taper more slowly to reduce the chance of a recurrent ("rebound") flare. Complete discontinuation of treatment for a gout flare can typically be done safely within two to three days of complete resolution of the flare.
Treatment for a gout flare may last anywhere from a few days (for example, in a patient treated shortly after experiencing symptoms) to several weeks (eg, in a patient begun on treatment after four or five days of symptoms). If anti-inflammatory medicine is started within 12 to 36 hours of symptom onset, many patients only need it for five to seven days to manage a gout flare. (Gafflo, 2022).
Gout flare prophylaxis
Early on in urate-lowering therapy, low-dose anti-inflammatory therapy should often be continued. Antiinflammatory gout flare prophylaxis, a form of treatment, aims to lessen the likelihood of further flares, which are frequent early in the course of urate-lowering therapy.
Continuing urate-lowering therapy during flares
If a patient is already on urate-lowering medicine (such as allopurinol, febuxostat, probenecid, lesinurad, benzbromarone, or pegloticase) and their gout flares up, they should keep taking it continuously. Temporary discontinuance is not advantageous, and reinitiating the medication after a break from it could trigger another flare.
Although urate-lowering medications don't directly help in treating a gout flare, starting one together with anti-inflammatory therapy is still a viable option because it doesn't prevent the flare from going away.
Tophaceous gout
Although the presence of tophi is an indication for the beginning of long-term urate-lowering pharmacotherapy either during or after resolution of a gout flare to prevent or reverse chronic gouty arthritis and joint damage, the treatment of a gout flare does not differ significantly in patients with or without clinically apparent tophi.
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Gout flare prophylaxis
Continuing urate-lowering therapy during flares
Tophaceous gout
Comorbidities (Gafflo, 2022).
Important comorbidities that are common in gout patients may alter the safety or effectiveness of antiinflammatory drugs, especially in older patients, taking these factors into account is crucial when selecting an antiinflammatory medication for a gout flare. When choosing an agent, the following elements should be taken into consideration:
•Renal function
•Cardiovascular disease, including heart failure, poorly controlled hypertension, and coronary artery disease
•Gastrointestinal disease, including peptic ulcer disease
•Concurrent medication use
•Diabetes mellitus, especially if poorly controlled
•Drug allergy or intolerance
•Concurrent infection
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Initial Treatment
Initial treatment (Gafflo, 2022).
There is no one therapy that works best for all gout patients undergoing a flare; instead, a variety of medications, including systemic and intraarticular glucocorticoids, nonsteroidal anti-inflammatory medicines (NSAIDs), and colchicine, are all beneficial. The opportunity to select the therapy that is most likely to achieve benefit and minimize the risk of negative therapeutic consequences is made possible by the availability of multiple classes of agents and approaches likely to provide treatment benefit. This choice can be made based on an assessment of specific features of the individual patient and the flare history.
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Gout Education Society (2022).
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Non-pharmacological approach
To stop further episodes, gout patients are urged to change their lifestyles. Dietary suggestions include minimizing alcohol use, avoiding meals high in purines (such as meat, shellfish, high fructose corn syrup, and sweetened soft drinks), and choosing low-fat or non-fat dairy products in place of those with higher fat contents. Reduced gout flare-up frequency can also be achieved with weight loss and proper hydration (Fenando et al. (2022).
A good diet can, at most, help lose 1.0 mg/dL of uric acid, but it can also help lose weight, which reduces your risk of gout by three times. Making dietary modifications can also assist you in identifying and avoiding items that set off flares. So along with uric acid-lowering medication, maintaining a healthy weight and adhering to excellent eating habits should be goals (Gout Education Society, 2022). It is recommended to eat low-purine meals. When attempting to eat healthy, the DASH diet and the Mediterranean diet are both excellent guides.
Alterations to your way of life can help lessen the effects of gout on your body. Exercise on a regular basis is a fantastic way to maintain your body in shape. The CDC advises individuals to engage in moderate-intensity physical activity most days of the week for at least 30 minutes. Maintaining a healthy body weight is essential because crash diets and other quick weight loss methods raise the body's uric acid levels. Additionally, it's important to stay hydrated because, according to research, doing so may help prevent kidney stones and constipation, two diseases that can be influenced by gout (Gout Education Society, 2022).
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References
Fenando A, Rednam M, Gujarathi R, et al. (2022). Gout. StatPearls Publishing
Gafflo, A. (2022). Treatment of Gout Flares
Gout Education Society (2022). What is Gout
Merriman, T. (2022). Pathophysiology of Gout
