Efficacy And Tolerability Of Pegloticase For The Treatment Of Chronic Gout In Patients Refractory To Conventional Treatment

Content

• The Link Between Gout And Kidney Stones
• How Is Gout Treated?
• Management
• Risk Factors
• How Can I Manage My Gout And Improve My Quality Of Life?

Increased uric acid blood levels and formation of uric acid crystals in the joints are associated with gout. The primary risk factor is hyperuricemia, although only a small proportion of patients with hyperuricemia develop gout, often taking 20 to 30 years to develop. The two mechanisms by which hyperuricemia can develop are either undersecretion of uric acid by the kidneys or overproduction of uric acid (only 10% of cases).

For the latter, even a very strict diet only reduces the blood uric acid by about 1 mg/dL- not enough, in general, to keep uric acid from precipitating in the joints. The cutoff where patients with gout seem to dramatically reduce their number of attacks is when their uric acid level is taken below 6.0 mg/dL. Whatever the mechanism of the elevated uric acid, the key event in gout is the movement of uric acid crystals into the joint fluid. The body’s defense mechanisms, including the white blood cells engulf the uric acid crystals, which leads to a release of inflammatory chemicals which cause all the signs of inflammation, including heat, redness, and swelling and pain. This cycle also recruits more white blood cells to the joint, which accelerates the inflammatory process.

The Link Between Gout And Kidney Stones

Symptoms of dehydration include headache, lightheadedness, constipation, and bad breath. Treatment for dehydration is to replace lost fluids and electrolytes. Uric acid can deposit in the soft tissues, especially around joints, and cause nodules known as tophi, which can be large and unsightly.

How Is Gout Treated?

Aggressive medical treatment improved hyperuricemia and facilitated the surgical approach that was initially aimed to control inflammation and avoid amputation. Heterologous, native type I collagen has a known role in tissue repair, promoting fibroblast deposition in the dermal matrix and stimulating angiogenesis, granulation tissue formation, and reepithelization. It is a valid therapeutic option in chronic wound management and along with the usage of silver-containing foam dressings it resulted in an acceptable healing of the ulcer. As is true for many painful conditions, the first-line treatment for a gout attack is taking one of the nonsteroidal anti-inflammatory drugs , such as diclofenac, ibuprofen, or indomethacin. For people who can't take NSAIDs, a drug called colchicine is an alternative.

Therefore, for decades, the purine analogue XO inhibitor urate has remained the mainstay of gout therapy . Since oxipurinol, its metabolite, is renally excreted, allopurinol requires dose reduction in patients with renal impairment . In addition, allergic reactions to allopurinol are not uncommon, and may be severe . In these cases, the nonpurine xanthin oxidase inhibitor febuxostat represents an alternative, because it is chemically distinct and metabolized by the liver and excreted via both liver and kidneys.

The Link Between Gout And Chronic Kidney Disease

Gout must be distinguished from conditions that can cause similar symptoms, such as calcium pyrophosphate deposition , a condition caused by the deposit of calcium pyrophosphate crystals, septic arthritis , and rheumatoid arthritis . The treatment of these conditions is different than those used in the management of gout. A pegylated uricase has been approved for the treatment of chronic gouty arthritis in patients refractory to convent-ional therapy. The recommended dose is 8 mg as an intravenous infusion every 2 weeks. No dose reduction has been recommended in patients with CKD, but pegloticase has not been formally studied in patients with CKD. Radiographs of joints affected by acute gout attacks typically are not useful for the diagnosis of acute gout.

Is gout a symptom of kidney disease?

Kidney disease can lead to gout
When you have kidney disease, your kidneys cannot filter out uric acid as well as they should. Too much uric acid building up in the body may cause gout. Most people with early stage kidney disease do not know they have it. Gout can be a warning sign of kidney disease.

In addition to lifestyle changes, medications play a vital role in gout treatment. There are 2 main classes of medication which lower uric acid levels, thereby reducing the risk of an attack. The first class of medications decreases the amount of uric acid that is produced in the body. These medications are called xanthine oxidase inhibitors, and they block the breakdown of purine into uric acid in the liver.

It is important that damage to bone from gout be diagnosed, since documented damage is a clear indication for long-term therapy . Once damage has begun, it’s important to reduce the total body uric acid level, which, by equilibration, causes uric acid to move out of the joints. This is because the blood and joint levels of uric acid reach a certain level, called a “steady state,” at a given level of blood uric acid.

What is the difference between gout and chronic gout?

It occurs when uric acid builds up in blood and causes inflammation in the joints. Acute gout is a painful condition that often affects only one joint. Chronic gout is the repeated episodes of pain and inflammation. More than one joint may be affected.

Many types of arthritis cannot be prevented and lack medical treatments that reliably work. Gout is different - the treatment is usually straightforward and highly effective. So, if you have gout, ask your doctor about treatment options. Although gout is on the rise, there are now good treatment options for this ancient disease. Like allopurinol, it's been on the market for decades, so it has a long track record. Probenecid works by increasing uric acid excretion by the kidneys so it can trigger the development of kidney stones and is not a good option for people with kidney problems.

Those with gout are at increased risk of hypertension, diabetes mellitus, metabolic syndrome, and kidney and cardiovascular disease and thus are at increased risk of death. It is unclear whether medications that lower urate affect cardiovascular disease risks. This may be partly due to its association with insulin resistance and obesity, but some of the increased risk appears to be independent. No specific agent is significantly more or less effective than any other. Improvement may be seen within four hours and treatment is recommended for one to two weeks.

Oxypurinol is the major active metabolite of allopurinol and is only available in the United States for use on a compassionate basis. Gouty tophi involving the proximal interphalangeal joint with erythema of the overlying skin. The patient should also be counseled about limiting alcohol consumption and gradually losing weight, if obese. This clinical content conforms to AAFP criteria for continuing medical education . By sharing your experience, you’re showing decision-makers the realities of living with arthritis, paving the way for change.

Increased urate production may also occur as a primary hereditary abnormality and in obesity, because urate production correlates with body surface area. People diagnosed with obstructive sleep apnea face a higher risk of developing gout, the most common type of arthritis, according to new research. In people with gout, the joints are the most commonly affected part of the body.

Gout is considered a chronic disease, meaning it does not have a cure and will usually last your whole life. Gout is a chronic condition that causes recurring episodes of acute inflammatory arthritis. Gout involves redness, tenderness, stiffness, and swelling of the affected joints. If the big toes become infected, it is sometimes referred to as podagra. Crystal deposits in the joints can cause some disability because of stiffness and pain.

From developing new therapies that treat and prevent disease to helping people in need, we are committed to improving health and well-being around the world. The Merck Manual was first published in 1899 as a service to the community. The legacy of this great resource continues as the Merck Manual in the US and Canada and the MSD Manual outside of North America.Learn more about our commitment to Global Medical Knowledge. treatment begins with 250 mg orally 2 times a day, with doses increased as needed, to a maximum of 1 g orally 3 times a day. Hyperuricemia is not usually treated in the absence of gout flares. The usual reasons include inadequate education provided to patients, nonadherence, alcoholism, and undertreatment of the hyperuricemia by physicians.

How Can I Manage My Gout And Improve My Quality Of Life?

It has been estimated that there may be as many as five million gout sufferers in the United States. Even more conservative estimates put this number at greater than two million . Population studies from both the Mayo Clinic and from Taiwan have shown significant increases in the prevalence of gout recently as compared to during the early 1990s. It’s important to identify and treat it early to avoid pain and complications.

In contrast, large erosions, with sclerosis and overhanging edges, are very typical radiographic abnormalities in gout, but were not considered here because they are late manifestations of the disease14,15. For all these reasons, radiographic abnormalities were not included in the CGD proposal. We included 549 patients with gout (96% men) of mean age 50 years, disease duration 12 years, and education level 8 years.