Using Genetic Testing From Theory To Reality
An area of research with the potential to change the field of gout is understanding the underlying genetics. This may lead to personalized treatment in gout patients. However, the knowledge gap regarding the effect of genetic testing on clinical outcomes contributes to this approach not being part of the standard of care.
Numerous genetic markers associated with hyperuricemia and gout were identified in genome-wide association studies . Many of those associated with gout are related to urate transporters and the NLRP3 inflammatory process.53,54
One of the most important susceptibility loci for hyperuricemia and gout is the adenosine triphosphate binding cassette subfamily G located on chromosome 4q. ABCG2 is a urate-transporter gene involved mainly in urate excretion. ABCG2 variants have been associated with earlier onset of gout, development of tophi, and inadequate response to allopurinol.55 The predictive role of the ABCG2 variants on gout susceptibility varies with gender and ethnicity, as seen in a meta-analysis of 7 case-controlled studies.56 Identifying gene variants may be used in the future to counsel patients of their genetic risk, which may factor in the decision to treat a patient with ULT earlier. However, there is currently not enough data to support the clinical use of the ABCG2 gene variant.
Why Was Gout So Common
Gouturic aciduric acidgoutGoutmore commonly
. Keeping this in view, why is gout becoming more common?
Gout on the Rise in the U.S. July 28, 2011 — Gout has become more common in the United States in the past two decades, in part because of the nation’s obesity crisis and a greater frequency of high blood pressure, new research indicates. And the risk of getting gout increases with age.
how did they treat gout in the old days? An Ancient Gout RemedyColchicine, which is a drug derived from a flowering plant called the autumn crocus, was first used as a laxative in ancient Greece. Cochicine, if given early during an attack, will relieve gout pain. Other medications, including probenecid and allopurinol, are used to prevent gout.
In this manner, why was gout referred to as the King’s Disease?
Gout. Perhaps the oldest known type of arthritis, gout or gouty arthritis, has a long and colorful history with some of the earliest descriptions dating back as far as the 5th century B.C. Historically, gout as been âthe disease of kingsâ due to its association with rich foods and alcohol consumption.
Who gets gout more?
Gout is about four times more common in men than women. It can affect men of any age, but the risk is greater as you get older. Women rarely develop gout before the menopause. This is because the female hormone oestrogen increases how much urate is filtered out by the kidneys.
Getting The Most From Your Treatment
- Try to keep your regular appointments with your doctor. This is so your doctor can check on your progress. Your doctor will want you to have a blood test to check that the level of uric acid has come down. This is often done a month or so after starting allopurinol.
- Remember, allopurinol should be taken every day to prevent a gout attack. It can take 2-3 months to become fully effective. It does not have any effect during a gout attack, although you should continue to take it regularly every day even if this happens.
- During the first few weeks of taking allopurinol, your blood levels of uric acid may rise for a short while before they fall. This can cause a gout attack. Your doctor will prescribe an anti-inflammatory treatment or colchicine tablets for you to take alongside allopurinol during this time.
- Treatment with allopurinol is usually long-term unless you experience an adverse effect. Continue to take the tablets unless you are advised otherwise by a doctor.
- There are a number of lifestyle changes that you can make to help reduce the risk of having a gout attack. These include losing weight , eating a healthy diet and not drinking much alcohol or sugar-sweetened soft drinks. Your doctor will advise you about the changes which could benefit you.
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What Does Allopurinol Do In Acute Gout Attack: What You Need To Know
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How Acute Worsen Gout Allopurinol Does
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What Are The Main Risk Factors For Gout
The single most important risk factor is sustained hyperuricaemia, which can be caused by overproduction or underexcretion of urate.23 Pathological hyperuricaemia has been defined as the serum uric acid concentration above which monosodium urate crystals form in vitro at physiological pH and temperature. For most people with gout, underexcretion is the main cause of hyperuricaemia. Other factors associated with the development of gout include drugs , renal impairment, excessive consumption of red meat or seafood, fructose-sweetened
Why Does The Allopurinol Worsen Acute Gout
As mentioned earlier, if it is left undisturbed, the uric acid crystal may deteriorate on the assumption that there will be no uric acid. If it so happens to deteriorate, the uric acid crystal bits being disconnected from it may trigger some autoimmune responses.
Bear in mind that we dont endorse the use of allopurinol. The uric acid crystals may worsen, however, the purine that isnt broken down stays in the bloodstream. This will now then be a long term problem for the liver. With the proviso that the liver perceives the purine, itll keep on pumping more and more xanthine oxidase enzyme.
We actually have lots of other articles which may discuss the side effects of the allopurinol, as well as the natural alternative treatments, which may help in easing the pain and treat gout without depending on a drug that may risk the life.
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Clinical Features And Pathogenesis
Gout is characterised by the acute onset of excruciating joint pain, with associated swelling, erythema and tenderness. The first metatarsophalangeal joint is most commonly affected in the first attack .
Always consider bacterial infection in the differential diagnosis. Other causes of an acute monoarthritis include other crystal arthropathies, such as pseudogout, osteoarthritis, trauma, and rheumatoid and seronegative arthritis.
Gout can be diagnosed on the basis of good history-taking and examination, but when in doubt, the affected joint should be aspirated.
The underlying risk factor for gout is an elevated serum uric acid level, but not all patients with hyperuricaemia will develop the disease. Hence, the clinician should be wary of checking a uric acid level in a well person with no history of gout. The diagram below summarises the pathogenesis of gout which is important to appreciate, in order to understand the aim of therapeutic treatment.
Use Of Prophylaxis When Starting Ult
The flare risk is most significant when urate-lowering is rapid, independent of the ULT chosen. It has been suggested that a slow up-titration of ULT with anti-inflammatory prophylaxis is recommended.48 This approach may delay achieving the SU target of 6mg/dL, but the risk of flares is reduced and may lead to better patient compliance.49 On the other hand, the dramatic SU lowering by pegloticase is associated with a high flare rate due to a marked SU reduction.23 However, it is followed by the cessation of flares after several months of treatment.
The choice of anti-inflammatory prophylaxis should be based on patient factors. The most commonly used drugs are low-dose oral colchicine , NSAIDs, and IL-1 inhibitors . A study of 1167 gout patients found only 37% of patients on anti-inflammatory prophylaxis. Most were on colchicine.50 Another study, the administrative database , found that the proportion of patients receiving prophylaxis with ULT initiation is deficient .52
How long should prophylaxis be prescribed? For at least 36 months, continued prevention as needed if the patient continues to experience flares. Many patients were on prophylaxis for greater than one year.50 Further studies are required to assess the appropriate duration of the prophylaxis cohort .52
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The Irony Of Allopurinol Being A Medication For Gout
It is for a certain that gout has a handful of devastating effects. For this very reason, a lot of medications were invented too. All of which are applying different mechanisms in approaching gout from different sides and angles. The allopurinol, febuxostat, and colchicine are just none but few.
Due to the differences in the medications, a lot of questions arise. All of these questions may be inquiries about the effectiveness, dosage, time of intake, mechanisms, as well as the side effects of the medications.
One common question thats being raised is, Why does allopurinol worsen acute gout? this article wishes to explain the irony of allopurinol being a medication for gout. As well as a medication that may worsen the gout attacks.
What Does A Gout Attack Look And Feel Like What Would A Foot Or Toe With Gout Look Like
When gout occurs, the joint tends to be extremely painful and is warm, red and swollen . The inflammation that is part of a gout attack is systemic, so that fever and chills, fatigue and malaise are not uncommonly part of the picture of a gout attack.
Figure 6: Toe with Acute Attack of Gout
Gout attacks can occur in joints that look normal, or in joints that have easily visible deposits of uric acid. These deposits are called tophi and can be in numerous locations, but especially on the feet and elbows. In Figure 9, the little finger of the right hand is bandaged since fluid was just removed from it, which demonstrated innumerable uric acid crystals.
Figure 7a: Tophi on Foot
Figure 7b: Tophus Over Achilles’ Tendon
Figure 8: Tophus on Elbow
Figure 9: Tophi on Hands
Figure 10: Large Tophus of Finger
While some gout attacks will solve quickly by themselves, the majority will go on for a week, several weeks, or even longer if not treated. Since gout attacks are usually quite painful and often make walking difficult, most gout sufferers will request specific treatment for their painful condition.
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How To Take Allopurinol
- Before you start the treatment, read the manufacturer’s printed information leaflet from inside the pack. It will give you more information about allopurinol and will provide you with a full list of the side-effects which you may experience from taking it.
- If you have recently had a gout attack, make sure your symptoms have completely gone before you start taking allopurinol tablets.
- Take allopurinol exactly as your doctor tells you to. The usual starting dose is one tablet each day, although this may be increased as you go on. Your dose will be adjusted in line with how much uric acid is in your blood.
- Swallow the tablet with a full glass of water, preferably just after a meal. It’s also important that you have plenty to drink throughout the day. Aim to drink 2-3 litres of fluid each day.
- You can take allopurinol at whatever time of day you find easiest to remember however try to take your doses at the same time of day each day, as this will help you to take it regularly.
- If you forget to take a dose, take it as soon as you remember. If you do not remember until the following day, skip the forgotten dose. Do not take two doses at the same time to make up for a missed dose.
Worries That It Might Prove Unfounded In Randomized Trial
Initiating allopurinol during an acute gout attack doesn’t adversely affect the resolution of the attack, according to results of a new placebo-controlled, double-blind study.
The acute gout attack resolved after an average of 13.4 days in patients who received placebo and 15.4 days in those taking allopurinol, but the difference was not statistically significant , Erica H. Hill, DO, San Antonio Military Medical Center, San Antonio, Texas, and colleagues reported in the Journal of Clinical Rheumatology.
- Allopurinol given during an acute gout attack does not adversely affect the resolution of the acute episode.
- Urate-lowering therapy during an acute gout attack should be accompanied by appropriate acute management.
Most patients in both groups had very low Physician Global Assessment scores, and patient-rated pain scores were relatively low for both groups even early into the study.
The results support the 2012 American College of Rheumatology guidelines recommending that urate-lowering therapy can be started during an acute attack, provided patients receive effective acute management.
The analysis included patients with gout who were randomized to receive either placebo or allopurinol for 28 days. The drug was initiated at 100 mg daily for the first 14 days and then increased to 200 mg daily for the next 14 days.
In addition to the study drug, all patients were given prophylactic colchicine, except one placebo patient who took meloxicam.
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Are There Any Side Effects
Most people do not experience side effects from allopurinol. Tell your doctor if you are concerned about any possible side effects.
If you do experience side effects, a reduction in dose may minimise these so that you can continue to take the medicine. Your doctor will advise on any dose changes that are necessary.
Most common possible side effects
- The most common side effects are nausea or vomiting. These can be reduced if you eat little and often. If you are sick, drink plenty of liquid.
Less common or rare possible side effects
There are some rare but potentially serious side effects with allopurinol.
- Skin problems: Allopurinol can cause a rash or flaking skin. Very rarely, severe skin rash and mouth ulceration can occur. If any of these occur contact your doctor straight away.
- Tiredness: Drowsiness can occur. If it makes you feel sleepy, avoid driving or operating machinery.
- Liver: Allopurinol can inflame the liver. Blood tests can pick this up if it occurs. The dose of allopurinol may need to be reduced or it may need to be stopped if problems occur. Contact your doctor immediately if you notice yellowing of the skin and/or whites of the eyes.
- Other: Headache, dizziness, taste disturbances, high blood pressure, feeling generally unwell, and hair loss can occur.
Long term side effects
Allopurinol can be taken for long periods to manage gout. There seems to be no long-term side effects.
Differences Between The American College Of Physicians And Rheumatology Guidelines For Gout Management
Given the lack of good management of gout at the point of care,12,76,77 using gout treatment guidelines may help educate the community of Rheumatologists as well as non-Rheumatologists who are often the first medical contacts for gout patients. There is a disagreement between the ACP guidelines and the rheumatologic ACR and European League Against Rheumatism guidelines on gout treatment. Rheumatologists view gout as a chronic inflammatory, metabolic disease leading to acute flares, while the ACP guidelines suggest that treating the acute gout flare is most important. The Rheumatology associations recommend use of ULT and monitoring the SU, and lowering to a SU target of 6mg/dL while in contrast, the ACP does not provide a clear recommendation for
Table 1 Comparison of Rheumatology and Primary Care Recommendations/Guidelines
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Allopurinol And Renal Impairment
One of the only ways allopurinol will be forbidden from therapy in gout is related to renal impairment. Patients with kidney damage can have life-threatening complications when they start using allopurinol, either in the acute or the chronic phase. Renal injury is a risk factor to develop a condition called allopurinol hypersensitivity syndrome.
Allopurinol hypersensitivity syndrome is a severe systemic reaction to allopurinol. It includes symptoms such as fever, skin manifestations, eosinophilia , and multiorgan dysfunction. There is a 25% mortality in patients who develop this syndrome, which is quite high and alarming. Thus, even though there are guidelines to prevent this from happening, doctors might prefer to use other urate-lowering alternatives in this group of patients.
In a nutshell, the main goal of allopurinol is to lower uric acid levels in chronic gout patients. There is current debate on the matter, but the majority of doctors agree that initiating allopurinol in patients recently diagnosed with acute gout is not recommended and does not have any benefit. It is only maintained in patients with chronic gout under treatment with allopurinol, and the only side effect doctors will try to avoid is allopurinol hypersensitivity syndrome, which is more common in patients with renal impairment.
Drug and Therapeutics Bulletin Editorial Office. . Latest guidance on the management of gout. BMJ, 362, k2893.
The Role Of Physical Activity In Prevention Of Gout
Along with diet, physical activity can help with weight loss, and gout has been associated with being overweight.7 in patients with well-established gout, especially if X-rays have demonstrated joint damage in the foot, a low-impact exercise program is reasonable. An exercise program combined with diet in gout can reduce risk for attacks.7 If an attack seems to be coming on in the lower extremity, patients are well-advised to try to get off their feet, since impact seems to worsen gout attacks. Clues to an attack of gout coming on include local swelling, heat, redness, and tenderness in a joint, especially in the foot, ankle, or knee. Some patients have fever and chills as the first warning that an attack of gout is coming on.
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