Medicine for Africa - Medical Information Service

YPERURICEMIA - OUT

Definition:

The word ‘gout’ is derived from the Latin word of “gutta”, meaning ‘a drop’ (of liquid).

Gout is the result of elevated levels of uric acid in the blood, called hyperuricemia or hyperuricaemia; uric acid is one of the breakdown products of purines which are found in many food products.  The uric acid crystallizes and these sharp crystals deposit themselves in form of a so-called tophus (Latin for ‘stone’) in about 10% of cases in some of the following areas:

• Various joints, most often in the big toe (medical term – ‘podagra’);
• Tendons;
• Under the skin, looking like lumps;
• The kidneys resulting in kidney stones.

The gout tophi result in recurrent attacks of acute joint inflammation (arthritis) with red, tender, hot, swollen, stiff and painful joints – in fact, gout is one of the most painful forms of arthritis.

In chronic gout, the crystal deposits lead to hard lumps of uric acid in and around the joints, resulting in joint destruction, or, if the deposits are in the kidney, to decreased kidney function, kidney stones and even kidney failure.

Gout affects about 1% of the Western population at some point in their life.  The prevalence of gout has been on the increase worldwide; however, different populations have different sensitivities to gout.  In the USA, gout is twice as prevalent in African American males as compared to European Americans.

There are many risk factors that can cause hyperuricemia with the potential to develop into gout, such as:

• Alcoholic beverages – the most important cause of gout (!);
• Diet – high consumption of meat (especially organ meats such as liver, kidneys, brain and sweetbread) and/or seafood/shellfish;
• Certain medications – some diuretics, etc.;
• Genetics – inherited predisposition;
• Hypertension;
• Insulin resistance (in patients with diabetes);
• Obesity – overweight;
• Organ transplantation – common adverse side effect;
• Renal insufficiency à under-excretion of urates;
• Tumor lysis syndrome – can result in extremely high levels of hyperuricemia.

Lifestyle is the cause of gout in about 12% of cases, mostly associated with the high consumption of alcohol, sugars, as well as meat and seafood products.  In addition, a sedentary lifestyle can also increase the risk of developing gout.   Usually, food products that are high in purine, adenine and hypoxanthine may result in exacerbating hyperuricemia that has been the result of other causes.

Diseases that can lead to excessive production of uric acid include:

• Certain hemoglobin disorders – e.g. polycythemia (abnormal increase of red blood cells, also called erythrocytosis);
• Leukemias;
• Lymphomas
• Metabolic syndrome – a combination of hypertension, diabetes, high cholesterol levels, body fat around the waist, and increased risk of cardiovascular diseases.

In addition to the big toe, which is the ‘classic’ joint of involvement, gout can also affect the:

• Ankles;
• Heels;
• Knees;
• Elbows,
• Wrists, and
• Fingers.

The relationship between hyperuricemia (increased blood levels of uric acid) and gout are still not entirely understood.   While many patients with hyperuricemia do not develop gout, some patients with repeated gout attacks have normal or low blood uric acid levels. In fact, uric acid blood levels often decrease during an acute attack of gout.

And finally, in patients who are already at risk to develop gout, certain conditions can precipitate an acute gout attack, including;

• Dehydration;
• Injury to a joint;
• Recent surgery – possibly related to irregular fluid intake around surgery;
• Excessive eating and/or alcohol intake.

            Historic review

Gout is one of the most frequently recorded medical illnesses throughout history.

A type of gouty arthritis of the big toe has first been described by the Egyptians as early as 2,600 BC.  The word ‘gout’ itself was first used to describe this disease in 1,200 AD.

Historically, gout has been known as ‘the disease of kings’ or ‘rich man’s disease’.  The former group of patients probably, because of gout’s genetic predisposition, and aristocracy was well known to marry among each other, which resulted in a certain degree of ‘in-breeding’.  The latter group, because rich people could afford to eat and drink all of the ‘high risk’ food items and alcohol beverages associated with the development of gout.

Lead poisoning also correlates with a significant increase of gout – thus, people who used to consume regularly large amounts of ‘moonshine’ alcohol (home-made alcohol, containing considerable amounts of lead due to the improper distilling equipment and procedures) were also predisposed to the development of gout and gouty arthritis.

If you suffer of gout, you are part of a large group of very prominent patients – here, a short selection of famous people with gout throughout history:

Symptoms:

Most patients experience their first attack of gout at the base of the big toe (partly caused by the lower temperature in the toes), which often wakes them up in their sleep.  Classic symptoms include:

• Pain;
• Swelling;
• Redness;
• Warm to hot feeling over the joint;
• Stiffness in the affected joints.

An acute gout attack can be brought on by stress, alcohol, certain drugs or another illness (see above).

Early attacks usually improve over three to 10 days, even without treatment; a second attack may occur as late as months or even years later.

Patients with long-standing hyperuricemia develop uric acid crystal deposits (tophi), which are hard, non-painful deposits in soft tissues.  As these tophi grow, they can invade adjacent bones resulting in bone erosion and associated arthritis.  These tophi are most frequently found around the fingers, at the elbows, in earlobes and around the big toe, but can invade any other body tissue as well.

Some of the uric acid crystals may also deposit in the small fluid-filled sacs around the joints, which are called bursae, resulting in inflammation of these bursae (bursitis) with subsequent pain and swelling.  As gout turns more and more chronic, the joint inflammation starts to mimic rheumatoid arthritis, which has to be excluded as differential diagnosis in chronic cases.

 
Diagnosis:

Gout can be suspected when the patient reports of attacks of painful arthritis occurring at the base of the toes, followed by ankles or knees.

A blood test for uric acid can establish the patient’s blood level of uric acid; the upper end of normal range blood levels is 6.2 mg/dl (380 μmol/L) for women and 7 mg/dl (420 μmol/L) for men.  However, as mentioned above, hyperuricemia is not diagnostic of gout.

The most reliable test for diagnosing gout is to identify uric acid crystals in joint fluids.  This can be done by obtaining joint fluid by way of joint aspiration, called arthrocentesis.  An arthrocentesis is a common procedure that can be performed at the doctor’s office under local anesthesia and sterile conditions.  Using a syringe and needle, fluid from the inflamed joint is withdrawn (aspirated) and analyzed for uric acid crystals and signs of inflammation (increased white blood cell count).  The uric acid crystals can be viewed under a polarizing microscope where they appear looking like this:

These mono-sodium urate crystals can also be found in material aspirated from tophus nodules or in bursitis fluid (see above).

It is important to diagnose gout appropriately, as other diseases may mimic gout – the differential diagnosis of gout includes:

• Pseudogout – chondrocalcinosis of ‘Calcium Pyrophosphate Dihydrate Disease’, CPPD, with calcium pyrophosphate crystals in connective tissues (acute synovitis) and most commonly, the knee joint;
• Psoriatric arthritis – associated with psoriasis;
• Rheumatoid arthritis;
• Joint infections (of other origin) – septic arthritis.

X-rays can be helpful in showing intra-articular crystal deposits and inflammation associated bone damage; they can also be used for monitoring the effects of chronic gout under treatment.

 
Treatment:

Therapy for gout consists of three major phases – first, pain relievers to manage the acute pain, secondly, anti-inflammatory agents to decrease joint inflammation, and thirdly, long-term management, aimed at preventing future gouty arthritis attacks and to shrink the uric acid crystal deposits.

• Phase 1 – stop the acute pain of the inflamed joints with pain relievers, such as:
• Acetaminophen or other potent analgesics;

• Phase 2 – decrease the joint inflammation with anti-inflammatory agents such as:
• NSAIDS – non-steroidal anti-inflammatory drugs such as indomethacin or naproxen (common side effects: irritation of the gastro-intestinal system, ulceration of the stomach and intestines);
• Colchicine – for acute gout to reduce inflammation, and to correct hyperuricemia in connection with allopurinol or febuxostat (see below);
• Corticosteroids – e.g. prednisone, are given by mouth (orally) or via intra-articular injection.  Must be slowly tapered off after the inflammation is gone; intra-articular injections can have fast pain-relieving results, but are associated with the risk of infections and often lead to bone destruction upon repeated usage (and is therefore not recommended by the author of this article), and;
• Adequate fluid intake to decrease the risk of developing kidney stones;
• Dietary changes – to exclude purine rich foods and alcohol from the diet and to lose overweight.

• Phase 3 – long-term management, depends on whether the patient is a so-called:
1. ‘over-producer’ of uric acid – due to high purine containing diet, increased purine production;
2. ‘under-excreter’ of uric acid – secondary to kidney disease, certain drugs, competition for excretion by other compounds.

• Allopurinol – blocks the conversion from purines in foods to uric acid;
• Febuxostat – a recently approved drug, works similar as allopurinol, but is also effective in shrinking tophi deposits in fingers, elbows and ears. Furthermore, since febuxostat is not metabolized in the kidneys, it is better tolerated than allopurinol in patients with kidney disease.

              Ad 2) Treatment for patients with decreased excretion of uric acids is done with uricosuric drugs:

• Probenecid and
• Sulfinpyrazone – l both increase the excretion of uric acids into the urine, and thus, decrease its blood levels. These medications have to be taken with plenty of fluid, in order to promote rapid passage of uric acids through the urinary system and to prevent the formation of kidney stones.

Uric acid lowering medications (e.g. allopurinol, febuxostat) are usually not given during an acute attack, because then they can actually worsen the acute inflammation.  If the patient is already on these medications, when an acute attack occurs, the same dosage should be maintained, as increasing the dosage but worsen the gout attack.

It is important to maintain adequate fluid intake throughout the treatment phases, as this helps to prevent the risk of kidney stone formation in patients with gout. Alcohol is known to have diuretic effects that can contribute to dehydration and precipitate acute gout attacks, it can also affect uric acid metabolism, worsening the hyperuricemia, and should be abstained from during therapy.

In addition, dietary changes should be done and foods with high purine content (see above) should be avoided.

Home remedies such as ice packs can alleviate the symptoms of acute attack, such as inflammation and pain.  Aspirin-containing medications or solutions should be avoided, because aspirin prevents uric acid excretion by the kidneys.

 
Prevention:

The best prevention is to adjust your lifestyle, if necessary, and limit the high risk food products (see above), alcohol and fructose intake, while assuring adequate Vitamin C intake.  Overweight should be avoided and regular exercise is not only recommended for preventing gout, but many other healthcare related problems, such as cardiovascular disease, hypertension, diabetes, etc.  

There are some new medications in research and currently evaluated in clinical trials.  One of those experimental drugs can affect the chemical messengers involved in gouty inflammation.

In obese men, a low-calorie diet can decrease uric acid levels by 100 μmol/L, while the intake of 1,500 mg of Vitamin C is said to decrease the risk of gout by 45% as compared to 250 mg of Vitamin C per day.  Coffee, but not tea, consumption is also associated with a lower risk of developing gout.

A recent study from Harvard Medical School reported that uric acid levels clearly decreased with increasing intake of dairy products, such as one or more glasses of milk a day, or yogurt at least every other day.  It also confirmed that uric acid levels increased with increasing meat and seafood consumption (see above).

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