CHAPTER 99

Gout and Pseudogout

Gout and pseudogout are characterized by joint inflammation (arthritis) and pain. Both disorders are caused by deposits of crystals in the joints, although the type of crystal differs.

Gout

Gout is a disorder that results from deposits of sodium uric acid crystals, which accumulate in the joints because of high blood levels of uric acid (hyperuricemia), leading to attacks of painful joint inflammation.

Accumulations of uric acid crystal can intermittently cause severe joint or tissue pain and inflammation.

Doctors remove fluid from the joint and check it for uric acid crystals.

Drugs are given to relieve inflammation and pain, prevent further attacks, and sometimes decrease blood levels of uric acid.

Gout is more common among men than women. Usually, gout develops during middle age in men and after menopause in women. Gout is rare in younger people but is often more severe in people who develop the disorder before age 30. Gout often runs in families.

Causes

Normally, uric acid, a by-product of cell nucleic acid breakdown, is present in small amounts in the blood because the body continually breaks down cells and forms new cells. Also, the body readily transforms substances in foods called purines into uric acid. Purines are part of proteins. Foods high in purines include anchovies, asparagus, consommé, herring, meat gravies and broths, mushrooms, mussels, all organ meats, sardines, and sweetbreads. Most often, the uric acid level in the blood becomes abnormally high when the kidneys cannot eliminate enough uric acid in the urine. Too much uric acid in the blood can result in uric acid crystals being formed and deposited in joints. Additionally, combining a high-purine diet with alcohol can worsen matters, because alcohol both increases the production of uric acid and interferes with its elimination by the kidneys.

Risk Factors for the Development of Gout

Beer and alcoholic beverages

Low dairy intake

Certain cancers and blood disorders

Certain drugs (such as thiazide diuretics, cyclosporine, pyrazinamide, ethambutol, nicotinic acid, and high doses of aspirin)

Certain foods (such as anchovies, asparagus, consommé, herring, meat gravies and broths, mushrooms, mussels, all organ meats, sardines, and sweetbreads)

Hypothyroidism

Lead poisoning (from “moonshine” whiskey)

Obesity

Radiation therapy

Chronic kidney disease

Starvation

Less commonly, gout may be caused by an identifiable underlying disorder and is then called secondary gout. For instance, large amounts of uric acid may be produced because of an inherited enzyme abnormality or a disease such as leukemia, in which cells multiply and are rapidly destroyed. Some types of kidney disease and certain drugs (eg, thiazide diuretics) impair the kidneys’ ability to eliminate uric acid, so levels of uric acid rise.

High levels of uric acid in the blood lead to high levels of uric acid in the joints. This process may then result in the formation of uric acid crystals in the joint tissue and the fluid within the joints (synovial fluid). Gout most often affects the joints in the feet, particularly at the base of the big toe (podagra). However, it also commonly affects other areas: the ankle, instep, knee, wrist, and elbow. Gout tends to affect these cooler areas because uric acid crystals form more readily in cool than in warm areas. Rarely, gout affects the joints of the warmer, central part of the body, such as the spine, hips, or shoulders.

Symptoms

Attacks of gout (acute gouty arthritis) can occur without warning. They may be triggered by an injury, surgery, consumption of large quantities of alcohol or purine-rich food, or illness. Typically, severe pain occurs suddenly in one or more joints, often at night (probably because of the metabolic changes that occur when a person lies down). The pain becomes progressively worse and is often excruciating, particularly when the joint is moved or touched. The joint becomes inflamed—it swells and feels warm, and the skin over the joint may appear red or purplish, tight, and shiny.

Other symptoms of an attack can include fever (which may reach 102° F [38.9° C]) and a general sick feeling. The first few attacks usually affect only one joint and last for a few days. The symptoms gradually disappear, joint function returns, and no symptoms appear until the next attack. However, if the disorder progresses, untreated attacks last longer, occur more frequently, and affect several joints.

After repeated attacks, gout can become severe and chronic and may lead to joint deformity.

Over time, joint motion becomes progressively restricted by damage caused by deposits of uric acid crystals in the joints and tendons. Hard lumps of uric acid crystals (tophi) are first deposited in the joint (synovial) lining or cartilage or in bone near the joints and then under the skin around joints. Tophi can also develop in the kidney and other organs, under the skin on the ears, in the tough band extending from the calf muscles to the heel (Achilles tendon), or around the elbows. They commonly develop in the fingers, hands, and feet. If untreated, tophi can burst and discharge chalky masses of uric acid crystals through the skin.

Did You Know…

In past times, when protein was scarce, gout, which can be caused or worsened by eating too much protein, was considered a rich person’s disease.

About one fifth of people who have gout develop kidney stones (urolithiasis) that are composed of uric acid (see page 299). The stones may block the urinary tract, resulting in excruciating pain and, if untreated, infection and kidney damage. In people with gout who also have another disorder that damages the kidneys (such as diabetes or high blood pressure), increasingly poor kidney function reduces the excretion of uric acid and makes the gout and its joint damage progressively worse.

Diagnosis

Doctors often diagnose gout on the basis of its distinctive symptoms and an examination of the affected joints. A high level of uric acid in the blood supports the diagnosis; however, this level is often normal, especially during an acute (sudden severe) attack. The diagnosis is confirmed when needle-shaped uric acid crystals are identified in a sample of a tophus or in joint fluid removed (joint aspiration) with a needle and viewed under a microscope with polarized light. X-rays may show joint damage and the presence of tophi (uric acid crystal tophi that displace bone and produce cysts). Gout is often similar to and sometimes misdiagnosed as another type of arthritis.

Treatment

Treatment has three goals:

Relieve the acute attack of inflammation

Prevent further attacks

Prevent further deposition of uric acid in the tissues by lowering blood levels of uric acid

Relieving the Acute Attack: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often effective in relieving pain and swelling in the joint (see page 644). Sometimes, additional analgesics such as oxycodone are needed to control pain. The inflamed joint may be immobilized with a splint, and ice can be applied to reduce pain.

Colchicine is the traditional, but no longer the most common, first-step treatment. Usually, joint pain begins to subside after 12 hours of treatment with colchicine and is gone within 36 to 48 hours. Colchicine is usually taken in tablet form each hour until symptoms are relieved. Colchicine can cause abdominal pain and diarrhea. It can occasionally cause more serious side effects, including damage to the bone marrow.

Corticosteroids, such as prednisone, are sometimes useful to reduce joint inflammation (including the swelling) in people who cannot tolerate the other drugs. If only one or two joints are affected, a corticosteroid suspension, such as prednisolone tebutate, can be injected using the same needle that is used to remove fluid from the joint.

Preventing Further Attacks: Avoiding alcoholic beverages, losing weight, stopping drugs that cause elevated blood levels of uric acid, and eating smaller amounts of purine-rich foods will help and rarely be all that is needed. Most people who have primary gout are overweight. As they gradually lose weight, their blood levels of uric acid often return to normal or near normal, and gout attacks subsequently cease.

Preventive daily drug treatment may be needed for people who experience repeated, severe attacks. Colchicine may be taken daily to prevent attacks or to greatly reduce their frequency. NSAIDs taken daily can also prevent attacks. However, preventing attacks does not prevent or heal existing joint damage caused by uric acid crystals because the crystals still persist in the joints, and the drugs do pose some risks for people who have kidney or liver disease.

DRUGS USED TO TREAT GOUT

DRUG	SOME SIDE EFFECTS	COMMENTS
Nonsteroidal anti-inflammatory drugs (NSAIDs)
All NSAIDs (see table on page 646)	Upset stomach Bleeding Kidney damage High potassium levels Retention of sodium and potassium Sometimes cause swelling or high blood pressure	Used to treat an acute (sudden) attack or to prevent an attack
Antigout drug
Colchicine	Diarrhea (occurs often) Suppression of blood cell production in the bone marrow (occurs very rarely if the drug is used properly) Muscle pain and weakness (uncommon)	Used to prevent and treat attacks
Corticosteroids
Prednisone (taken by mouth)	Retention of sodium, with swelling or high blood pressure Multiple side effects if used long term	Used only if other treatments cannot be used, but the benefit is rapid
Prednisolone tebutate or triamcinolone hexacetonide (taken by injection)	Pain Discomfort Joint damage with overuse Inflammation (occasionally) Infection (rarely)	Injected into the joint if only one or two joints are affected
Uricosuric drugs (drugs that increase uric acid secretion in the urine)
Probenecid Sulfinpyrazone	Headache Nausea Vomiting Kidney stones	Can be used long-term to lower blood levels of uric acid to prevent attack
Drugs that block uric acid production
Allopurinol	Upset stomach Skin rash Decrease in the number of white blood cells Liver damage (rare)	Can be used long-term to lower blood levels of uric acid to prevent attacks and to remove crystals in the body or stones in the kidneys

Lowering Blood Levels of Uric Acid: A high level of uric acid in the blood causes problems for most people. People who especially need their blood level of uric acid lowered include those who have the following:

Frequent, severe attacks despite taking colchicine or NSAIDs

Tophi

Very high blood levels of uric acid

Uric acid kidney stones

Conditions that make NSAIDs or corticosteroids risky to take (such as peptic ulcer disease and chronic kidney disease)

People taking drugs to lower the blood level of uric acid should know their level, just as patients with hypertension should know their blood pressure. The goal of drug therapy is to decrease the level to 10 to 15% less than normal.

Drugs can lower blood levels of uric acid by decreasing the body’s production of uric acid or increasing the excretion of uric acid in the urine. Allopurinol is most often used to lower the blood level of uric acid. This drug blocks the production of uric acid in the body and is especially helpful for people who have a high blood level of uric acid and uric acid stones or kidney damage. However, allopurinol can upset the stomach, cause a skin rash, decrease the number of white blood cells, or cause liver damage or inflammation of vessels (vasculitis). Allopurinol also can cause a gout attack when it is first taken. Because low-dose colchicine or an NSAID can decrease this risk, one of these drugs is usually given for a few months as well.

Drugs that cause excretion of uric acid in the urine (uricosuric drugs), such as probenecid or sulfinpyrazone, also can be used to lower the levels of uric acid in the blood (in people who have normal kidney function) by increasing the kidney’s excretion of uric acid. Aspirin can block the effects of probenecid and sulfinpyrazone, and high doses of aspirin should not be used at the same time as either of these drugs. Low doses that protect the heart (81 milligrams daily) should be continued, because heart disease is a considerable risk in people with gout.

Although drugs that increase the excretion of uric acid in the urine (uricosuric drugs) lower the concentration of uric acid in the blood, they can increase the concentration of uric acid in the urine. Drinking plenty of fluids—at least 3 quarts a day—may help reduce the risk of uric acid stones developing in the urinary tract. Making the urine alkaline by taking acetazolamide or potassium citrate (which increases the solubility of uric acid in the urine) can further help reduce the risk of uric acid stones forming in the urinary tract. However, if the urine becomes too alkaline, crystals or stones of another and more dangerous kind—calcium oxalate—may form. When starting a uricosuric drug, there is a risk of causing a gout attack. Low-dose colchicine or an NSAID is given at the same time for a few months to decrease this risk.

Other Treatments: Most tophi on the ears, hands, or feet shrink slowly when the uric acid level becomes sufficiently low. However, extremely large tophi may have to be removed surgically.

Uric acid stones in the urinary tract can be broken up, and thereby washed out in the urine, by using ultrasound directed at the stones from outside the body (extracorporeal shock wave lithotripsy—see art on page 301).

Pseudogout

Pseudogout (calcium pyrophosphate dihydrate crystal deposition disease) is a disorder caused by deposits of calcium pyrophosphate dihydrate crystals in the cartilage and then in the fluid of the joints, leading to intermittent attacks of painful joint inflammation.

Crystals accumulate in joints and cause varying degrees of inflammation and tissue damage.

The diagnosis is confirmed by finding calcium pyrophosphate crystals in joint fluid.

Treatment is with nonsteroidal anti-inflammatory drugs and sometimes injection of corticosteroids into joints.

Pseudogout usually occurs in older people and affects men and women equally.

Causes

The reason that calcium pyrophosphate dihydrate crystals deposit in the joints of some people is unknown. It may occur in people who have other diseases, such as an abnormally high calcium level in the blood caused by a high level of parathyroid hormone (hyperparathyroidism), an abnormally high iron level in the tissues (hemochromatosis), or an abnormally low magnesium level in the blood (hypomagnesemia). However, most people with pseudogout have none of these conditions. The disorder can be hereditary. The calcium crystals frequently occur in joints affected by osteoarthritis (see page 559).

Symptoms

Symptoms vary widely. Some people have attacks of painful joint inflammation, usually in the knees, wrists, or other relatively large joints. Other people have lingering, chronic pain and stiffness in joints of the arms and legs, which may be similar to rheumatoid arthritis or osteoarthritis. Sudden painful (acute) attacks are usually less severe than those of gout, but as in gout, attacks in pseudogout can cause fever. Some people have no pain between attacks, and some have no pain at any time, despite large deposits of crystals. Unlike in gout, people with pseudogout do not develop hard lumps of uric acid crystals (tophi).

Diagnosis

Doctors make the diagnosis by taking fluid from an inflamed joint through a needle (joint aspiration). Calcium pyrophosphate dihydrate crystals are found in the joint fluid. They can be distinguished from uric acid crystals (which cause gout) using a special polarized light microscope. Masses of calcium pyrophosphate crystals, unlike uric acid crystals, can be seen on an x-ray.

Prognosis and Treatment

Often, the inflamed joints heal without any residual problems, but in many people, permanent joint damage can occur, with some joints so severely destroyed that they can be confused with Charcot’s joints (see page 572).

Usually, treatment can stop acute attacks and prevent new attacks but cannot reverse changes in already damaged joints. Most often, nonsteroidal anti-inflammary drugs (NSAIDs) are used to reduce the pain and inflammation (see page 644). Colchicine can be given by mouth in daily low doses to limit the number of attacks. Sometimes, excess joint fluid is drained and a corticosteroid suspension is injected into the joint to reduce the inflammation and pain.

No specific effective long-term treatment is available; however, physical therapy (such as muscle-strengthening and range-of-motion exercises) may be helpful to maintain joint function.