What Are the Crystals That Cause Gout and Pseudogout?

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Crystal-induced arthropathies are diseases in which tiny crystals form in joint spaces, causing inflammation and joint damage. Gout is the most well-known condition of this category, and is caused by monosodium urate (or uric acid) crystals. Pseudogout, or calcium pyrophosphate deposition (CPPD) disease, is caused by crystals of calcium pyrophosphate dihydrate.

Gout is a common disease, affecting more than 3% of American adults. Pseudogout is also common: About 3% of people in their 60s and as many as half of people in their 90s have this condition. Although the two diseases are different, the symptoms may overlap, a fact underlined by the name “pseudogout.”

Both diseases have variable manifestations, ranging from asymptomatic disease to severe debilitating illness. Regardless, the diseases are treatable, but the specific approach will vary from person to person.

Gout Crystals
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Types of Crystals

Monosodium Urate Crystals

Monosodium urate crystals come from uric acid, a substance that occurs naturally in the blood as a result of the metabolism of purines.

Normally, excess uric acid is eliminated in the urine or by the gut. In some patients, the kidneys become less efficient at excreting uric acid, causing levels to increase in the blood. Other patients, due to one of several metabolic disorders, may produce too much uric acid, also leading to increased levels.

Diet and alcohol intake can affect serum uric acid levels as well. For example, meat and seafood are rich in purines, and overconsumption of these foods is associated with gout. 

Calcium Pyrophosphate Dihydrate (CPPD) Crystals

Calcium pyrophosphate dihydrate crystals, the cause of pseudogout, arise from joint cartilage. Cartilage cells (chondrocytes) naturally produce a substance called pyrophosphate. For reasons not completely understood, pyrophosphate levels may increase in cartilage, leading to the formation of CPPD crystals.

The two types of crystals are not mutually exclusive, and 5% of patients with gout also have CPPD crystals in their joints.

Causes

Monosodium Urate Crystals

Elevated levels of uric acid in the blood must be present for the formation of monosodium urate crystals in gout to occur. Uric acid is primarily produced in the liver, as purines synthesized in the body and ingested from food are processed. Most uric acid is excreted through the urine and gut.

Most cases of elevated blood uric acid levels (hyperuricemia) are caused by reduced efficiency of uric acid excretion by the kidneys. Conditions that can cause this are common and include obesity, chronic kidney disease, dehydration, and hypothyroidism. Less commonly, inherited disorders can lead to decreased uric acid excretion or increased uric acid production.

Diet can affect uric acid levels in the blood. Gout has historically been called the “disease of kings” because of its association with obesity and the consumption of rich foods. Although food habits and other lifestyle factors have a definite effect, your genes likely have a more important impact on the levels of uric acid in your blood.

Calcium Pyrophosphate Dihydrate Crystals

The causes of CPPD crystal formation in the joints are less well understood. Crystal formation in the joints may be inherited (familial chondrocalcinosis). Also, joint trauma and certain metabolic conditions may be associated with the development of pseudogout. For example, hemochromatosis and hyperparathyroidism may be associated with the disease, as are some rare genetic disorders.

Symptoms and Complications

Gout

Gout is variable in its manifestations, and may affect different joints and the kidneys. Broadly, gout may cause acute or chronic inflammation of the joints, accumulation of urate crystals in soft tissues (tophi), kidney stones, or chronic kidney disease. Patients may also have more general symptoms like fever or malaise.

An acute gout flare-up usually involves one joint and is characterized by intense pain, redness, and swelling. The disease can involve any joint, although gout has a particular affinity for the first metatarsophalangeal joint (the joint at the base of the big toe) or the knee. Some patients may experience flare-ups that affect multiple joints.

Flare-ups may be brought on by a number of factors:

  • Trauma
  • Surgery
  • Starvation
  • Dehydration
  • Certain foods
  • Alcohol intake
  • Certain drugs

They usually resolve within days or weeks, and patients in between acute episodes may be completely asymptomatic. Eventually, attacks may occur more often, last longer, and do not resolve completely between episodes. This may lead to chronic gout disease, which can cause long-term joint damage.

Tophaceous gout occurs when solid collections of uric acid form in soft tissues, causing inflammation and tissue damage. These collections, or tophi, may occur around joints, in tendons, or in bursae. They may also occur in the ears or other soft tissues. They may be visible and are often palpable (detectable by touch), but are usually not painful or tender.

Chronically elevated levels of uric acid may also affect the kidneys. The two main complications are kidney stones (caused by formation of uric acid stones in the urine) or chronic renal disease related to hyperuricemia (chronic urate nephropathy).

Pseudogout

CPPD disease can also vary widely in its presentation. Patients may be asymptomatic. Symptomatic patients may have acute or chronic disease. CPPD disease attacks larger joints more commonly than gout.

Acute CPPD disease attacks may affect one or several joints. Joint injury, surgery, or severe illness may precede an attack. The knee is commonly affected, though the disease can also involve the wrists, shoulders, ankles, feet, and elbows.

Patients commonly experience pain, redness, warmth, and decreased function of the affected joint. The illness usually goes away on its own, though it may take days or weeks to do so.

Chronic CPPD disease may mimic other forms of arthritis. Symptoms may coexist with those of degenerative osteoarthritis, which causes progressive joint degeneration.

Chronic CPPD disease may also imitate rheumatoid arthritis (RA) and present with symptoms normally associated with RA, including morning stiffness, fatigue, and restricted joint motion. This type of CPPD disease may affect multiple joints of the arms and legs, and the inflammation may wax and wane over several months.

Diagnosis

Gout

If an acute gout attack is suspected, a physician will use your history, physical exam results, lab findings, and X-rays to support the diagnosis. Your blood may be checked to determine if you have high levels of uric acid. Definitive diagnosis is based on the identification of monosodium urate crystals in an affected joint, especially if this is the first episode of arthritis.

Identification of uric acid crystals is done by first drawing fluid from the joint in a simple procedure called an arthrocentesis. The joint fluid is examined under polarized light microscopy. Under polarized light, gout crystals appear needle-shaped and yellow, a property called negative birefringence.

If crystals in joint fluid cannot be established, your doctor may still be able to make a diagnosis of gout based on your history, X-rays, and physical exam findings.

Patients with uric acid kidney stones may present with symptoms such as flank pain or blood in the urine. If kidney stones are suspected, your doctor may order a CT scan, which can identify the presence, number, and location of kidney stones.

Once the presence of stones is established, your doctor must determine the chemical composition of the stones to guide treatment. The best way to do this is to analyze stones that have already been passed. Tests of urine uric acid levels and acidity (pH) may be evaluated to further guide treatment.

Pseudogout

Like gout, the diagnosis of CPPD disease ultimately rests on the identification of CPPD crystals in joint fluid.

Under polarized light microscopy, CPPD crystals appear blue, a property called positive birefringence. This distinguishes them from the negatively birefringent crystals of gout. SPECT CT and musculoskeletal ultrasound are also used.

If crystal analysis is not available, the diagnosis of CPPD disease may be strongly suspected based on your history and X-ray findings. Your doctor may suspect that you have CPPD disease if you have acute arthritis of large joints, especially of the knees.

CPPD disease is more common in patients over 65, and may mimic osteoarthritis or rheumatoid arthritis.

Treatment

Gout

The treatment of acute gout focuses on reducing pain and inflammation. This can be achieved with nonsteroidal anti-inflammatory agents (NSAIDs), steroid medications, or colchicine.

All three types of medications can be given orally, and the choice of drug depends on patient tolerance of the drug and whether there are any coexisting diseases that preclude the use of a specific drug. Treatment should be started within 24 hours of the onset of symptoms.

In chronic gout, treatment focuses on lowering uric acid levels to prevent acute attacks. There are two main ways to do this: give drugs that lower uric acid production (allopurinol, febuxostat), or give drugs that increase urine excretion of uric acid (probenecid).

Another drug, pegloticase, actively breaks down uric acid, and can be used when other uric acid-lowering therapies are not effective.

The decision of whether to start uric acid-lowering therapy should be individualized and depends on how often a person has attacks, how high their uric acid level is, and whether tophi are present.

Although uric acid-lowering therapy prevents gout attacks in the long term, they can actually bring about or worsen an acute attack when they are first started. For that reason, these drugs are not started during an acute flare. Anti-inflammatory medications may be given when starting uric acid-lowering therapy.

Once started, therapy with uric acid-lowering medications is usually lifelong, so adhering to the medications is important. Since diet and lifestyle can affect uric acid levels, your doctor may prescribe a healthy diet and avoidance of certain foods and alcohol.

Pseudogout

The treatment of pseudogout aims mostly to relieve symptoms. As with gout, anti-inflammatory medications such as NSAIDs, steroids, or colchicine may be used to treat acute episodes.

If only one joint is affected, doctors may try draining the fluid from the joint (arthrocentesis) and injecting steroids directly into the joint, which can rapidly relieve joint pain and inflammation. Patients with frequent CPPD attacks may be prescribed low-dose colchicine to reduce the number of episodes.

A Word From Verywell

Crystal-induced arthropathies like gout and CPPD disease can be painful and debilitating. Fortunately, a variety of treatment options exist, and the diseases can usually be managed effectively with medications.

Treatment is individualized and depends on the severity of your disease, as well as the presence of any coexisting diseases. Talk to your healthcare provider about the treatment strategy that makes the most sense for you.

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