eMedicine Specialties > Emergency Medicine > Rheumatology

Gout and Pseudogout

Author: Joseph Kaplan, MD, MS, FACEP, Attending Physician, Department of Emergency Medicine, Martin Army Community Hospital, Fort Benning, Georgia
Contributor Information and Disclosures

Updated: Aug 27, 2009

Introduction

Background

Gout and pseudogout are the 2 most common crystal-induced arthropathies. They are debilitating illnesses in which pain and joint inflammation are caused by the formation of crystals within the joint space.

Gout is inflammation caused by monosodium urate monohydrate (MSU) crystals.

Pseudogout is inflammation caused by calcium pyrophosphate (CPP) crystals and is sometimes referred to as calcium pyrophosphate disease (CPPD).

Gout is the most common crystal-induced arthritis. Lowenhook first described symptoms in the 1600s. In 1848, Sir Alfred Garrod linked gout with hyperuricemia, but the pathophysiology of acute gouty arthritis was not described fully until 1962. Since then, gout has been associated with a large number of different autoimmune and metabolic disorders. Specific therapies and prophylactic measures have been developed to address the underlying problem. The inflammatory reaction caused by gout is felt to come in two stages. In the first stage, monosodium urate crystals stimulate interleukin 1B maturation and production. This sets off the second part of the inflammatory cascade, which includes cytokines, chemokines, monocyte chemotactic proteins, and inflammatory mediators.

Pseudogout, which may be clinically indistinguishable from gout, was recognized as a distinct disease entity in 1962. As with gout, pseudogout has been associated with a variety of metabolic disorders as well as with aging and trauma. Treatment of the acute phase of pseudogout is identical to that of gout. Unlike gout, however, no specific therapeutic regimen exists to treat the underlying cause of pseudogout, and no known prophylactic therapy exists.

Clinical Image Atlas Click to view clinical images on the features and diagnosis of gout.

Pathophysiology

Pain and joint edema of acute arthritis in patients with gout and pseudogout are caused by an inflammatory response triggered by the lysis of polymorphonuclear white blood cells that have ingested monosodium urate monohydrate (MSU) crystals or calcium pyrophosphate (CPP) crystals. MSU crystals are formed in synovial fluid when the fluid becomes supersaturated with MSU. This supersaturation can result from overproduction or reduced excretion of MSU. Many conditions and drugs have been associated with an increase in plasma (and subsequent synovial) urate levels. A genetic predisposition for the disease exists. CPP crystals are produced by nucleoside triphosphate pyrophosphohydrolase (NTPPPH), a catalytic enzyme found in vesicles that develop within osteoarthritic cartilage. A genetic predisposition exists for the condition, but any process that leads to osteoarthritis also can be associated with subsequent pseudogout.

Frequency

United States

Gout affects 2.7 of every 1000 adults. Prevalence is approximately 20% in patients with a family history of gout.

Frequency of pseudogout varies with age. The annual incidence of acute attacks of arthritic pain and swelling is about 1.3 per 1000 adults, but nearly half of adults develop radiographic changes typical of calcium pyrophosphate disease (CPPD) by age 80 years.

Gout has been noted to occur more frequently in the spring and less frequently in the winter, although the reason for this is unknown.

International

Prevalence of gout varies widely from country to country. In England, gout affects 16.4 of every 1000 men and 2.9 of every 1000 women.

Mortality/Morbidity

• Pain and edema of inflammatory crystalline arthritis is extremely debilitating.
• Chronic injury to intra-articular cartilage leaves the joints more susceptible to subsequent joint infections.

Race

• Limited data suggest an increased prevalence of gout in American blacks compared with whites; however, clinically recognized gout is extremely rare in blacks living in Africa.
• Diet may be linked to racial prevalence since diet has a large influence on the clinical expression of gout.

Sex

• For gout, the male-to-female ratio is 9:1.
• For pseudogout, the male-to-female ratio is 1.5:1.

Age

• The predominant age range is 30-60 years.

Clinical

History

• The history and physical examination alone cannot reliably determine the cause of new-onset acute monoarticular arthritis.
• Septic arthritis, gout, and pseudogout can present in very similar ways.
• The spontaneous onset of pain, edema, and inflammation in the metatarsal-phalangeal joint of the great toe (podagra) is highly suggestive of acute crystal-induced arthritis. This is the most common presentation of gout.
• Other than the great toe, the most common sites of gouty arthritis are the ankle, wrist, and knee. Consider the diagnosis in any patient with acute monarticular arthritis of any peripheral joint except the glenohumeral joint of the shoulder, in which a crystal-induced arthritis is more likely to be due to pseudogout.
• The most common sites of pseudogout arthritis are the knee, wrist, and shoulder. Case reports have documented carpal tunnel syndrome as an initial presentation of pseudogout. Case reports of pseudogout forming masses in the spinal ligamentum flavum have been documented.¹ These have lead to both single and multi-level myelopathy.
• Crystal-induced arthritis is most commonly monarticular; however, polyarticular acute flares are not rare, and many different joints may be involved simultaneously or in rapid succession. Multiple joints in the same limb often are involved, as when inflammation begins in the great toe and then progresses to involve the midfoot and ankle.
• Although gout and pseudogout cannot reliably be distinguished on clinical grounds, a tendency exists for gout symptoms to develop rapidly over a few hours, whereas the onset of symptoms in pseudogout is usually more insidious and may occur over several days.
• When a patient presents with an identical recurrent attack of crystal-induced arthritis, the diagnosis is rarely in question, but the possibility of septic arthritis must always be considered.
• Fever, chills, and malaise do not distinguish cellulitis or septic arthritis from crystal-induced arthritis because all 3 illnesses can produce these signs and symptoms.
• A careful history may uncover risk factors for cellulitis or septic arthritis, such as possible exposure to gonorrhea, a recent puncture wound over the joint, or systemic signs of disseminated infection.
• Gout is also associated with hyperlipidemia, hypertension, hypertriglyceridemia, kidney failure, obesity, and insulin resistance.² Social factors such as alcohol intake also increase the risk of gout.^3,2
• It has been suggested that a link exists between several autosomal dominant disorders and the development of gout. However, there has not been a specific genetic marker for those predisposed to developing gout.
• Pseudogout attacks have been reportedly induced by etidronate disodium therapy and post vascular angiography.^4,5

Physical

• Patients with gout or pseudogout most often present with a single joint that is hot, erythematous, tender, and affected with asymmetric edema. If inflammation is severe, desquamation of overlying skin may be present.
• Extra-articular deposits of MSU, known as tophi, may be seen along the Achilles tendon or on the ear helix, olecranon bursa, or prepatellar bursa.
• Migratory polyarthritis is a rare presentation.
• An inflammatory synovial effusion may be present.
• Although uncommon, acute gout may present with signs of carpal tunnel syndrome.

Causes

• Although the pathophysiology, clinical presentation, and acute-phase treatment of gout and pseudogout are very similar, the underlying causes of the 2 diseases are very different.
• Acute gouty arthritis results from overproduction or reduced secretion of uric acid. Thiazide diuretics and foods that are rich in purines will increase the frequency of attacks.
• Many cases of pseudogout are idiopathic, but pseudogout has also been associated with aging, trauma, and many different metabolic abnormalities, the most common of which are hyperparathyroidism and hemochromatosis.
• Lead poisoning
• Hemo-proliferative disorders
• Renal disease
• Risk factors include obesity, alcohol consumption, urate elevating drugs and age, hyperlipidemia, and hyperglycemia.

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