INTRO

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.

Pseudogout, which may be clinically indistinguishable from gout, was recognized as a distinct disease entity only 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. However, unlike gout treatment, no specific therapeutic regimen exists to treat the underlying cause of pseudogout, and no known prophylactic therapy for pseudogout exists.

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 MSU crystals or 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. CPPD 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:

  • In the US: 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 CPPD by age 80 years.

  • Internationally: 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 intraarticular cartilage leaves the joints more susceptible to subsequent joint infections.

Race:

  • Limited data suggest an increased prevalence of gout in American blacks as compared to 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:

 

 

CLINICAL

 

History:

  • 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 because 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.
  • 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 borne in mind.
  • 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.

Physical:

  • Patients with gout or pseudogout most often present with a single joint that is hot, erythematous, tender, and affected with asymmetrical edema. If inflammation is severe, desquamation of overlying skin may be present.
  • Extraarticular 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.
  • Inflammatory synovial effusion
  • Carpal tunnel syndrome
  • Kidney stones

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


WORK-UP

 

Lab Studies:

  • Diagnostic arthrocentesis is indicated for every patient in whom a diagnosis has never been proven by joint aspiration and for those in whom a possibility of septic arthritis exists. A prior history of gout or pseudogout does not rule out the possibility of acute septic arthritis. Septic arthritis must be diagnosed and treated promptly. Irreversible damage can occur within 4-6 hours, and the joint can be completely destroyed within 24-48 hours.
  • Joint fluid analysis
    • Send joint fluid for fluid analysis, including cell count and differential, Gram stain, culture and sensitivity, and microscopic analysis for crystals. If crystals are seen, their shape and appearance under polarized light can aid in diagnosis.
    • In gout, crystals of MSU appear as needle-shaped intracellular and extracellular crystals. When examined with a polarizing filter, they are yellow when aligned parallel to the axis of the red compensator, but they turn blue when aligned across the direction of polarization (ie, they exhibit negative birefringence).
    • In pseudogout, CPP crystals appear shorter and often rhomboidal. Under a polarizing filter, CPP crystals do not change color depending upon their alignment relative to the direction of the red compensator.
    • In crystal arthritis, the WBC count in the joint fluid is usually 50,000-100,000.
  • Even in the presence of crystals in the joint fluid, blood cultures are indicated if any sign of systemic toxicity is present. Septic arthritis can occur in patients with active crystalline arthropathy.
  • Gouty attacks are triggered by crystal formation in synovial fluid. They are not related to serum levels of uric acid.
  • Pseudogout attacks can be triggered by many metabolic abnormalities. Thus, patients who have an initial attack of arthritis with CPP crystals should have a workup including a chemistry screen; magnesium, calcium, and iron levels; and thyroid function tests.
  • White blood cell (WBC) count usually is elevated.
  • Erythrocyte sedimentation rate (ESR) usually is elevated during acute attacks.
  • Hyperuricemia may be present but is not diagnostic.

Imaging Studies:

  • Radiographs
    • Plain radiographs of the affected joint(s) are indicated.
    • Radiographic lesions of chronic gout may appear as rat-bitten, sclerotic regions on the joint surfaces, with overhanging margins.
    • Patients with new onset of acute gout usually have no radiographic findings.
    • Patients with pseudogout usually have degenerative joint changes and may have calcifications in the soft tissues, tendons, or bursae.
  • Bone scan reveals increased nuclide concentration at affected sites.
  • Magnetic resonance imaging
    • Magnetic resonance imaging (MRI) is capable of detecting deposits of gout and pseudogout crystals but is not part of any routine evaluation for acute arthritis.
    • MRI can be very useful in determining the extent of the disease and may help in the differential diagnosis.
    • It is recommended that MRI studies be done with gadolinium to evaluate any tendon sheath involvement and to evaluate for osteomyelitis in the differential.
    • Large deposits of crystals may be seen in bursae or ligaments. Tophi usually are low or intermediate signal intensity on T1-weighted images.

Procedures:

  • Aspiration and biopsy
    • Joint aspiration is the principal procedure used to make the diagnosis of crystal-induced arthritis and to rule out septic joint effusion.

 

TREATMENT

 

Emergency Department Care:

  • The temptation to treat patients without a proven diagnosis must be resisted. Unrecognized septic arthritis can lead to loss of life or of limb. Distinguishing septic arthritis from crystal-induced arthritis is not possible without an examination of joint fluid.
  • Arthrocentesis is mandatory for all patients with new onset of acute monoarthritis and is very strongly recommended for those with recurrent attacks whose diagnosis has never been proven by microscopic visualization of crystals.
  • Treatment for proven crystal-induced arthritis is directed at relief of the pain and inflammation. Narcotic pain relievers, nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids are the mainstays of treatment.
  • When physiological conditions cannot allow the use of NSAIDs or steroids (eg, when a patient has brittle diabetes with bleeding ulcers), colchicine is recommended.

Consultations:

  • Orthopedic consultation is indicated for any patient with septic arthritis or for any patient in whom a septic arthritis cannot be ruled out.
  • If the diagnosis has not been proven by microscopic examination of crystals under polarized light, refer the patient to a rheumatologist as soon as possible.