This patient has acute gouty arthritis. He had sudden onset of atraumatic pain and swelling in the left fourth MCP joint. Needle aspiration demonstrates monosodium urate crystals, a negative gram stain, and a WBC count of 22,000.
Since the time of Hippocrates, the symptoms of gout have been described. In fact, monosodium urate crystals were first described more than 300 hundred years ago by Van Leewenhoeck, the inventor of the microscope. Since that time, the chemical composition of uric acid and its role in gout have been identified. Uric acid is the breakdown product of purine degradation in humans. Humans lack the enzyme uricase that can further degrade uric acid to allantoin, a more water soluble substance.
Uric acid is a weak acid with two pKa levels of 5.75 and 10.3. In serum, uric acid is in equilibrium with its salt, monosodium urate (MSU). The significance of this is that at a physiologic pH of 7.4, the overwhelming majority of uric acid in the serum is in the form of the more soluble monosodium urate, often referred to as urate. With decreasing pH, a greater proportion is in the form of the less soluble uric acid. The limit of solubility for monosodium urate in plasma is 6.8 mg/dL. At higher concentrations, precipitation of monosodium urate crystals may occur. Absolute concentration is not the only determination of solubility. MSU/uric acid is more likely to precipitate with decreasing pH and temperature. That is one reason why most attacks of gouty arthritis occur in the distal extremities. Also, in acidic urine, uric acid predominates, which is less soluble and more likely to crystallize and form stones.
Gout is most often used to describe an acutely painful joint which when aspirated is found to contain MSU crystals. These crystals demonstrate negative birefringence on polarized light microscopy. It is, however, a heterogeneous group of conditions that are best described in the following four categories: asymptomatic hyperuricemia, acute gouty arthritis, intercritical or interval gout, and tophaceous gout.
Asymptomatic hyperuricemia refers to a serum urate level greater than 7 mg/dL, the level at which MSU is supersaturated in plasma. Hyperuricemia may develop due to overproduction of uric acid, underexcretion of uric acid, or a combination of both. Purines are metabolized to uric acid via xanthine oxidase. Dietary intake of foods rich in purines such as liver, kidney, anchovies, veal, venison, turkey, bacon, and alcoholic beverages, increase urate levels. Urate levels may increase secondary to increased cell turnover, such as in myeloproliferative disorders or increased degradation of purine nucleotides during cytotoxic therapy for malignancy. They also may increase during periods of strenuous exercise, rhabdomyolysis, or status epilepticus. Other causes include enzymatic abnormalities that may increase the amount of uric acid.
Most patients with hyperuricemia are secondary to decreased excretion of urate. Two-thirds to three-fourths of urate is excreted in the urine with the remainder lost in the GI tract. Any disease process which results in a decreased glomerular filtration rate (hypertension, CHF, diabetes mellitus) will decrease excretion. Medications such as thiazide diuretics, loop diuretics, low-dose aspirin, and levodopa decrease excretion. Alcohol not only decreases renal excretion of urate, but is an exogenous source for urate formation.
Hyperuricemia is not synonymous with gout and uric acid stone development. Patients may be entirely asymptomatic and never develop clinical manifestations. Patients may have MSU crystals in their joint synovium and be asymptomatic. At the opposite end of the spectrum, patients may have normal urate levels and have symptoms of gout. The exact mechanisms, inciting arthritis and urate deposition, have yet to be fully elucidated.
Acute gouty arthritis is the most common initial presentation of gout in the emergency department. Patients present with usually sudden onset of a monoarticular arthritis typically of the lower extremity (podagra refers to the acute attack of the first metatarsal). Patients may complain of fevers and malaise. The joint is warm, red, swollen, and extremely tender to palpation and range of motion. Patients may be febrile, and laboratory tests often demonstrate an increased WBC count and an increased sedimentation rate. Radiographs, if done, are normal in the early stages of gout. Joint aspiration is the mainstay of diagnosis not only for the identification of MSU crystals within the joint but also to rule out a septic joint.
The pathophysiology of acute intraarticular inflammation is well described. MSU crystals are shed into the synovium. Proteins are absorbed onto the MSU crystal surface that activates the complement system. Neutrophils phagocytose the protein-crystal molecule. Membranolysis, intracytoplasmic release of lysosomal enzymes and cell death ultimately result. The release of chemotactic factor from neutrophils and the release of proteolytic enzymes from cell lyses further increase the degree of inflammation.
Treatment of acute gouty arthritis is symptomatic. The initial medication of choice is an NSAID. While traditionally indomethacin was used, any NSAID may be used if given at anti-inflammatory dosages. Caution is advised in patients with a history of hypertension, renal disease, or GI bleeding and in patients taking oral anticoagulants. Many patients who present to the ED have already tried an NSAID with insufficient relief. Remaining symptomatic treatments include colchicine, corticosteroids, or other analgesics.
The main mechanisms of action of colchicine are the prevention of phagocytosis of the protein-crystal complex by neutrophils and blocking the release of chemotactic factor. Both actions decrease the inflammatory response. Colchicine may be given IV or PO. The oral route is the safer method of administration although at therapeutic dosages gastrointestinal side effects often occur. Intravenous use is contraindicated in patients with renal or hepatic insufficiency and patients already taking PO colchicine. It has been associated with bone marrow suppression, renal failure, disseminated intravascular coagulation, and death. A good flowing intravenous access is required to limit the possibility of extravascular extravasation and subsequent tissue necrosis. The use of colchicine has decreased over the years for the treatment of symptomatic gout because of well described adverse reactions. It is frequently given as a prophylactic medication to prevent subsequent episodes of gouty arthritis, and is used in combination with urate-lowering medications.
Corticosteroids are becoming more widely used in patients presenting with an acute gouty attack. The mechanism of action is anti-inflammatory, and patients quickly feel symptomatically better. They can be given to patients for whom NSAIDS and colchicine are either contraindicated or ineffective. Intraarticular instillation of triamcinolone acetonide (Kenalog) or methylprednisolone (Medrol) dramatically improves symptoms, and is ideal for patients presenting with monoarticular involvement of larger joints. Intramuscular or PO steroids can be used, and are preferred for those with polyarticular involvement. It cannot be emphasized enough that a septic joint must be ruled out for any atraumatic swollen joint, and is particularly important when steroids are to be used.
Following resolution of a gouty attack, a patient may be asymptomatic for months to years. This is referred to as intercritical gout. Therapy may involve diet changes or urate-lowering medications. Probenecid and sulfinpyrazone are uricosuric agents best for those patients who underexcrete uric acid. Allopurinol, a xanthine oxidase inhibitor, is best for those patients who overproduce uric acid. Tophaceous gout refers to deposits of MSU in the soft tissues, ligaments, and bones that occur over the long term.