The Diagnosis and Treatment of Gout

Robert G. Smith, DPM, MSc, RPh, CPed

Disclosures

US Pharmacist. 2009;34(5):40-47. 

In This Article

Clinical literature has recently reported that gout is the most common inflammatory arthritis in the United States, with 3 to 5 million sufferers.[1,2] Both the incidence and the prevalence of gout appear to be increasing worldwide.[3] Gout is perhaps the oldest known type of arthritis; it has been colorfully depicted in art and literature along with commentaries on the moral character of the gout sufferer(Figure 1). Literature accounts have referred to gout;s association with rich foods and excessive alcohol consumption—thus the description, "the disease of kings."

Gout is a monosodium urate, monohydrate crystal deposit disease with a very rich history mirroring the evolution of medicine itself.[4,5] It was among the earliest diseases to be recognized as a clinical entity. Since gout has been recognized for so many centuries, its diagnosis and treatment generally have not elicited much interest; thus, the management of gout is a challenge for the clinician caring for the patient with this disease.[6]

Recent medical literature recognizes that most patients with gout visit a primary care physician for disease management, but there are challenges to diagnosing and treating gout in this setting.[7] Further, Weaver et al stated that the arrival of newer investigational agents in the market has prompted rheumatologists to consider how they can share current information to improve gout management.[7] It is this concept of sharing current information on the management of gout that is the main impetus for the preparation of this review. It is hoped that pharmacists will be empowered with this knowledge to assist the prescribing clinician to maximize patient outcomes when treating gout. First, to serve as a foundation, new insights into the pathogenesis of hyperuricemia and gout will be discussed. Second, risk factors, typical presentation of symptoms, and key diagnostic parameters will be reviewed so that the pharmacist may achieve an appreciation of the disease. Finally, nonpharmacologic treatment modalities and both current as well as newer investigational therapeutics will be offered so that the pharmacist may facilitate greater patient adherence through medication counseling.

Pathogenesis

Biologically significant hyperuricemia occurs when serum urate levels exceed solubility (~6.8 mg/dL). Hyperuricemia is a common serum abnormality that does not always progress to gout. Humans generate about 250 to 750 mg of uric acid per day. The uric acid comes from dietary purines and the breakdown of dying tissues. The exact cause of gout is not yet known, although it may be linked to a genetic defect in purine metabolism. Uric acid, the most insoluble of the purine substances, is a trioxypurine containing three oxygen groups. The pathogenesis of gout starts with the crystallization of urate within the joint, bursa, or tendon sheath, which leads to inflammation as a result of phagocytosis of monosodium urate crystals; the disease is usually associated with an elevated concentration of uric acid in the blood.[2,8] Specifically, uric acid is a breakdown product of the purines adenine, guanine, hypoxanthine, and xanthine. Adenine and guanine are found in both DNA and RNA. Hypoxanthine and xanthine are not incorporated into the nucleic acids as they are being synthesized, but they are important intermediates in the synthesis and degradation of the purine nucleotides. Both undissociated uric acid and monosodium salt, which is the primary form found in the blood, are only sparingly soluble.

The amount of urate in the body depends on the balance between dietary intake, synthesis, and excretion.[9] In people with primary gout, defects in purine metabolism lead to hyperuricemia, or high levels of uric acid in the blood. This can be caused by increased production of uric acid, abnormal retention of uric acid, or both. Urate in the blood can accumulate either through an overproduction or an underexcretion of uric acid. Hyperuricemia results from the overproduction of urate found in 10% of gout patients and from underexcretion of urate found in the remaining 90%.[9] The majority of patients with endogenous overproduction of urate have the condition as a result of salvaged purines arising from increased cell turnover in proliferation and inflammatory disorders, from pharmacologic intervention resulting in increased urate production, and from tissue hypoxia.[9]

The renal mechanism for handling urate is one of glomerular filtration followed by partial tubular reabsorption.[10] The final fractional excretion of uric acid is about 20% of what was originally filtered. Uric acid levels independently predict renal failure in patients with preexisting renal disease. Hyperuricemia causes interstitial and glomerular changes that are independent of the presence of crystal, and the changes very much resemble what hypertensive changes would look like chronically. In addition, serum hyperuricemia is epidemiologically linked to hypertension and seems to be an independent factor for the development of hypertension. Finally, hyperuricemia is defined as a serum uric acid level greater than 6.8 mg/dL. Serum uric acid can be normal, especially during the gout attack. The target goal for uric acid treatment is to achieve a level less than 6.0 mg/dL.

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