A 45-year-old man presents with right great toe pain and swelling for two days. He claims to have had right knee pain and swelling a few weeks prior, which self-resolved. He denies fever, chills, rash, or local trauma.
He has hypertension and consumes alcohol daily, but denies other medical issues.
What is the likely diagnosis, and how would you treat this condition? See p. 20.
By Jennifer L. Wiler, MD, MBA
Gout is the most common inflammatory arthropathy (Arthritis Res Ther 2010;12:223), characterized by deposits of monosodium urate crystals in joint, bone, and soft tissue after a transient episode of hyperuricemia (urate saturation of serum). The deposition of crystals at times produces a native inflammatory response. Although the exact mechanism of that response is not known, the phagocytosis of urate crystals by macrophages is thought to be an important step.
The clinical manifestations of gout are typically a continuum of asymptomatic hyperuricemia that in some progresses to acute gouty arthritis flares with intermittent asymptomatic periods that can ultimately progress to chronic gouty arthropathy and tophaceous gout. Interestingly, most hyperuricemic patients do not develop acute gout. Chronic hyperuricemia is also a risk factor for uric acid renal stones and chronic nephropathy.
Hyperuricemia (defined as serum urate levels >6.8mg/dL; Arthritis Rheum 1972;15:189) is caused by overconsumption of purine-rich foods (metabolized in urate) and overproduction or underexcretion of uric acid by the kidneys. Known precipitants of gout are obesity, alcohol ingestion, trauma, surgery, starvation, dehydration, metabolic syndrome, insulin resistance, congestive heart failure, certain medications (allopurinol, aspirin, cyclosporine, thiazide, and loop diuretics), a diet high in meat and seafood, soft drinks, and microtrauma from degenerative disease and genetic predisposition. (Curr Opin Rheumatol 2011;23:192.) Folate intake and coffee consumption have been found to be protective. Decreased environmental temperature is also a known precipitant of urate crystals, and may explain why the metatarsophalangeal joint is commonly involved. Despite these numerous risk factors, some attacks are spontaneous.
Classically, an acute gouty attack is characterized by severe pain, disability, swelling, and redness of the joint with maximal symptoms within 12-24 hours of symptom onset. Eighty percent of initial attacks occur in an isolated lower extremity joint, most often in the metatarsophalangeal joint (MTP). Other bursa or joints, including the sternoclavicular, sacroiliac, hip, and shoulder joints, also can be involved, mimicking a septic joint. Swelling may involve the surrounding joint tissues, creating a dactylitis (sausage digit) or appearance of cellulitis. (Ann Rheum Dis 2010;69:316.) Polyarticular involvement is less common as an initial presentation of the disease, but is more common in untreated individuals who have recurrent attacks.
Without treatment, patients typically have a recurrence within two years. As recurrent acute inflammatory arthritis attacks go untreated, the period between episodes typically shortens and the attacks become more severe, prolonged, and debilitating. As a result, chronic arthropathy (bony erosions and deformities) and tophi develop (mean: 12 years). It has been reported that approximately 75 percent of patients with untreated gout for 20 or more years develop tophi. (Arthritis Rheum 1972;15:189.)
Tophi are deposits of urate crystals in the connective tissue surrounded by granulomatous inflammation that is made of subcutaneous lumpy deposits that are palpable, nontender, raised, and hard, and give the overlying skin a yellow-red appearance. Most often located in joints and skin, tophi have also been found in the larynx, kidney, and heart valve as well as the spine, bursa, shoulder, and hip joints. Tophi cause bony erosions with a characteristic “overhanging” appearance on radiologic imaging that differentiates them from other chronic inflammatory polyarthropathies. (Ann Rheum Dis 2010;69:1907.)
The diagnosis of gout is made by identifying the pathognomonic negative birefringent urate crystals from involved tissue or fluid by light microscopy. Crystals can be detected during attacks, but can also be found in recently inflamed synovial fluid and tissues. Uric acid levels are not helpful during an acute attack because they are not typically elevated. (N Engl J Med 2011;364:443.) A definitive diagnosis is recommended because gout can mimic other clinical conditions including cellulitis, septic joint, and pseudogout. And prophylactic therapy is helpful to prevent recurrent gouty attacks, but has notable side effects to which a patient should not be subjected if he definitely does not have gout. The clinical diagnosis of gout is limited because of the common clinical overlay with rheumatoid and osteoarthritis. (Clin Rheumatol 2011;30:887.)
Gouty attacks initially self-resolve within days to weeks, but treatment of acute exacerbations is warranted because the attacks are debilitating. The American College of Rheumatology is currently developing guidelines for managing gout. (N Engl J Med 2011;364:443.) The first-line treatment includes anti-inflammatory medications (NSAIDs). (Ann Rheum Dis 2006;65:1301.) Studies have not found one type of NSAID superior over another, but many patients have contraindications to NSAID use, including renal insufficiency and peptic ulcer disease. Aspirin is contraindicated because it increases renal retention of uric acid. Colchicine is used for-treating an acute attack and as prophylaxis, and is considered a first-line treatment for an acute exacerbation by many. (N Engl J Med 2011;364:443.) Oral colchicine has a small therapeutic-window, with GI side effects (vomiting and/or diarrhea), limiting its widespread use. Low-dose oral colchicine (1.8 mg total over 1 hour) has been shown to be as efficacious as a high-dose regimen (4.8 mg total over 1 hour), with significantly fewer side effects (37 vs. 77%, mostly gastrointestinal). (Arthritis Rheum 2010;62:1060.) IV colchicine is no longer manufactured in the United States because of reported associated deaths. Glucocorticoids (systemic or intraarticular) are also the mainstay of therapy for an acute attack to decrease inflammation and swelling. It can be considered in patients who have previously tolerated it and found it efficacious. Interleukin-1 inhibitors are also being investigated as possible treatments for acute gout attacks. (Nat Rev Rheumatol 2011;7:77.)
Although prophylaxis and urate-lowering therapy for chronic gout are not typically within the purview of emergency physicians, these medications are common precipitants of an acute gouty attack and are contraindicated in the acute phase. Familiarity with the treatments is helpful because many patients are on chronic hyperuricemic lower medications. These include NSAIDs, colchicine, Interleukin-1 inhibitors for prophylaxis, and xanthine oxidase inhibitors (allopurinol), uricosuric agents (probenecid), and pegloticase (urate-lowering) therapies. (Nat Rev Rheumatol 2011;7:77.) Urate-lowering medications should not be stopped during acute flares. (N Engl J Med 2011;364:443.)
This patient had an arthrocentesis (see photograph) of the MTP joint with acquisition of cloudy fluid that was positive for urate crystals. He was started on oral glucocorticoids and a short course of NSAIDs, and instructed to follow up with his primary care physician.
• Read Dr. Leon Gussow's-article, “Lessons from the Courtroom: Colchicine Toxicity,” at http://bit.ly/Colchicine.
• Read Dr. James Roberts' series on gout at http://bit.ly/GoutSeries.
• Read all of Dr. Wiler's past columns in the EM-News.com archive.
• Comments about this article? Write to EMN at firstname.lastname@example.org.