damage evaluated with levels of biomarkers, radiography, and BMI: data from the SAMURAI study. Mod
Haraoui B. Assessment and management of rheumatoid arthritis. J Rheumatol Suppl. 2009;82:2–10.
drugs in rheumatoid arthritis. Cochrane Database Syst Rev. 2004(3):CD000189.
Intern Med. 2004;141(10):764–770.
patients with rheumatoid arthritis. Rheumatology (Oxford). 2008;47(1):72–75.
Weiss MM. Corticosteroids in rheumatoid arthritis. Semin Arthritis Rheum. 1989;19(1):9–21.
Prakken B et al. Juvenile idiopathic arthritis. Lancet. 2011;377(9783):2138–2149.
treatments. Horm Res. 2009;72(Suppl 1):4–12.
systemic features. Arthritis Care Res (Hoboken). 2011;63(4):465–482.
arthritis:second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–392.
Aggarwal A, Misra DP. Enthesitis-related arthritis. Clin Rheumatol. 2015;34(11):1839–1846.
Shenoi S, Wallace CA. Remission in juvenile idiopathic arthritis: current facts. Curr Rheumatol Rep.
year followup. J Rheumatol. 2003;30(3):579–584.
Curr Opin Rheumatol. 2010;22(2): 213–217.
Phys Sportsmed. 2012;40(3):77–82.
juvenile idiopathic arthritis: a double-blind trial. Rheumatology (Oxford). 2004;43(10):1288–1291.
oligoarticular juvenile idiopathic arthritis. Rheumatology (Oxford). 2003;42(10):1254–1259.
Goldmuntz EA, White PH. Juvenile idiopathic arthritis: a review for the pediatrician. Pediatr Rev.
U.S. Department of Health and Human Services. Recommendations of the Advisory Committee on
Immunization Practices (ACIP): use of vaccines and immune globulins for persons with altered
immunocompetence. MMWR Recomm Rep. 1993:42(RR4):1.
Arthritis Rheum. 1998;41(7): 1210–1214.
extended oligoarticular or systemic arthritis. Arthritis Rheum. 2000;43(8):1849–1857.
clinical response to IL-1 blockade. J Exp Med. 2005;201(9):1479–1486.
Ilaris (canakinumab) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2014.
Arcalyst (rilonacept) [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals; 2014.
Arthritis Rheum. 2013;65(9):2486–2496.
rheumatoid arthritis. Arthritis Rheum. 2006;54(6):1987–1994.
arthritis. J Pediatr. 1998;133(2):179–180.
Gout is a disease that causes acute joint inflammation and pain
secondary to the deposition of monosodium urate (MSU) crystals within
the synovial fluid and lining. Clinically, acute gout presents as
monoarticular inflammation in 85% to 90% of patients with the first
metatarsophalangeal joint (great toe) typically affected; this is called
podagra. Patients presenting with acute gout may or may not have
A definitive diagnosis of gout can be made if MSU crystals are present
in a synovial fluid sample. However, this is rarely done in clinical
practice, and other diagnostic criteria are available.
The primary goal of treating acute gout attacks is the relief of pain and
inflammation. It is not necessary to lower the serum uric acid (SUA)
Low-dose oral colchicine is as effective as and safer than traditional
high-dose regimens, which are dosed to toxicity (diarrhea); Avoid
potential colchicine drug–drug interactions.
Nonpharmacologic therapy for acute and chronic gout includes limiting
daily alcoholic beverages, purine-rich meats, and fructose-containing
beverages/foods. Specifically, beer and, to a smaller extent, spirits are
associated with increased gout attacks; wine is less likely to be a risk
factor. Increasing low-fat dairy protein has a favorable effect on SUA.
Urate-lowering therapy (ULT) should not be initiated or discontinued
during treatment for an acute gout attack. Chronic ULT should be
started only if the patient has two or more gout episodes in 1 year or the
patient has comorbidities such as renal failure, uric acid stones, or urate
Patients should be evaluated for drug-induced hyperuricemia before
The goal of ULT is to lower the SUA to less than 6 mg/dL. If this goal is
achieved, most patients can be “cured” of acute gout attacks.
The preferred first-line treatment of gout and hyperuricemia is xanthine
oxidase (XO) inhibitors. Monitor for drug–drug interactions.
Initiation of ULT can precipitate acute gout attacks, so prophylaxis with
either colchicine or NSAIDs is recommended and should be continued
Gout is a disease that most commonly manifests as recurrent episodes of acute joint
pain and inflammation secondary to the deposition of monosodium urate (MSU)
crystals in the synovial fluid and lining. MSU deposition in the urinary tract can
cause urolithiasis and urinary obstruction.
1 Patients with gout cycle between flares of
acute joint pain and inflammation and intercritical gout (i.e., periods of quiescence
with no symptoms of the disease). In addition, they can also exhibit chronic
tophaceous gout and hyperuricemia.
Tophi are hard nodules of MSU crystals that have deposited in soft tissues and are
most commonly found in the toes, fingers, and elbows. Although gout is often
associated with hyperuricemia (defined as a serum urate level of greater than or
equal to 6.8 mg per deciliter)
, elevated serum uric acid (SUA) is not a prerequisite
In a retrospective review of two studies on gout, 14% of
patients presenting with acute symptoms had a normal SUA concentration less than 6
mg/dL and 32% had an SUA concentration less than 8 mg/dL.
considered a clinical diagnosis and hyperuricemia a biochemical one. These two
terms are not synonymous and are not interchangeable.
Uric acid serves no biologic function; it is merely the end product of purine
metabolism. Unlike animals, humans lack the enzyme uricase, which degrades uric
acid into more soluble products for excretion. As a consequence, uric acid is not
metabolized in humans and is primarily excreted renally, although up to one-third of
the daily uric acid produced can be eliminated through the gastrointestinal (GI)
5,6 Therefore, increased SUA concentrations arise from an increase in
production or a decrease in renal excretion of uric acid, or a combination of the two.
Overproduction of uric acid accounts for approximately 10% of gout cases
result from excessive de novo purine synthesis, which is primarily associated with
rare genetic enzyme mutation defects, some neoplastic diseases, aggressive cytotoxic
chemotherapy (causing tumor lysis syndrome), and certain myeloproliferative
disorders. Overproduction of uric acid can also be the result of excessive intake of
dietary purines from meat, seafood, dried peas and beans, certain vegetables (e.g.,
mushrooms, spinach, asparagus), beer, and other alcoholic beverages.
consumption (especially soft drinks) has also been linked with increased uric acid
9 Many patients attempt to avoid intake of these foods; however, dietary
restrictions are seldom of much benefit (with the exception of avoiding excessive
alcohol, yeast, or liver supplements), and patients should feel comfortable in eating
modest quantities of meats, seafood, and vegetables.
A defect in the renal clearance of uric acid is the main cause of hyperuricemia and
gout in about 90% of patients. Uric acid is filtered in the renal glomerulus and is
almost completely (98%–100%) reabsorbed in the proximal tubule. Uric acid is then
secreted distal to the proximal tubular reabsorption site, and most is reabsorbed
In normal patients, homeostasis between reabsorption and secretion of urate
is maintained. However, many factors (e.g., renal impairment, certain drugs, alcohol
excess, metabolic syndrome, hypertension [HTN], coronary heart disease [CHD])
can cause this balance to fail, resulting in excess serum concentrations of uric acid
Classically, gout presents during middle age. The onset of gout is uncommon in
prepubertal children, premenopausal women, and men younger than 30 years of age.
The appearance of gout in these populations should alert the clinician to the
possibility of renal parenchymal disease. The risk of gouty arthritis is approximately
the same for both men and women at any given SUA concentration; however, many
more men are hyperuricemic. For example, men are six times more likely than
women to have SUA concentrations greater than 7 mg/dL. Overall, gout occurs as
often in postmenopausal elderly women as in men.
11 Emerging evidence suggests the
incidence of gout in increasing in the black population.
QUESTION 1: M.D. is an obese 60-year-old woman who has been referred to a medication management
it.” What signs and symptoms did M.D. exhibit that are typical of acute gout?
M.D.’s symptoms of severe, acute pain and an obviously inflamed joint are
consistent with the usual presentation of gout. Also, M.D.’s age is consistent with the
epidemiologic data that are commonly associated with gout.
The pain of gout rapidly reaches its maximum within 6 to 12 hours of onset and is
usually accompanied by erythema.
It is often so severe that patients cannot even
tolerate a sheet lying on top of the affected area.
M.D.’s report of a very painful big toe is typical, because acute gout attacks affect a
single joint 85% to 90% of the time, and most often affect a joint of the lower
6 The first metatarsophalangeal joint (the great toe) is the most commonly
affected joint, and the term podagra specifically refers to gout in this joint.
Although initial gout attacks are primarily monoarticular, as many as 39% of the
patients in one study experienced polyarticular involvement as their first
14 Generally, recurrent attacks are of longer duration than initial
attacks, more likely to be polyarticular, and more smoldering in onset.
Acute gouty arthritis commonly begins at night. According to the Simkin hypothesis,
small amounts of effusion fluid gravitationally enter into degenerative joints of the
feet (or other joints) during the day, when most people are busily walking around,
and are reabsorbed during the night when the lower extremities are elevated. Thus,
the onset of pain in M.D. during the night is typical of gout.
Gout attacks also seem to be more common during episodes of increased physical
exercise. Long walks, hikes, golf games, or tight new shoes have historically been
associated with the subsequent onset of podagra.
16 The acute episode of toe pain
experienced by M.D. after a night of dancing is consistent with the appearance of
gout after increased physical exercise.
CASE 45-1, QUESTION 2: What findings in M.D. place her at risk for gout?
The diagnoses of HTN, type 2 diabetes, hyperlipidemia, and obesity in M.D. have
been associated with an increased risk of gout and hyperuricemia.
Common risk factors include alcohol consumption, the use of urate elevating drugs,
and certain comorbidities. Conditions associated with an increased risk of
hyperuricemia and gout include insulin resistance, obesity, metabolic syndrome,
chronic kidney disease, heart failure, organ transplant, history of urolithiasis, and
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