Gout - StatPearls - NCBI Bookshelf

9/27/22, 11:16 AM Gout - StatPearls - NCBI Bookshelf
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Gout
Ardy Fenando; Manjeera Rednam; Rahul Gujarathi; Jason Widrich.
Author Information
Last Update: May 21, 2022.
Continuing Education Activity

Gout is one of the most common causes of chronic inflammatory arthritis in the United States,
characterized by monosodium urate (MSU) monohydrate crystals deposition in the tissues. Gout
was first recognized even before the common era. Hence it is arguably the most understood and
manageable disease among other rheumatic diseases. This activity reviews the evaluation and
management of gout and highlights the role of interprofessional team members in collaborating
to provide well-coordinated care and enhance patient outcomes.
Objectives:
Identify the etiology of gout.
Explain the common physical exam findings associated with gout.
Describe the pathophysiology of gout arthritis.
Summarize interprofessional team strategies for improving care coordination and

communication to advance gout and improve outcomes.
Access free multiple choice questions on this topic.
Introduction
Gout, once known as the "disease of kings and king of diseases," is among the most prevalent
etiologies of chronic inflammatory arthritis in the United States, characterized by monosodium
urate (MSU) monohydrate crystals deposition in the tissues.[1][2] Gout was first recognized even
before the common era, and hence it is the most understood and manageable disease among all
rheumatic diseases.[3][4]
Gout is characterized biochemically by extracellular fluid urate saturation, which is reflected by

hyperuricemia in the blood, with plasma or serum urate concentrations exceeding 6.8 mg/dL
(approximately 400 micromol/L); this level is the approximate limit of urate solubility.[5] The
clinical manifestations of gout may include:
Acute gout flare (recurrent flares of inflammatory arthritis)
Chronic gouty arthropathy
Accumulation of urate crystals in the form of tophaceous deposits
Uric acid nephrolithiasis
Chronic nephropathy
https://www.ncbi.nlm.nih.gov/books/NBK546606/ 1/24
Etiology
Risk Factors
Humans are the only known mammals to develop spontaneous gout, as hyperuricemia commonly
develops in humans. Hyperuricemia is the leading cause of gout.[1][6] People with higher serum
urate levels are at an elevated risk for gout flare-ups and will also have more frequent flare-ups
over time. In a study of more than 2000 older adults with gout, those with levels more than 9
mg/dl were three times more likely to have a flare over the next 12 months than those with levels
less than 6 mg/dl.[7]
Hyperuricemia is not the only risk factor for gout, and in fact, only a minority of these patients
develop gout. The lower physiological uric acid range can assess the impact of diet on the uric
aid levels in other non-uricase-producing species. Dietary sources that can contribute to
hyperuricemia and gout include the consumption of animal food such as seafood (e,g., shrimp,
lobster), organs (e.g., liver and kidney), and red meat (pork, beef). Some drinks like alcohol,
sweetened beverages, sodas, and high-fructose corn syrup may also contribute to this disease.[1]
epidemiological studies reported an increased disease burden of gout, which is largely explained

by lifestyle changes like increased protein consumption and a sedentary lifestyle.
Other factors implicated in gout and/or hyperuricemia include older age, male sex, obesity, a
purine diet, alcohol, medications, comorbid diseases, and genetics. Offending medications
include diuretics, low-dose aspirin, ethambutol, pyrazinamide, and cyclosporine. Genome-wide
association studies (GWAS) have found several genes associated with gout. These include
SLC2A9, ABCG2, SLC22A12, GCKR, and PDZK1.[8]
Risk factors of Hyperuricemia and Gout
Table
Causes of Hyperuricemia
Table
Causes of hyperuricemia due to decreased uric acid

clearance
Triggers
Every condition that causes alterations in extracellular urate concentration can trigger a flare-up.
These conditions include stress (surgical procedure, recent trauma, or starvation), dietary factors
(e.g., fatty food, beer, wine, and spirits), and drugs (e.g., aspirin, diuretics, or even allopurinol).
Epidemiology
Epidemiological estimates depend on the disease definition. A definitive diagnosis of gout is
accepted in the presence of monosodium urate monohydrate crystals in the joint fluid or the
presence of tophus. Since identification by this definition is impractical, a number of case
definitions have been developed like self-reports, Rome criteria, the New York criteria, the
American College of Rheumatology criteria(ACR), and the 2015 ACR/European League Against
Rheumatism (EULAR) criteria. The 2015 ACR/EULAR criteria have a sensitivity of 92% and
specificity of 89% and are superior to all previous criteria.
The prevalence of gout can vary by age, sex, and country of origin. In general, the prevalence of
gout is 1 to 4%. Older age and male sex are two common risk factors noted globally. In western
nations, the prevalence of gout in men (3 to 6%) is 2 to 6 fold higher than in women (1 to 2%).
Prevalence increases with age but plateaus after 70 years of age. From 2007 to 2008, around
3.9% of U.S. adults received a diagnosis of gout.[9] Estimates of the gout prevalence in the
United States range from less than three million to eight million or more individuals. The last of
these estimates suggest gout prevalence of over 3% of the adult American population.[10][11]
[12]
The incidence rates of gout have seen an increasing trend over the past several decades, with a
higher incidence noted in men than women, and the incidence increased with age. In men, adult
serum urate levels of 5 to 6 mg/dL are usually reached at puberty, with a slight increase thereafter
due to age alone.[13] The serum urate levels differ in women, whose serum urate concentrations
average 1.0 to 1.5 mg/dL lower than men of corresponding ages.[14][15] This is likely due to
renal uric acid clearance under the influence of estrogen in women. The urate concentrations in
women after menopause rise to levels comparable to those in adult men.[16] The gender
differences in patterns of urate concentration tend to affect the clinical differences between
women and men in the age of onset of gout.[17][18]
Comorbidities
Hypertension, diabetes mellitus, hyperlipidemia, and metabolic syndrome are often associated
with gout. Individuals with psoriasis have increased urate production and are prone to gout. On
the other hand, patients with renal insufficiency have decreased urate excretion, resulting in
gouty attacks. The prevalence of gout is also higher among individuals with chronic diseases
such as hypertension, chronic kidney disease, diabetes mellitus, obesity, congestive heart failure,
and myocardial infarction.[19]
Pathophysiology
Gout is an inflammatory arthritis that occurs in response to the deposition of MSU crystals, the
end product of human purine metabolism, in joints, soft tissues, and bones. It may manifest as a
gout flare (acute arthritis), chronic gouty arthritis (chronic arthritis), tophaceous gout (tophi),
renal functional impairment, and urolithiasis.[20][21]
Following are a number of complex and interacting processes responsible for the
pathophysiology of gout:
Genetic, metabolic, and other factors that result in hyperuricemia
Metabolic, physiologic, and other characteristics are responsible for MSU crystal
formation.
The soluble inflammatory, cellular, and innate immune processes and characteristics of
MSU crystals themselves promote the acute inflammatory response.
Immune mechanisms that mediate the resolution of acute MSU crystal-induced acute
inflammation
Chronic inflammatory processes and effects of immune cells and crystals on osteoblasts,
chondrocytes, and osteoclasts contribute to cartilage attrition, bone erosion, joint injury,
and formation of tophi.
Uric Acid Physiology
Uric acid is the final product of purine metabolism in humans and higher primate species as the
gene decoding the enzyme uricase is silenced by mutation. Uric acid is the most abundant natural
antioxidant in the human body, the traditional role of which was believed to be to remove
reactive oxygen species. However, recent studies revealed that it is not a significant factor in
controlling oxidative stress in the body. It is believed to have a role in immune surveillance and
maintaining blood pressure and intravascular volume. Uric acid is a weak organic acid. It exists
in the ionized form at pH 7.4 and functions as monosodium urate(which is less soluble) due to
the high sodium concentration. In acid fluids like urine, uric acid exists in the non-ionized form,
which is less soluble even in the physiological range. This explains the presence of uric acid
crystals and stones in the urinary tract in distinction to MSU.
The bulk of urate in the body is from endogenous production in the liver with a small
contribution from the small intestines. The glomerulus filters nearly all urate; hence under
steady-state conditions, the body pool of urate is managed through renal excretion. The urate
pool is expanded in a hyperuremic state. In men, the normal urate range is from 800 to 1000 mg,
and in women 500 to 1000 mg. The daily turnover of urate is between 500 to 1000 mg. Serum
urate concentrations in children are lower, and during male puberty, the value increases to the
adult range. Serum urate levels remain low in women of reproductive age. The difference results
from the effect of estrogen on renal urate transporters, resulting in less renal urate reabsorption
and increased clearance in women. In menopausal and postmenopausal women, the urate levels
approach those of adult males and may be altered by hormone replacement therapies.
Table
Hyperuricemia
Hyperuricemia is a crucial factor in developing gout as it can promote monosodium urate crystal
nucleation and growth by reducing urate solubility. Several factors promote hyperuricemia in
humans, like the genetic absence of uricase, reabsorption of 90% of filtered uric acid, and limited
solubility of MSU and urate in body fluids. Overproduction and/or underexcretion of uric acid is
the foundation for rising serum uric acid levels.[6] When renal urate excretion is decreased, the
intestinal uricolysis increases to half of the total urate disposal, and the transporter ABCG2 plays
a key role. Serum urate concentrations exceeding 6.8mg/dl are saturating and increase the risk of
deposition. It is seen in 20% of adult white men in the united states and is associated with several
chronic disorders.
Hyperuricemia may be primary/idiopathic or secondary. Overproduction is seen in several

diseases, toxic states, and due to medications, like acute leukemia, tumor lysis syndrome,
psoriasis, etc.
Purine Metabolism
Purines contain nine carbon purine nuclei of fused pyrimidine and imidazole rings.
Purines perform essential functions in all living cells through purine-based nucleic acids adenine,
guanine, and hypoxanthine. The dietary purine contribution to the urate pool is significant.
Purine removal from the diet of normal individuals for a period of 10 days reduces the urate
levels by 25% and urinary uric acid excretion by 50%. But severe purine restricted diets are
impractical, and diets high in fructose, meat, alcohol, and fish promote hyperuricemia.
The endogenous pathway of purine production is called the de-novo purine synthesis and
involves the conversion of ribose-5-phosphate from PRPP (5-phosphoribosyl 1-pyrophosphate)
into nucleotide inosine monophosphate through 10 ey steps. This is an energy-costly process;
hence energy is saved by interconversion and salvage of purine nucleotides. The urate precursors
of purine degradation are hypoxanthine and guanine. These are mostly salvaged, and the unused
guanine is deaminated to xanthine. The hypoxanthine is oxidized to xanthine by xanthine
oxidoreductase.
Xanthine oxidoreductase is a molybdenum-pterin and iron sulfide cluster containing

flavoprotein. It exists in oxidase form that uses oxygen to convert hypoxanthine to xanthine and
xanthine to urate and in a dehydrogenase form that uses NAD+. Inhibition of xanthine
oxidoreductase is the most common target of urate-lowering in patients with gout.
The major steps in purine synthesis targetted by regulation are
1. The synthesis of PRPP in the PRPP synthetase pathway
2. The utilization of PRPP in the first step of de-novo purine synthesis
The pathway is inhibited by purine nucleotide products of purine synthesis and activated by
increased PRPP. This antagonistic control mechanism malfunctions in two rare X-linked
disorders—deficiency of salvage enzyme HPRT and overactivity of PRS1. Excessive
ATP(adenosine triphosphate) depletion in tissue hypoxia or acute alcohol intoxication leads to
decreased concentration of inhibitory nucleotides and excess urate productions.
Renal Uric Acid Secretion
Uric acid clearance in adults averages only 5 to 10% that of creatinine clearance, despite 100%
uric acid filtration at the glomerulus. This is because 90% of the filtered uric acid is reabsorbed
in the renal tubules. People with hyperuricemia due to impaired renal excretion have normal
urinary urate levels due to impaired clearance of uric acid. Genomic and molecular studies have
identified several transporters involved in renal uric acid clearance; two of them, GLUT9 and
URAT1 (members of the organic acid transporter family), strongly affect serum urate levels.
Glucose Transporter 9 (GLUT9)
GLUT9 is a product of the SLC2A9 gene. It is a voltage-driven urate transporter that mediates
uric acid reabsorption from tubular cells. GLUT9 exists in 2 isoforms GLUT9L on the
basolateral side of the proximal renal tubular epithelium and GLUT9S on the apical side. It is
also expressed in the hepatocytes and regulates serum urate concentrations by dual effects in the
kidney and the liver. It also transfers glucose and fructose, which might explain the dietary
influence of these substances on hyperuricemia. Mice with a knockout of GLUT9 had moderate
hyperuricemia, massive hyperuricosuria, and early onset nephropathy.
URAT1
URAT1 is encoded by the SLC22A12 gene and is highly specific for uric acid. It affects renal
uric acid transport by mediating the exchange of various anions. Mutations in SLC22A12 lead to
hypouricemia, hyperuricosuria, and exercise-induced renal functional impairment. The uricosuric

drugs probenecid and benzbromarone and lesinurad inhibit URAT1 and increased uric acid
excretion. Other urate transporters include ABCG2, NPT1, NPT4, MRP4 (multidrug resistance
protien4), etc.
Autosomal Dominant Tubulointerstitial Kidney Disease caused by UMOD pathogenic

variants is characterized by early-onset hyperuricemia (with or without gout), hypertension, and
progressive tubulointerstitial inflammation and fibrosis leading to end-stage renal failure by the
age of 40 years. This was previously described as familial juvenile hyperuricemia nephropathy
and medullary cystic kidney disease. Most show a mutation in uromodulin(Tamm-Horsfall
protein) which maintains the integrity of the ascending loop of Henle by forming a gel-like
lattice that coats the luminal side of the tubule. Defects in the lattice alter solute fluxes, reducing
Na and Cl reabsorption, leading to decreased extracellular volume and compensatory
enhancement of sodium-dependent urate transport in the proximal tubule.
Extra-renal Urate Excretion
This is by the ABCG2 transporter in the intestines. A reduced intestinal urate excretion in
ABCG2 knockout mice caused an increased serum urate, but this was partially compensated by
increased renal uric acid excretion. Hence, urate overproduction hyperuricemia is a renal
overload type consisting of "extrarenal underexcretion" type and "genuine urate overproduction"
subtypes.
Urate Crystal Formation
The formation of MSU crystals requires sustained supersaturated concentrations of urate. Crystal
formation is influenced by factors like the presence of particulate seed, local cation
concentrations, pH, temperature, and dehydration. Immunoglobulin G and Ig M may also aid in
crystal formation and growth in patients with gout. MSU crystals formation is seen preferentially
in the first metatarsophalangeal joint, midfoot, and Achilles tendon. Growing evidence shows the
relation between OA and sites of MSU crystal deposition. The osteoarthritic joint, with products
of cartilage degradation like chondroitin sulfate, lowers the urate solubility and promotes
nucleation and growth of crystals.[22] The solubility of MSU drops rapidly with decreasing
temperature.[5]
Table
Inflammatory Response
microscopic and imaging studies have shown the presence of urate crystals within the joints for
prolonged periods without overt inflammatory reactions. Heavily crystal-laden fluids(urate milk)
are sometimes found in uninflamed bursae and joints. The dense urate crystal mass in tophi
sometimes reaches massive dimensions with little inflammation and symptoms till there is
critical compression of the surrounding tissues. The crystals initiating inflammation are
microcrystals usually shed from preexisting synovial tophi. This is supported by observing acute
gout flares with rapid changes in urate concentrations. Initiation of inflammation depends on
multiple factors like crystal size, the proteins and molecules coating them, and inflammatory
cells encountered. MSU crystal surface binds to various proteins, lipoproteins, and lipids,
including IgG.
The IgG conformational changes encourage phagocytosis by cells with Fc-y receptors. The IgG
also activates the classical complement pathway. The MSU crystals directly activate both
complement pathways. This promotes further opsonization by depositing the complement split
product C3b on the crystals. Apolipoprotein coating on the MSU crystals counters the opsonic
effects of the IgG Fc and complements. It also inhibits neutrophil stimulation. Thus the
inflammatory potential of the MSU crystals is a balance between the pro and anti-inflammatory
elements coating the surface. In acute gout, the predominant inflammatory cell in the synovial
tissue and fluid is the neutrop[hil, which contributes to the bulk of the proinflammatory stimulus.
Synovial fluid macrophages in patients with asymptomatic tophi often contain MSU
microcrystals. This indicates the absence of overt inflammation despite active engagement with
phagocytes. Immortal macrophages and blood monocytes mount a vigorous response to MSU
crystals compared to well-differentiated macrophages due to the release of TGF-b1. Two broad
mechanisms of MSU crystal interaction with phagocytes have been studied.
1. activation of phagocytes leading to lysosomal fusion, respiratory burst, and release of

inflammatory mediators,
2. the more predominant pathway of cytosolic protein complex activation(NLRP2

inflammasome).[23] These complexes subsequently recruit caspase-1, which activates pro-IL-
1beta to IL-1beta. IL-1beta plays an important role in the inflammatory response to gout.[3][23]
[24] It promotes vasodilatation and recruitment of monocytes and initiates and amplifies the
inflammatory cascade. Further IL-1beta secretion can result in bone and cartilage breakdown.
Other cytokines, such as TNF-1, IL-6, CXCL8, and COX-2, are also involved in the
inflammatory response.[24]
Most external stimuli activate inflammatory cells by a carefully coordinated cell surface signal
transduction by a cascade of tyrosine kinase phosphorylation. But MSU crystals bypass and
directly activate second messenger systems.
Table
8. ACTIVATION OF NEUTROPHILS 11. REMOVAL OF

CRYSTAL COATING AND PHAGOLYSOSOMAL
RUPTURE, ENZYME AND MEDIATOR RELEASE
Termination Of The Acute Flare
Acute gout is always self-limiting, even without medication. It resolves spontaneously in a week
or two. Given the similarity in the molecular mediators of inflammation in gout and other
arthropathies and the persistence of MSU crystals, this is an intriguing phenomenon. After MSU
crystal ingestion, neutrophils undergo NETosis (neutrophil extracellular traps). The NETs
aggregate and densely pack MSU crystals and degrade the pro-inflammatory cytokines,
including IL-beta, TNF-alpha, IL-6, etc. The increased vascular permeability after acute
synovitis allows increased entry of antiinflammatory cytokines crystal coating molecules like
ApoB. This coating with ApoB and locally produced ApoE and TGF-beta inhibit neutrophil
activation. Systemic anti-inflammatory mediators like melanocortins decrease joint inflammation
by the MCRs(macrophage melanocortin receptors), adenosine monophosphate-activated protein

kinase inhibits NLRP3 expression and inhibits caspase1 and IL-1beta.
Advanced Gout
Tophi are deposits of MSU crystals encompassing granulomatous inflammation. They are nests
of crystals with a corona zone of differentiated macrophages and multinucleated giant cells
surrounded by a fibrous layer. Proinflammatory cytokines like IL-1 and TNF-alpha are expressed
within the corona. Aggregated NETs are also part of the tophus. The tophus is a dynamic chronic
inflammatory response to MSU crystal deposition that is complex and organized. Tophi are most
often found in periarticular, articular, and subcutaneous areas, including cartilage, bone, joints,
tendons, and skin, rich in proteoglycan. The tissue reaction to tophus is generally chronic
inflammation and involves both adaptive and innate immunity. Few patients with tophaceous
gout also present with chronic gouty arthritis (chronic synovitis). There is a close relationship
between MSU crystal deposits and the development of cartilage and bone erosions.[25]
Tophi contribute to joint damage and bone erosion in gout.[26] MSU crystal deposits are
surrounded by osteoclast-like cells at the interface of the bone and a tophus.[27] T-cells in the
tophus express RANKL and contributor to bony erosions. Urate crystals also decrease the
function, viability, and differentiation of osteoblasts and reduce osteoprotegerin expression.
Hence, a high number of osteoclasts and reduced osteoblasts are present at the bone tophus
interphase.
The double contoured ultrasound sign is seen in the superficial articular cartilage in patients with
chronic gout and represents urate deposits. Urate crystals degrade cartilage matrix by inducing
nitric oxide generation and expression of matrix metalloprotease 3. Hence, joints with persistent
crystals have ongoing progressive damage in the absence of acute flares.
Histopathology
Monosodium urate crystal deposition, under polarizing light microscopy, is typically described as
a rod or long needle-shaped crystals with negative birefringence.[28] Under light microscopy,
tophi consist of several zones; the crystalline center, the surrounding corona zone, and then the
fibrovascular zone. Multinucleated giant cells, histiocytes, and plasma cells are present in the
corona zone.[29]
History and Physical

Gout has been described as a chronic disease characterized by four distinct stages.
1. Asymptomatic hyperuricemia
2. Acute gout attacks
3. Inter-critical period
4. Chronic tophaceous gout.
Asymptomatic Hyperuricemia
majority of patients with asymptomatic hyperuricemia never develop gout. The risk of acute gout
attack increases with the level of serum urate. This stage ends with the first gout attack.
Acute Gout Attack
This is the initial manifestation of gout. It is characterized by abrupt onset of severe pain and
swelling. The maximum inflammation occurs within 12 to 24 hours. Gout flare is typically
monoarticular, often occurring in the lower extremities.[30] The most commonly involved joint
is the first metatarsophalangeal joint. The talar, subtalar, ankle, and knee can also be involved in
some cases. Although affliction of the joints mentioned above is common in gout, the physician
should pay attention to other joints, specifically those with underlying osteoarthritis. Besides
joints, other periarticular structures such as tendons and bursa may also be affected.[1] Gout can
occur in axial joints such as sacroiliac joints and the spine, though much less common than
peripheral involvement, leading to diagnostic confusion.[31][32] The initial attack resolves
within 3 to 14 days, even in the absence of pharmacotherapy, but the subsequent attacks are
prolonged.
Polyarticular gout flares are more likely to occur in patients with longstanding disease. Initial
presentation of polyarticular gout is more frequent in patients in whom gout and hyperuricemia
arise secondary to lymphoproliferative or myeloproliferative disorder or in organ transplant
recipients receiving tacrolimus or cyclosporine.[33][34] In women, a polyarticular presentation
has been reported in South Africa, with only a small number starting with acute podagra.
Gout flares are more common at night and in the early morning when cortisol levels are low.
[35] The pain is often sudden, waking the patient from sleep or may have developed gradually
over a few hours before the presentation, with the maximum intensity of pain at 24 hours.
[35] Signs of inflammation extend beyond the joint involved; this may give the impression of
cellulitis or dactylitis (sausage digit) or may actually be due to tenosynovitis or arthritis in
contiguous joints. The pain is usually severe and not responsive to the usual home remedies;
even touching the joint can be excruciatingly painful. Gout flare-ups often incite local
inflammation, which presents as erythematous, swollen, and a warm joint. The erythema over the
affected joint during an attack is characteristic of gouty synovitis. Systemic features of joint
inflammation may include fever, general malaise, and fatigue.[1]
Around 60% of the patients experience a second attack within one year and 80 % within three
years. Local trauma, alcohol binges, overeating or fasting, weight changes, use of diuretics, and
initiation of urate-lowering drugs may precipitate an acute attack. in a hospital setting, post-
operative status or acute severe medical illnesses may precipitate attacks. The spring season has
been reportedly associated with an increase in gout attacks.
The physical exam findings align with the patient's history. The affected joint is typically red,
swollen, warm, and tender.[36] In patients with chronic gout, the flare-up may involve multiple
joints. With the involvement of many joints, it can cause a systemic inflammatory response
syndrome that may masquerade as sepsis.[37] Tophi, which are subcutaneous depositions of
urate that form nodules, can also be found in patients with persistent hyperuricemia. Tophi
typically occur in the joints, ears, finger pads, tendons, and bursae.[1]
Intercritical Gout
After resolution of the acute attack, the patient is in the inter-critical stage. in some patients, a
stage of incomplete remissions is present with the persistence of pain. Although the disease
seems to be inactive, hyperuricemia persists, and subclinical inflammation may be present in the
joints.
Chronic Tophaceous Gout
Gouty tophi are foreign body granulomas around deposits of MSU crystal. They appear as chalk-
like subcutaneous nodules under transparent skin with increased vascularity, which may or may
not drain. Although patients may present with tophi as their initial symptom, chronic tophaceous
gout usually develops ten or more years after an acute attack. However, microtophi are
documented early in the disease in patients with hyperuricemia. MSU crystal deposition is seen
in joints affected by osteoarthritis. It usually occurs in the connective tissue and articular
cartilage. Tophi may be intraarticular, periarticular, or extra-articular, the most common sites
being the digits of hands and feet, knees, and the olecranon bursa. They lead to destructive
deforming arthritis with extensive bone destruction and grotesque deformities. Women develop
tophaceous deposits on the Heberden nodes and Bouchard nodes. 30% of the patients with
chronic tophaceous gout had finger pad deposits. In postmenopausal women with CKD finger
pad, tophi were seen before the onset of an acute attack.
Tophaceous deposits have been reported in the cornea in the eye and the heart valves.
Evaluation
Synovial Fluid Analysis
Monosodium urate crystal identification remains the gold standard for gout diagnosis. Gout flare
is marked by the presence of MSU crystals in synovial fluid obtained from affected joints of
bursas visualized by direct examination of a fluid sample using compensated polarized light
microscopy. This technique may also identify uric acid crystals from previously affected
tophaceous deposits and joints during the inter-critical period.[38] Synovial fluid during a gout
flare-up usually is yellow in color and cloudier in appearance, and it contains crystals and white
blood cells with neutrophil predominance. The synovial fluid will be more opaque in patients
with septic arthritis with a yellow-green appearance. Under a microscopic examination, synovial
fluid for septic arthritis will have a higher white blood cell count (over 50000/ml) than in gout
and a positive gram stain. Additionally, cultures will be positive for bacteria and negative for
crystals.
Under polarizing microscopy, synthetic fluid or tophus aspiration analysis reveals needle-shaped,
negatively birefringent crystals.[1][3][39] Arthrocentesis is also necessary to confirm the
diagnosis and rule out other septic arthritis, Lyme disease, or pseudogout (calcium
pyrophosphate).[39]
Laboratory Study
The examination usually reveals elevations in the white blood cell count, erythrocyte
sedimentation rate (ESR), and C-reactive protein (CRP) during a gout flare-up. Still, these
features are non-specific and do not confirm the diagnosis.
During an acute gout flare-up, serum urate level may be high, normal, or low. The physician
should repeat the serum urate level in patients with an uncertain gout diagnosis after the
resolution of the flare-up. Hyperuricemia is helpful in the clinical diagnosis of gout in
symptomatic patients, but hyperuricemia alone does not definitively confirm the diagnosis.
Asymptomatic hyperuricemia is not uncommon in the general population. Persistently low serum
urate concentrations make the diagnosis of gout less likely.[3] In patients suspected of gout based
on clinical features, elevated serum urate level (>6.8 mg/dL) can support the diagnosis but is
neither diagnostic nor required to establish the diagnosis. The most accurate time for assessing
serum urate level to establish a baseline value is two weeks or more after a gout flare completely
subsides.
Urinary fractional excretion of uric acid can be measured, especially in young populations with a
non-specific cause of hyperuricemia. It will help differentiate between overproduction or under
excretion of uric acid and can act as a guide for therapy.
Imaging
Although not routinely used, ultrasonography and dual-energy CT (DECT) can assist in
diagnosing gout. Monosodium urate deposition will be apparent on ultrasound as a hyperechoic
enhancement over the cartilage, also known as a double contour sign. DECT can identify urate
due to the beam attenuation after exposure to two different X-ray spectra.[1][3]
Treatment / Management
The treatment of gout is based on the goals of treatment. During acute flares, the goal is solely to
reduce the inflammation and symptoms. Long term goal is to reduce serum urate levels to
achieve suppression of flare-ups and regression of tophi.[3]
General Principles of Therapy
The earlier the treatment is introduced for a gout flare, the rapid and complete resolution of
symptoms occurs.[40]
The duration of gout flare therapy ranges from a few days to several weeks, depending on
the timing of treatment initiation.[41]
Anti-inflammatory gout flare prophylaxis should generally be continued during the early
months of urate-lowering therapy.[42]
For patients receiving urate-lowering therapy at the time of gout flare, the urate-lowering
medication should be continued without interruption as there is no benefit to temporary
discontinuation.
Tophus is an indication to initiate long-term urate-lowering therapy either during or

following the resolution of a gout flare to reverse or prevent joint damage and chronic
gouty arthritis.
Acute Gout Flare
Management of acute flares aims at decreasing the inflammation and the resulting pain. The
physician should start the treatment within the first 24 hours of onset to reduce the severity and
duration of the flare-up.[6] Non-pharmacological management such as rest with topical
application of ice packs can combine with medications that reduce inflammation.[43] First-line
treatments for gout flares are (nonsteroidal anti-inflammatory drugs) NSAIDs, colchicine, or
systemic glucocorticoids.[44] The length of the treatments should be at least 7 to 10 days to
prevent rebound flare-ups.[45]
NSAIDs
NSAIDs are most effective when therapy is initiated within 48 hours of the onset of gout
symptoms. A potent oral NSAID, such as indomethacin (50 mg three times daily) or naproxen
(500 mg twice daily), is initiated. Other NSAIDs include meloxicam (15 mg daily), ibuprofen
(800 mg three times daily), diclofenac (50 mg two to three times daily, and celecoxib (200 mg
twice daily). Typically NSAID treatment for gout flare lasts for five to seven days. No data
favors one NSAID over the other. High-dose, fast-acting NSAIDs such as naproxen or diclofenac
are options, and indomethacin is not preferable due to its toxicity profile.[6] NSAIDs are usually
given in full doses for the first three days and then tapered according to the progress. COX2
selective inhibitors like celecoxib can be given to prevent adverse GI effects.
Contraindications for the use of NSAIDs include active duodenal or gastric ulcer, cardiovascular
disease (uncontrolled hypertension or heart failure), NSAID allergy, and chronic kidney disease
with creatinine clearance (CrCl) of less than 60 ml/minute per 1.73 square meters. Aspirin is not
used to treat gout flare due to the paradoxical effects of salicylic acid on serum urate levels.[46]
[47] This results from uricosuria at higher doses and renal uric acid retention at low doses (less
than 2 to 3 g/day).[48][49]
Oral Glucocorticoids
Glucocorticoids are recommended in gout patients with contraindications to NSAIDs and/or

colchicine. These agents are also drugs of choice for patients with renal insufficiency. The initial
dose for gout flare is 30 to 40 mg of prednisolone or prednisone once daily or given in a divided
twice-daily dose until flare resolution begins, and then taper the dose of glucocorticoids over the
next 7 to 10 days. This has been proven to be at least comparable to NSAID efficacy. High
starting doses of systemic steroids(>0.5mg/kg body weight) are required for acute gout,
especially in patients with a polyarticular presentation. a depot preparation for triamcinolone
(60mg once) or methylprednisolone has been reported to be effective.[50][51] However, the dose
may need to be repeated at intervals of 48 hours to achieve resolution of the flare.
Glucocorticoids can be administered intra-articularly for a monoarticular gout flare-up or orally
for polyarticular flare-ups. The efficacy of glucocorticoids is similar to or superior to other
agents and has no greater risk of adverse effects in most patients.[52]
In patients with an unclear diagnosis of an acute gout flare, arthrocentesis and synovial fluid
analysis should be performed, and oral and intra-articular glucocorticoids must be avoided until
the results are available initiation of other agents like NSAID or colchicine be
considered. Frequent adverse effects of moderate- to high-dose, short-term glucocorticoid use
include hyperglycemia, fluid retention, increased blood pressure, and mood changes. Repeated
and frequent courses of glucocorticoids should be avoided to limit adverse effects. In patients
with concomitant or suspected infections, uncontrolled diabetes mellitus, prior glucocorticoid
intolerance, and in post-operative status, glucocorticoids may heighten the risk of impaired
wound healing.
Initiation of daily low dose adjunctive colchicine may be done to prevent rebound flare-ups
during tapering. Extended tapering doses of glucocorticoids up to 14 or even 21 days are advised
in patients with rebound flares, shortened inter-critical periods, and not receiving anti-
inflammatory prophylaxis.
Parenteral Glucocorticoids
Intravenous or intramuscular glucocorticoids are suggested in patients who are not candidates for
intraarticular glucocorticoid injection or cannot take oral medications. A typical dose of
methylprednisolone is 20 mg intravenously twice daily, with stepwise reduction and rapid
transition to oral prednisone when improvement begins. Adrenocorticotropic hormone (ACTH)
has also been described as efficacious for treating gout flare, but limited availability and cost
restrict its use.
Colchicine
Colchicine is comparably effective to other agents if taken within 24 hours of gout flare onset.
Colchicine has been shown to reduce pain by over 50% in a randomized control trial at 24 hours
compared to a placebo. The lipophilic nature of colchicine makes it readily bioavailable for
cellular uptake after oral administration. Its primary target is tubulin, and it is eliminated by
hepatic elimination. It acts by binding tightly to unpolymerised tubulin and forms a colchicine -
tubulin complex which regulates microtubule and cytoskeletal function. It regulates cell
proliferation, gene expression, signal transduction, chemotaxis, and neutrophil secretion of
granule contents. It decreases neutrophil adhesion by suppressing E-selectin redistribution in the
endothelial membrane.
EULAR consensus guidelines for treating acute gout with colchicine advise a maximum of 3
doses of 0.5mg per day. The total dose of colchicine should not exceed 1.8 mg on day 1 (either
1.2 mg for the first dose followed by 0.6 mg an hour later [US Food and Drug Administration
(FDA) approved dose] or 0.6 mg three times on the first day.[53] On subsequent days, colchicine
should be taken once or twice daily until the resolution of a gout flare.[54]
A reduced dose of colchicine may be required for patients with diminished hepatic or renal
function or potential drug interactions. ABCB1 inhibitors like cyclosporin and clarithromycin
may cause colchicine toxicity. Colchicine neuromyopathy may develop weeks after initiation of
cyclosporin. High-dose colchicine regimens should not be encouraged due to unacceptably high
toxicity. The adverse effects of colchicine comprise gastrointestinal symptoms (nausea and
diarrhea), myotoxicity, and myelosuppression (leukopenia, thrombocytopenia, and aplastic
anemia).[55] The frequent adverse effects of colchicine are abdominal cramping and diarrhea.
[53][56] Intravenous colchicine is strongly advised against due to serious adverse effects,
including death.
Colchicine dosing adjustments for certain high-risk groups of patients should follow the
guidelines provided in the manufacturer's FDA-approved information. Usually, no more
than 0.3 mg dose is administered on the day of a gout flare, and the dose is not repeated for
at least three to seven days or more in such patients. Following are the high-risk groups:
Patients taking colchicine prophylaxis within the past 14 days, with normal hepatic
and renal function, who have taken a medication that inhibits P-gp and a potent
CYP3A4 inhibitor within the last 14 days
Patients taking colchicine prophylaxis within the past 14 days, with any hepatic and
renal impairment, who have taken a medication that is a moderate CYP3A4 inhibitor
within the last 14 days
Patients with advanced hepatic or renal impairment (Child-Pugh C cirrhosis or

equivalent CrCl of <30 mL/minute) regardless of recent colchicine use.
Prophylaxis For Acute Gout
The subclinical joint inflammation in gout forms the basis for colchicine prophylaxis. An acute
gout flare is the most common adverse effect of urate-lowering therapy. For prophylaxis, low-
dose colchicine therapy is the first choice. It is commenced 1 or 2 weeks before using urate-
lowering drugs and continued for up to 6 months after normalization of the uric acid levels or
until the clinically visible tophi resolve. Low-dose NSAIDs and low-dose corticosteroids are
rarely used. The recommended dosage of colchicine is 0.5mg once or twice daily in the absence
of any renal or hepatobiliary compromises.
Interleukin 1 Inhibition
Interleukin 1 antagonists have shown efficacy in refractory cases of gouty arthritis. Soluble IL1
receptor antagonist - ANAKINRA 100mg/day subcutaneously for three days or IL1 beta specific
monoclonal antibody canakinumab. A single dose of 150 mg subcutaneously was more effective
than a single-dose IM dose of triamcinolone acetonide though the risk-benefit ratio is uncertain.
Non-acute Flares
Pharmacologic
The clinician should not start urate-lowering therapy (ULT) in patients with asymptomatic
hyperuricemia or gout with rare attacks (1 flare/year). The American College of Rheumatology
(ACR) 2012, Guidelines for starting ULT include the following:
1. Frequent or disabling gout flares (greater than or equal to two per year) that are difficult to
treat
2. Gout with chronic kidney disease (stage 3 or higher)
3. Tophus diagnosis on physical examination or imaging
4. Past urolithiasis
5. chronic tophaceous gout
Urate-lowering therapy is started at a low dose to monitor the side effects and response to
treatment. Titration of the dose is every 2 to 6 weeks to achieve serum urate levels of less than 6
mg/dl or 5 mg/dl in those patients with tophi.[43]
During the initiation of ULT, there is an increased risk of gout flare-ups, so colchicine
prophylaxis is recommended for three months after achieving the serum urate goal in the patients
without tophi or six months with tophi to reduce the flare-up risk.[57]
ULT can categorize into three classes (based on the mechanisms).
Xanthine oxidase inhibitors (XOI) - XOI works by inhibiting uric acid synthesis. This class
includes allopurinol and febuxostat. Allopurinol is the recommended first-line pharmacologic
ULT in gout.[43] The physician should monitor liver enzymes, renal, and blood count regularly.
Adverse effects from allopurinol can range from skin rashes to life-threatening severe allopurinol
hypersensitivity (especially in HLA-B*5801 positive patients).[1]
Allopurinol
Allopurinol is covert to its active metabolite oxypurinol in the liver; the drug has a half-life of 24
hours. The initial allopurinol dose is 100 mg daily in patients with CrCl greater than 60
mL/minute and is titrated upward by 100 mg every 2 to 4 weeks. A dose of 300 mg of
allopurinol once daily reduces serum urate levels in 33% of the population. Doses less than 300
mg are given in a once-daily regimen, and more than 400 mg are given in two divided doses.
Allopurinol and oxypurinol lower the serum urate by a dual action of inhibiting xanthine oxidase
inhibitor as well as by competing with phosphoribosylpyrophosphate in the salvage pathway and

by suppressive effects of drug nucleotides on the aminotransferase activity. Allopurinol non-
selectively also inhibits pyrimidine metabolism. A starting dose of allopurinol of <1.5 mg per
mL/minute of estimated glomerular filtration rate (eGFR) is advised in patients with stage 3 or
greater chronic kidney disease.
Adverse effects of allopurinol - may precipitate gout flares, pruritic and maculopapular rashes,
leukopenia, thrombocytopenia, diarrhea, and severe cutaneous adverse reactions. bone marrow
impression is uncommon but may occur at very high doses or in patients with CKD. (DRESS)
syndrome - drug reaction with eosinophilia and systemic symptoms is a potentially life-
threatening reaction to allopurinol. Steven johnson syndrome or toxic epidermal necrolysis may
occur in major allopurinol hypersensitivity(AHS). The highest risk for AHS occurs in the first 60
days after initiation of allopurinol therapy. Allopurinol can potentiate the cytolytic and
immunosuppressive effects of azathioprine and 6-mercaptopurine (6-MP), which are in part
metabolized by xanthine oxidase.[58] Hence, allopurinol should be avoided in patients treated
with these agents.[59] in patients taking warfarin, anticoagulation status must be carefully
monitored.
Febuxostat
it is a selective xanthine oxidase inhibitor that occupies the access channel to the molybdenum-
pterin active site of the enzyme. Renal elimination plays a minor role in febuxostat kinetics.
Febuxostat received FDA approval to treat gout patients with hyperuricemia at daily doses of 40,
and if the urate levels do not normalize in 2 weeks dose is increased to 80 mg daily.
Cardiovascular and hepatic abnormalities may be more common with febuxostat compared with
allopurinol. In patients with CKD, the urate-lowering effect of febuxostat is superior to
allopurinol. Patients taking azathioprine, 6-MP, and theophylline are considered
contraindications to the use of febuxostat.
Uricosuric Drugs
The uricosuric agents work by increasing renal urate clearance.[1] Patients with low or normal
urinary uric acid excretion in the presence of hyperuricemia are potential candidates for
uricosuric therapy. Drugs in this class include probenecid and lesinurad (withdrawn from the
market in the United States). They inhibit URAT1 at the apical membrane of the renal proximal
tubule epithelial cell. These agents are ineffective as monotherapy in patients with low creatinine
clearance (less than 30 ml/minute) and contraindicated with patients with a history of
nephrolithiasis.[60] Probenecid is the only agent approved for use as a monotherapy. Probenecid
is initiated at a dose of 250 mg twice daily, and dose increments are titrated according to the
serum urate concentration level. The dose is typically increased every several weeks to a usual
maintenance dose of 500 to 1000 mg (taken 2 to 3 three times daily), aiming for the target urate
levels of <6 mg/dL (<357 micromol/L). The major side effects of uricosuric drugs are the
precipitation of a gout flare, uric acid urolithiasis, gastrointestinal intolerance, and rash.
Uricase Pegloticase (urate oxidase) - Uricase is present in non-primates and lower primates.
Pegloticase (a pegylated recombinant form of uricase) is a potent agent that rapidly reduces
serum urate levels. It directly degrades the uric acid to highly soluble allantoin. PEGylation of
the recombinant porcine-baboon uricase pegloticase has a circulating half-life of days to weeks
and decreases but does not eliminate immunogenicity. Uricase is reserved only for patients with
refractory gout. Patients have to discontinue urate-lowering therapy while starting this
medication because they may develop antibodies against uricase. Pegloticase is administered as
intravenous infusions every two weeks, and before each infusion, serum urate levels should be
monitored to confirm urate-lowering efficacy.
For at least the first six months of treatment, all patients treated with pegloticase should receive
gout flare prophylaxis. In patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency,
pegloticase is contraindicated. Another agent Rasburicase (non-pegylated recombinant uricase),
has not been approved by FDA for use in gout. It is used to prevent acute uric acid nephropathy
due to tumor lysis syndrome in patients with high-risk leukemia and lymphoma. phase 3 studies
of pegloticase have shown complete resolution of one or more tophi on 20% of patients by 13
weeks and lowered uric acid levels to less than 6mg/dl in 42% of subjects by six months.[61]
Acute gout flares are seen in 80% of patients on pegloticase in the first few months of therapy,
even with prophylaxis. Moderate infusion reactions like flushing, urticaria, and hypotension are
seen, and in 2%, severe reactions like anaphylaxis are seen. Reactions also include severe muscle
pain and cramping due to unknown mechanisms.
Non-Pharmacologic
Patients with gout are encouraged to modify their lifestyles to prevent future attacks.[62]
Diet recommendations include reducing alcohol consumption, limiting purine-rich foods (meat,
seafood, high fructose corn syrup, and sweetened soft drinks), and substituting low-fat or non-fat
dairy products for their higher fat content counterparts. Weight loss and adequate hydration will
also help reduce gout flare-up frequency.
Differential Diagnosis
Gout Flare
Calcium pyrophosphate crystal deposition disease
Basic calcium phosphate crystal disease
Septic arthritis
Osteoarthritis
Psoriatic arthritis
Cellulitis
Trauma
Tophaceous Gout
Dactilytis
Rheumatoid arthritis
Osteomyelitis
Prognosis
The prognosis of gout depends on the comorbidity of each individual. Mortality is higher in
individuals with cardiovascular comorbidity. When gout receives proper treatment, most patients
will live a normal life with mild sequelae. Patients whose symptoms appear earlier in life will
usually have a more severe disease at presentation. For those who do not modify their lifestyle,
recurrent flare-ups are common.
Complications
Tophi, joint deformity, osteoarthritis, bone loss.
Urate nephropathy and nephrolithiasis.
Gout might also cause ocular complications, such as conjunctivitis, uveitis, or scleritis from the
urate crystal precipitation.[63]
Deterrence and Patient Education

Lifestyle Modification and Strategies to Reduce the Risk of Out Flares and Progression of
Gout
Lifestyle changes are encouraged in gout patients, including weight loss, limiting alcohol
intake, and avoiding certain foods. These changes will complement medical therapy but
often are not enough by themselves to combat or reverse gout.
Weight gain and increased adiposity are risk factors for gout, while in overweight patients
with established gout, weight loss likely benefits in reducing serum urate and gout
symptoms.[64][65]
The diet composition optimum for gout is likely to be one with adequate protein intake,
especially from plant sources and low-fat dairy sources, with reduced intake from animal
sources of purine such as shellfish or red meat; decreased saturated fat; and replacement of
simple sugars with complex carbohydrates.
Avoid or minimize the frequency of sugar-sweetened juices and alcohol-containing

beverages or beverages containing high-fructose corn syrup.
Pearls and Other Issues

Interleukin (IL) 1 is an important mediator of inflammation in gout and a potential target for
therapy in gout flares.[66] For patients with multiple medical comorbidities and those on
anticoagulation, a short-acting (IL) 1 inhibitor, such as anakinra, can be used to treat gout flare as
an alternative to the first-line therapies.
Enhancing Healthcare Team Outcomes

Most patients with gout have other comorbidities. The prevalence of gout is higher among
individuals with chronic diseases such as hypertension, chronic kidney disease, diabetes, obesity,
congestive heart failure, and myocardial infarction.[19]
Gout treatment requires the collaboration of an entire interprofessional healthcare team approach.
The physician (MD, DO, NP, PA) must promptly identify the pathology and rule out differentials.
Some cases may require a rheumatology consult. The pharmacological approaches to gout
require considering these comorbidities and monitoring their response to treatment. The
pharmacist and nurse both must educate the patient on medication compliance. Also, the
pharmacist should assist the team by performing medication reconciliation, verifying appropriate
dosing, and consulting on agent selection in the event of initial treatment failure. The dietitian
should urge the patient to abstain from alcohol, avoid meat-containing foods, and maintain a
healthy body weight. The role of specialists, primary care physicians, nurses, nurse practitioners,
and dieticians are all critical in reducing gout morbidities. The medical team should coordinate
the patient's education on lifestyle modification, which can contribute to reducing the risk and
frequency of gout flare-ups; this is only possible via open communication between all disciplines
on the interprofessional team.
All healthcare providers, including primary care and nurse practitioners, should identify classic
gout symptoms and have a low threshold for referring the patients for an arthrocentesis if they
are uncertain of the diagnosis. Then, working with the interprofessional team as outlined above,
direct the treatment as needed and interact with the interprofessional team to drive outcomes.
[Level 5]
Referral to a specialist/rheumatologist should be a consideration in the following patients with

joint pain:
Unclear etiology with hyperuricemia
Unclear etiology with normal serum urate level
Patients with renal impairment
Failed trial of xanthine oxidase inhibitor treatment
Multiple side effects from the medications
Refractory gout[43]
Only through an interprofessional team approach with close communication can the morbidity of
gout be lowered.
Review Questions
Access free multiple choice questions on this topic.
Comment on this article.
Figure
Hand Radiograph Gout. Contributed by Scott Dulebohn, MD
Figure
Gout, [SATA]. Contributed by Steve Bhmji, MS, MD, PhD
Figure
Gout in the Ear. Image courtesy S Bhimji MD
Acute gout Figure

attack
Acute gout attack. Image courtesy O.Chaigasame
Gout Tophi Figure
Gout Tophi. Contributed by Dr. Shyam Verma, MBBS, DVD,

FRCP, FAAD, Vadodara, India
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Continuing Education Activity

Identify the etiology of gout.

Explain the common physical exam findings associated with gout.

Describe the pathophysiology of gout arthritis.

Summarize interprofessional team strategies for improving care coordination and

Access free multiple choice questions on this topic.

Gout is characterized biochemically by extracellular fluid urate saturation, which is reflected by

Acute gout flare (recurrent flares of inflammatory arthritis)

Chronic gouty arthropathy

Accumulation of urate crystals in the form of tophaceous deposits

Uric acid nephrolithiasis

epidemiological studies reported an increased disease burden of gout, which is largely explained

Risk factors of Hyperuricemia and Gout

Causes of hyperuricemia due to decreased uric acid

Genetic, metabolic, and other factors that result in hyperuricemia

Uric Acid Physiology

Hyperuricemia may be primary/idiopathic or secondary. Overproduction is seen in several

Xanthine oxidoreductase is a molybdenum-pterin and iron sulfide cluster containing

The major steps in purine synthesis targetted by regulation are

1. The synthesis of PRPP in the PRPP synthetase pathway

2. The utilization of PRPP in the first step of de-novo purine synthesis

Renal Uric Acid Secretion

Glucose Transporter 9 (GLUT9)

hypouricemia, hyperuricosuria, and exercise-induced renal functional impairment. The uricosuric

Autosomal Dominant Tubulointerstitial Kidney Disease caused by UMOD pathogenic

Extra-renal Urate Excretion

Urate Crystal Formation

1. activation of phagocytes leading to lysosomal fusion, respiratory burst, and release of

2. the more predominant pathway of cytosolic protein complex activation(NLRP2

8. ACTIVATION OF NEUTROPHILS 11. REMOVAL OF

Termination Of The Acute Flare

by the MCRs(macrophage melanocortin receptors), adenosine monophosphate-activated protein

History and Physical

2. Acute gout attacks

4. Chronic tophaceous gout.

Acute Gout Attack

Chronic Tophaceous Gout

General Principles of Therapy

Tophus is an indication to initiate long-term urate-lowering therapy either during or

Acute Gout Flare

Glucocorticoids are recommended in gout patients with contraindications to NSAIDs and/or

Patients with advanced hepatic or renal impairment (Child-Pugh C cirrhosis or

Prophylaxis For Acute Gout

2. Gout with chronic kidney disease (stage 3 or higher)

3. Tophus diagnosis on physical examination or imaging

5. chronic tophaceous gout

ULT can categorize into three classes (based on the mechanisms).

inhibitor as well as by competing with phosphoribosylpyrophosphate in the salvage pathway and

Calcium pyrophosphate crystal deposition disease

Basic calcium phosphate crystal disease

Urate nephropathy and nephrolithiasis.

Deterrence and Patient Education

Avoid or minimize the frequency of sugar-sweetened juices and alcohol-containing

Pearls and Other Issues

Enhancing Healthcare Team Outcomes

Referral to a specialist/rheumatologist should be a consideration in the following patients with

Unclear etiology with hyperuricemia

Unclear etiology with normal serum urate level

Patients with renal impairment

Failed trial of xanthine oxidase inhibitor treatment

Multiple side effects from the medications

Access free multiple choice questions on this topic.