gout
GOUT
Gout is a condition that resulted from deposition of monosodium urate crystals in various tissues (eg joints, connective tissue, kidney).
The patient experiences acute and chronic arthritis, soft tissue inflammation, tophus formation, gouty nephropathy and nephrolithiasis.
Primary hyperuricemia is called when uric acid saturation arises without coexisting diseases or drugs that alter uric acid production and excretion.
While in secondary hyperuricemia there is an excessive uric acid production or diminished renal clearance that occurs as a result of a disease, drug, dietary product or toxin.

Diagnosis

Criteria for Diagnosis of Acute Gouty Arthritis1

  • Presence of characteristic urate crystals in joint fluid
  • A tophus proven by chemical means or polarized light microscopy to contain urate crystals
  • Six of the following 12 clinical, laboratory & radiographic findings:
    • More than 1 attack of acute arthritis
    • Maximum inflammation developing within 1 day
    • Monoarticular arthritis attack
    • Redness observed over affected joints
    • First metatarsophalangeal joint pain or swelling
    • Unilateral first metatarsophalangeal joint attack
    • Unilateral tarsal joint attack
    • Tophus (proven or suspected)
    • Hyperuricemia
    • Asymptomatic swelling within a joint on x-ray
    • Subcortical cysts without erosions on x-ray
    • Joint fluid culture negative for organisms during attacks

The combination of crystals, tophi &/or 6 or more criteria is highly suggestive of gout

1Adapted from Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of acute arthritis of primary gout. Arthritis Rheum. 1977;20:895-900.

Classification

Classification of Hyperuricemia

  • Primary hyperuricemia
    • Uric acid saturation arises without coexisting diseases or drugs that alter uric acid production or excretion
  • Secondary hyperuricemia
    •  Excessive uric acid production or diminished renal clearance occurs as a result of a disease, drug, dietary product or toxin

Causes of Secondary Hyperuricemia

  • Excessive uric acid production:
    • Inherited enzyme defects (eg hypoxanthine-guanine phosphoribosyltransferase deficiency)
    • Clinical disorders (eg myeloproliferative & lymphoproliferative disorders, malignancies, psoriasis, Down syndrome)
    • Induced by diet, drugs, or toxins (eg ethanol, excessive purine in diet, fructose, vitamin B12 deficiency, Nicotinic acid, cytotoxic drugs, Warfarin)
  • Decreased renal clearance:
    • Chronic renal insufficiency, volume depletion (eg heart failure, volume loss), obesity, diabetic or starvation ketoacidosis, lactic acidosis, hyperparathyroidism, hypothyroidism, sarcoidosis
    • Induced by diet or drugs (eg Aspirin, diuretics, Cyclosporine, Tacrolimus, Ethambutol, Pyrazinamide, ethanol, Levodopa)

Clinical Phases of Gout 

Acute Gout

  • Usually manifests as an acute, self-limiting, monoarticular inflammatory arthritis in majority of patients
  • Lower extremity joints are affected more often than upper extremity joints
    • Joints most commonly affected include the 1st metatarsophalangeal joint (podagra), forefoot, ankle, knee, wrist, elbow & finger joints
  • Extra-articular sites (eg olecranon bursa & Achilles tendon) may also be involved
  • Attacks may occur & last from a few days to 2-3 week, with resolution of all inflammatory signs
    • Early attack: <12 hours after onset of attack
    • Well-established attack: 12-36 hours after onset of attack
    • Late attack: >36 hours after attack onset
  • Severity of acute gouty arthritis attack (based on patients’ pain assessment):
    • Mild: ≤4
    • Moderate: 5-6
    • Severe: ≥7

Intercritical Gout

  • Periods in between attacks when patient is free of symptoms

Chronic Gout

  • After intermittent attacks (>3 acute attacks/year) & remissions, the chronic phase follows
  • Polyarticular flares of gouty arthritis occur, & associated with bony erosions & deformities
  • Chronic tophaceous gout:
    • Marked by polyarticular arthritis & the formation of tophi which are chalky deposits of monosodium urate
    • Tophi are usually painless, appearing as firm, nodular or fusiform masses, located subcutaneously
    • Risk factors include polyarticular presentation, serum urate level >0.54 mmol/L (9 mg/dL), age of ≥40 years old at disease onset
  • Disease severity
    • Mild - simple chronic tophaceous gouty arthropathy, 1 joint affected, stable
    • Moderate - simple chronic tophaceous gouty arthropathy, 2-4 joints affected, stable
    • Severe - chronic tophaceous gouty arthropathy of >4 joints OR ≥1 unstable, complicated, severe articular tophus/tophi

  • Presence of urate nephropathy or urate renal calculi

Gout Classification Criteria1

  • Developed by the American College of Rheumatology (ACR) & the European League Against Rheumatism (EULAR) in 2015
  • The new criteria is based on the presence of MSU crystals, imaging modalities, & clinical parameters
  • Provides a scoring system for a patient’s symptomatic episode, regardless of the clinical phase
  • A total score of >8 confirms the diagnosis of gout
  • Entry criterion is defined as at least 1 episode of swelling, pain, or tenderness in a peripheral joint or bursa
  • Sufficient criterion should be considered with the presence of urate crystals in a symptomatic joint or bursa, or a positively-identified tophus
  • The classification criteria should be used if sufficient criterion is not met
Criteria Categories Score
Clinical Parameters (Per Symptomatic Episode)
 Pattern of joint or bursa involvement Ankle or midfoot
1st metatarsophalangeal joint
1
2
Characteristics
   Erythema overlying affected joint
   Unable to tolerate touch or pressure on the affected joint
   Difficulty with walking or unable to use affected joint

1 characteristic
2 characteristics
3 characteristics
 
1
2
3
Time course: presence of >2 of the following regardless of anti-inflammatory treatment
   Time to maximal pain <24 hr
   Resolution of symptoms happen in <14 days
   Complete resolution between symptomatic episodes
 

1 typical episode
Recurrent typical episode

1
2

Clinical evidence of tophus2  Present  4
Laboratory Parameters
Serum urate3,4  <4 mg/dl (<0.24 mmol/L)
6-<8 mg/dl (0.36-<0.48 mmol/L)
8-<10 mg/dl (0.48-<0.60 mmol/L)
>10 mg/dl (>0.60 mmol/L)
 -4
2

3

4
Synovial fluid analysis per symptomatic episode  MSU negative -2
Radiologic Parameters5
Evidence of urate deposition: double-contour sign seen with ultrasound or urate deposition seen by dual-energy computed tomography (DECT)   Present
 4
Evidence of gout-related joint damage: at least 1 erosion seen using conventional radiography of the hands &/or feet   Present
 4
1Adapted from Neogi T, Jansen TL, Dalbeth N, et al. 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatol. 2015 Oct;67(10):2557-2568.
2Tophus characterized as a draining or chalk-like subcutaneous nodule under transparent skin, often with overlying vascularity, usually located in joints, ears, olecranon bursae, finger pads, &/or tendons.
3Obtained using the uricase method; scoring should be done while the patient is not taking urate-lowering drugs & >4 wk have passed since the occurrence of symptoms.
4For serum urate results of >4-<6 mg/dl (>0.24-<0.36 mmol/L), score to be given is 0.
5A score of 0 is given if imaging modalities are unavailable.

Evaluation

Risk factors for gout & associated comorbidity should be assessed

Risk factors associated with gout:

  • Hyperuricemia
    • Single most important risk factor for developing gout
  • Male sex
  • Purine-rich diet (eg meat, seafood)
  • Alcohol intake
  • Diuretics

Metabolic abnormalities associated with gout:

  • Hypertension
  • Obesity
  • Dyslipidemia
  • Hyperglycemia & insulin resistance

Comorbidities associated with gout:

  • Coronary artery disease
  • Type 2 diabetes mellitus
  • Renal insufficiency
  • Metabolic syndrome
  • Kidney stone

Additional laboratory exams to detect the presence of associated comorbidities in patients with gout:

  • Upon detection of associated risk factors & comorbidities, these should be addressed as an important part of the management of gout
    • Complete blood count to exclude infection, lymphoproliferative or myeloproliferative disorders
    • Serum creatinine/urea to exclude renal disease leading to hyperuricemia or to detect renal disease secondary to urate nephropathy or nephrolithiasis
    • Blood glucose to detect the presence of diabetes/insulin resistance
    • Lipid profile to detect hypertriglyceridemia & low HDL cholesterol
    • Urinalysis showing presence of blood &/or protein may suggest renal disorders
    • Rapid polymerase chain reaction-based HLA-B*5801 screening detects patients at high risk for severe Allopurinol hypersensitivity reaction (eg Koreans with > stage 3 CKD, Han Chinese, Thai)

Laboratory Tests

Specific investigations for confirmation of gouty arthritis

Synovial fluid analysis

  • Demonstration of MSU crystals in synovial fluid or tophus aspirates gives a definitive diagnosis of gout
    • MSU crystals are needle-shaped & they exhibit strong birefringence under polarized light
  • It is recommended to search for MSU crystals in all synovial fluid samples obtained from undiagnosed inflamed joints
  • Identification of MSU crystals from asymptomatic joints may allow definite diagnosis in intercritical periods wherein patients are free of symptoms

Serum urate levels

  • Hyperuricemia defined as serum urate level >6.8-7 mg/dl
  • Although hyperuricemia is the most important risk factor for gout, this does not confirm or exclude gout
    • Many patients with hyperuricemia do not develop gout
    • During acute attacks, serum urate levels may be normal in about 10% of cases
  • It will be best to measure serum urate levels 2-3 week after an attack
  • Upper limit of serum urate level:
    • Male & postmenopausal women: 0.42 mmol/L or 7 mg/dL
    • Premenopausal women: 0.36 mmol/L or 6 mg/dL

Imaging

Plain Radiography/Skeletal X-ray

  • Usually normal in acute gouty arthritis, although there may be reversible soft tissue swelling around the involved joint
  • In chronic tophaceous gout, typical radiographic findings include erosions with sclerotic margins & overhanging edges of bones, or calcification in some tophi
    • Presence of a thin, overhanging calcified edge is highly suggestive of gout
    • Joint space is usually preserved until late stages of the disease

Ultrasonography (US)

  • Can detect crystals deposited on cartilaginous surfaces as well as tophaceous material & typical erosions

Computed Tomography (CT)

  • Allows excellent visualization of tophi
  • May assist in differentiating tophi from other subcutaneous nodules

Magnetic Resonance Imaging (MRI)

  • Findings are not specific for the diagnosis of gout but allow early detection of tophi & bone erosion
  • Method of determining the extent of disease in tophaceous gout & may provide information regarding the patterns of deposition & spread of MSU crystals
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Rheumatology digital copy today!
DOWNLOAD
Editor's Recommendations
Most Read Articles
Elvira Manzano, 5 days ago
Bisphosphonates have proven antifracture efficacy and remain to be the cornerstone of osteoporosis treatment. However, a drug holiday is of particular importance with bisphosphonates due to some signals with long-term use of the drug, including rare incidence of atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ), says a leading endocrinologist at AFOS 2017.
Yesterday
Breast cancer patients have notably different microbiomes in the local breast tissue and urinary tract, a recent study reveals. Particularly, species in the Methylobacterium genus are reduced in the local breast tissue while the urinary tract is enriched in gram-positive bacteria.
Tristan Manalac, 2 days ago
Statin use, particularly in smokers, obese patients and nondiabetics, has a strong and dose-dependent association with decreasing risk of pancreatic ductal adenocarcinoma (PDAC), according to a new study.
15 Oct 2017
Second eye cataract surgery provides greater improvement in visual function and quality of life compared with first eye cataract surgery alone, a recent study claims.