Updated: 7/11/2019

Gout

Topic
Review Topic
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Questions
5
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Evidence
3
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Snapshot
  • A 55-year-old woman presents to the emergency department with acute pain in the left proximal interphalangeal (PIP) joint of the second digit. She reports that the pain is excruciating and has happened once a few years ago but self-resolved over the course of 2 weeks. She states that she recently increased her alcohol and red meat consumption and was recently started on hydrochlorothiazide. On physical exam the PIP joint is swollen, erythematous, warm, and tender to palpation. Preparations are made for an arthrocentesis to be performed. 
Introduction
  • Clinical definition
    • deposition of monosodium urate crystals leading to a crystal-induced arthropathy
  • Epidemiology
    • demographics
      • more common in men and the elderly
    • risk factors
      • conditions that increase serum urate levels (hyperuricemia)
  • Etiology
    • hyperuricemia 
      • defined as a serum urate level > 6.8 mg/dL
      • causes of hyperuricemia include
        • dietary habits
          • alcohol
          • red meat
          • seafood
        • medications
          • thiazide diuretics
          • loop diuretics
          • allopurinol
          • cyclosporine
          • low-dose aspirin
          • pyrazinamide
        • disorders of urate overproduction
          • hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency
            • also known as Lesch-Nyhan syndrome
          • type I glycogen storage disease (Von Gierke disease)
          • tumor lysis syndrome
  • Pathogenesis
    • purine catabolism results in uric acid production
      • factors that influence serum uric acid level include
        • purine intake
        • purine synthesis
        • uric acid excretion by the kidneys and gut
    • conditions that increase the serum uric acid concentration increases the risk of crystal formation
      • deposition of uric acid crystals lead to an inflammatory response
        • resulting in a gout flare
  • Prognosis
    • acute attacks typically self-resolve
    • patients have an increased risk of recurrence
    • advanced gout and tophi may result without proper treatment
Presentation
  • Symptoms
    • acute gout
      • extreme pain of the affected joint (e.g., foot or ankle)
    • chronic tophaceous gout
      • stiff or swollen joint
      • deformity of the affected joint (e.g., nodules)
  • Physical exam
    • acute gout
      • typically mono-articular
        • e.g., involvement of the first metatarsophalangeal joint (podagra)
      • sudden onset of joint
        • tenderness
        • erythema and warmth
        • swelling
    • chronic tophaceous gout
      • subcutaneous nodules
      • typically non-tender
      • overlying skin can be taut
      • abnormal color
        • white or yellow deposits
Studies
  • Labs
    • hyperuricemia (> 6.8 mg/dL)
      • not sufficient for the diagnosis
      • the level may be lower during an attack
  • Synovial fluid analysis
    • joint fluid aspiration and crystal analysis is the gold-standard
      • negatively birefringent needle-shaped crystals under polarized light  
        • yellow under parallel light and blue under perpendicular light
  • Making the diagnosis
    • demonstrating monosodium urate crystals in an affected joint via polarizing light microscopy
      • when this is not possible, the diagnosis can be clinically made
Differential
  • Septic arthritis 
    • a highly important differential diagnosis to exclude since this changes management 
    • distinguishing factors
      • a synovial fluid analysis will demonstrate
        • no crystals
        • > 50,000 cells/mcL
        • Gram stain may be positive
  • Pseudogout 
    • distinguishing factors
      • caused by deposition of calcium pyrophosphate crystals
      • crystal analysis will demonstrate weakly positive birefringent rhomboid crystals under polarized light
        • blue under parallel light
Treatment
  • Management approach
    • acute attacks can be managed with nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or colchicine
      • acute gout attacks typically self-resolve in 1-2 weeks; however, treatment will hasten recovery
      • choice of treatment is dependent on certain patient factors (e.g., comorbidities, gout history, attack characteristics, availability, and cost)
    • preventing future attacks are managed by urate-lowering therapy
  • Conservative
    • lifestyle modification 
      • indication
        • a preventative measure for patients with gout
      • examples
        • decrease alcohol, red meat, and seafood consumption
        • weight loss
        • discontinuing or modifying medication (e.g., changing their loop diuretic)
  • Medical  
    • medical management of acute attacks
      • NSAIDs 
        • indication
          • monotherapy agent for acute gout attacks
      • colchicine 
        • indication
          • monotherapy agent for acute gout attacks
      • corticosteroids 
        • indication
          • monotherapy agent for acute gout attacks
          • intraarticular therapy 
            • patients who can't tolerate systemic steroids (such as psychosis or hyperglycemia)
            • symptoms limited to 1-2 joints
    • medical management for preventing a future attack
      • urate-lowering therapy
        • indication
          • to prevent future attacks
        • medications
          • xanthine oxidase inhibitors (first-line)
            • e.g., allopurinol and febuxostat
          • uricosuric agents (second-line)
            • e.g., probenecid 
Complications
  • Recurrent flares
  • Tophi
  • Chronic gouty arthritis
  • Erosion or destruction of the joint
 

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Questions (5)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.RH.4725) A 66-year-old man with a past medical history of coronary artery disease and obesity complains of left great toe swelling on the second day of his hospital stay for melena due to peptic ulcer disease. He describes significant pain at the metatarsal-phalangeal joint, and the radiographic findings are shown in Figure A. He also complains of chronic bilateral hip pain that has worsened during his admission. Temperature is 99.4°F (37.4°C), blood pressure is 142/91 mmHg, pulse is 92/min, respirations are 16/min. On examination, his left great toe is red, swollen and feels hot to the touch. Palpation of the hips does not elicit tenderness but active range of motion is slightly decreased. The patient's CBC shows a hemoglobin of 11.1 g/dL, white blood cell count of 10.3 x 10^9/L, and platelet count of 200,000/mL. A medication with which of the following mechanisms is the best treatment option for this patient’s acute joint symptoms? Review Topic

QID: 108564
FIGURES:
1

Inhibition of the enzyme xanthine oxidase

11%

(2/18)

2

Inhibition of the enzymes cyclooxygenase-1 (COX-1) and -2 (COX-2)

39%

(7/18)

3

Increase in urinary uric acid excretion

6%

(1/18)

4

Downregulation of gene expression by nuclear receptor binding

0%

(0/18)

5

Inhibition of microtubule polymerization by binding of tubulin

44%

(8/18)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(M2.RH.4693) A 40-year-old obese man with a history of diabetes and chronic kidney disease presents with one day of excruciating pain, swelling, and redness in his greater toe. He denies any inciting trauma or similar prior episodes. Vital signs are stable. On examination, the right first toe is grossly erythematous and edematous, with range of motion limited due to pain. Deposition of which of the following is associated with the most likely underlying joint disorder? Review Topic

QID: 107678
1

Cholesterol

0%

(0/0)

2

Calcium phosphate

0%

(0/0)

3

Calcium oxalate

0%

(0/0)

4

Monosodium urate

0%

(0/0)

5

Copper

0%

(0/0)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

(M3.RH.101) A 58-year-old man presents to the emergency department with rapid onset of severe pain and swelling in his right great toe overnight. He reports experiencing a similar episode several years ago but cannot recall the diagnosis or the medication he was given for treatment. His medical history is significant for hyperlipidemia, poorly controlled diabetes, and stage 3 chronic kidney disease. Laboratory studies are ordered as seen below.

Serum:
Na+: 139 mEq/L
Cl-: 101 mEq/L
K+: 5.9 mEq/L
HCO3-: 22 mEq/L
BUN: 20 mg/dL
Glucose: 259 mg/dL
Creatinine: 3.1 mg/dL

The interphalangeal joint of the right great toe is aspirated, with the synovial fluid aspirate shown under polarized light microscopy in Figure A. Which of the following is the most appropriate management for this patient? Review Topic

QID: 103124
FIGURES:
1

Aspirin

0%

(0/3)

2

Colchicine

33%

(1/3)

3

Indomethacin

0%

(0/3)

4

Intrarticular triamcinolone

0%

(0/3)

5

Intravenous prednisone

67%

(2/3)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 4
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