Updated: 1/24/2019

Gout

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Snapshot
  • A 46-year-old man presents to the emergency department due to severe pain of the first metatarsophalangeal (MTP) joint of acute onset. He describes the pain as 10/10 and sharp. Medical history is significant for obesity and hypertension and was recently started on furosemide. Social history is notable for alcohol use disorder managed with naltrexone. He reports to recently increasing his alcohol intake due to environmental stresses. On physical exam, the right first MTP joint appears erythematous, swollen, and is warm. Preparations are made to perform an arthrocentesis.
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 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 
    • this is 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
    • 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 

 

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Questions (4)
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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(M1.MK.10) A 60-year-old man has had intermittent pain in his right great toe for the past 2 years. Joint aspiration and crystal analysis shows thin, tapered, needle shaped intracellular crystals that are strongly negatively birefringent. Radiograph demonstrates joint space narrowing of the 1st metatarsophalangeal (MTP) joint with medial soft tissue swelling. What is the most likely cause of this condition? Review Topic

QID: 101947
1

Monosodium urate crystal deposition

75%

(107/143)

2

Calcium pyrophosphate deposition

4%

(6/143)

3

Uric acid crystal deposition

19%

(27/143)

4

Tuberculosis

0%

(0/143)

5

Rheumatoid arthritis

1%

(2/143)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M1.MK.4666) A 75-year-old woman presents with worsening "nodules" on her body. She describes several years of intermittent, severe joint pain, which she ascribed to arthritis with "old age." Her hand is shown in Figure A. Which of the following interventions is best for long-term treatment of this condition? Review Topic

QID: 107093
FIGURES:
1

Probenecid

6%

(1/16)

2

Colchicine

25%

(4/16)

3

Allopurinol

62%

(10/16)

4

Non-steroidal anti-inflammatory agents

0%

(0/16)

5

Thiazides

0%

(0/16)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3
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