Gout/Pseudogout, Emergency Medicine

Basics

Description

Uric acid deposition into tissues, affecting mainly middle-aged men and postmenopausal women:
- Most common crystalline diseases
- 4 phases:
  - Asymptomatic hyperuricemia (serum urate >7 mg/dL)
  - Acute gout
  - Intercritical gout: Quiet intervening periods
  - Tophaceous gout (up to 45% of cases)
- Risk factors:
  - Age >40
  - Male/female ratio 2:1-6:1 <65 yr old; 1:1 ≥65 yr old
  - Hypertension
  - Use of loop or thiazide diuretics
  - High intake of alcohol, meat, seafood, and fructose-sweetened beverages
  - Obesity
- Urologic deposition of uric acid calculi may cause renal dysfunction.
- Associated with avascular necrosis and deforming arthritis
- Most frequent in previously damaged joints, tissues:
  - Synovium
  - Subchondral bone
  - Bursae (olecranon, infrapatellar, prepatellar)
  - Achilles tendon
  - Extensor surface of the forearms, toes, fingers, ear
  - Rarely CNS or cardiac (valves)
Pseudogout: A disorder caused by calcium pyrophosphate crystal deposition:
- Most common cause of acute monoarthritis >60 yr of age
- Risk factors:
  - Hypercalcemia (e.g., hyperparathyroidism, familial)
  - Hemochromatosis; hemosiderosis
  - Hypothyroidism and hyperthyroidism
  - Hypophosphatemia, hypomagnesemia
  - Amyloidosis
  - Gout

Etiology

Deposition of monosodium urate crystals in tissues from supersaturated extracellular fluid owing to:
- Underexcretion (most commonly) or excessive production of uric acid
- Any rapid change in uric acid levels
  - Initiation or cessation of diuretics
  - Alcohol, salicylates, niacin
  - Cyclosporine
  - Lead acetate poisoning
  - Uricosurics or allopurinol
Pseudogout occurs secondary to excess synovial accumulation of calcium pyrophosphate crystals
Precipitants for both gout and pseudogout include minor trauma and acute illnesses:
- Surgery, ischemic heart disease

Diagnosis

Signs and Symptoms

Gout and pseudogout both present as acute monoarticular or polyarticular arthritis:
- Increased warmth, erythema, and joint swelling are present.
- Early attacks subside spontaneously within 3-21 days, even without treatment.
- Later attacks may last longer, cluster, be more severe, and be polyarticular.
Gout:
- Symptoms present maximally within 12-24 hr.
- Tophi and joint desquamation may be present.
- Women predominantly present after menopause and have polyarticular predominance (up to 70%).
- Less dramatic presentations in immunosuppressed and elderly
- Most common: 1st metatarsophalangeal joint (75%) > ankle; tarsal area; knee > hand; wrist
Pseudogout:
- Typically involves larger joints than with gout
- Most common: Knee > wrist > metacarpals; shoulder; elbow; ankle > hip; tarsal joints
- Monoarticular (25%)
- Asymptomatic (25%)
- Pseudo-osteoarthritis (45%): Progressive degeneration, often symmetric
- Pseudorheumatoid arthritis (in elderly)
Polyarticular variant with fever and confusion

Essential Workup

Arthrocentesis and aspiration of tophi:
- Examine aspirant for crystals, Gram stain, cultures, leukocyte count, and differential
- Fluid is typically thick pasty white:
  - Gout: 20,000-100,000 WBC/mm3; poor string and mucin clot; no bacteria
  - Pseudogout: Up to 50,000 WBC/mm3; no bacteria
Microscopic exam of crystals under polarized light:
- Gout:
  - Needle shaped
  - Strong birefringence
  - Negative elongation
- Pseudogout:
  - Rhomboid
  - Weak birefringence
  - Positive elongation

Diagnosis Tests & Interpretation

Lab

CBC often shows leukocytosis.
Chemistry panel to assess for renal impairment
Magnesium and calcium, thyroid-stimulating hormone (TSH), and serum iron
Uric acid level has limited value.
If infectious arthritis is suspected:
- Blood and urine cultures
- Urethral, cervical, rectal, or pharyngeal gonococcal cultures

Imaging

Plain radiographs to assess the presence of:
- Effusion
- Joint space narrowing
- Baseline status of joint
- Contiguous osteomyelitis
- Fractures or foreign body
Acute gout: Soft tissue swelling; normal mineralization; joint space preservation
Chronic gout: Calcified tophi; asymmetric bony erosions; overhanging edges; bony shaft tapering
Pseudogout: Chondrocalcinosis; subchondral sclerosis or cysts (wrist); radiopaque calcification of cartilage, tendons, and ligaments; radiopaque osteophytes
Dual energy CT to assess for kidney stones or soft tissue urate crystals

Diagnostic Procedures/Surgery

Arthrocentesis
Aspiration of tophi

Differential Diagnosis

Infectious arthritis
Trauma
Osteoarthritis
Reactive arthritis
Miscellaneous crystalline arthritis
Aseptic necrosis
Rheumatoid arthritis
Systemic lupus erythematosus
Sickle cell
Osteomyelitis
Psoriatic arthritis

Treatment

Initial Stabilization/Therapy

Relieve pain.
Rule out infectious cause.

Ed Treatment/Procedures

NSAIDs are 1st-line treatment.
If NSAIDS ineffective or contraindicated:
- Steroids (oral, intravascular, IM, intra-articular)
- Colchicine (limited by toxicity)
Joint aspiration
Avoid aspirin
Reduction of hyperuricemia and long-term management of gout and pseudogout are not within the usual scope of ED care:
- Careful withdrawal of gout-producing agent
- Uricosurics (e.g., probenecid, sulfinpyrazone)
- Allopurinol to reduce uric acid synthesis
- Increased fluid intake and urine alkalization to prevent renal stones
- Long-term colchicine or NSAIDs prophylactically

Medication

Anakinra: 100 mg SQ QD:
- Off label use for chronic, treatment refractory gout or pseudogout and with renal failure
Allopurinol: 100 mg PO QD, increased weekly to max. 800 mg QD:
- Start 1-2 wk after attack has resolved
- Adjust for kidney disease
- Discontinue with rash or fever
- Treatment of choice with uric acid kidney stones
- Doses >400 mg should be taken in divided doses
Colchicine: 1.2 mg PO upon gout flare followed by 0.6 mg 1 hr later:
- Can cause bone marrow suppression at high doses
- Not dialyzable
- Long-term use may cause myopathy.
- Adjust dose for liver or kidney disease.
- Does not prevent monosodium urate deposition or joint damage of chronic gout
Corticosteroids:
- Corticotropin: 40 units IM, q8h, up to 2 doses
- Methylprednisolone: 40 mg (peds: 1-2 mg/kg) IM or IV QD for 3-4 days
- Prednisone: 40 mg (peds: 1-2 mg/kg) PO QD for 3-4 days; taper over 7-14 days
- Triamcinolone: 10-40 mg + dexamethasone 2-10 mg intra-articularly
Febuxostat: 40-80 mg QD:
- Give with NSAID or colchicine when 1st started
- Inhibits urate production
- Safe for mild or moderate kidney disease
NSAIDs in maximal doses initially for 3 days, then taper over 4 days:
- Ibuprofen: 800 mg (peds: 10 mg/kg) PO QID
- Indomethacin: 25-50 mg PO TOD-QID (peds: 2 mg/kg/d TID-QID; not for children <14 yr old)
- Ketorolac: 15-30 mg IM/IV in ED, may repeat for 1 dose (peds: 1 mg/kg to max. 30 mg IM or 0.5 mg/kg to max. 15 mg IV) IM:
- Naproxen: 500 mg PO TID (peds: 5 mg/kg PO BID)
- Sulindac: 200 mg PO TID
Pegloticase: 8 mg IV over 2+ hr q2wk
- For gout refractory to conventional treatment
- Premedicate with antihistamine and steroids
- Associated with anaphylaxis
- Stop if uric acid increases to >6 mg/dL
- Contraindicated with G6PD deficiency
Probenecid: 250-500 mg PO q12h, max. 3 g QD:
- Promotes excretion of uric acid
- Not effective or less effective with renal disease or aspirin or diuretic use
- Relatively contraindicated with presence of uric acid kidney stones
Rilonacept: 2 — 160 mg (2 — 2 mL) SC injected into 2 different sites on the same day, then 160 mg (1 — 2 mL) SC every week -Off label use for acute gout or prophylaxis
- Given during initiation of urate-lowering therapy
Sulfinpyrazone: 200-400 mg PO in divided doses BID with food, maintenance dose 400 mg in divided doses BID, max. 800 mg QD

NSAIDs may worsen renal function, fluid retention, gastropathy, hepatotoxicity, and cognitive function, particularly in the elderly.
Gout not usually seen in children, although possible during chemotherapy treatment for cancer.

Follow-Up

Disposition

Admission Criteria

Suspected infectious arthritis
Acute renal failure
Intractable pain

Discharge Criteria

No evidence of infection
Adequate pain relief

Issues for Referral

Septic arthritis
Renal failure

Follow-Up Recommendations

Rheumatology follow-up in severe or difficult to control cases
Renal follow-up if renal insufficiency is present
Urology follow-up if uric acid stones are present
Orthopedic follow-up in cases of septic arthritis or significant joint damage
Advise patient to follow a low-purine diet.

Pearls and Pitfalls

Septic arthritis can occur simultaneously with an acute gout attack.
NSAIDs are 1st-line treatment if tolerated.
Attacks generally tend to be self-limited.
Gout and pseudogout can lead to bony and cartilaginous damage.

Additional Reading

Crittenden DB, Pillinger MH. New therapies for gout. Annu Rev Med. 2013;64:325-337.
Laubscher T, Dumont Z, Regier L, et al. Taking the stress out of managing gout. Can Fam Physician. 2009;55:1209-1212.
Smith HS, Bracken D, Smith JM. Gout: Current insights and future perspectives. J Pain. 2011;12:1113-1129.
Terkeltaub R. Update on gout: New therapeutic strategies and options. Nat Rev Rheumatol. 2010;6:30-38.
Yanai H, Yoshida H, Tada N. Clinical, radiologic, and biochemical characteristics in patients with diseases mimicking polymyalgia rheumatica. Clin Interv Aging. 2009;4:391-395.

Codes

ICD9

274.00 Gouty arthropathy, unspecified
274.9 Gout, unspecified
712.30 Chondrocalcinosis, unspecified, site unspecified
712.37 Chondrocalcinosis, unspecified, ankle and foot
712.33 Chondrocalcinosis, unspecified, forearm
712.34 Chondrocalcinosis, unspecified, hand

ICD10

M10.00 Idiopathic gout, unspecified site
M10.9 Gout, unspecified
M11.20 Other chondrocalcinosis, unspecified site
M11.279 Other chondrocalcinosis, unspecified ankle and foot
M11.239 Other chondrocalcinosis, unspecified wrist

SNOMED

90560007 Gout (disorder)
60782007 Pseudogout (disorder)
239838005 Chondrocalcinosis (disorder)
442941002 Chondrocalcinosis of joint of ankle AND/OR foot
201666003 Gouty arthritis of the hand (disorder)
201669005 Gouty arthritis of the ankle and/or foot (disorder)
442884002 Chondrocalcinosis of joint of hand (disorder)

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