GOUT AND PSEUDOGOUT

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GOUT AND PSEUDOGOUT

• ANDRES QUICENO, MD
• Rheumatology Division
• Presbyterian Hospital of Dallas

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Definition

• Gout is a syndrome caused by the inflammatory
  response to tissue deposition of monosodium urate
  crystals (MSU).

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Classification

• Acute gout.
• Tophaceus Gout.
• Asymptomatic Hyperuricemia.
• Primary Gout.
• Secondary Gout.

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Etiology

• Hyperuricemia is the common denominator in gout.
• Two-thirds of uric acid are excreted by the
  kidney and the rest in the GI tract.
• 90 of cases of gout are secondary to
  under-excretion.
• Overproduction is secondary to defects in the
  HGPRT or PRPP.

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Etiology

• The inflammatory response is secondary to the
  response of the leukocytes to the MSU crystals.
• Acute gout is most likely secondary to the
  formation of new crystals.
• Factors that precipitate gout includes surgery,
  trauma, alcohol, starvation and medications.

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Pathology

• The most frequent sites of deposition of MSU
  crystals are cartilage, epiphyseal bone,
  periarticular structures and the kidney.
• A tophus is a foreign body reaction that includes
  the MSU crystals surrounded by fibrous tissue.
• In the kidney the deposition of MSU crystals
  causes interstitial fibrosis and arteriosclerosis.

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Epidemiology

• The prevalence of asymptomatic hyperuricemia is 5
  to 8.
• The prevalence of gout is 13 cases per 1000 men
  and 6.4 cases per 1000 women.
• The higher the uric acid, the higher the risk to
  develop gout.
• 90 of patients with primary gout are men.

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Epidemiology

• Women rarely develop gout before the menopause,
  because estrogens are thought to be uricosuric.
• Peak incidence in men is in the fifth decade.
• Primary gout is associated with obesity,
  hyperlipidemia, diabetes mellitus, hypertension
  and atherosclerosis.

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Epidemiolgy

• Causes of secondary gout include Excessive
  dietary purine intake, increase nucleotide
  turnover (e.g., lymphoproliferative disorders,
  hemolytic anemia, psoriasis), Glycogen storage
  diseases, diminished renal function,
  ketoacidosis, lactic acidosis, hyperparathyroidsm
  and medications.

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Clinical Manifestations

• Acute gout acute arthritis is the most common
  manifestation. The most common is the podagra.
• 50 of patients experience their first attack in
  this joint.
• 80 of the attacks are monoarticular and
  typically involve the lower extremities. (MTPs,
  ankle and knee).

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Clinical Manifestations

• Less common sites of involvement include wrist,
  fingers and elbow.
• Differential diagnosis includes septic arthritis,
  cellulitis or thromboflebitis.
• Attacks subside in 3 to 10 days.
• Recurrent attacks can involve more joints and
  usually persist longer.

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Clinical manifestations

• Repeated attacks could cause joint erosions.
• Polyarticular attacks are common in patients with
  established poor controlled disease.
• These attacks could also involve periarticular
  structures.

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Clinical Manifestations

• Intercritical gout It is the asymptomatic period
  between crises, but MSU crystals can still be
  recovered if necessary.
• The duration of this period varies, but untreated
  patients may have a second episode within two
  years.
• Some patients evolve to chronic polyarticular
  gout without pain free intercritical episodes.

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Clinical Manifestations

• Chronic tophaceus Gout The clinical
  characteristic is the deposition of solid urate
  in the connective tissue.
• It is associated with early age of onset, long
  duration of untreated disease, frequent attacks,
  upper extremity involvement, polyarticular
  disease and elevated serum uric acid.

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Clinical Manifestations

• Transplant patients treated with cyclosporine
  and/or diuretics have an increased risk for
  tophaceus gout.
• The most common sites for tophi are the
  olecranon, prepatellar bursa, ulnar surface and
  Achilles tendon.

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Clinical Manifestations

• Tophi in the hands can cause joint destruction.
• Tophi can ulcerate the skin and excrete a chalky
  material composed of MSU crystals.
• Tophi progress insidiously with increased
  stiffness and pain.

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Clinical Manifestations

• Renal disease this includes urolithiasis, urate
  nephropathy (deposition of MSU crystals in the
  interstitium), and uric nephropathy ( deposition
  of MSU crystals in the collecting tubes).
• The prevalence of urolithiasis is 22 in primary
  gout and 42 in secondary gout.

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Clinical Manifestations

• Uric acid nephropathy may present acutely in
  patients being treated for malignancy.
• Urate nephropathy is slowly progressive and
  associated with hypertension and proteinuria.

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Diagnostic Tests

• Uric Acid normal values range from 4.0 to 8.6
  mg/dl in men to 3.0 to 5.9 mg/dl in women.
  Urinary levels are normal below 750 mg/ 24h.
• Urinary levels above 750 mg/dl in 24h in gout or
  gt 1100 mg/dl in asymptomatic hyperuricemia
  indicates urate overproduction.

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Diagnostic tests

• Joint Fluid in acute gout it is inflammatory
  (gt2000 cells/ml) MSU crystals are identified
  with the polarized light microscope. In acute
  gout the crystals are usually intracellular. The
  MSU crystals do not exclude the possibility of
  septic arthritis, for this reason it is also
  recommended to request a Gram smear.

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Diagnostic Tests

• 24 urine collection for uric acid determination
  is useful in assessing the risk of renal stones
  and planning for therapy.
• Radiological examination is helpful to exclude
  other kinds of arthritis. Long term gout shows
  erosive arthritis with the characteristic
  punched-out erosions.

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Differential Diagnosis

• Acute Gout septic arthritis, pseudogout,
  Reactive arthritis, acute rheumatic fever and
  other crystalline arthropathies.
• Chronic tophaceus gout Rheumatoid Arthritis,
  Pseudogout, seronegative spondyloarthropathies
  and erosive osteoarthritis.

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Therapy

• Usually there is no justification for treatment
  of asymptomatic hyperuricemia. But some
  physicians treat if serum uric acid is gt 12 mg/dl
  and there is risk of nephrolithiasis.
• In the setting of malignancy, when tumor lysis
  can cause hyperuricemia, allopurinol is
  recommended.

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Therapy

• Acute Gout NSAIDs, corticosteroids or oral
  colchicine can be used.
• NSAIDs are the preferred modality.
• When NSAIDs are contraindicated, corticosteroids
  are effective.

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Therapy

• Intra-articular corticosteroids are an
  alternative when systemic therapy is
  contraindicated.
• Colchicine has been the medication traditionally
  used for acute gout, but it has significant GI
  toxicity and delayed onset of action.

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Therapy

• Intercritical Gout the focus in this stage is
  prevention and prophylaxis.
• Patients with only one or few attacks it is
  acceptable to wait and treat the acute attacks.
• Patient with frequent attacks should be offered
  medical therapy.

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Therapy

• Diet is usually impractical, ineffective and
  rarely adhered to in clinical practice.
• Indications for pharmacological therapy includes
  inability to reverse secondary causes, tophaceus
  gout, recurrent acute gout and nephrolithiasis.

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Therapy

• The pharmacological agents indicated for gout
  include uricosuric (probenecid, sulfinpyrazone)
  or inhibitors of uric acid production
  (allopurinol).
• Uricosuric agents are indicated in patients with
  normal renal function, under-excretion and no
  evidence of tophi.

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Therapy

• Patients taking uricosuric agents are at risk for
  urolithiasis. This can be decreased by ensuring
  high urinary output and by adding sodium
  bicarbonate 1 gram TID.
• The available agents include probenecid (1-2
  g/day) and sulfinpyrazone (50-400 mg BID).
• Dose should be increased to decrease uric acid lt
  6.0 mg/ml

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Therapy

• Allopurinol decreases uric acid in overproducers
  and underexcreters it is also indicated in
  patients with a history of urolithiasis,
  tophaceus gout, renal insufficiency and in
  prophylaxis of tumor lysis syndrome.

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Therapy

• Allopurinol usual dose is 300 mg/day. Maximal
  recommended dose is 800 mg/day.
• In renal insufficiency dose should be decreased
  to 200 mg/day for creatinine clearance lt 60ml/min
  and to 100 mg/day if clearance lt 30 ml/min).

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Therapy

• Start with small doses of allopurinol to reduce
  the risk of precipitating an acute gout attack.
• Most common side effects are rash (2 of
  patients) but rarely patients can develop
  exfoliative dermatitis that can be lethal.
• Chronic use of colchicine (0.6-1.2 mg/day) is
  used as prophylaxis for acute attacks.

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PSEUDOGOUT

• Calcium pyrophosphate Crystal Deposition Disease
  (CPPD) is the syndrome secondary to the calcium
  pyrophosphate in articular tissues.
• This includes Chondrocalcinosis, Chronic CPPD
  and Pseudogout.

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Pseudogout

• Etiology It is unknown, but can be secondary to
  changes in the cartilage matrix or secondary to
  elevated levels of calcium or inorganic
  pyrophosphate.
• Pathology CPPD crystals are found in the joint
  capsule and fibrocartilaginous structures. There
  is neutrophil infiltration and erosions.

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Pseudogout

• Demographics It is predominantly a disease of
  the elderly, peak age 65 to 75 years old. It has
  female predominance (FM, 2-71).
• Prevalence of chondrocalcinosis is 5 to 8 in the
  general population.

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Pseudogout

• Disease Associations hyperthyroidsm,
  hypocalciuria, hypercalcemia, hemochromatosis,
  hemosiderosis, hypophosphatasia, hypomagnesemia,
  hypothyroidsm, gout, neuropathic joints,
  amyloidosis, trauma and OA.

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Pseudogout

• Clinical Manifestations
• Pseudogout Usually presents with acute
  self-limited attacks resembling acute gout. The
  knee is involved in 50 of the cases, followed by
  the wrist, shoulder, ankle, and elbow.

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Pseudogout

• In 5 of patients gout can coexist with
  pseudogout.
• The diagnosis is confirmed with the synovial
  fluid analysis and/or the presence of
  chondrocalcinosis in the radiographs.
• Acute Pseudogout primarily affects men.

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Psedogout

• Chronic CPPD predominately affects women it is
  a progressive, often symmetric, polyarthritis.
• Usually affects the knees, wrists, 2nd and 3rd
  MCPs, hips, spine, shoulders, elbows and ankles.
• Chronic CPPD differs from pseudogout in its
  chronicity, involvement of the spine and MCPs.

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Pseudogout

• Chondrocalcinosis Generally is an incidental
  finding in XRays.
• Diagnostic Tests Inflammatory cell count in the
  synovial fluid. Rhomboidal or rodlike
  intracellular crystals. Imaging studies reveal
  chondrocalcinosis usually in the knee, but can be
  seen in the radial joint, symphisis pubis and
  intervertebral discs.

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Pseudogout

• Differential Diagnosis Includes septic
  arthritis, gout, inflammatory OA, Rheumatoid
  Arthritis, neuropathic arthritis and Hypertrofic
  Osteoarthropathy.

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Pseudogout

• Therapy It is similar to gout and includes
  intrarticular corticosteroids. Colchicine can be
  used in acute attacks and also in prophylaxis.
  There is no specific treatment for chronic CPPD.
  It is important to treat secondary causes and
  colchicine could be helpful.

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