Crystal-Induced Arthropathies (Pseudogout (Etiology and Pathophysiology ( …
purine metabolism resulting in hyperuricemia
urate crystal deposits in tissues (tophi)
Etiology and Pathophysiology
Uric acid is an end product of purine degradation by xanthine oxidase, It Is synthesized mainly in the liver and 70 % is excreted by the kidneys
10% of hyperuricemia
, excretion of 800 mg of uric acid in the urine,
Acquired disorders: Excessive cell turnover such as myleoproliferative disorders, Paget’s disease, hemolytic anemias, carcinoma, severe psoriasis
Genetic disorders: Deficiency HGPRT, or superactivity PRPP synthetase
Diminished tubular secretory rate, increased tubular reabsorption, diminished uric acid filtration
Uric acid underexcretion:
Chronic renal failure
, Dehydration, Obesity,
(ethanol,diuretics, low-dose salicylate, cyclosporine, ethambutol, pyrazinamide,levodopa), Increased lactic acid production from alcohol, exercise
Acute gouty arthritis - the response of polymorphonuclear leukocytes to formation of MSU crystals (phagocytosis, disruption leukocytes, releasing inflammatory mediators)
Tophaceous gout -deposition of MSU in joints causes damage to them: cartilage degeneration, erosion of marginal bone, and synovial proliferation
Interstitial fibrosis and renal stone formation - crystal deposition in the kidney
Synovial Fluid Findings:
Needle shaped crystals of monosodium urate monohydrate that have been engulfed by neutrophils
In polarized microscopy, the crystals appear as bright yellow birefringent crystals (negatively birefringent)
clinical picture is often diagnostic, as is the rapid response to NSAIDs
Joint fluid microscopy
Serum Uric Acid (Levels may be normal during acute attack)
Serum WBC (Mild
may be present during acute attack)
or may be 2-3 times higher than normal during acute attack)
during acute attack)
DECT-Dual-energy computed tomography
Asymmetry, (punched out) bone cyst Erosive arthritis
, The joint space is preserved until late in the disease
Trauma, Infections (septic arthritis, gonococcal arthritis, cellulitis), Inflammatory (Rheumatic arthritis, Reiter’s syndrome, Psoriatic
arthritis), Metabolic (pseudogout), Miscellaneous (Osteoarthritis)
control of pain and inflammation
preventing future attacks
preventing complications such as renal stones, tophi, and destructive arthropathy
Acute gouty attacks:
NSAIDs, Colchicine, Corticosteroids systemic and intra-articular
prophylaxis: Oral colchicine, Low dose NSAIDs (GI toxicity), Low dose oral CS
Recurrent acute attacks:
ULT should not be discontinued during an acute attack of gout
Corticosteroids (safest in chronic renal insufficiency)
NSAIDs (should be avoided in chronic renal insufficiency)
Urate lowering therapy (ULT):
Used for urate
Goal is for serum urate concentration to 6mg/dL or less
can precipitate acute attack
Xanthine oxidase inhibitors
Allopurinol and febuxostat
blocks conversion of xanthine to uric acid.
works for underexcretors and overproducers.
Probenecid or Sulfinpyrazone
increase renal clearance of uric acid
inhibiting tubular absorption
Side effects: prohibit use-GI and kidney stones.
- line therapies:
Enzyme that breaks down uric acid
oxidizes uric acid to a more soluble form-allantoin
Natural Uricase from Aspergillus flavus Rasburicase approved for use in tumor lysis syndrome and Pegloticase is a pegylated mammalian (porcine-like) recombinant uricase approved for the treatment of severe tophaceous gout.
IL-1 inhibitors: anakinra
- an IL-1R antagonist, rilonacept - an IL-1 decoy receptor, or Trap, and canakinumab - an anti-IL-1b monoclonal antibody.
: lesinurad - inhibit uric acid reabsorption by URAT1,which is the major trans- porter of uric acid from the renal
proximal tubule, arhalofenate
IL-1 pathway inhibitors: small molecule drugs that inhibit the active site of caspase-1,VMX-740 (pralnacasan) and VMX-765,
Immobilization of Joint
Abstinence of Alcohol
Consumption can increase serum urate levels by increasing uric acid production.When used in excess it can be converted to lactic acid which inhibits uric acid excretion in the kidney
-Increase in protein and unsaturated fats
-Decrease in dietary purine-rich food.
Most common form of crystal–induced arthritis.
common in males
Stages of Classic Gout
uric acid level above 7 mg/dl.
Majority of people with hyperuricemia never develop symptoms of uric acid excess
Acute Intermittent Gout (
Initially monoarthritis, later polyarthritis
most common and first site is the metatarsophalangeal joint of the big toe
main complaint is agonizing pain of the affected joint accompanied by signs of inflamation (swelling, erythema, warmth, tenderness)
Low-grade fever may occur
Symptom- free period between attacks. May have hyperuricemia and MSU crystals in synovial fluid.
Chronic Tophaceous Gout
Established deformity disease with deposition of MSU crystals in the soft tissues and joints.
develops after 10 or more years of acute intermittent gout.
Late stage of gout
Affected joints becomes more inflamed and MSU crystals (tophi) are deposited
Complications of tophi include: pain,soft tissue damage and deformity, joint destruction and nerve compression syndromes
joint inflammation caused by calcium pyrophosphate crystals
Etiology and Pathophysiology
acute inflammatory arthritis due to phagocytosis of IgG-coated CPPD crystals by neutrophils and release of inflammatory mediators within joint space
slower in onset in comparison to gout, lasts up to 3 wk but is self-limited
old age, advanced OA, neuropathic joints.
other conditions: hyperparathyroidism, hypothyroidism, hypomagnesemia, hypophosphatasia (low ALP), DM, hemochromatosis
Signs and Symptoms
affects knees, wrists, MCPs, hips, shoulders, elbows, ankles, big toe.
asymptomatic crystal deposition (seen on radiograph only)
pseudo-OA (progressive joint degeneration).
maybe triggered by dehydration, acute illness, surgery, trauma
CPPD crystals: present in 60% of patients, often only a few crystals, positive birefringence (blue) and rhomboid shaped
x-rays show chondrocalcinosis in 75%: radiodensities in fibrocartilaginous structures, or linear radiodensities in hyaline articular cartilage
• joint aspiration, rest, and protection
• NSAIDs: also used for maintenance therapy
• prophylactic colchicine PO (controversial)
• IA or oral steroids to relieve inflammation