Crystalline Arthropathies Flashcards
What are the four diseases associated with hyperuricemia?
Hypertension
Renal insufficiency
Obesity
Arteriosclerotic heart disease
What is the etiology of hyperuricemia due to underexcretion of uric acid?
Reduced filtration of uric acid, enhanced tubular reabsorption or decreased tubular secretion
What is the frequency of hyperuricemia due to underexcretion of uric acid?
90% of patient with gout has hyperuricemia due to underexcretion of uric acid
What is the etiology of hyperuricemia due to overproduction of uric acid?
Hypoxanthineguanine phosphoribosyltransferase deficiency or 5-phosphoribosyl-1-pyrophosphate synthetase over activity. Both are X-linked inborn errors of murine metabolism
What is the frequency of hyperuricemia due to overproduction of uric acid?
10%
What is the error responsible for Lesch-Nyhan syndrome?
complete deficiency of hypoxanthine-guanine phosphoribosyltransferase
What is the genetic inheritance for Lesch-Nyhan syndrome?
X-linked disorder
What are the clinical findings for Lesch-Nyhan syndrome?
by hyperuricemia, self-mutilation, choreoathertosis, spasticity, growth retardation & severe gouty arthritis
What is the genetic inheritance of xanthine oxidase deficiency?
AR
What are the clinical findings of xanthine oxidase deficiency?
hypouricemia, xanthinuria with xanthine stones and myopathy associated with deposits of xanthine & hypoxanthine
What is mechanism of hypouricemia seen in Fanconi syndrome?
Diminished reabsorption of uric acid causing hyporuricemia.
What are the diseases associated with Fanconi syndrome?
Wilson disease, carcinoma of the lung, acute myelogenous leukemia, light-chain diseases, and use of outdated tetracycline
What are the causes of hypouricemia associated with increased excretion of uric acid?
Fanconi syndrome
Malignant neoplasm (carcinoma)
Hodgkin disease
Sarcoma
What are the causes of hypouricemia associated with the decreased synthesis of uric acid?
Taking allopurinol which inhibits the enzyme xanthine oxidase
Congenital deficiencies in enzymes involved in purine biosynthesis: 5-phosphoribosyl-1-pyrophosphate synthetase deficiency, adenosine deaminase deficiency, purine nucleoside phosphorylase deficiency and xanthine oxidase deficiency (xanthinuria).
Acquired deficiency in xanthine oxidase activity (metastatic adenocarcinoma of lung)
Acute intermittent porphyria
What are the factors that can predispose a patient to an attack of gout or pseudogout?
Trauma
Operation (3 days after- cardiac transplant)
Major medical illness (MI, cerebrovascular accident, pulmonary embolus)
Fasting
Alcohol use
Infection
Acidosis
What are the drugs that cause secondary hyperuricemia?
Thiazide diuretics Furosemide Ethacrynic acid Ethambutol Pyrazinamide Low-dose aspirin Cyclosporine Nicotinic acid Laxative abuse Levodopa Rasburicase
What is the most commonly affected joint in gout?
50%= metatarsophalangeal joint of the great toe (Podagra)
What is the clinical presentation of gout?
Rapid joint swelling with extreme tenderness and redness, Monarticular and most often involves the joints in the lower extremities. Mostly in middle aged men or women after menopause
How do you Dx gout?
Uric acid crystals that are needle shaped and strongly negatively birefringent under polarized light. High amount of polymorphonuclear neutrophil in joint fluid
What is the therapeutic option of choice for the treatment of acute gouty arthritis?
Indomethacin
NSAID
What are the contraindications to NSAID or indomethacin use?
Contraindicated in patients with congestive heart failure, active peptic ulcer disease or renal insufficiency.
NSAID should not be used in patients with nasal polyps and aspirin sensitivity because they may cause bronchospasm.
What are the therapeutic options for the treatment of acute gouty arthritis in patients with contraindications to colchicines and NSAIDs?
Intra-articular or oral corticosteroid and subcutaneous adrenocorticotropic hormone
What is the toxicity associated with oral versus IV colchicines?
High dose oral colchicines can give severe GI side effect so it’s given in IV form
What are the contraindications to colchicines?
Renal insufficiency, bone marrow depression, sepsis and immediate prior use of oral colchicine. Repeated dose should be avoided.
What is the use of prophylactic colchicines to prevent exacerbation of acute gout?
Oral colchicine (0.6mg) is given twice day prophylactically with probenecid or allopurinol for 6-12months to prevent exacerbation of acute gout.
What are the indications for the use of allopurinol rather than probenecid for lowering the uric acid level in gout?
Allopurinol is xanthine oxidase inhibitor and is the drug of choice to prevent gouty attack if the patient has a history of renal stones, tophi or renal insufficiency. It can also precipitate gout
It is used rather than probenecid for lowering the uric acid level are tophaceous gout, gout complicated by renal insufficiency, uric acid excretion more than 1,000mg/day, history of uric acid calculi, use of cytotoxic drugs and allergy to uricosuric agent
What are the diseases associated with calcium pyrophosphate disease (CPPD)?
Acute inflammatory arthritis (pseudogout)
What are the most commonly affected joints in pseudogout?
Mostly commonly affects the knees, but the wrists, elbows, ankles and intervertebral disks may be involved
What are the findings on joint aspiration of pseudogout?
CPPD crystals are weakly positively birefringent and are rhomboid.
What are the findings on radiography of pseudogout?
Most patients have chondrocalcinosis on radiography
What are the therapeutic options of choice for the treatment of acute pseudogout?
NSAIDs
Injection of a steroid
IV colchicine is effective for acute attacks
Prophylactic oral colchicine can be given to decrease in the frequency and severity of attacks.
What is the the clinical presentation of hydroxyapatite deposition disease?
Acute inflammation, including calcific tendinitis, osteoarthritis with inflammatory episodes, periarthritis or arthritis dialysis syndrome and calcinotic deposits in scleroderma
Chronic inflammation, including severe osteoarthritis and Milwaukee shoulder or knee: advanced glenohumeral and knee osteoarthritis, rotator cuff tear, noninflammatory, paste like joint fluid containing hydroxyapatite.
What are the microscopic findings of hydroxyapatite deposition disease?
Individual crystals can’t be seen in polarization microscopy instead small, round bodies are seen. One needs electron microscopy to see needle shaped crystals.
Alizarin red stain shows calcium staining and this can also help diagnose the disease if CPPD is excluded.
