How does allopurinol work? Name 3 indications for its use.
Allopurinol inhibits the enzyme xanthine oxidase, which is responsible for the conversion of the purine metabolites hypoxanthine and xanthine into uric acid. With the use of allopurinol, uric acid concentration falls and the concentrations of these precursors rise. This also provides a negative feedback signal that decreases purine production.
- Recurrent gouty attacks (more than 3 in the span of 1 year)
- Gouty tophi
- Renal insufficiency with hyperuricemia
Other indications include recurrent nephrolithiasis with hyperuricemia, and prophylaxis for tumour lysis syndrome.
*Note that allopurinol is generally a life-long therapy and that both its initiation and discontinuation can exacerbate gout or cause a flare. It should not be started or stopped during an acute flare of gout.
What proportion of the general population is ANA-positive at a titer of 1:40? 1:160?
ANA titers of 1:40 are thought to be present in about 30% of the healthy population. The likelihood of a connective tissue disease rises with the ANA titer.
An ANA of 1:80 is seen in 13% of individuals, while an ANA of 1:160 is found in 5%. An ANA of 1:320 is seen in only 3.3% of healthy people.
Name four rheumatologic diagnoses that are associated with a positive ANA and four non-rheumatologic conditions that are associated with a positive ANA.
Estimates of the prevalence of ANA positivity in rheumatologic diseases:
- SLE: 98%
- Scleroderma: 85%
- Sjogren’s: 48%
- Rheumatoid arthritis: 41%
- Dermatomyositis and polymyositis: 61%
- Mixed connective tissue disease: 93%
- Drug-induced lupus: 100%
- Discoid lupus: 15%
- Pauciarticular juvenile idiopathic arthritis: 71%
Non-rheumatologic diseases associated with ANA-positivity:
- Grave’s disease or Hashimoto’s thyroiditis
- Hepatitis C
- Pimary biliary cirrhosis
- Autoimmune hepatitis
- Idiopathic pulmonary hypertension
- Subacute bacterial endocarditis
Tan EM, Feltkamp TE, Smolen JS et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum 1997 Sep; 40(9): 1601-11
What are the clinical features of scleroderma renal crisis? What subset of scleroderma patients is at higher risk of scleroderma renal crisis?
Clinical features of scleroderma renal crisis:
- Abrupt onset hypertension
- Progressive decline in renal function
- Acute retinal changes of hypertensive crisis
- Microangiopathic hemolytic anemia
- New onset proteinuria
- Oliguria or anuria
- Flash pulmonary edema
- Characteristic kidney biopsy
The highest risk for scleroderma renal crisis is in those with the diffuse subtype of scleroderma. They are most vulnerable within the first 5 years of disease, particularly while skin changes are progressing.
List the 11 classification criteria for systemic lupus erythematosus.
- Malar rash
- Discoid rash
- Oral ulcers
- Renal disorder (persistent proteinuria or casts)
- Hematologic disorder (including hemolytic anemia, thrombocytopenia, leucopenia or lymphopenia)
- Neurologic disorder
- ANA positivity
- Immunologic abnormality (including double-stranded DNA positivity, anti-Sm antibody positivity, antiphospholipid antibodies or false-positive VDRL)
List four medications that contribute to the risk of developing osteoporosis.
- Anticonvulsants (particularly phenobarbitol and phenytoin)
- GnRH agonists
Cyclosporine and certain chemotherapeutic agents also contribute to osteoporosis risk, as does heavy alcohol intake.