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Permanent Organ Damage Risk In Long-term Prednisone For Lupus

Patients with systemic lupus erythematosus (SLE) on long-term prednisone therapy face significant morbidity risks because of permanent organ damage.

Cumulative prednisone dosage is associated with the development of osteoporotic fractures, symptomatic coronary artery disease and cataracts in SLE patients, Johns Hopkins researchers report.

Each two-month exposure to high-dose prednisone is linked with a 1.2-fold increase in risk of avascular necrosis and stroke. Pulse methylprednisone is connected with cognitive dysfunction in lupus patients, indicates the study of associations between corticosteroid use and organ damage.

A total of 539 of the consecutive consenting SLE patients enrolled in the Hopkins Lupus Cohort Study since 1987 participated in the study. Patients were predominantly female (94 per cent), and the majority (93 per cent) met at least four American College of Rheumatology classification criteria.

Patients were followed quarterly by a faculty rheumatologist. Clinical activity indices, laboratory data and treatment notes were recorded at each visit. Data on the average daily dose of prednisone was recorded for each month since diagnosis.
Cumulative prednisone dose at a given month was defined as the total number of milligrams taken that month, and high-dose prednisone as exposure at a dosage equal to or greater than 60 mg/day for two consecutive months or more.

Researchers used the dosage of 1,000 mg of methylprednisone by intravenous bolus daily for one to three days as the definition for pulse therapy.

Only 11 per cent of patients had never taken prednisone. Most (79 per cent) had not received high-dose prednisone, although 11 per cent had one high-dose exposure, 6 per cent had two to four exposures and 4 per cent had more than four exposures.

Pulse therapies ranged from 0 to 10 per person. Approximately 70 per cent had none, 19 per cent had one, 9 per cent had two to four and 2 per cent had more than four.

Organ damage was seen in 60 per cent of patients. It occurred most frequently in the musculoskeletal, neuropsychiatric and renal systems.

Cumulative corticosteroid dose was most strongly associated with osteoporotic fractures. Patients showed a 2.5-fold increased risk for each decade of prednisone at 10 mg/day, after adjustments were made for age, sex, race and exposure to high-dose and pulse therapy.

Investigators suggest that additional research is needed to determine the relative contributions of SLE disease activity and corticosteroids to the pathogenesis of individual damage items.
Arthritis & Rheumatism, 2000; 43: 1801-1808.

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