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By Louis Kuritzky, MD
Sulfonamide Antibiotics and Sulfonamide Nonantibiotics
Sulfonamide antibiotics (SULF-a) are the drugs most commonly associated with both the dread consequences of Stevens-Johnson syndrome and agranulocystosis. More commonly, clinicians see modest allergic dermatitis in SULF-a allergic patients. The allergen responsible for inducing allergic reactions is common both to SULF-a and nonantibiotic sulfonamides, such as thiazide diuretics (SULF-na).
Strom and colleagues used the General Practice Research Database from the United Kingdom, to scrutinize the relationship between SULF-a allergic reactions and subsequent SULF-na allergic reactions. Because Strom et al entertained the possibility that reactions to SUFL-na reflect a patient with an allergic diathesis, rather than specific intolerance to sulfonamides, they also examined adverse experiences in persons who had been prescribed a nonsulfonamide antibiotic, penicillin.
Approximately 10% of persons receiving SULF-na after an adverse SULF-a experience developed an allergic reaction (compared with a background incidence of 1.6% allergic reactions to a SULF-na in persons without a prior allergic sulfonamide reaction). Surprisingly, the likelihood of an adverse reaction to penicillin after an experience of SULF-a allergy was actually greater than that of an adverse reaction to SULF-na! These data support the concept that it may be allergic diathesis, rather than sulfonamide crossreactivity, which is responsible for the substantial degree of dermatologic intolerance manifestations to SULF-na among persons with demonstrated SULF-a allergy.
Strom BL, et al. N Engl J Med. 2003;349:1628-1635.
Autoantibodies Before Onset of SLE
The diagnosis of systemic lupus erythematosus (SLE) is based, in part, upon laboratory findings, including measurement of autoantibodies (AAB) such as antinuclear antibody (ANA), anti-double-stranded DNA (aDS-DNA). Indeed, such AAB are contributors to the pathology of SLE. The timing of presentation of SLE AAB is not yet clearly established, since clinicians seek AAB status usually at the time of clinical presentation and are rewarded almost universally with positive AAB findings in persons with SLE diagnosis confirmation.
Among 130 patients with SLE, one or more AAB was present a mean of 3.3 years prior to diagnosis (range up to 9.4 years earlier). The most commonly detected AAB was ANA (78% at 1:120 or greater dilution), and the least common was antiphospholipid antibody (18%). Matched controls were positive 3.8% of the time.
The appearance of SLE AAB years prior to symptomatic presentation is established by these data to be commonplace and occurs in a predictable pattern much of the time. It appears that the number of different AAB increases over time until clinical presentation, after which the number remains constant, as if there is some self-limited aspect to AAB development.
Arbuckle MR, et al. N Engl J Med. 2003;349:1526-1533.
Prevention of VTE with Ximelagatran
Typically, after a first episode of DVT, prophylaxis will be advised for 3-6 months, although recent data show no diminution of benefit when warfarin prophylaxis for recurrent DVT is continued for as long as 24 months. The rationale for 3-6 months of DVT prophylaxis is based upon a risk-benefit analysis that includes expense, adverse effects (primarily bleeding), and need for repeated long-term monitoring on the downside of the equation.
Ximelagatran (XIM) is an orally administered direct thrombin inhibitor that has already demonstrated efficacy equal or superior to well-titrated warfarin prophylaxis in settings of DVT or atrial fibrillation. The remarkable difference between XIM and warfarin is that consistent anticoagulation responsivity seen with XIM results in no need for coagulation monitoring; that is, once patients are started on the twice-daily drug, no further INR testing or other coagulation monitoring is required.
In this trial, persons who had successfully completed 6 months of warfarin (n = 1223) were randomized to either placebo or XIM twice daily for an additional 18 months. Confirmed symptomatic venous thromboembolism was seen in 12/612 XIM patients vs 71/611 placebo recipients. There was no significant difference in all-cause mortality or bleeding between XIM and placebo. XIM may be available as an oral anticoagulant in the very near future.
Schulman S, et al. N Engl J Med. 2003;349:1713-1721.
Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.