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Sulfonamides and Lupus (Sulfa Drugs)

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This article is about sulfa drugs, which can be separated into two categories: antibiotic and non-antibiotic.  What I hope to do in writing this post is offer some insight into the issues  surrounding sulfonamide hypersensitivity.

Recently I wrote about sulfasalazine, which is a sulfonamide (sulfa drug). In that blog I report that sulfasalazine can cause drug-induced lupus. Though there always exists the possibility of adverse reaction to medication, sulfa drugs as a class seem to pose a particular threat to lupus patients.

Sulfa drugs were the first antibiotics ever discovered; in 1936 a researcher at Bayer Laboratories in Germany formulated a drug called Prontosil. One of the first patients treated with this drug was the researcher’s own daughter.

Prontosil was considered a “wonder drug” and revolutionized medical care; in time, other sulfa drugs were formulated. However, resistance to sulfa drugs soon developed as some microorganisms became immune to them. Eventually, alternative antibiotics, such as penicillin, were discovered.
Sulfonamides still have a place in the doctor’s bag of tricks. These drugs are especially effective in treating urinary tract infections. Though a doctor might be tempted to resort to a sulfa drug when susceptible organisms are detected, caution is advised, especially caution in patients who have certain conditions. These conditions include lupus and HIV. Individuals who have an established sensitivity to penicillin are also at increased risk.
There is little question today about the risk of using sulfonamide antibiotics in lupus patients—that question has been asked and answered. There is an elevated risk. The question still open is whether the sensitivity to sulfonamide antibiotics carries over to non-antibiotic sulfonamides.
Non-antibiotic sulfonamides have a different chemical structure from their antimocrobial cousins; this different structure seems to limit the number of adverse reactions. I have read a number of research articles and a few case reports about the possibility of a cross-over hypersensitivity between the antibiotic sulfonamide and the non-antibiotic. Not all researchers agree about the level of risk.
It seems that most researchers feel non-antibiotic sulfonamides are safer for lupus patients (or anyone with a sulfonamide hypersensitivity) than antimicrobial sulfonamides. However, case reports do exist which show that there can be a crossover–people can be allergic to both antibiotic and non-antibiotic sulfonamides. This is especially true in people who are allergic to penicillin.

One case illustrates the dilemma a doctor may face when sorting through the conflicting research: A Canadian physician reports that a 70-year old patient has symptoms of mild heart failure.  She also has a history of antibiotic sulfonamide hypersensitivity. The doctor prescribes furosemide (Lasix), an non-antibiotic sulfonamide diuretic, despite the patient’s history of allergy. He’s not concerned about a cross-over hypersensitivity between the two types of sulfonamides.

A few hours after the patient leaves his office, the doctor receives a call from the pharmacist. He points out that the patient also has a history of hypersensitivity to hydrochlorothiazide, a non-antibiotic sulfonamide. The doctor reconsiders his prescription; he agrees that a non-sulfonamide diuretic might be wiser in this case. In a follow-up consult with his patient, the doctor recommends she wear a Medic Alert bracelet.
In the mind of at least this one doctor, there is now a heightened concern about cross-over sensitivity between anti-biotic and non-anti-biotic sulfonamides. He concludes his report by suggesting that in the future he will proceed more cautiously in prescribing sulfonamides of any kind to someone with a demonstrated sulfonamide hypersensitivity.

Some researchers have concluded that a cross-over sensitivity between sulfonamides is not due so much to a sulfonamide allergy as it is to a general sensitivity to all medication. This would explain why people with penicillin allergy are more likely to have a allergy to both kinds of sulfonamides.
Non-antibiotic sulfonamides are present in many prescription drugs. The names of some of these are (this is not a comprehensive list–always check with your doctor and pharmacist if sulfonamide allergy is a concern): furosemide (one brand name of this drug is Lasix), Celecoxib (one brand name is Celebrex) and hydrochlorothiazide (which is sold under a variety to names and which is also used in the preparation of a number of hypertensive drugs, including Atacand, Benicar and Zestoretic).
The names of a few antibiotic sulfonamides are (once again, this is not a comprehensive list; check with your doctor and pharmacist if sulfonamide sensistivity is a concern): Septra and Bactrim; Silvadene; Azulfadine; Gantrisin; and Erythromycin-sulfisoxazole (combination drug sold under a number of brand names).
I emphasize here, as I always do: have a conversation with your doctor if you think sulfonamide sensitivity may be an issue. Report to your doctor any history of adverse reaction to medication of any kind. Patients cannot always know the class of drugs to which a medication belongs (I didn’t know, for example, that Celebrex was a sulfonamide). Pharmacists are also good sources of information.  As the example from Canada (described above) illustrates, sometimes pharmacists catch things doctors miss.

A few articles that were helpful to me in putting together this blog were:

Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics: N
Eng. J Med.

Sulfonamide cross-reactivity: Fact or Fiction: Virginia Commonwealth University Medical Center

Frequency of adverse drug reactions in patients with systemic lupus erythematosus: University of Western Ontario

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