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A variety of mechanisms, presumably unrelated to hypersensitivity, account for the majority of these reactions Table
- Silver sulfadiazine
- Sulfonamide Allergies
- Advances in Diagnosis and Management of Cutaneous Adverse Drug Reactions
- What to know about sulfa allergies
Diuretics that do not contain a sulfonamide group eg, amiloride hydrochloride, eplerenone, ethacrynic acid, spironolactone, and triamterene are safe for patients with an allergy to sulfa. The evidence is contradictory as to whether a history of allergy to sulfonamide antibiotics increases the risk of subsequent allergic reactions to commonly used sulfonamide-containing diuretics eg, carbonic anhydrase inhibitors, loop diuretics, and thiazides strength of recommendation: C, based on case series and poor quality case-control and cohort studies. Are all sulfa drugs created equal? Historical bromides commonly fall by the wayside as better evidence becomes available. Who would have thought 15 years ago that we would be promoting beta-blockers for patients with congestive heart failure?
Diuretics that do not contain a sulfonamide group eg, amiloride hydrochloride, eplerenone, ethacrynic acid, spironolactone, and triamterene are safe for patients with an allergy to sulfa.
The evidence is contradictory as to whether a history of allergy to sulfonamide antibiotics increases the risk of subsequent allergic reactions to commonly used sulfonamide-containing diuretics eg, carbonic anhydrase inhibitors, loop diuretics, and thiazides strength of recommendation: C, based on case series and poor quality case-control and cohort studies. Are all sulfa drugs created equal?
Historical bromides commonly fall by the wayside as better evidence becomes available. Who would have thought 15 years ago that we would be promoting beta-blockers for patients with congestive heart failure? Likewise, with closer inspection, we have learned that not all sulfa drugs are created equal. The stereospecificity due to the absence of aromatic amines in common diuretics means they are safe for patients with known sulfa antibiotic allergies.
Given that diuretics are older agents and off-patent, with no company to take up their cause, no one has been willing to challenge outdated package insert warnings. As clinicians who regularly work without a net, we are accustomed to prescribing medications in less than ideal circumstances. Thankfully, reasonable evidence is available to support what many of us are already doing—using cheap thiazides for patients despite a history of sulfa allergy. Little research has been performed on sulfonamide antibiotic and sulfonamide diuretic allergic cross-reactivity.
What we do know is that there are 2 classes of sulfonamides—those with an aromatic amine the antimicrobial sulfonamides and those without eg, the diuretics acetazolamide, furosemide, hydrochlorothiazide, and indapamide.
Hypersensitivity reactions occur when the aromatic amine group is oxidized into hydroxylamine metabolites by the liver. Sulfonamides that do not contain this aromatic amine group undergo different metabolic pathways, suggesting that allergic reactions that do occur in this group are not due to cross-reactivity in sulfa-allergic patients. But that point is far from settled by the research.
On one side, a large cohort study shows some cross-reactivity. Reasonable evidence supports what many of us are doing: Using cheap thiazides for patients with a history of sulfa allergy.
Patients were identified as being allergic using both narrow definitions anaphylaxis, bronchospasm, urticaria, laryngospasm, or angioedema and broad ones. As only 18 patients out of the 20, patients were reported as having an allergic reaction using the narrow definition, analysis was based on the broad definition. Using this broad definition, researchers identified allergies to sulfonamide antibiotics in patients. Of this group, 96 patients 9.
It was unclear if any patients taking a carbonic anhydrase inhibitor experienced an allergic reaction. For comparison purposes, of the 19, patients who were not identified as having an allergy to a sulfonamide antibiotic, again using the broad definition, 1.
When the results were adjusted for age, sex, history of asthma, use of medications for asthma or corticosteroids, the adjusted odds ratio for individuals experiencing an allergy to a nonantibiotic sulfonamide in those persons with a history of allergy to a sulfonamide antibiotic was 2.
Of note, the adjusted odds ratio for the occurrence of a penicillin allergy in a patient with a history of sulfonamide antibiotic allergy was significantly higher at 3.
Some limitations of the study included uncertainty of cause and effect of prescribed medications and subsequent reactions, possible inconsistency of physician diagnosis and coding, and lack of precision in the diagnosis of allergic reactions. Skip to main content.
Coronavirus News Center. Clinical Inquiries. Which diuretics are safe and effective for patients with a sulfa allergy? J Fam Pract. PDF Download. Clinical commentary Are all sulfa drugs created equal? Evidence-based answers from the Family Physicians Inquiries Network.
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Concerns about cross-allergenicity between sulfonamide antibiotics and nonantibiotic sulfonamide-containing drugs continue to complicate pharmacotherapy. Several elegant investigations have demonstrated unequivocal lack of interaction between the sulfonamide group and either cellular or humoral immunity. The immunologic determinant of type I immunologic responses to sulfonamide antibiotics is the N1 heterocyclic ring, and nonantibiotic sulfonamides lack this structural feature. Many non-type I hypersensitivity responses to sulfonamide antibiotics are attributable to reactive metabolites that cause either direct cytotoxicity or humoral or cellular responses. Metabolite formation is stereospecific to the N4 amino nitrogen of the sulfonamide antibiotics, a structure not found on any nonantibiotic sulfonamide drugs. Cellular immune responses to sulfonamide antibiotics are responsible for many non-immunoglobulin E-mediated dermatologic reactions; however, the stereospecificity of T-cell response renders cross-reactivity between sulfonamide antibiotics and nonantibiotics highly unlikely. Apparent cross-reactivity responses to sulfonamide-containing drugs likely represent multiple concurrent, rather than linked, drug hypersensitivities.
Broad St. Wood St. As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic options for the empiric and definitive treatment of various infectious diseases. Sulfonamide allergies can result in various physical manifestations; however, rash is reported as the most frequently observed. In patients with human immunodeficiency virus HIV , dermatologic reactions to sulfonamide antimicrobial agents occur 10 to 20 times more frequently compared to immunocompetent patients. This article describes the incidence, manifestations, and risk factors associated with sulfonamide allergies.
Advances in Diagnosis and Management of Cutaneous Adverse Drug Reactions
A sulfa allergy occurs when a person has an allergic reaction to drugs that contain chemicals called sulfonamides. Sulfa is a constituent of some antibiotics and other medications. Doctors and pharmacists use drugs that contain sulfa to treat many conditions, including skin disorders, eye infections, and rheumatoid arthritis. People should note that there is a difference between sulfa and sulfite despite their similar names. Sulfites are used as additives and preservatives in many wines and foods.
Neil H. He chaired the University Division of Dermatology from to His research is in all aspects of Drug Safety.
What to know about sulfa allergies
Silver sulfadiazine , sold under the brand Silvadene among others, is a topical antibiotic used in partial thickness and full thickness burns to prevent infection. Common side effects include itching and pain at the site of use. Silver sulfadiazine was discovered in the s. Tentative evidence has found other antibiotics to be more effective in the healing of superficial and partial thickness burn injuries; therefore, it is no longer generally recommended. A noninfection-related clear fluid may form on the wound's surface. Burning and painful sensations are not uncommon but are only temporary.
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Use may be considered in other Sulfa allergic patients. If treatment is prescribed or recommended, check that the Sulfa allergy has been considered, discussed.
As the average age of the general population increases, the incidence of glaucoma follows. As a result, ophthalmologists are seeing more patients for whom eye drops and laser therapy may be insufficient and for whom surgery may be impractical, making it crucial to consider additional medical options such as oral carbonic anhydrase inhibitors CAIs. The first report of a reaction to acetazolamide was published in , when Moseley and Baroody discussed a patient with congestive heart failure and a history of sulfa allergy who experienced gait abnormality, vertigo, paresthesias, and facial numbness 20 minutes after receiving oral Diamox acetazolamide; Wyeth Pharmaceuticals. The term sulfonamide refers to molecules that contain the SO 2 NH 2 functional group Figure 1 , and it refers to two subsets: antibiotic and nonantibiotic sulfonamides. It should not be confused with sulfates, sulphites, or sulfurs, which are all chemically distinct from sulfonamides and demonstrate no cross-reactivity. The basic sulfonamide functional group structure has not been shown to incite an immune response. The two structures responsible for the immune reactions induced by sulphonamides, the arylamine group at the N4 position and a five- or six-membered nitrogen-containing ring attached to the N1 nitrogen of the sulfonamide group Figure 2 , are only present on sulphonamide antibiotics Figure 3.
Metrics details. Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination.
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