O slideshow foi denunciado.
Utilizamos seu perfil e dados de atividades no LinkedIn para personalizar e exibir anúncios mais relevantes. Altere suas preferências de anúncios quando desejar.

Sulfonamide allergy

Sulfonamide allergy
Presented by Pornsiri Sae-lim, MD.
April 2, 2021

  • Seja o primeiro a comentar

  • Seja a primeira pessoa a gostar disto

Sulfonamide allergy

  1. 1. Sulfonamide allergy PORNSIRI SAE-LIM , MD PEDIATRIC ALLERGY AND IMMUNOLOGY DEPARTMENT KING CHULALONGKORN MEMORIAL HOSPITAL
  2. 2. Overview Introduction Epidemiology Classification Clinical presentation Diagnosis Investigation Management
  3. 3. IIntroductionion Sulfa allergy = sulfonamide antibiotic allergy In the general population : 3–8% of patients are reported to experience a sulfonamide allergy Sulfonamide antibiotics allergy reported range from ◦ minor types : maculopapular eruption, fixed drug eruption ◦ major life-threatening types : Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and anaphylactic reaction Rash is reported as the most frequently observed reaction ◦ Immunocompetent : 1.5–3% of patients ◦ human immunodeficiency virus (HIV) : high as 30% in patients
  4. 4. Sulfonamide Structure Contain an NH2-SO2 moiety ◦ Sulfur atom double bonded to two oxygens along with nitrogen and a functional R1 group Two main groups ◦ According to chemical structure and therapeutic action ◦ Sulfonamide antibiotics ◦ An aryl-amine (-Ar-NH2) at the N4 position ◦ A five or six membered, nitrogen-containing ring at the N1 position ◦ Sulfonamide nonantibiotics N1 and N4 positions are the primary determinants of drug allergy instead of the common sulfonamide moiety
  5. 5. Sulfonamide Structure
  6. 6. Sulfonamide antibiotics Sulfamethoxazole (Bactrim®, Comox®, Spectrim®) Sulfadiazine Sulfasalazine (Salazopyrin EN®, Salazine®)
  7. 7. Sulfonamide non -antibiotics Loop diuretics Sulfonamide non antibiotics • Loop diuretics – Furosemide (Lasix®) – Tidorsemid e ( Unat®) • Thaizide diuretics – Hydrochlorothaizide (HCTZ) – Indapamide (Natrilix®) • Carbonic anhydrase inhibitors – Acetazolamide (Diamox® ) – Dorzolamide (Cozopt®) – Brinzolamide (Azo pt®, Aza gra® ) • Sulfonylureas – Chlorpropamide (Diabenese®) – Glibenclamide (Daonil®) – Glipizide (Minidiab®) – Gliclazide (Diamicron®) – Glimeperide (Amaryl®) • Cox -II inhibitors II inhibitors – Celecoxib (Celebrex®) – Parecoxib (Dynastat®) • Others – Topiramate (Topamax®) – Zonisamide (Zonigrane®)
  8. 8. Sulfonamide antibiotics Sulfonamide nonantibiotics Dorn JM,. Current allergy and asthma reports. 2018 Jul;18(7):1-0
  9. 9. Giles A, Sulfonamide allergies. Pharmacy. 2019 Sep;7(3):132. Mechanisms of action of antimicrobial sulfonamides microbial dihydropteroate synthetase Competitive inhibition
  10. 10. Antibacterial spectrum of sulfonamides •Primary bacteriostatic against many gram-positive and gram-negative bacteria In higher concentration it may be act as bactericidal. •Sensitivity patterns among microbes changed time-to-time and place-to-place. Sulfonamides are sensitive to Streptococcus pyogenes, Haemophilus influenza, Vibrio cholerae. • Sulfonamides are primarily used to prevent urinary tract infections
  11. 11. Classification of SulfonamideHypersensitivity Reactions Immediated (IgE-mediated) reaction Nonimmediate reaction
  12. 12. Manifestation of sulfonamide allergy Immediated (IgE-mediated) reactions are rare manifestations such as anaphylaxis, angioedema, and urticaria N1 heterocyclic ring has been found to be recognized by IgE ◦ especially if a methyl group is in the position on the isoxazole ring the sulfonamide-defining NH2-SO2 moiety has not been found to be bound by IgE Giles A, Sulfonamide allergies. Pharmacy. 2019 Sep;7(3):132.
  13. 13. nonimmediate manifestations are most common Cutaneous reactions : Maculopapular exanthemas are the most common form of cutaneous reaction to sulfonamides Risk of SJS/TEN is higher for sulfonamide antibiotics than for most other antibiotics Extracutaneous reactions: Drug-induced liver injury ◦ TMP-SMX : the most common single causative agents ◦ Occur within 2 to 12 days of initiation of therapy ◦ Pattern of injury being a mixed hepatocellular cholestasis ◦ Rare cases of hepatotoxicity and concomitant hemorrhagic pancreatitis Khan DA, The Journal of Allergy and Clinical Immunology: In Practice. 2019 Sep 1;7(7):2116-23 Manifestation of sulfonamide allergy
  14. 14. Extracutaneous reactions Gastrointestinal complaints (common), eosinophilic gastroenteritis ( rarely reported ) Hematologic abnormalities : neutropenia, leukopenia, thrombocytopenia and pancytopenia Renal impairment : reported to be rare with TMP-SMX ◦ Most cases were asymptomatic ◦ Reversible on discontinuation of therapy but one did require dialysis ◦ unclear with little evidence for acute interstitial nephritis Aseptic meningitis : started hours to several days after initiation of therapy ◦ headache and neck stiffness ◦ fever and 50%had nausea and vomiting ◦ Most patients became afebrile ◦ resolution of headache within 2 to 3 days of stopping therapy ◦ mechanism remainsunclear
  15. 15. Manifestation of sulfonamide allergy Three potential mechanisms (1) the parent molecule or reactive metabolites acting as haptens (2) the molecule binding to a native protein stimulating a cellular or humoral immune response, or (3) a cellular protein causing direct cytotoxicity, or stimulation of T-cells to produce an immune response Giles A, Sulfonamide allergies. Pharmacy. 2019 Sep;7(3):132.
  16. 16. Manifestation of sulfonamide allergy Non-type-1 hypersensitivity reactions are typically associated with metabolites of the sulfonamide antimicrobial agents ◦ undergo acetylation, glucuronidation, and hydroxylation to various metabolites N4-hydroxylated metabolite : ◦ A particular metabolite associated with allergic immunogenicity ◦ oxidized to a reactive nitroso compound ◦ reactive nitroso compound can bind directly to T cells to illicit maculopapular eruptions, including SJS Reactive nitroso compound : ◦ reduced through a reaction utilizing glutathione, or acetylated using the NAT 2 enzyme ◦ Slow - acetylator phenotypes ( involves cytochrome P450 isoenzyme 2C9.6 ) or have deficiencies in glutathione may be predisposed Giles A, Sulfonamide allergies. Pharmacy. 2019 Sep;7(3):132.
  17. 17. Giles A, Sulfonamide allergies. Pharmacy. 2019 Sep;7(3):132.
  18. 18. Risk factor - HIV positive patient - Genetic predisposition three HLA alleles (HLA-B*15:02, HLAC*06:02, and HLA-C*08:01) with sulfonamide-induced SJS/TEN reactions
  19. 19. Objective - To explore the cutaneous manifestations induced by sulfonamide antibiotics in a large number of Thai patients, including ◦ Human immunodeficiency virus (HIV) ◦ Non-HIV infected - To determine the risk factors for development of sulfonamide cutaneous reactions
  20. 20. Chantachaeng W. Asian Pacific journal of allergy and immunology. 2011 Sep 1;29(3):284
  21. 21. Cross reaction Cross-Reactivity Within Sulfonamide Antibiotics Cross-Reactivity Between Antibiotic and Non-antibiotic Sulfonamides 1.Khan DA, The Journal of Allergy and Clinical Immunology: In Practice. 2019 Sep 1;7(7):2116-23
  22. 22. Cross-Reactivity Within Sulfonamide Antibiotics • Structural similarities between antimicrobial agents • Contain a five or six membered ring at the N1 position and an N4-arylamine group. these positions are associated with the degree of immunologic response >> high risk of cross-reactivity • No large-scale clinical trials to determine true rates of cross reactivity among sulfonamide antibiotics • Some data in vitro and in vivo test Dorn JM,. Current allergy and asthma reports. 2018 Jul;18(7):1-0
  23. 23. Cross-Reactivity Between Antibiotic and Non-antibiotic Sulfonamides - thiazide and loop diuretics, carbonic anhydrase inhibitors, nonsteroidal anti-inflammatory drugs, sulfonylureas, antiretrovirals, and 5HT-3 receptor agonists - None of the nonantimicrobial sulfonamides have an N-containing ring attached to the N1 - Based on review of the available evidence, sulfonamide antimicrobial agents do not appear to have cross-reactivity with nonantimicrobial sulfonamide agents - Develop reactions to a sulfonamide non-antimicrobial, there is no evidence to suggest that sulfonamide antimicrobials and other sulfonamide non antimicrobials would cross-react Dorn JM,. Current allergy and asthma reports. 2018 Jul;18(7):1-0
  24. 24. Dorn JM,. Current allergy and asthma reports. 2018 Jul;18(7):1-0 fosamprenavir • contain sulfur, sulfites or bisulfate salts • None of these medications are sulfonamides, and there is no risk of crosssensitivity with sulfonamide antimicrobials
  25. 25. Dorn JM,. Current allergy and asthma reports. 2018 Jul;18(7):1-0
  26. 26. Khan DA, The Journal of Allergy and Clinical Immunology: In Practice. 2019 Sep 1;7(7):2116-23
  27. 27. Khan DA, The Journal of Allergy and Clinical Immunology: In Practice. 2019 Sep 1;7(7):2116-23
  28. 28. - Sulfasalazine is not active in its ingested form but broken down by colon bacterial enzyme azoreductase into 2 products: 5-aminosalicylic acid and sulfapyridine - Sulfapyridine structurally related sulfamethoxazole Zawodniak A, International archives of allergy and immunology. 2010;153(2):152-6.
  29. 29. Diagnosis Validated diagnostic testing is not currently available for SMZ-TMP hypersensitivity IgE-mediated : concentration of 1:100 dilution of 80 mg/mL, or 0.8 mg/mL ◦ positive result could suggest IgEmediated sensitization ◦ negative result would not rule out an IgE-mediated reaction to SMZ-TMP Delayed skin testing including patch tests to sulfonamides is rarely positive Drug challenges are a useful tool for patients with both immediate and delayed reactions as a single full dose as 1/10th of the dose followed by the full dose may be considered on the basis of clinical history and skin test results Broyles AD,The Journal of Allergy and Clinical Immunology: In Practice. 2020 Oct 1;8(9):S3-15
  30. 30. Management Severe DHRs (SJS, TEN, DRESS, and others) to SMZ-TMP ◦ The drug should be avoided If no alternatives exist and the benefits of treatment with SMZ-TMP outweigh the risk of death from a severe hypersensitivity reaction ◦ a previously reported temporary induction of tolerance protocol that was successfully used for 2 patients may be considered Desensitization to SMZ-TMP focuses on the HIV patient population ◦ various protocols for temporary induction of tolerance to SMZ-TMP have shown similar success rates (initial success: 80%-90%; longterm: 60%-80%) ◦ no current consensus on the best protocol for SMZ-TMP temporary induction of tolerance Broyles AD,The Journal of Allergy and Clinical Immunology: In Practice. 2020 Oct 1;8(9):S3-15
  31. 31. Broyles AD,The Journal of Allergy and Clinical Immunology: In Practice. 2020 Oct 1;8(9):S3-15
  32. 32. Management Pyle et al : reported that 90% of 72 patients with a history of SMZ-TMP hypersensitivity who required the drug and underwent temporary induction of tolerance had successful outcomes appears to result in success rates comparable to those seen in patients with HIV >> suggest that SMZ-TMP temporary induction of tolerance may be considered in non-HIV patients with a history of related hypersensitivity Temporary induction of tolerance to SMZ-TMP can be used safely and effectively in patients with and without HIV who have SMZ-TMP hypersensitivity. Broyles AD,The Journal of Allergy and Clinical Immunology: In Practice. 2020 Oct 1;8(9):S3-15
  33. 33. Management Few studies have examined the temporary induction of tolerance to SMZ-TMP in non-HIV patient populations ◦ Mann et al: described 4 patients with a history of SMZ-TMP hypersensitivity (leukopenia, hives, macular rash, morbilliform rash) who underwent a successful temporary induction of tolerance using either an 8-day protocol or a 22-day protocol Broyles AD,The Journal of Allergy and Clinical Immunology: In Practice. 2020 Oct 1;8(9):S3-15
  34. 34. Patients with a history of mild to moderate SMZ-TMP hypersensitivity were randomized to temporary induction of tolerance or full-dose challenge, they showed similar success rates in tolerating the drug Therefore, a full-dose challenge could be considered for patients with mild reactions to SMZ-TMP as an alternative to an induction of tolerance procedure Broyles AD,The Journal of Allergy and Clinical Immunology: In Practice. 2020 Oct 1;8(9):S3-15
  35. 35. A standardized temporary induction of tolerance protocol for SMZ-TMP - not currently available, and a range of temporary induction of tolerance protocols - may be appropriate for use with HIV-positive patients For HIV-positive patients with a history of a mild SMZ-TMP hypersensitivity ◦ a full-dose challenge can be considered ◦ may result in higher rates of ADRs than those associated with the temporary induction of tolerance. Management Broyles AD,The Journal of Allergy and Clinical Immunology: In Practice. 2020 Oct 1;8(9):S3-15
  36. 36. Broyles AD,The Journal of Allergy and Clinical Immunology: In Practice. 2020 Oct 1;8(9):S3-15
  37. 37. Broyles AD,The Journal of Allergy and Clinical Immunology: In Practice. 2020 Oct 1;8(9):S3-15
  38. 38. Reported hypersensitivity reactions to NBLAs in children and the results of allergy evaluation Include : NBLA allergy who had skin testing and/or an intravenous or oral challenge test (OCT) ช่วง May 2011 and June 2018 Exclude : > 18 years old or did not complete the allergy evaluation Positive OCT results being highest for trimethoprim-sulfamethoxazole (15 of 46; 32.6%) and macrolides (8 of 77; 10.4%) Grinlington L . Pediatrics. 2020 Jan 1;145(1).
  39. 39. Grinlington L . Pediatrics. 2020 Jan 1;145(1).

×