title: Role of Histamine Release Test for the Evaluation of Patients with Immediate Hypersensitivity Reactions to Clavulanic Acid.
abstract: BACKGROUND
  Immediate hypersensitivity reactions to clavulanic acid (CLV) seem to be on the increase. Diagnosis is mainly based on skin testing and the drug provocation test (DPT), procedures that are not risk free. The aim of this study was to evaluate whether the histamine release test (HRT) could help evaluate patients with selective hypersensitivity to CLV.
  
  
  METHODS
  Eighteen patients with immediate selective hypersensitivity reactions to CLV (positive skin tests to CLV but negative to the major and minor determinants of benzylpenicillin and amoxicillin; negative DPT to benzylpenicillin and amoxicillin) and 21 controls with tolerance to CLV were included. Direct and passive HRT, using patient whole blood or 'IgE-stripped' donor blood sensitized by patient serum, respectively, were performed by stimulating the blood with CLV, and basophil histamine release was detected by fluorometric determination.
  
  
  RESULTS
  The clinical symptoms were anaphylaxis (n = 6), urticaria (n = 9) and urticaria-angioedema (n = 3). The median time interval between the reaction and the study was 225 days (interquartile range, IQR: 120-387.5) and between drug intake and the development of symptoms 30 min (IQR: 6.25-30). We obtained similar data for both the direct and passive HRT, with a sensitivity and specificity of 55 and 85%, respectively, a positive predictive value of 76% and a negative predictive value of 69%.
  
  
  CONCLUSIONS
  The sensitivity of both the direct and passive HRT for diagnosing patients with immediate allergy to CLV is less than 60%. However, the passive HRT has the advantage that it is based on the testing of serum samples that can be handled more easily than fresh blood samples.
authors.affiliation: DIATER Laboratories, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pineda
authors.forename: Adriana
authors.initials: A
authors.lastname: Ariza
authors.forename: Cristobalina
authors.initials: C
authors.lastname: Mayorga
authors.forename: Francisca
authors.initials: F
authors.lastname: Arribas
authors.forename: Rosario
authors.initials: R
authors.lastname: González-Mendiola
authors.forename: Natalia
authors.initials: N
authors.lastname: Blanca-López
authors.forename: Galicia
authors.initials: G
authors.lastname: Davila
authors.forename: Nieves
authors.initials: N
authors.lastname: Cabañes
authors.forename: Gabriela
authors.initials: G
authors.lastname: Canto
authors.forename: José Julio
authors.initials: JJ
authors.lastname: Laguna
authors.forename: Carlos
authors.initials: C
authors.lastname: Senent
authors.forename: Per
authors.initials: P
authors.lastname: Stahl-Skov
authors.forename: Ricardo
authors.initials: R
authors.lastname: Palacios
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
authors.forename: María José
authors.initials: MJ
authors.lastname: Torres
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000139:chemically induced / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D000799:Angioedema / Q000139:chemically induced / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001681:Biological Assay; D016022:Case-Control Studies; D019818:Clavulanic Acid / Q000009:adverse effects*; D005260:Female; D006636:Histamine Release; D006801:Humans; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods*; D012680:Sensitivity and Specificity; D012882:Skin Tests; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D019818:Clavulanic Acid