title: Induction of accelerated reactions to amoxicillin by T-cell effector mechanisms.
abstract: BACKGROUND
  Although allergic drug reactions have been considered to be immediate (IgE mediated) or delayed (T-cell effector mechanisms), accelerated reactions have also been defined; however, they have not been sufficiently studied.
  
  
  OBJECTIVE
  To study the mechanisms involved in accelerated reactions to amoxicillin.
  
  
  METHODS
  We monitored the response in 3 patients who had an accelerated reaction to amoxicillin. A T-cell effector response was searched after a Drug Provocation Test. Symptoms were recorded after initiation of the reaction, and sequential samples were taken at different intervals after challenge. Skin biopsy specimens were also taken, and a lymphocyte transformation test (LTT) was performed.
  
  
  RESULTS
  After the drug provocation test, all 3 patients had a positive response within 2 to 6 hours of drug administration, with full expression at 6 hours, requiring corticoids and antihistamine treatment. They had generalized erythema with facial angioedema but no cardiovascular or respiratory symptoms. Monitoring of the response revealed the presence in the skin of CD4 and CD8 lymphocytes with increased expression of homing and cell activation markers. Immunohistochemistry revealed a perivascular mononuclear cell infiltrate with activated CD4 and CD8 cells expressing perforin and granzyme B. No tryptase release was detected in either the affected tissue or the peripheral blood. The LTT result was positive in all 3 patients.
  
  
  CONCLUSIONS
  We found that accelerated reactions to β-lactams are mediated by effector T cells. The increase in different T-cell markers and a positive LTT result to amoxicillin, in parallel with the occurrence of symptoms after challenge, support this mechanism.
authors.affiliation: Research Laboratory for Allergic Diseases, Carlos Haya Hospital, Malaga, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Gómez
authors.forename: Natalia
authors.initials: N
authors.lastname: Blanca-Lopez
authors.forename: Maria
authors.initials: M
authors.lastname: Salas
authors.forename: Gabriela
authors.initials: G
authors.lastname: Canto
authors.forename: Paloma
authors.initials: P
authors.lastname: Campo
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Torres
authors.forename: Cristobalina
authors.initials: C
authors.lastname: Mayorga
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
mesh_terms: D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012882:Skin Tests; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000658:Amoxicillin