title: Safety and outcomes of test doses for the evaluation of adverse drug reactions: a 5-year retrospective review.
abstract: BACKGROUND
  Graded challenges are the criterion standard for evaluating adverse drug reactions (ADR). Evidence-based guidelines regarding the optimal number of steps for challenges are lacking.
  
  
  OBJECTIVE
  To determine the safety and outcomes of 1- or 2-step test doses among patients with ADRs seen by the allergy/immunology consult service and to compare the outcomes of 1- or 2-step test doses with multistep challenges performed during the same time period.
  
  
  METHODS
  We conducted a retrospective chart review of all 1- or 2-step test doses and multistep challenges at a single academic center between 2008 and 2013. Patient demographics, symptoms of initial ADRs, and outcomes of test doses and multistep challenges were reviewed. ADRs were classified by type and were graded by severity. Outcomes of 1- or 2-step test doses were compared with multistep challenges.
  
  
  RESULTS
  We identified 456 patients who underwent 497 one- or 2-step test doses (mean age, 51 years; 67.5% female patients). The most common drugs that prompted test doses were β-lactams (62%). The majority of patients (n = 444 [89%]) did not experience any ADRs during test doses. ADRs that occurred during test doses (n = 53 [11%]) were most commonly non-immune-mediated (45%) or IgE-mediated (32%), with grade 1 or 2 severity (100%). Forty-nine percent of ADRs during test doses did not receive any treatment. The ADR rate during multistep challenges (10/82 [12%]) was similar to test doses.
  
  
  CONCLUSIONS
  One- or 2-step test doses were safe for evaluation of ADRs. Multistep challenges did not confer added safety. Furthermore, 1- or 2-step test doses did not raise concern for induction of tolerance.
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass. Electronic address: miammatteo@partners.org.
authors.forename: Melissa
authors.initials: M
authors.lastname: Iammatteo
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Kimberly G
authors.initials: KG
authors.lastname: Blumenthal
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Saff
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Aidan A
authors.initials: AA
authors.lastname: Long
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Aleena
authors.initials: A
authors.lastname: Banerji
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D000486:Allergy and Immunology; D001900:Boston; D064907:Diagnostic Uses of Chemicals; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000208:ethnology / Q000276:immunology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000208:ethnology / Q000276:immunology; D005260:Female; D006801:Humans; D007159:Immunologic Tests / Q000379:methods*; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D004364:Pharmaceutical Preparations; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D012882:Skin Tests; D013997:Time Factors
chemical_list: D064907:Diagnostic Uses of Chemicals; D004364:Pharmaceutical Preparations
keywords: Adverse drug reaction; Drug allergy; Drug provocation test; Graded challenge; Hypersensitivity reaction; Test dose