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  • 1. WHAT YOU SHOULD HAVE READ BUT….2010
    • drug allergy
    University of Verona, Italy Attilio Boner
  • 2. Cefaclor anaphylaxis in children Novembre Allergy 2009:64:1233 5.1% In Children with Anaphylaxis 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 13/253 10 –
    • 253 children (3-14 years)
    • with immediate reactions to β-lactams.
  • 3. Cefaclor anaphylaxis in children Novembre Allergy 2009:64:1233 8 N° of Children with Anaphylaxis (N=13) 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 10 – 1 2 2 CEFACLOR CEFTRIAXONE AMOXICILLIN BENZYL- PENICILLIN
    • 253 children (3-14 years)
    • with immediate reactions to β-lactams.
  • 4. Cefaclor anaphylaxis in children Novembre Allergy 2009:64:1233 8 N° of Children with Anaphylaxis (N=13) 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 10 – 1 2 2 CEFACLOR CEFTRIAXONE AMOXICILLIN BENZYL- PENICILLIN
    • 253 children (3-14 years)
    • with immediate reactions to β-lactams.
    The 8 children with cefaclor-induced anaphylaxis, all experienced symptoms within 30 min after cefaclor ingestion.
  • 5. Cefaclor anaphylaxis in children Novembre Allergy 2009:64:1233 Amoxicillin at concentrations of 2 and 20 mg/ml in normal saline for both prick and intradermal tests , cefaclor at concentrations of 2 and 50 mg/ml in normal saline for prick testing , and 2 mg/ml for intradermal one. We prepared cefaclor sterile solutions no more than 2 h before testing, using the powder obtained from a capsule, as previously described. (Romano A, Clin Exp Allergy 2005;35:1234–1242) When prick tests were negative, 0.02 ml of the reagent solution was injected intradermally on volar forearm skin . Readings were made 20 min after injections. Results were considered positive when an increase larger than 3 mm in the initial wheal diameter accompanied by erythema was present.
  • 6. 7.6% (9/118) % of patient with a non-immediate reaction
    • Provocation tests with
    • beta-lactams are included in the diagnostic algorithms for immediate and non-immediate
    • hypersensitivity reactions
    • Immediate reactions are those occurring within the first hour
    • Non-immediate reactions occur more than one hour after the last drug administration
    • 118 patients with an initial negative provocation test repeated the challenge at least 6 mo later
    10 – 5 – 0 Determining the negative predictive value of provocation tests with beta-lactams P. Demoly , Allergy 2010:65;327
  • 7. 7.6% (9/118) % of patient with a non-immediate reaction
    • Provocation tests with
    • beta-lactams are included in the diagnostic algorithms for immediate and non-immediate
    • hypersensitivity reactions
    • Immediate reactions are those occurring within the first hour
    • Non-immediate reactions occur more than one hour after the last drug administration
    • 118 patients with an initial negative provocation test repeated the challenge at least 6 mo later
    10 – 5 – 0 Determining the negative predictive value of provocation tests with beta-lactams P. Demoly , Allergy 2010:65;327 Only 4 accepted a re-challenge, negative in 2 cases and positive in the 2 others
  • 8. 7.6% (9/118) % of patient with a non-immediate reaction
    • Provocation tests with
    • beta-lactams are included in the diagnostic algorithms for immediate and non-immediate
    • hypersensitivity reactions
    • Immediate reactions are those occurring within the first hour
    • Non-immediate reactions occur more than one hour after the last drug administration
    • 118 patients with an initial negative provocation test repeated the challenge at least 6 mo later
    10 – 5 – 0 Determining the negative predictive value of provocation tests with beta-lactams P. Demoly , Allergy 2010:65;327 The negative predictive value was 94.1% (111 out of 118 patients)
  • 9. Resting basophils do not express CD63 (anchored in the basophilic granule) and weakly express CD203c. The cross-linking of two FcεRI (induced by an allergen or anti-IgE antibodies) provokes the histamine release (and as a consequence the CD63 expression ) and the upregulation of CD203c. The rise in CD63 or CD203c expression (measured by fluorescence 2 / Phycoerythrin) before and after allergen challenge reflects thus the basophil activation / degranulation in response to an allergen. basophil activation test by flow cytometry * *
  • 10.
    • IgE-mediated allergy to quinolones (Q) is rare and its diagnosis is hampered by the lack of sensitive in vivo or in vitro assays;
    • Skin tests have an as yet unknown sensitivity because
    • of the high incidence of false-positive results, probably
    • related to direct quinolone-induced histamine release by mast cells.
    Usefulness of basophil activation test for the diagnosis of IgE-mediated allergy to quinolones B. Ben Said, Allergy 2010;65;535
  • 11.
    • 5 patients with a clinical history of immediate hypersensitivity (IHS) to Quinolones (Q);
    • They all developed an anaphylactic reaction 5–45 min following the first taking of one tablet of levofloxacin, ofloxacin or moxifloxacin;
    • Skin tests were performed using prick tests (5 mg/ml) and intradermal tests (IDT) (5 mcg/ml). Skin tests were positive in the five patients, confirming the diagnosis of immediate allergic HS.
    Usefulness of basophil activation test for the diagnosis of IgE-mediated allergy to quinolones B. Ben Said, Allergy 2010;65;535
  • 12.
    • The basophil activation test (BAT) analyzing by FACS the expression of CD203c on the patient’s basophils was carried out on patient’s blood. The results are expressed as % of basophils expressing CD203c after in vitro re-stimulation with Q compared to this % without in vitro restimulation;
    • Basophil activation test to the culprit Q was strongly positive in the five patients.
    • Indeed, 70–83% of basophils expressed CD203c upon Q exposure compared to a control expression ranging from 1% to 2%.
    Usefulness of basophil activation test for the diagnosis of IgE-mediated allergy to quinolones B. Ben Said, Allergy 2010;65;535
  • 13. Immunogloblin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Gómez C EA 2010;39:1217
    • N on-steroidal anti-inflammatory drugs (NSAIDs) are among the most common cause of adverse drug reactions (asthma and urticaria, anaphylaxis).
    • The mechanism involved in urticaria and asthma is based on the inhibition of cyclooxygenase-1 enzymes . This diminishes the synthesis of prostaglandin E2, leading to an exacerbated production of leukotrienes and cross-intolerance with other NSAIDs.
    • Alternatively, patients with hypersensitivity reactions to NSAIDs can react to just one drug and have good tolerance to other NSAIDs from the same group or from different groups. In these selective responders, an IgE mechanism has been proposed . Pyrazolones are the most frequent drug involved in this category.
  • 14. Immunogloblin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Gómez C EA 2010;39:1217 Background: Pyrazolones are a major cause of immediate IgE-mediated reactions to drugs in many countries. Objective: The aim of the study was to evaluate a group of patients with this type of reaction by basophil activation test (BAT), focusing on the influence of the time since the reaction on the rate of positive results.
  • 15. Immunogloblin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Gómez C EA 2010;39:1217
    • 51 patients with selective immediate allergic reactions to pyrazolones and 56 controls.
    • Skin testing using metamizol 0.1 mg/mL (Boehringer Ingelheim)
    85.7% % Patients with (+) SPTs 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 100 –
  • 16. Immunogloblin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Gómez C EA 2010;39:1217
    • 51 patients with selective immediate allergic reactions to pyrazolones and 56 controls.
    • Skin testing using metamizol 0.1 mg/mL (Boehringer Ingelheim)
    Comparison of the basophil activation test with dipyrone at two concentrations in patients who were skin-test positive or negative to dipyrone.
  • 17. Immunogloblin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Gómez C EA 2010;39:1217
    • 51 patients with selective immediate allergic reactions to pyrazolones and 56 controls.
    • Skin testing using metamizol 0.1 mg/mL (Boehringer Ingelheim)
      Basophil activation test survival analysis over a 30-month period
  • 18. Immunogloblin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Gómez C EA 2010;39:1217
    • 51 patients with selective immediate allergic reactions to pyrazolones and 56 controls.
    • Skin testing using metamizol 0.1 mg/mL (Boehringer Ingelheim)
      Basophil activation test survival analysis over a 30-month period Follow-up of the BAT-positive patients showed a decrease over time, with 60% of these patients becoming negative after 6 months.
  • 19. Immunogloblin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Gómez C EA 2010;39:1217
    • 51 patients with selective immediate allergic reactions to pyrazolones and 56 controls.
    • Skin testing using metamizol 0.1 mg/mL (Boehringer Ingelheim)
      Basophil activation test survival analysis over a 30-month period The time of performance of the test is critical to obtain a positive response.
  • 20.
    • A case of anaphylactic shock reaction due to intravenous methylprednisolone (MP);
    • Skin tests were positive for MP according to the prick test (10 mg/ml) and the IDT (positive at 100 and 10 mcg/ml);
    • The BAT analyses, by flow cytometry, the percentage of polynuclear basophils expressing CD203c after in vitro MP re-stimulation compared with the percentage of basophils expressing CD203c without re-stimulation.
    • was positive at 71% (control 2%);
    Methylprednisolone-induced anaphylaxis: diagnosis by skin test and basophil activation test B. Ben Said, Allergy 2010;65;531
  • 21.
    • In a corticoid battery of skin tests and found a positive cross-reaction with hydrocortisone , while the prick and IDT tests were negative for prednisone;
    • The patient was challenged with prednisone in intensive care unit without allergic reaction;
    • Flow cytometry is a reliable tool for monitoring basophil activation upon allergen challenge by detecting membrane expression of degranulation/activation markers (CD63 or CD203c);
    • BAT seems to be a reliable tool for the diagnosis of IgE mediated allergy to betalactams or muscles relaxants (curare).
    Methylprednisolone-induced anaphylaxis: diagnosis by skin test and basophil activation test B. Ben Said, Allergy 2010;65;531
  • 22.
    • Il Cefaclor è il beta-lattamico che induce più facilmente anafilassi,
    • Il test di attivazione dei basofili può essere utilizzato per la diagnostica in vitro dell’allergia ai farmaci,
    • Nel sospetto di reazione allergica al farmaco il paziente va studiato prontamente, a distanza di tempo il test potrebbe risultare falsan+mente negativo.
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