NSAIDs/ASA hypersensitivity diagnostic tests

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NSAIDs/ASA hypersensitivity diagnostic tests

Presented by Theerapan Songnuy, MD.

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  • I like the presentation it is clear and to the point; did you ever do a research or a litterature review on how to give NSAIDs if the pt is already allergic to one of them .. how do you evaluate the allergy and give another NSAID without putting the life in danger?
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NSAIDs/ASA hypersensitivity diagnostic tests

  1. 1. NSAIDs/ASA Hypersensitivity: Diagnostic test Theerapan Songnuy
  2. 2. Outlines• Definition• Epidemiology• Classification and clinical manifestation• Diagnostic tests
  3. 3. NSAID/ASA Hypersensitivity• Unintended and not predictable from the known pharmacology of the drug adverse reaction to NSAIDsJohansson SG. Allergy, 2001;56:813-824.
  4. 4. Epidemiology• NSAIDs/ASA is the 2nd most common cause of drug-induced hypersensitivity reaction*• NSAIDs are responsible for 21-25% of adverse drugs events** including immunological and non-immunological reaction* Gomes ER, Demoly P. Epidemiology of hypersensitivity drugs reactions. Curr Opin Allergy Clin Immunol 2005; 5: 309-316.** Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J et al. Hypersensitivity to nonsterooidal anti-inflammatory drugs ( NSAIDs) – classification, diagnosis and management: review of the EAAC/ENDA and GA2LEN/HANNA. Allergy 2011; 66: 818-829.
  5. 5. Mechanism
  6. 6. Classification of Hypersensitivity reaction to ASA & NSAIDS• Acute ( immediate to several hours after exposure) 1. Rhinitis/ asthma : - cross-reactive - inhibition of COX-1 - underlying; asthma, rhino-sinusitis, nasal polyps 2. Anaphylaxis/ angioedema/urticaria : - single drug-induced - IgE-mediated - underlying; atopy, food or drug allergy
  7. 7. Classification of Hypersensitivity reaction to ASA & NSAIDS• Acute ( immediate to several hours after exposure) 3. Urticaria /angioedema - cross-reactive - inhibit COX-1 - underlying; chronic urticaria 4. Urticaria/ angioedema - multiple NSAIDs-induced - presumably COX-1 inhibition - no underlying disease
  8. 8. Classification of Hypersensitivity reaction to ASA & NSAIDS• Delayed ( more than 24 hours after exposure) - Various clinical manifestations ; fixed drug eruption maculopapular rash bullous lesion contact dermatitis photo contact dermatitis pneumonitis aseptic meningitis nephritis
  9. 9. Classification of Hypersensitivity reaction to ASA & NSAIDS• Delayed ( more than 24 hours after exposure) - T cell-mediated, Cyto-toxic T cells,NK cells - Single drug or multiple drug-induced - No underlying diseaseStevenson DD, Sanchez-Borges M, Szczeklik A. Classification of allergic and pseudoallergic reactionto drugs that inhibit cyclooxygenase enzymes. Ann Allergy Asthma Immunol 2001; 87: 177-180
  10. 10. Clinical Patterns of NSAIDs Reactions• Demographic characteristics of 164 children with suspected hypersensitivity to COX inhibitors Number and sex 164 (102 M, 62 F) Age Mean = 7.2 y ( 7 m-17.3 y) Time between last reaction Mean = 8 m ( 4-20 m) and follow up Familial history of atopy 85 (52%) Personal atopy 102 ( 62%) Previous known exposure to 23 (14%) the suspected drug Suspected allergic reactions to other drugs 60 (37%)EDJ, vol 18, n 5, September-October 2008
  11. 11. Clinical characteristics of 213 suspected allergic reactions to COX inhibitors reported by 164 children• Type and chronology Immediate (≤ 2 h) Accelerated (≤ 48 h) Delayed (> 48 h) Total: n (%) of the reactions Isolated urticaria and/or angioedema 45 69 15 129 (61%) Cutaneous + respiratory symptom 16 7 10 33 ( 15.6%) Anaphylactic shock 18 6 0 24 ( 11.4%) (± skin and/or respiratory symptoms) Isolated rash 6 7 3 16 ( 7.5%) Isolated respiratory symptoms 0 10 0 10 ( 4.3%) (rhinitis, asthma) Isolated conjunctivitis 0 1 0 1 ( 0.5%) Total 85 (40.1%) 100 (46.7%) 28 (13.2%) 213 (100%) EDJ, vol 18, n 5, September-October 2008
  12. 12. Hypersensitivity to nonsteroidal anti‐inflammatory drugs (NSAIDs) – classification, diagnosis and management: review of the EAACI/ENDA# and GA2LEN/HANNA*Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J et al. Hypersensitivity to nonsterooidal anti-inflammatorydrugs ( NSAIDs) – classification, diagnosis and management: review of the EAAC/ENDA and GA2LEN/HANNA. Allergy 2011; 66:818-829.
  13. 13. Oral Provocation Test Clinical characteristics of pt. with NSAID-Induced Cross-Reactive Reaction Challenge R. N Underlying Atopy SBPCOC ( /-)Noso-ocular 8(5.3) rhinitis and/or 69.2% 42/90 asthma ( 100%)Asthma w/wo 18 ( 12)Noso-ocularAngioedema w 14 ( 9.3)Asthma and/or Naso-ocularIsolated angioedema 51 ( 34) rhinitis and/or asthma 100% 58/81 ( 100%)Urticaria/angioedema 59 ( 39.3) chr. Urticaria ( 21.0%) 10.1% 60/135Total 150 76.6% 54% 160/306Quiralte J, Blanco C, Delgado J, Ortega N, Ancantara M, Castillo R, et al. Challenge-Based Clinical Patterns of 223 Spanish Patients With Nonsteroidal Anti-Inflammatory-Drug-Induced- Reactions. J Investig Clin Immunol. 2007; 17(3):182-188.
  14. 14. ASA Provocation Tests• Oral Provocation Test as a gold standard*• Bronchial ( inhalation) L-lysine aspirin challenge - safer, faster, but less sensitive**• Nasal L-ASA challenge - predominantly nasal symptom - contraindicated from oral & bronchial - negative predictive value is lower - negative test should be followed by oral or bronchial challenge test *** * Quiralte J, et al. Allergy 1996;98: 678-685.** Melillo G, et al. Allergy 2001; 56: 899-911.*** Casadevall J, et al. Thorax 2000;55: 921-924.
  15. 15. EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity General considerations 1. Oral challenges have to be carried out under the direct supervision of a physician & technicians skilled in performing provocation tests with aspirin. 2. Emergency resuscitative equipment should be readily available. 3. The patients should be in a stable clinical condition. 4. Baseline FEV1 should be at least 70% of the predicted value for oral challenges with aspirin. Contraindications for oral aspirin challenges: 1. A history of very severe anaphylactic reactions precipitated by aspirin or other NSAIDs (nasal aspirin challenge should be considered in any such case ) 2. Severe disease of the heart, digestive tract, liver, kidney. 3. Infection of respiratory tract within 4 weeks prior to the challenge. 4. Pregnancy. 5. Current treatment with β-receptor blocker.Niżankowska-Mogilnicka E, Bochenek G, Mastalerz L, Świerczyoska M, Picado C,Scadding C, et al. Allergy. 2007;62 ( 10): 1111-1118.
  16. 16. Nasal Provocation Test with ASA 40 20 Pt. Control Nasal Provocation Test L- ASA ( 900 mg/ml) 16/20 37/40 positive positiveAlonso-Liamazares, et al. Allergy 2002; 57: 632-635.
  17. 17. Nasal Provocation Test with ASA• Test sensitivity 80%• Test specificity 92.5%• Positive predictive value 84.2 %• Negative predictive value 89.2 %• N o bronchial or systemic symptom• No decrease over 20% were recorded in the FEV1Alonso-Liamazares, et al. Allergy 2002; 57: 632-635.
  18. 18. The values of nasal provocation test (NPT) and basophil activation test in the different patterns of ASA/NSAID hypersensitivity Wismol P, Putivoranat P, Buranapraditkun S, Pinnobphan P, Ruxrungtham K, Klaewsongkram JAllergol Immunopathol ( Madr). 2012; 40: 156-63. vol.40 num 03
  19. 19. Background• Oral provocation test is the current gold standard*• It’s time-consuming and has some systemic risks• Role of nasal provocation test with l-ASA to diagnose aspirin-induced cutaneous reaction is still unclear.**• A few papers used nasal provocation test to diagnose ASA- induced urticaria.* Genton C. et al. J Allergy Clin Immunol. 1985;76 ( july): 40-5.** Tomaz EM. Et al. Allergy Asthma Proc. 1997; 18 ( October) : 19-22.
  20. 20. Objective• Evaluate the efficacy of the nasal provocation test and the basophil activation test in the diagnosis of various subtypes of ASA hypersensitivity
  21. 21. Materials & Methods• Inclusion criteria: - aged 15-70 y - history of immediate hypersensitivity reaction to ASA/NSIADs at least 2 times - and/or had a nasal provocation test positive - total 30 patients were enrolled
  22. 22. Materials & Methods• Exclusion criteria : - massive nasal polyps - nasal septal perforation - total nasal obstruction of at least one nostril - pregnancy - exacerbation of rhinitis/asthma - URI within 2 Wk prior to the test - nose surgery within 8 Wk prior to the test - severe systemic diseases
  23. 23. Materials & Methods• Normal control : 15 healthy people with no history of ASA/NSAIDs hypersensitivity• Single-blind placebo controlled nasal provocation test• Using 0.9%NaCl to exclude non-specific nasal hyper-reactivity• Using lysine- ASA ( Aspegic, Sanofi-Aventis, France) 80 ul ( total dose 16 mg)• Interpreting with EAACI/GA2LEN guidelines• Nasal symptoms were recorded with 13-point score method• Acoustic rhinometry was used to measure nasal volume• Positive NPT test: - nasal symptoms after challenge - a 25% decrease of total nasal volume at 12 cm from baseline
  24. 24. Materials & Methods• Basophil ActivationTest ( BAT) - 100 ml of pt’s whole blood - incubated with l-ASA at concentrations of 0.31, 1.25, and 5 mg/ml at 37 C. for 40 min - reaction was stopped ( putting on ice) - centrifuged for 5 min at 4 C, 1000 g - add anti-CD203c-PE & anti-IgE fluorescine isothiocyanate-FITC to label basophil - incubated for 30 min at 4 C
  25. 25. Materials & Methods• Erythrocyte were lysed• Using to FACScan flowcytometer analyse at 488nm by CellQuest software.• Double-positive IgE+ and CD203c+ cell were defined as activated basophil Receiver operating characteristic ( ROC) analysis was used to determine the accuracy of BAT to diagnose ASA/NSAIDs hypersensitivity by using different doses of lysine-ASA
  26. 26. Characteristics of patients with a ASA/NSAID sensitivity (n=30). Cutaneous Respiratory predominant (n=15) predominant (n=15)Age (years)/range 44.3 (31–66) 42.1 (16–67)Gender (M/F) 1/14 2/13Underlying diseases- Chronic rhinosinusitis 1 (6.7%) 4 (26.7%)- Nasal polyps 0 (0%) 5 (33.3%)- Asthma 2 (13.3%) 5 (33.3%)- Chronic urticaria 6 (40%) * 1 (6.7%)SPT +ve to aeroallergens 8 (53.3%) 13 (86.7%)Symptom onset after drug exposure (minutes) 92 (5–360) 37 (10–60) *Symptom episodes 3.4 (2–10) 5 (2–25)Multiple NSAID hypersensitivity 5 (33% ) 9 (60%)• = P value < 0.05. Wismol P, et al. Allergol Immunopathol ( Madr). 2012; 40: 156-63. vol.40 num 03
  27. 27. Wismol P, et al. Allergol Immunopathol. 2012;40:156- 63.
  28. 28. Wismol P, et al. Allergol Immunopathol. 2012;40:156- 63.
  29. 29. Wismol P, et al. Allergol Immunopathol.2012;40:156- 63
  30. 30. Wismol P, et al. Allergol Immunopathol.2012;40:156- 63
  31. 31. In conclusion• NPT was able to detect 60% of ASA sensitivity patients both in skin & respiratory symptoms• The combination of using NPT & BAT with l-ASA increases test’s sensitivity• A good method to diagnose ASA/NSAIDs hypersensitivity syndrome - good sensitivity - less side effects - less time- consuming
  32. 32. Thank you verymuch

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