NSAIDs hypersensitivity
•Als PPTX, PDF herunterladen•
6 gefällt mir•1,308 views
NSAIDs hypersensitivity Presented by Athit Wutthisanwatthana, MD. November23, 2018
Empfohlen
Empfohlen
Weitere ähnliche Inhalte
Was ist angesagt?
Was ist angesagt? (20)
Ähnlich wie NSAIDs hypersensitivity
Ähnlich wie NSAIDs hypersensitivity (20)
Mehr von Chulalongkorn Allergy and Clinical Immunology Research Group
Mehr von Chulalongkorn Allergy and Clinical Immunology Research Group (20)
Kürzlich hochgeladen
Kürzlich hochgeladen (20)
NSAIDs hypersensitivity
- 2. Outline • Chemical structures of NSAIDs • Arachidonic acid metabolism • Definition and classification • NSAID-exacerbated cutaneous disease (NECD) • NSAID-induced urticaria/angioedema (NIUA) • Single-NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA) • Single-NSAID-induced delayed reactions (SNIDR) • Diagnostic algorithm
- 3. Chemical Structure of NSAIDs • Salicylic acid derivates • Para-aminophenol • Propionic acid derivates • Acetic acid derivatives • Enolic acid derivatives • Fenamic acid derivatives (fenamates) • Selective COX-2 inhibitors (Coxibs) Kowalski ML, Asero R, Bavbek S, Blanca M, Lopez B, Bochenek G, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68:1219-32
- 4. Salicylic Acid Derivates • Aspirin • Sodium salicylate • Salsalate • Diflunisal • Salsalate • Sulfasalazine
- 6. Propionic Acid Derivates • Ibuprofen • Naproxen • Fenoprofen • Fluriprofen • Ketoprofen • Oxaprozin
- 7. Acetic Acid Derivatives • Diclofenac • Etodolac • Ketorolac • Indomethacin • Sulindac • Tolmetin • Nabumetone
- 8. Enolic Acid Derivatives • Pyrazolones • Phenylbutazone • Dipirone • Oxicams • Piroxicam • Meloxicam • Tenoxicam • Lornoxicam
- 9. Fenamic Acid • Mefenamic acid • Meclofenamic acid • Flufenamic acid • Tolfenamic acid
- 10. Selective COX-2 Inhibitors • Celecoxib • Etoricoxib • Rofecoxib • Valdecoxib • Product: Parecoxib
- 11. Kumar V, Abbas AK, Aster JC. Robbins & Cotran pathologic basis of disease. 9th edition. Philadelphia; Elsevier Saunders; 2010
- 12. Hanna VS, Hafez EAA. Sypnosis of arachidonic acid metabolism: a review. J Adv Res. 2018 Mar 13;11:23-32
- 13. Hanna VS, Hafez EAA. Sypnosis of arachidonic acid metabolism: a review. J Adv Res. 2018 Mar 13;11:23-32
- 14. The biochemical selectivity of cyclooxygenase inhibitors in whole blood assays of COX-isozyme activity in vitro Kumar V, Abbas AK, Aster JC. Robbins & Cotran pathologic basis of disease. 9th edition. Philadelphia; Elsevier Saunders; 2010
- 15. NSAIDs Hypersensitivity • Type B adverse drug reaction (WHO, 1972) • EAACI/WAO nomenclature • Allergic (immunologically mediated) • Nonallergic
- 16. Park HS, Kowalski ML, Borges MS. Hypersensitivity to aspirin and other nonsteroidal antiinflammatory drugs. In: Adkinson NF, Jr, Bocher BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al. Middleton’s allergy principles and practice. Philadelphia; Elsevier Saunders; 2014. 1296-307.
- 17. Kowalski ML, Asero R, Bavbek S, Blanca M, Lopez B, Bochenek G, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68:1219-32 Novel Classification of Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs
- 18. Epidemiology • Second highest after antibiotics • 0.6-5.7% • NERD • 4.3-20% • Higher prevalence in CRS with nasal polyps, severe asthma, female • Associated with atopy • NECD and NIUA • 10-30% in chronic urticaria
- 20. Clinical Manifestation • Urticaria/angioedema after 0.5-6 h of ingestion • 15 min – 24 h • Persists few hours to several days • Magnitude of symptoms • Dose dependent • Disease status
- 21. Pathomechanisms • Not immunologically mediated • Cross-react only with COX-1 inhibitors • Mechanism similar to AERD • ↓Prostaglandin production • ↑Cysteinyl leukotrienes • Support by release of same eicosanoids in AERD
- 22. Diagnosis • Oral provocation is gold standard (grade of recommendation D) • Unclear history • Definite diagnosis required • Balance risk/benefit • +alternative NSAIDs, aspirin (grade of recommendation C) • Skin tests has no diagnostic value (grade of recommendation D) • Basophil activation test have limited diagnostic value with low negative predictive value (grade of recommendation D)
- 23. Diagnosis • Provocation protocol (grade of recommendation D) • Start 1/10 • Increase 2x-3x every 2 h • Until symptoms or single therapeutic dose
- 24. Oral Provocation Test EAACI/GA2LEN • After 1-2 weeks without skin eruptions • First day • 4 capsules of placebo • Second day • Aspirin 71, 117, 312, 500 mg • 1.5-2 h interval Nizankowska-Mogilnicka E, Bochenek G, Mastelerz L, Swierczynska M, Picado C, Scadding G, et al. EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity. Allergy. 2007;98;174-4
- 25. Management: Avoidance Kolwakski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management; review of the EAACI/ENDA and GA2LEN/HANNA. Allergy. 2011;66:818-29
- 26. Kolwakski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management; review of the EAACI/ENDA and GA2LEN/HANNA. Allergy. 2011;66:818-29
- 27. Kolwakski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management; review of the EAACI/ENDA and GA2LEN/HANNA. Allergy. 2011;66:818-29
- 28. Management: Urticaria • According to guidelines • Add on leucotriene receptor antagonists may benefit
- 29. Desensitization • Controversial • Limited number of studies
- 31. Clinical Manifestation • Onset usually within 1 h • Range 15 min– several hours • Drugs culprits • Almost: aspirin, strong COX-1 inhibitors • Weak COX-1 inhibitors in 25% (esp. high doses)
- 32. Pathomechanisms • Unknown • IgE-mediated unlikely – different structure • Inhibition of COX-1
- 33. Underlying Disease • 79% no underlying chronic skin disease • 37% developed chronic urticaria
- 34. Diagnosis • History of reactions to ≥2 NSAIDs • Oral provocation test if equivocal history (grade of recommendation D) • If aspirin is culprit, choose alternative strong COX-1 inhibitor to confirm/exclude cross-reactivity (grade of recommendation C) • Skin test and in vitro have no diagnostic value (grade of recommendation D) • Not relevant • To exclude single drug reaction
- 35. Management • Avoidance of culprit NSAIDs + strong COX-1 inhibitors (grade of recommendation C) • Recommend weak COX-1 inhibitors (grade of recommendation C) • Perform oral tolerance tests (grade of recommendation D) • 80% tolerate paracetamol and nimesulide
- 37. Single-NSAID-Induced Urticaria/Angioedema or Anaphylaxis • Urticaria, angioedema, anaphylaxis induced by a single NSAID or a group of closely chemically related compounds • Most are case report
- 38. Drugs • Pyrazolones • Paracetamol • Ibuprofen • Diclofenac • Naproxen • Frequently cause anaphylaxis • Pyrazolones • Diclofenac • Ibuprofen Kolwakski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management; review of the EAACI/ENDA and GA2LEN/HANNA. Allergy. 2011;66:818-29
- 39. Clinical Manifestations • Generalized urticaria, angioedema • Generalized pruritus • Rhinitis • Bronchospasm • Anaphylactic shock 18-30% in pyrazolones • Onset usually shorter (seconds to minutes) • Most within 1 h
- 40. Underlying Disease • May precede chronic urticaria (30%) • Higher atopic background • Pyrazolones (78%) • Others (86%)
- 41. Pathomechanisms • IgE-mediated reaction • Spectrum and timing • Specific IgE detected in skin test, serum, peripheral blood basophils • Significant proportion of positive skin test in pyrazolones • Associated with HLA-DQ and HLA-DR in pyrazolones
- 42. Diagnosis • History of immediate symptoms by a single NSAID • Provocation test • Controversial • Oral challenge with aspirin and other NSAIDs to exclude cross-reactive (grade of recommendation D) • Skin test (grade of recommendation C) • Progressive loss of sensitivity to skin testing with time • Specific IgE not recommended (grade of recommendation C)
- 43. Management • Safely take other chemically unrelated NSAIDs • +/- oral challenge • Desensitization not documented
- 45. Clinical Presentation • More than 24 h after exposure • Several days or weeks • Fixed drug eruption • Maculopapular eruption • Delayed urticaria • Acute generalized exanthematous pustulosis • Stevens-Johnson syndrome/toxic epidermal necrolysis • Contact and photocontact dermatitis
- 46. Clinical Manifestation • Pneumonitis • Aseptic meningitis • Nephritis
- 47. Clinical Manifestation • Fixed drugs eruption • 10% of all drug eruption • NSAIDs among the most common causes • Drugs • Pyrazolones Piroxicam Phenylbutazone • Paracetamol Aspirin Mefenamic acid • Diclofenac Indomethacin Ibuprofen • Diflunisal Naproxen Nimesulide
- 48. Clinical Manifestation • Severe bullous cutaneous reaction • SJS, TEN • 1-8 week-onset • Drugs • Oxicams Phenylbutazone Oxyphenbutazone • COX-2 • DRESS • Reported with celecoxib and ibuprofen
- 49. Clinical Manifestation • Meculopapular eruptions • Among the most common • Drugs • Ibuprofen Pyrazolones Flurbiprofen • Diclofenac Celecoxib • Pneumonitis • Sulinac Ibuprofen Naproxen
- 50. Clinical Manifestation • Aseptic meningitis • Ibuprofen, sulindac, naproxen, tolmetin, diclofenac, ketoprofen, piroxicam, indomethacin, rofecoxib, celecoxib • Pathomechanism • Not known • Not related to prostaglandin inhibition • Nephritis • AKI (presume AIN), proteinuria, nephrotic syndrome • Onset 2-3 weeks • Minimal change disease, membranous GN, FSGS • 50% blood eosinophilia
- 51. Clinical Manifestation • Nephritis • Immunologically mediated interstitial nephritis • AKI, proteinuria, nephrotic syndrome • Onset 2-3 weeks • Minimal change disease, membranous GN, FSGS • 50% blood eosinophilia • Both COX-1 and COX-2 inhibitors
- 52. Clinical Manifestation • Contact and photocontact dermatitis • Diclofenac, indomethacin, flurbiprofen, bufexamac, etofenamate, flufenamic acid, ibuprofen, ketoprofen, tiaprofenic acid • Cross-reactivity • May develop severe cutaneous reaction with systemic use = systemic contact dermatitis
- 53. Diagnosis • Mainly clinical history • Patch tests • Contact dermatitis • Fixed drug eruption (‘in loco patch testing’) • Photopatch tests • Photoallergic reactions • Patch testing and delayed reading of intradermal reading • Low sensitivity, high specificity
- 54. Diagnosis • Provocation test (grade of recommendation C) • Maculopapular eruptions • Urticaria • Fixed drugs eruptions • Contraindicated in (grade of recommendation C) • Bullous drug eruption i.e. SJS, TEN, AGEP • Organ specific reactions • Can perform alternative NSAIDs (grade of recommendation D) • Lymphocyte transformation test (grade of recommendation D)
- 55. Algorithm for the Diagnosis of Acute Forms of Nonsteroidal Anti-Inflammatory Drugs Hypersensitivity Kowalski ML, Asero R, Bavbek S, Blanca M, Lopez B, Bochenek G, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68:1219-32
- 56. Provocation Challenges in Patients with a History of Acute Reactions to Nonsteroidal Anti-Inflammatory Drugs Kowalski ML, Asero R, Bavbek S, Blanca M, Lopez B, Bochenek G, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68:1219-32
- 57. Diagnostic Procedure in Delayed Type of Hypersensitivity to NSAIDs Kowalski ML, Asero R, Bavbek S, Blanca M, Lopez B, Bochenek G, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68:1219-32