Hypersensitivity Reactions to Contrast Media : - New concepts - Practical implications - Comparison of guidelines

Transcription

1 Hypersensitivity Reactions to Contrast Media : - New concepts - Practical implications - Comparison of guidelines Olivier Clément, MD, PhD Hôpital Européen Georges Pompidou Paris, France

2 Conflicts of Interest Teaching seminars with Bracco, Guerbet

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4 Classification of Adverse Reactions to Iodinated and Gadolinium-based CM Immediate (Acute) Occur within 1-2 hours following CM injections Delayed Occur 1-2 hours to 7 days after exposure to CM Morcos & Thomsen. Eur Radiol. 2001;11: Yasuda et al. Invest Radiol 1998;33:1. Christiansen et al. Eur Radiol 2000;10:1965. Yoshikawa H. Radiology 1992;183:737. Webb et al. Eur Radiol 2003;13:181.

5 Iodinated Contrast Media Non Ionic Monomer Iobitridol Xenetix Iohexol Omnipaque Iopentol Ivepaque Iopamidol Iopamiron Iopromide Ultravist Ioversol Optiray Iomeprol Iomeron

6 Non-Specific MRI CM HOOC COOH N N Gd N N HOOC COOH HOOC N N N HOOC Gd COOH DOTA (Dotarem ) DTPA (Magnevist ) COOH COOH HOOC N N Gd COOH H O O 3 C CH 3 N C C N H N N N H N N HOOC OH HOOC C CH 3 Gd COOH COOH HP-DO3A (ProHance ) DTPA-BMA (Omniscan )

7 Mild (up to 3% of patients) Signs and symptoms are self-limited without evidence of progression Nausea, vomiting Cough Warmth Headache Dizziness Shaking Altered taste Itching Pallor Flushing Chills Sweats Rash, hives Nasal stuffiness Swelling; eyes, face Anxiety usually no treatment ACR Manual on Contrast Media, Version 7; 2010.

8 Moderate (up to 0.5% of patients) Signs and symptoms are more pronounced Tachycardia/bradycardia Hypertension Generalized or diffuse erythema Dyspnea Bronchospasm, wheezing Laryngeal edema Mild hypotension Treatment ACR Manual on Contrast Media, Version 7; 2010.

9 Severe (0.04% (1/2,500) of patients) Signs and symptoms are often life-threatening Laryngeal edema (severe or rapidly progressing) Unresponsiveness Cardiopulmonary arrest Convulsions Profound hypotension Clinically manifest arrhythmias Hospitalisation Fatal reactions: < % (<1/200,000) of patients ACR Manual on Contrast Media, Version 7; 2010.

10 RING and MESSMER Classification Hypersensitivity Reactions Grades I II III IV Symptoms Cutaneous Mucosa: erythema, urticaria, angioedema Moderate multivisceral cutaneous hypotension tachycardia cough, dyspnea digestive signs Severe mono- or multivisceral signs: cardiovascular collapse, tachycardia or bradycardia arrythmia bronchospasm digestive signs Cardiac Arrest

11 RING and MESSMER Classification Hypersensitivity Reactions Specific for Hypersensitivity symptoms Usefull for treatment

12 ADVERSE REACTIONS Acute Adverse Reactions Allergy-like = Hypersensitivity Physiologic / Chemotoxic / osmotic Mild urticaria Mild itching Erythema Marked urticaria Mild Bronchospasm Facial Laryngeal edema Hypotensive shock Respiratory arrest Cardiac arrest Nausea vomiting Warmth chills Vasovagal Severe vomiting Vasovagal attack Arrythmia Convulsion

13 EAACI Nomenclature Task Force Acute Adverse Reactions Hypersensitivity Chemotoxic / osmotic Allergic Hypersensitivity (immunologic mechanism defined or strongly suspected) Nonallergic Hypersensitivity (immunologic mechanism excluded) Johansson SGO et al. Allergy. 2001;56:

14 Published Clinical Cases of Allergic Hypersensitivity to ICM Study/Reference (n) Contrast Agent Reaction Grade Reaction Occurrence (minute) Histamine Tryptase Cutaneous Test Kanny et al. 1 diatrizoate ioxitalamate IV? NF NF IDR with diatrizoate and ioxitalamate Brockow et al. 1 iopamidol IV death immediate NF Alvarez-Fernandez et al. 1 ioversal II immediate NF NF PT + ioversal Dewachter & Mouton-Faivre 5 ioxaglate ioxaglate ioxaglate iopromide iopentol III III IV death III III 30 immediate NF NF > NF NF 36 > IDR ioxaglate IDR ioxaglate - IDR iopromide IDR iopentol Valfrey et al. 2 ioxaglate Dewachter Clément ioxaglate III III 10 immediate 38 I to IV immediate Yes Yes Yes NF NF NF NF PT + ioxaglate IDR ioxaglate PT + ioxaglate IDR ioxaglate Dewachter et al. Ann. Fr. Anesth. Réanim. 2005; 24: 40-52

15 Published Clinical Cases of Allergic Hypersensitivity to GBCA Hasdenteufel, 2008, J Allergy Cl Immunol. 2 cases DOTA-Gd with skin tests Girard, 2010, Vet Anaesth Analg. 3 dogs Galera, Allergy in press, DOI review

16 Diagnostic ALLERGIC Hypersentivity Severe reaction Elevated tryptase Positive skin tests Non-Allergic Hypersensitivity Less severe Low tryptase Negative skin tests

17 1st Argument in Favor of HYPERSENSITIVITY: Clinical Symptoms - Ring and Messmer Grades I II III IV Symptoms Cutaneous Mucosa: erythema, urticaria, angioedema Moderate multivisceral cutaneous hypotension tachycardia cough, dyspnea digestive signs Severe mono- or multivisceral signs: cardiovascular collapse, tachycardia or bradycardia arrythmia bronchospasm digestive signs Cardiac Arrest Grade 1 Ring J & Messmer K. Lancet. 1977;26;1(8009):466-9.

18 2nd Argument in Favor of Hypersensitivy: Biology Mediator Release Histamine: basophils & mast cells Tryptase: mast cells IgE specific : test does not exist Non-allergic hypersensitivity: histamine or normal Allergic hypersensitivity: histamine AND tryptase Laroche D et al, Radiology 1998;209: Mita H et al. Allergy 1998;53:

19 Hypersensitivity Reactions IgE-dependent Antigen Non-specific Toxicity Basophil Mast cell Basophil Histamine Histamine Tryptase Histamine Dewachter. Rev Med Interne 2009;30:

20 Kinetics Histamine (nmol/l) 1000 Tryptase (µg/l) Delay (min) Controls: < 5.3 nmol/l 1 Grade 4 Grade 3 Grade 2 Grade Delay (min) Controls: < 2 µg/l Laroche D et al, Radiology 1998;209:

21 3rd Argument in Favor of Hypersensitivity: Cutaneous Tests Delay > 4 weeks post reaction Reproduces at the minimum reaction on the skin Read at 20 min Confirm immunologic mechanism: Y or N Confirm responsibility of the injected contrast: Y or N Look for cross reactivity Brockow, Allergy 2009;64:

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25 Example: Allergic Reaction CT Scanner with iohexol, 2 previous with iobitridol without reaction Severe shock: ICU with adrenalin No history of allergy

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27 Non-Specific MRI CM HOOC COOH N N Gd N N HOOC COOH HOOC N N N HOOC Gd COOH DOTA (Dotarem ) DTPA (Magnevist ) COOH COOH HOOC N N Gd COOH H O O 3 C CH 3 N C C N H N N N H N N HOOC OH HOOC C CH 3 Gd COOH COOH HP-DO3A (ProHance ) DTPA-BMA (Omniscan )

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30 Dealing With a Reaction TREAT the patient EXPLORE the patient for FUTURE examinations Blood sampling - 2 tubes (histamine and tryptase) Allergologic testing 6 weeks later

31 Centers Lille Brest Cherbourg Rouen Caen Rennes Paris 3 Amiens Reims Strasbourg Nancy Colmar Angers Nantes Tours Dijon Besançon Lyon 2 Saint-Etienne Grenoble Bordeaux Toulouse Nîmes Nice Montpellier Martigues Marseille 2

32 Cirtaci Study Remplissage Dossier allergie allergy ( INCLUSION Inclusion 6 semaines weeks to à 66 months mois après after the la réaction reaction Allergic reaction Treatment Histamine Tryptase D0 H0 D0 H2 D1 H24 Contact Regional Investigator Consultation Regional investigator Consultation Allergology Skin tests Photos Conclusion Pharmaco vigilance Laroche D, et al.. Contrast Med Mol Imaging. 2005;1:81

33 Blood Tests Kits Laboratory Sheet H0 2 tubes H2 2 tubes

34 Percent Percent of Specific Reactions Initial Consensus G1 G2 G3 G4 Reaction Grade

35 Risk Factors History of: Prior reaction to CM Severe allergies (requiring medical treatment) Allergy to shellfish is not a risk factor Asthma (usually with bronchospasm) Hypersensitivity to drugs or chemicals Treatment with beta-blockers For hypersensitivity reactions, but is it for ALLERGIC HR? NON-ALLERGIC HR?

36 LITERATURE and GUIDELINES Acute Adverse Reactions Allergy-like = Hypersensitivity Physiologic / osmotic

37 LITERATURE and GUIDELINES Acute Adverse Reactions Allergy-like = Hypersensitivity Physiologic / osmotic Physiologic reactions to ICM likely relate to specific molecular attributes that lead to direct chemotoxicity, osmotoxicity Cardiac arrhythmias, depressed myocardial contractility, cardiogenic pulmonary edema, vaso vagual seizures Physiologic reactions are frequently dose and concentration dependent

38 ACR guideline : Allergy like reactions The pathogenesis of most allergic-like reactions is unclear. There are multiple possible mechanisms that result in activation of immunologic effectors [14]. It is believed that some allergic-like contrast reactions may involve activation, deactivation, or inhibition of a variety of vasoactive substances or mediators (such as histamine, complement, and the kinin system) [3,12-15]. ICM are known to directly cause histamine release from basophils and mast cells [9]. Histamine release must have occurred when patients develop urticaria, but the precise cause and pathway of histamine release are not known [3,12,13]. Skin and intradermal testing are positive in a minority of individuals, indicating that an allergic IgE-mediated etiology may be responsible for some reactions [16], but this is the minority of cases

39 Spanish allergologists : JACI 2016

40 Diagnostic Algorithm

41 CIRTACI : French Society of Radiology

42 Australian Guideline Confirmation of Anaphylactic Reaction After a suspected anaphylactic reaction, timed blood samples for mast cell tryptase testing,should be considered and performed as follows: (a) The largest SST tube available should be used. (b) A sample should be taken as soon as possible after emergency treatment has started. (c) A second sample ideally within 1-2 hours (but no later than 4 hours) from the onset of symptoms should also be collected. Reference NICE Guidelines: Anaphylaxis: assessment to confirm an anaphylactic episode and the decision to refer after emergency treatment for a suspected anaphylactic episode

43 SUMMARY EXPLORE HYPERSENSITIVITY REACTIONS Blood sampling (tryptase, histamin) Clinical score (Ring and Messmer) Skin tests Try to identify the culprit CM, which should be contraindicated for life Identify cross reactivity > Necessitates Drug Allergy Consultations