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Allergologia e Immunologia Clinica Ospedale Nuovo San Giovanni di - - PowerPoint PPT Presentation
Allergologia e Immunologia Clinica Ospedale Nuovo San Giovanni di - - PowerPoint PPT Presentation
Allergologia e Immunologia Clinica Ospedale Nuovo San Giovanni di Dio Azienda Sanitaria di Firenze Responsabile: Donatella Macchia Responsabile: Donatella Macchia Stefania Capretti, Giuseppe Ermini, Maria L Iorno, Elisa Meucci, Sergio Testi
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Classificazione dei Mezzi di Contrasto per esami radiografici
La Radiologia Medica – Radiol Med 107 (suppl 1 al N. 4):8-31,2004 Edizione Minerva Medica -Torino
Il contrasto negli esami radiologici è generato dall’assorbimento dei raggi X
- perato dal mezzo presente
lungo il decorso del fascio radiante Sostanze a bassa densità (aria
- anidride carbonica)
riducono l’assorbimento delle radiazioni Sostanze che contengono elementi ad elevato numero atomico (bario o iodio) aumentano l’assorbimento delle radiazioni
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La Radiologia Medica – Radiol Med 107 (suppl 1 al N. 4):8-31,2004 Edizione Minerva Medica -Torino
- Anello benzenico
- Tre atomi di Iodio in posizione 2-4-6
- Catene laterali in posizione 1-3-5,
(a cui sono affidate le proprietà fisico-chimiche e biologiche)
Struttura di base e classificazione dei Mezzi di Contrasto iodati
1 2 3 4 5 6
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Jeffrey J Mayo Clin Proc 2012
Properties of the 4 classes of Iodinate Contrast Agents
Non vengono più usati per via e.v. per l’alto rischio di reazioni avverse Non vengono più usati per via e.v. per l’alto rischio di reazioni avverse
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Classification of adverse events after contrast medium administration
Brockow K Allergy 2005
The prevalence
- f
nonimmediate reactions, however, has increased in the last decade, to the extent that they are now more common than immediate reactions
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Rosado Ingelmo A J Investig Allergol Clin Immunol 2016
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Risk Factors for Immediate and Nonimmediate Reactions
- Female gender
- Acute or chronic kidney failure. Serum creatinine >2 mg/dL
- Other diseases with renovascular involvement, eg, diabetes, myeloma, dehydration
- Cardiopulmonary disease
- Previous reaction with ICM
- Repeated administration of ICM
- Using ionic monomeric high hosmolality ICM
- Treatment with IL-2
- Previous drug allergy
Rosado Ingelmo A J Investig Allergol Clin Immunol 2016
Additional risk factors for immediate reactions
(common to allergic drug reactions)
- poorly controlled bronchial asthma
- concomitant medications (eg, ß-blockers, ACE inhibitors)
- mastocytosis
- viral infections
- autoimmune diseases
- rapid administration of the drug
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Epidemiology
The prevalence of allergic reactions to ICM is estimated to be 1:170 000, that is,
0.05%-0.1% of patients undergoing radiologic studies with ICM
These percentages are generally higher for ionic ICM (0.16%-12.66%) than for nonionic ICM (0.03%-3%)
Rosado Ingelmo A et al. J Investig Allergol Clin Immunol 2016
Even the newer generation CM cause immediate and nonimmediate reactions in about 1–3% of applications
Brockow K et al. Allergy 2009
Total CM adverse reaction was 1.05%
Pradubpongsa P et al. Asian Pac J Allergy Immunol 2013
As low osmolality nonionic contrast agents replaced high-osmolality ionic ones, the incidence of immediate RCM hypersensitivity diminished remarkably from 3.8–12.7% to 0.7–3.1%
Kim MH et al. PLOS ONE 2014
The incidence of these reactions is difficult to establish (1–25% according to various sources)
Mruk B et al. Pol J Radiol 2016
The risk of reactions to ICM in children is lower
Rosado Ingelmo et al. J Investig Allergol Clin Immunol 2016
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Reazioni da Ipersensibilità immediata da Mezzi di Contrasto Prevalenza MORTALITA’
1 – 3/100.000 somministrazioni
(non dovute ad un particolare tipo di M. di C.)
1 – 3/100.000 somministrazioni
(non dovute ad un particolare tipo di M. di C.)
75 milioni di trattamenti/anno 75 milioni di trattamenti/anno
a causa della frequenza con cui i RCM vengono utilizzati, questi agenti diagnostici sono tra i farmaci che più frequentemente causano anafilassi fatale.
Pumphrey RS Clin Exp Allergy 20000
a causa della frequenza con cui i RCM vengono utilizzati, questi agenti diagnostici sono tra i farmaci che più frequentemente causano anafilassi fatale.
Pumphrey RS Clin Exp Allergy 20000
Ingelmo R J Investig Allergol Clin Immunol 2016
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Clinical Manifestations
Immediate Reactions Nonimmediate Reactions Nonallergic Reactions
(can occur immediately after administration of ICM and usually resolve spontaneously)
- erythema and urticaria
with or without angioedema (more than 70%)
- maculopapular rash
(30-90%),
- delayed urticaria, with
- r without angioedema
(40%-60%)
- heat
- facial flushing
- dizziness
- nausea
- dyspnea,
- nausea
- vomiting
- hypotension
- anaphylactic shock
- acute coronary syndrome
(Kounis syndrome)
- contact dermatitis
- fixed drug eruption
- Stevens-Johnson syndrome
- toxic epidermal necrolysis
- acute generalized pustulosis
- vasculitis
Rosado Ingelmo A J Investig Allergol Clin Immunol 2016
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Time to onset of reaction
Immediate reactors Immediate reactors
Time to onset of the reaction was known for 107 patients in the immediate group Reaction after CM injection:
- within 1–5 min 72
(67.2%)
- after 10–15 min 19
(17.7%)
- after 20–30 min 13
(12.1%)
- after 45–60 min 3
(2.8%)
Time to onset of immediate reactions for patients with ( ) or without ( ) previous contrast medium exposure.
Brockow K Allergy 2009
84.9% 84.9%
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Grade I …………………………………..in 38 patients (31%),
Generalized cutaneous and/or mucocutaneous symptoms
Grade II …………………………………..in 55 patients (45%),
Mild systemic reactions
Grade III ………………………………… in 27 patients (22%)
Life-threatening systemic reactions
Grade IV ………………………………….in 2 patients (1.6%)
Cardiac and/or respiratory arrest
Grade I …………………………………..in 38 patients (31%),
Generalized cutaneous and/or mucocutaneous symptoms
Grade II …………………………………..in 55 patients (45%),
Mild systemic reactions
Grade III ………………………………… in 27 patients (22%)
Life-threatening systemic reactions
Grade IV ………………………………….in 2 patients (1.6%)
Cardiac and/or respiratory arrest
Severity of the immediate reactions (122 patients) Severity of the immediate reactions (122 patients)
The scoring system of Ring and Messmer The scoring system of Ring and Messmer
Brockow K Allergy 2009
76% 76%
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Time to onset of reaction
Nonimmediate reactors Nonimmediate reactors
Time to onset of the reaction was known for 95 patients in the nonimmediate group
- 1–6 h 18 (18.9%)
- 7–12 h 21 (22.1%)
- 13–24 h 21 (22.1%)
- >1–2 days 14 (14.7%)
- >2–3 days 9 (9.4%)
- >3 days 12 (12.6%)
Time to onset of nonimmediate reactions for patients with ( ) or without ( ) previous contrast medium exposure.
Brockow K Allergy 2009
78% 78%
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Mild
When non treatmen was required
Moderate
When the patient responded readly to appropriate tretment and no hospitalization was nedeed
Severe
When the reaction required hospitalization or was life-threatening
Mild
When non treatmen was required
Moderate
When the patient responded readly to appropriate tretment and no hospitalization was nedeed
Severe
When the reaction required hospitalization or was life-threatening
Severity of the nonimmediate reactions (98 patients) Severity of the nonimmediate reactions (98 patients)
Brockow K Allergy 2009
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Occasionally, more severe skin eruptions were observed. (bullous exanthema, flexuralexanthema, palpable purpura, purpura/maculopapular eruption combined with eosinophilia, psoriasis-like exanthema, acute generalized exanthematous pustulosis (AGEP), exfoliative eruption) Occasionally, more severe skin eruptions were observed. (bullous exanthema, flexuralexanthema, palpable purpura, purpura/maculopapular eruption combined with eosinophilia, psoriasis-like exanthema, acute generalized exanthematous pustulosis (AGEP), exfoliative eruption)
Were mainly mild to moderate skin eruptions (81%) that were
- ften treated with either antihistamines (12%),
corticosteroids (29%) or a combination of the two (40%) Were mainly mild to moderate skin eruptions (81%) that were
- ften treated with either antihistamines (12%),
corticosteroids (29%) or a combination of the two (40%)
Severity of the nonimmediate reactions (98 patients) Severity of the nonimmediate reactions (98 patients)
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Diagnosis
(acute phase)
Immediate reactions Nonimmediate reactions
measurements of serum tryptase (at the onset of the reaction and 2 and 24 hours later) complete blood count and serum chemistry
- detection of peripheral blood
eosinophilia
- evaluation of renal and hepatic
function biopsy of the affected skin
Rosado Ingelmo A J Investig Allergol Clin Immunol 2016
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Clinical History
should be taken carefully, as with any adverse drug reaction
- time interval between reaction and allergological study
- the symptoms
- the interval between administration of the ICM and the onset of symptoms,
- the ICM administered
- treatment required to control symptoms
- possible previous administration of ICM
- subsequent tolerance to this ICM or others
Rosado Ingelmo RA J Investig Allergol Clin Immunol 2016
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Skin Tests
ICM (300–320 mgI/ml) diluted 10-fold in sterile saline
immediate reactions
(Sensitivity 4.2% to 73% ) (Specificity 96.3%)
nonimmediate reactions Skin Prick Test undiluted undiluted
reading after 20 min
Intradermal Test 1:10 1:10
reading after 20 min
(Undiluted)
Torres MJ et al. Allergy 2012 reading should be taken at 48, 72, and 96 hours and occasionally at 7 days
Patch Test undiluted
reading should be taken at 48, 72, and 96 hours and occasionally at 7 days
Brockow K et al Immunol Allergy Clin North Am 2009 Rosado Ingelmo A J Investig Allergol Clin Immunol 2016
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Tot: 122 Pos: 32 (26%) Tot: 122 Pos: 32 (26%)
FREQUENCY OF POSITIVE TESTS time period between reaction and skin testing
Tot: 98 Pos: 37 (38%) Tot: 98 Pos: 37 (38%) Tot: 28 Pos: 14 (50%) Tot: 28 Pos: 14 (50%) Tot: 62 Pos: 29 (47%) Tot: 62 Pos: 29 (47%)
Brockow K Allergy 2009
Clinical History
should be taken carefully, as with any adverse drug reaction
- time interval between reaction and allergological study
- the symptoms
- the interval between administration of the ICM and the onset of
symptoms,
- the ICM administered
- treatment required to control symptoms
- possible previous administration of ICM
- subsequent tolerance to this ICM or others
(should be performed 2-6 months after the reaction) (should be performed 2-6 months after the reaction)
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In Vitro Methods
immediate reactions nonimmediate reactions
Basophil Activation Test (BAT) Lymphocyte Transformation Test (LTT)
to detect basophil activation markers (CD45, CD18, and CD63) by means of flow cytometry ability of T cells to proliferate upon contact with ICM in sensitized patients
BAT was positive in 62.5% of cases confirmed as having hypersensitivity, showing a good correlation with the ST and DPT results, thus indicating that BAT may be a useful method for confirming the diagnosis, especially in severe cases
Salas M Allergy 2013
BAT was positive in 62.5% of cases confirmed as having hypersensitivity, showing a good correlation with the ST and DPT results, thus indicating that BAT may be a useful method for confirming the diagnosis, especially in severe cases
Salas M Allergy 2013
The basophil activation test is increasingly used with drugs
- ß-lactams
Torres MJ Clin Exp Allergy 2004
- quinolones
Aranda A Allergy 2011
- protein pump inhibitors
Pérez-Ezquerra PR Allergol Immunopathol (Madr) 2011
- corticosteroids
Aranda A Allergy 2010
- ICM
Salas M Allergy. 2013
The basophil activation test is increasingly used with drugs
- ß-lactams
Torres MJ Clin Exp Allergy 2004
- quinolones
Aranda A Allergy 2011
- protein pump inhibitors
Pérez-Ezquerra PR Allergol Immunopathol (Madr) 2011
- corticosteroids
Aranda A Allergy 2010
- ICM
Salas M Allergy. 2013
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Skin test results Immediate reactors
More extensive cross- reactivity testing with 8 or more CM was conducted in 11 patients
- six patients were positive
to only one product
- two patients were
positive to two products
- more extensive cross-
reactivity was observed in the remaining three patients
- six patients were positive
to only one product
- two patients were
positive to two products
- more extensive cross-
reactivity was observed in the remaining three patients
Brockow K Allergy 2009
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Skin test results Nonimmediate reactors
wenty-fjve of the 37 delayed skin test positive patients were tested with at least CM (T able 5). ross-reactivity was especially pronounced among the CM of very similar chemical structure such as iodixanol, iohexol, iopentol, iomeprol and ioversol.
The positive results in skin tests and
lymphocyte proliferation tests indicated that an important cross-reactivity exists
Torres MJ et al. Clinical and Experimental Immunology 2008
The positive results in skin tests and
lymphocyte proliferation tests indicated that an important cross-reactivity exists
Torres MJ et al. Clinical and Experimental Immunology 2008
VISIPAQUE VISIPAQUE OPTIRAY OPTIRAY IOMERON IOMERON
Brockow K Allergy 2009
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An alternative skin test–negative ICM could be eligible for future testing --- however --- tolerability is uncertain, since the negative predictive value of skin testing remains unknown.
Prieto-García et al. JIACI 2013
Confirmation of a presumptive diagnosis by a DPT is often the only reliable way to establish a diagnosis, if other diagnostic procedures such as in vivo skin testing and in vitro laboratory tests do not lead to conclusive results. Aberer W et al. Allergy 2003 DRUG PROVOCATION TEST
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Prieto-García A et al. JIACI 2013
Drug provocation test alternative skin test–negative ICM was administered intravenously day 1 5-30-60 mL
if this was well tolerated
day 2 120 mL
106 patients with IHR to ICM 11 patients had positive skin test results with the culprit contrast agent (10.4%) 7 tolerated subsequent exposure to an alternative skin test–negative ICM with no premedication.
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Torres MJ et al. Allergy 2012
Drug provocation test CM was administered intravenously diluted in saline at different doses at 1-h intervals first run 5, 10 and 15 cc of CM
if this was well tolerated
1 week later 20, 30 and 50 cc (cumulative dose = 100 cc)
48.4%
a DPT was carried
- ut with the CM
Involved DPT was carried
- ut selecting a CM
with a negative skin test 21%
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Reazioni immediate
Somministrazione endovenosa del mezzo di contrasto alternativo, negativo alle prove cutanee
1a somm. 5-30-60 mL (in fisiologica)
Somministrazione in 30 minuti 100ml Flusso 200 ml/h se ben tollerato
in radiologia Successiva somministraz.
Reazioni non immediate
Somministrazione endovenosa del mezzo di contrasto alternativo, negativo alle prove cutanee
1a somm. 5-30 mL (in fisiologica)
Somministrazione in 30 minuti 100ml Flusso 200 ml/h se ben tollerato
2° somm.
dopo una settimana
30-60 mL (in fisiologica)
Somministrazione in 30 minuti 100ml Flusso 200 ml/h se ben tollerato
in radiologia
(almeno dopo una settimana)
Successiva somministraz.
Allergologia e Immunologia Clinica
Ospedale Nuovo San Giovanni di Dio Azienda Sanitaria di Firenze
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Diagnostic algorithm
The guidelines were developed by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) with extensive clinical expertise in the evaluation and management of hypersensitivity reactions and broad research experience.
Rosado Ingelmo A J Investig Allergol Clin Immunol 2016
1
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Kemp SF et al. Allergy 2008
Physicians and other healthcare professionals who perform procedures or administer medications should have available should have available the basic therapeutic agents used to treat anaphylaxis:
- stethoscope and sphygmomanometer;
- tourniquets, syringes, hypodermic needles, large-bore needles (e.g. 14- or
16-gauge);
- equipment and supplies for administering supplemental oxygen;
- equipment and supplies for administering intravenous fmuids;
- oral or laryngeal mask airway;
- an automatic defibrillator, and one-way valve facemask with oxygen inlet port (and
- ther supplies that some clinicians might find desirable depending on the individual clinical
setting);
- injectable aqueous epinephrine 1 : 1000 (1 mg in 1 ml);
- diphenhydramine or similar injectable antihistamine;
- ranitidine or other injectable H2 antihistamine;
- corticosteroids for i.v. injection;
- vasopressor (e.g. dopamine or norepinephrine);
- glucagon;
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Le reazioni generali da MCR sono principalmente reazioni tossiche dipendenti sia dalla elevata osmolalità (relativamente ai MCR ionici), sia dalla chemotossicità, cioè dalla proprietà di legarsi alle proteine come ad esempio agli enzimi, sia da reazioni pseudoallergiche ed (eccezionalmente) allergiche.
Memoranda S.I.A.I.C 1992
The fact that up to 50% of patients up to 50% of patients had positive skin tests had positive skin tests when tested 2–6 months after the reaction 2–6 months after the reaction, indicates that a significant fraction of the CM-induced immediate and nonimmediate hypersensitivity reactions are immunologic reactions immunologic reactions, involving CM-reactive IgE antibodies and CM-reactive T cells, respectively
Brockow K et al Allergy 2009
CONCLUSIONI
Per quanto riguarda i Mezzi di Contrasto Radiologici, allo stato attuale delle conoscenze scientifiche è consigliabile, in un soggetto con pregressa reazione avversa al MC,
- non esporre di nuovo il paziente al MC responsabile della pregressa RA (quando noto),
- usare un MC risultato negativo alle prove cutanee,
- effettuare la procedura diagnostica radiologica in ambiente idoneo (attrezzatura e farmaci di pronto
intervento),
- essere consapevoli dei fattori di rischio per le reazioni da ipersensibilità ai M di C (r. immediate: precedente
reazione avversa al M. di C., asma bronchiale, malattie cardiache, trattamento con beta-bloccanti; r. ritardate: precedente reazione avversa al M. di C., trattamento con interleuchina-2, pregressa allergia farmaci e allergia da contatto).
- evitare la nuova somministrazione di MC in pazienti con precedenti severe reazioni cutanee (bollose)
ritardate. Per quanto riguarda i Mezzi di Contrasto Radiologici, allo stato attuale delle conoscenze scientifiche è consigliabile, in un soggetto con pregressa reazione avversa al MC,
- non esporre di nuovo il paziente al MC responsabile della pregressa RA (quando noto),
- usare un MC risultato negativo alle prove cutanee,
- effettuare la procedura diagnostica radiologica in ambiente idoneo (attrezzatura e farmaci di pronto
intervento),
- essere consapevoli dei fattori di rischio per le reazioni da ipersensibilità ai M di C (r. immediate: precedente
reazione avversa al M. di C., asma bronchiale, malattie cardiache, trattamento con beta-bloccanti; r. ritardate: precedente reazione avversa al M. di C., trattamento con interleuchina-2, pregressa allergia farmaci e allergia da contatto).
- evitare la nuova somministrazione di MC in pazienti con precedenti severe reazioni cutanee (bollose)
ritardate.
We propose controlled challenge testing based on skin test results to identify a safe ICM for future diagnostic procedures.
Prieto-García A et al. JIACI 2013 Torres MJ et al. Allergy 2012 Rosado Ingelmo A J Investig Allergol Clin Immunol 2016
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- Prevalenza 0.05% - 25%!
- Percentuale positività prove cutanee con quale R.A.
pregressa
- Prove cutanee con M di C I non diluito nelle RA di tipo
non immediato (nelle immediate?)
- Cross reazioni, veramente così significative?
- Valore predittivo negativo (necessari altri casi!)
In our study, the rate of a positive skin test result for immediate HSR was 13.5%. This result agrees with the literature: 17% from a recent metaanalysis (Yoon SH et al. Allergy 2015) and 10.4% from another study (Prieto-Garcıa A et al. J Investig Allergol Clin Immunol 2013)…………. our rate of positive skin test results increased to 20% when skin tests were performed during the year after the HSR. Sesé L et al. Clinical & Experimental Allergy 2016
Le reazioni avverse a mezzi di contrasto: dalle evidenze cliniche alla proposta di un Position Paper elisa.meucci@uslcentro.toscana.it
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