Transcript No Slide Title

Concetti chiave sulle “cosiddette”
reazioni allergiche
Antonino Romano
[email protected]
A revised nomenclature for allergy
An EAACI position statement from the EAACI nomenclature task force
Non-allergic drug hypersensitivity
Drug
hypersensitivity
IgE-mediated
Drug allergy
non-IgE-mediated
SGO Johansson et al, Allergy 2001
SGO Johansson et al, J Allergy Clin Immunol 2004
Types of allergic reactions to penicillin
Immediate (less than 1 hour)
- Urticaria
- Laryngeal edema
- Bronchospasm
- Anaphylactic shock
- Local swelling
Non-immediate (more than 1 hour)
- Morbilliform rash
- Serum sickness
- Urticaria
Other non-immediate reactions
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- AGEP
- Interstitial nephritis
- Vasculitis
- Hemolytic anemia
- Neutropenia
- Thrombocytopenia
A Saxon et al, Ann Intern Med 1987 (modified)
News and commentaries
Management of
hypersensitivity
reactions to iodinated
contrast media
K Brockow et al, Allergy 2005
Classification of adverse events after RCM
administration
Adverse event
Pharmacological
Hypersensitivity
Unrelated event
toxicity
Immediate reactions
Non-immediate reactions
1 hour
1 hour-7 days
Pharmacological
effect
Non-allergic or
IgE-mediated?
T-cell-mediated
Organ toxicity
Allergy-like
reactions
Exanthematous skin
eruptions
K Brockow et al, Allergy 2005
Unspecific symptoms
Pathophysiology
New concepts
Some immediate reactions, especially severe
ones, appear to be IgE-mediated
Most non-immediate skin reactions appear
to be T-cell mediated
Consequence
Patients with a previous allergic
reaction to RCM are at risk for a repeat
reaction of increased intensity
WJ Pichler, Ann Intern Med 2003
Hypersensitivity reactions to
iodinated contrast media
R-M Guéant-Rodriguez et al, Curr Pharm Des 2006
Clinical symptoms
When headache, nausea and vomiting are excluded, most
adverse reactions to RCM are allergy-like
Non-immediate
Immediate
0-60 min
1-24 h
24 h–7 d
Cardiovascular reactions,
anaphylactic shock
Respiratory reactions,
urticaria, angioedema
Fever, chill,
skin eruptions
Almost all life-threatening reactions are
immediate, anaphylactic reactions
C Christiansen, Curr Opin Allergy Clin Immunol 2002
Symptoms of immediate and non-immediate
hypersensitivity reactions to RCM
Immediate reactions
Urticaria
Pruritus
Dyspnea (bronchospasm)
Angioedema / facial edema
Rhinitis
Hypotension
Cardiovascular shock
Respiratory arrest
Cardiac arrest
Non-immediate reactions
Exanthematous drug eruptions
(macular, maculopapular)
Urticaria
Angioedema
Erythema multiforme minor
Fixed drug eruption
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Graft-versus-host reaction
Vasculitis
Pruritus
C Christiansen, Curr Opin Allergy Clin Immunol 2002
Clinical symptoms
As for other drugs, cutaneous reactions
are the predominant adverse reactions
Immediate
Urticaria
Angioedema
Maculopapular rash
Non-immediate
65-85%
5-15%
>50%
C Christiansen, Curr Opin Allergy Clin Immunol 2002
Duration of adverse reactions
Most immediate reactions fade within 1 hour.
Most non-immediate reactions last from 12 hours to 7 days
40
Percentage
30
20
10
0
0,5
1
2
3
4
5
6
7
>7
Duration of non-immediate reactions (days)
T Hosoya et al, Radiat Med 2000
IMMEDIATE REACTIONS
Diagnostic tests of hypersensitivity reactions
to drugs
Type of reaction
Immediate
Non-immediate
Type of tests
In vitro
Specific IgE assays
Flow cytometric BATs
In vivo
Skin tests
Provocation tests
In vitro
LTTs or LATs
ELISPOT assays for analysis of
antigen-specific, cytokineproducing cells
In vivo
Delayed-reading intradermal tests
Patch tests
Provocation tests
A Romano et al, J Allergy Clin Immunol 2011
Diagnosis of anaphylactic reactions
Shock (gradation)
Cell-mediator assays
tryptase + histamine (sensitivity 80%)
(serum)
(plasma, EDTA)
(1 month later)
- Consultation in allergology: skin tests
- Biology: serum specific IgE assays / BATs
Evaluation of immediate reactions to iodinated
contrast media by skin tests
No. of
patients
Reagents’
highest
concentration
No. of
positive
patients (%)
V Kvedariene et al,
Clin Exp Allergy 2006
32
1:10
9 (28.1)
J Trcka et al,
Am J Roentgenol 2008
96
1:10
4 (4.2)
K Brockow et al,
Allergy 2009
122
1:10
32 (26.2)
K Dewachter et al,
Eur J Radiol 2011
26
1:1
19 (73.1)
O Goksel et al,
Int Arch Allergy Immunol 2011
24
1:10
5 (20.8)
Author
Pathophysiology
New concepts
Some immediate reactions, especially severe
ones, appear to be IgE-mediated
Most non-immediate skin reactions appear
to be T-cell mediated
Consequence
Patients with a previous allergic
reaction to RCM are at risk for a repeat
reaction of increased intensity
NON-IMMEDIATE REACTIONS
Diagnostic tests of hypersensitivity reactions
to drugs
Type of reaction
Immediate
Non-immediate
Type of tests
In vitro
Specific IgE assays
Flow cytometric BATs
In vivo
Skin tests
Provocation tests
In vitro
LTTs or LATs
ELISPOT assays for analysis of
antigen-specific, cytokineproducing cells
In vivo
Delayed-reading intradermal tests
Patch tests
Provocation tests
A Romano et al, J Allergy Clin Immunol 2011
Evaluation of non-immediate reactions to
iodinated contrast media
No. of
patients
Method
No. of
positive
patients (%)
L Vernassiere et al,
Contact Dermatitis 2004
15
Skin tests, patch
tests, challenges
11 (73.3)
T Nakada et al,
Clin Exp Dermatol 2006
117
Patch tests,
intradermal tests
69 (58.9)
V Kvedariene et al,
Clin Exp Allergy 2006
11
Intradermal tests
1 (9)
Y Delgado-Jimenez et al,
Contact Dermatitis 2006
11
Patch tests
3 (27.2)
Author
Evaluation of non-immediate reactions to
iodinated contrast media
No. of
patients
Method
No. of
positive
patients (%)
MJ Torres et al,
Clin Exp Immunol 2008
14
Skin tests, patch
tests, challenges
6 (42.8)
K Brockow et al,
Allergy 2009
98
Skin tests,
patch tests
37 (37.7)
CS Seitz et al,
Eur J Radiol 2009
32
Skin tests,
patch tests
6 (18.7)
F Hasdenteufel et al,
J Allergy Clin Immunol in press
22
Skin tests,
patch tests
11 (50)
Author
Pathophysiology
New concepts
Some immediate reactions, especially severe
ones, appear to be IgE-mediated
Most non-immediate skin reactions appear to be
T-cell mediated
Consequence
Patients with a previous allergic
reaction to RCM are at risk for a repeat
reaction of increased intensity
Skin testing in patients with
hypersensitivity reactions to iodinated contrast
media –
a European multicenter study
Skin prick, intradermal, and patch tests with a series of
contrast media (CM) were conducted in 220 patients with
either immediate (122) or non-immediate (98) reactions
K Brockow et al, Allergy 2009
Skin testing in patients with
hypersensitivity reactions to iodinated contrast
media –
a European multicenter study
• Positive skin tests were observed in 32 (26%; 95% CI:
18% - 34%) of 122 patients with immediate reactions
• Positive immediate responses to at least one of the
tested CM were observed in 3 of the 71 unexposed
controls, but in none of the 11 CM-exposed controls
• The specificity of the intradermal tests was 96.3%
(95% CI: 92% – 100%)
K Brockow et al, Allergy 2009
Skin testing in patients with
hypersensitivity reactions to iodinated contrast
media –
a European multicenter study
• The frequency of positive test results was 14/28 (50%)
in patients tested within 2 to 6 months, but was only
17/92 (18%) for patients tested at other time points
(earlier than 2 months or later than 6 months)
K Brockow et al, Allergy 2009
Skin testing in patients with
hypersensitivity reactions to iodinated contrast
media –
a European multicenter study
• Delayed-reading skin tests were positive in 37 (38%;
95% CI: 28% - 47%) of 98 non-immediate reactors
• Patch tests were positive in 22 (28%) of 79 patients
• 9 patients presented delayed-reading intradermal-test
positivity and patch-test negativity, while 7 patients
were positive to patch tests and negative to intradermal
ones
K Brockow et al, Allergy 2009
Skin testing in patients with
hypersensitivity reactions to iodinated contrast
media –
a European multicenter study
• While 47% (29/62) of patients were skin-test positive
when tested within the first 6 months after reactions,
only 22% (8/36) were positive when tested at later time
points (p = 0.02)
K Brockow et al, Allergy 2009
Skin test results
Immediate reactors
More extensive crossreactivity testing with 8 or
more CM was conducted
in 11 patients
6 patients were positive to
only one product
2 patients were positive to
two products
more extensive crossreactivity was observed in
the remaining 3 patients
Skin test results
Non-immediate reactors
Twenty-five of the 37 patients with a delayed hypersensitivity were tested with at least
8 CM
Cross-reactivity was especially pronounced among the CM with a very similar
chemical structure, such as iodixanol, iohexol, iopentol, iomeprol, and ioversol
Delayed hypersensitivity reactions caused by iodixanol: An
assessment of cross-reactivity in 22 patients
F Hasdenteufel et al, J Allergy Clin Immunol in press
IgE-mediated reactions to gadolinium-containing
intravenous contrast media
Author
No. of
patients
Responsible
compound
Method
DC Kalogeromitros et al,
Int Arch Allergy Immunol 2007
1
Gadobenate
dimeglumine
Intradermal
test
F Hasdenteufel et al,
J Allergy Clin Immunol 2008
2
Gadoterate
dimeglumine
Skin tests,
LHRT
2
Gadoteridol,
Gadobenate
dimeglumine
Intradermal
tests
C Galera et al,
Allergy 2010
Diatesi allergica – Come identificare il paziente a rischio?
Si richiede la preparazione? Quando e come?
Antonino Romano
[email protected]
Main risk factors
Immediate
Prior RCM reaction

Bronchial asthma

β-Blocker

Cardiac disease

Severe allergy

Non-immediate

A history of drug allergy

A history of contact allergy

Serum creatinine level >2 mg/dl

Interleukin-2 treatment

C Christiansen, Curr Opin Allergy Clin Immunol 2002
K Brockow et al, Allergy 2005
Pharmacological
prevention
of
serious
anaphylactic reactions due to iodinated
contrast media: a systematic review
•
Nine
of
64
potentially
relevant
reports,
published between 1975 and 1996, met inclusion
criteria
MR Tramèr et al, BMJ 2006
Arbitrary symptom combinations (grades)
Grade 1 Single episode of emesis, nausea, sneezing, or vertigo
Grade 2 Hives, erythema, emesis more than once, and fever or
chills (or both)
“shock”, bronchospasm, laryngospasm or
oedema, loss of consciousness, convulsions, fall in blood
pressure, increase in blood pressure, cardiac arrhythmia,
angina, angio-oedema, or pulmonary oedema
Grade 3 Clinical
MR Tramèr et al, BMJ 2006
•
Grade 1 reactions were significantly reduced
with the double dose, but not with the single
dose methylprednisolone regimen:
87/3,093 (2.8%) patients who received the double dose
regimen had a grade 1 reaction compared with 89/2,178
(4.1%) controls (odds ratio 0.62, 0.46 to 0.84)
MR Tramèr et al, BMJ 2006
•
Grade 2 reactions were not significantly
reduced, either with the single dose or with
the double dose methylprednisolone regimen
MR Tramèr et al, BMJ 2006
•
Grade 3 reactions were significantly
reduced only with the double dose regimen:
7/3,093 (0.2%) patients who received the double dose
regimen had a grade 3 reaction compared with 20/2,178
(0.9%) controls (odds ratio 0.28, 0.13 to 0.60)
MR Tramèr et al, BMJ 2006
What is already known on this topic
•
Premedication with steroids, antihistamines, and other
drugs, alone or in combination, is widely used before
injection of iodinated contrast media
•
Premedication is thought to reduce the risk of lifethreatening anaphylactic reactions
MR Tramèr et al, BMJ 2006
What this study adds
•
Life-threatening anaphylactic reactions due to iodinated
contrast media are rare
•
In unselected patients, the usefulness of premedication
is doubtful, as a large number of patients need to receive
premedication to prevent one potentially serious reaction
•
Data supporting the use of premedication in patients with
a history of allergic reactions are lacking
MR Tramèr et al, BMJ 2006
Repeat contrast medium reactions in
premedicated patients: Frequency and severity
• Between January 1999 and December 2007, 175
patients experienced 190 breakthrough reactions to
intravenous low-osmolality contrast media (LOCM)
•
• Of 128 breakthrough reactions, in which the index
reaction severity was known, 103 (81%) were of
severity similar to that of the index reaction, 15 (12%)
were less severe, and 10 (8%) were more severe
MS Davenport et al, Radiology 2009
Repeat contrast medium reactions in
premedicated patients: Frequency and severity
• Of the 175 patients with confirmed breakthrough
reactions, 58 underwent 197 subsequent LOCMenhanced CT examinations during the study period
• There was no breakthrough reaction after 174 (88%)
of these 197 examinations
• Additional breakthrough reactions occurred after 23
(12%) examinations performed in 23 subjects
MS Davenport et al, Radiology 2009
Repeat contrast medium reactions in
premedicated patients: Frequency and severity
• Breakthrough reactions were significantly more likely
to be moderate or severe in patients with a history of
chronic corticosteroid use (P = .01), drug (P = .04) or
severe (P < .001) allergies, or allergies to 4 or more
allergens (P = .01)
MS Davenport et al, Radiology 2009
Prevention of recurrence
Premedication
• Immediate reactions:
Steroids and anti-histamines
Currently used premedication ineffective in
preventing severe immediate reactions
• Non-immediate reactions:
Cyclosporine and steroids