What 2012 urticaria anaphylaxis

WHAT YOU SHOULD HAVE READ BUT….2012

 urticaria
Attilio Boner
University of
Verona, Italy

Utility of routine laboratory testing in management of
chronic urticaria/angioedema
Tarbox Ann Allergy Asthma Immunol 2011;107:239
Diagnostic studies

 Chronic
urticaria/angioedema
(CUA).

 Retrospective analysis
of a random sample of
356 adult patients with
CUA from 2001–2009.

Abbreviations: CBC, cell blood count; CMP/BMP, complete/basic metabolic panel;
ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; TSH, thyroid-
stimulating hormone; THG, thyroglobulin; M, microsomal; ANA, anti-nuclear
antibody; IgE, immunoglobulin E; SPEP, serum protein electrophoresis;
UA, urinalysis.

Utility of routine laboratory testing in management of
chronic urticaria/angioedema
Tarbox Ann Allergy Asthma Immunol 2011;107:239
Diagnostic studies

 Chronic Only 1
urticaria/angioedema
patient benefited from a
(CUA).
subsequent change in
management.
 Retrospectivetesting rarely
Laboratory
analysis
of a random sample of
lead to changes in
356 adult patients with
management resulting
CUA from 2001–2009.
in improved outcomes
of care.
Abbreviations: CBC, cell blood count; CMP/BMP, complete/basic metabolic panel;
ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; TSH, thyroid-
stimulating hormone; THG, thyroglobulin; M, microsomal; ANA, anti-nuclear
antibody; IgE, immunoglobulin E; SPEP, serum protein electrophoresis;
UA, urinalysis.

Chronic palpable purpura mediated by Kiwi antigen
Act c 1-induced immune complex vasculitis
Gutermuth, Allergy 2011;66:982

 For 3 months, a 61 years old
female developed recurrent
palpable purpura with multiple
erythematous and
hyperpigmented papules
and macules on the dorsum of
the feet, lowerand upper legs.

Multiple erythematous macules
and papules on the lower
extremities

Chronic palpable purpura mediated by Kiwi antigen
Act c 1-induced immune complex vasculitis
Gutermuth, Allergy 2011;66:982

 Detailed history was taken concerning the circumstances under
which new purpuric lesions occurred and the patient reported
the ingestion of fruit salads preceding the active rashes;

 To verify or rule out foodstuff as elicitor of vasculitis, the
patient was put on elimination diet and then orally challenged to
40 g of fresh fruits that she consumes regularly, including
apple, banana, kiwi and pineapple;

 Six to ten hours after consumption of kiwi she reproducibly
developed an itchy rash consisting of confluent 3–5 mm purpuric
macules and papules on the legs, lower trunk and forearms with
consecutive bleeding in the central part of the lesions.

Response to a selective COX-2 inhibitor in patients with
urticaria/angioedema induced by nonsteroidal
anti-inflammatory drugs. Doña, Allergy 2011;66:1428

% patients intolerant to etoricoxib
 252 patients with urticaria 30 –
and/or angioedema caused
by hypersensitivity owing
to cross-intolerance to
25%
20 –
NSAIDs;
 (A) patients with
intolerance to paracetamol; 10 –
 (B) patients with tolerance
to paracetamol. 6%
0
GROUP A GROUP B

Response to a selective COX-2 inhibitor in patients with
urticaria/angioedema induced by nonsteroidal
anti-inflammatory drugs. Doña, Allergy 2011;66:1428

% patients intolerant to etoricoxib
 252 Selective with urticaria
patients COX-2 30 –
and/or angioedemabe
inhibitors may caused
by hypersensitivity owing
unsafe in subjects
to with urticaria and/or
cross-intolerance to
25%
20 –
angioedema caused by
NSAIDs;
hypersensitivity
 (A) patientsto NSAIDs
reactions with
intolerance to paracetamol; 10 –
with cross-intolerance
to paracetamol.
 (B) patients with tolerance
to paracetamol. 6%
0
GROUP A GROUP B

Factors that predict the success of cyclosporine
treatment for chronic urticaria
Hollander Ann Allergy Asthma Immunol 2011;107:523

% pts with complete
remission defined as ≤1 day
of hives per month
80 –
 68 adults with 70 –
Chronic urticaria (CU). 60 –
50 –
78%
 Cyclosporine at an average
dose of 1.8 ± 1.1 mg/kg. 40 –
30 –

 Follow-up = 6 weeks 20 –
10 –
00


% pts with complete
remission defined as ≤1 day
of hives per month
Recurrence 80 –
 68 adults with in only
occurred 70 –
Chronic urticaria (CU).
7 patients;
all achieved
60 –
50 –
78%
doseremission mg/kg.
of 1.8 ± 1.1 with 40 –
resumption of 30 –
cyclosporine.
 Follow-up = 6 weeks 20 –
10 –
00


•A history of hives (P =0.01),

 68 adults with •shorter duration of urticaria
Chronic urticaria (CU). (mean: 55.2 wks vs 259.63
weeks; P = 0.03), and
dose of 1.8 ± 1.1 mg/kg. •positive CU Index
(P = 0.05) predicted a
 Follow-up = 6 weeks favorable response to
cyclosporine.


Chronic urticaria indexes
(CU Index) is a nonspecific,
histamine release assay in
 68 adults with which donor blood cells are
Chronic urticaria (CU). mixed with the patient's serum
as well as positive and
 Cyclosporine at an average negative control serum.
dose of 1.8 ± 1.1 mg/kg. The amount of histamine
released from each of these
assays is measured, and an
 Follow-up = 6 weeks
index is reported, with a
normal result being less
than 10.


Chronic urticaria indexes
(CU Index) is a nonspecific,
Notably, autologous histamine release assay in
 68 serum skin testing,
adults with which donor blood cells are
prior response to
Chronic urticaria (CU). mixed with the patient's serum
steroids, atopic as well as positive and
status, or presence negative control serum.
dose of 1.8 ± 1.1 mg/kg.
of antithyroid The amount of histamine
antibodies was released from each of these
assays is measured, and an
 Follow-up predictive.
not = 6 weeks
index is reported, with a
normal result being less
than 10.

Treatment with propranolol of 6 patients
with idiopathic aquagenic pruritus
Nosbaum, JACI 2011;128:1113

• Idiopathic aquagenic pruritus (IAP) occurs after contact
with water, involving intense itching without visible skin changes
and without an underlying pathology (polycythemia vera,
Hodgkin disease and blood disorders) or drugs that could induce
this symptom.
• Conventional treatments are the addition of sodium bicarbonate
to bath water, antihistamines or phototherapy, which relieve
symptoms in 24%, 47% and 50% of patients, respectively.


6 patients received 10 to 40 mg/d propranolol for 3 months.


According to our results
(improvement of >90% in
5/6 patients with minimal
side effects),
the β-blocker appears
more effective
and better accepted
than conventional
treatments.


The therapeutic effect of propranolol,
a β-receptor antagonist of adrenaline,
suggests involvement of the sympathetic system
in the occurrence of IAP.

EB recommendations for the therapeutic management
of angioedema owing to hereditary C1 inhibitor deficiency:
consensus report of an Int’l Working Group
Cicardi, Allergy 2012;67:147
Long-term prophylaxis (LTP) of attacks.
1. Attenuated androgens
Dosage
recommended doses with acceptable long-term adverse effects are danazol
≤200mg/day & stanozol ≤2mg/day.
Contraindications
owing to residual androgenic hormonal activity, androgen derivatives are not
recommended for women in pregnancy/lactation or children until after growth
is complete.
Monitoring
Regular follow-up visit every 6 mo is recommended. Liver enzymes,
lipid profile, complete blood cell count, alpha-feto-protein, and
urinanalysis should be performed. Abdominal ultrasound yearly is advisable for
early diagnosis of liver tumors.

2. Plasma-derived C1-INH concentrates
Dosage
In USA, C1-INH (Cinryze®) is FDA and Europe-approved for LTP in
adolescents and adults at a dose of 1000 units every 3 or 4 days.
Adverse effects
The side-effects reported in published controlled trials are minimal. There
are concerns about infection at injection site and intrinsic infectivity risk of
human blood products; however, as for any chronic user of blood products,
hepatitis B vaccination is advisable.

Acute treatment (AT) for attacks.

1. Acute treatment aims to resolve angioedema symptoms as quickly as possible.
2. Evidence suggests that:
- C1-INH concentrates plasma-derived (Berinert®, Cinryze®, Cetor®);
- C1-INH concentrates plasma-recombinant (Rhucin®/Ruconest®);
- kallikrein inhibitor ecallantide (Kalbitor®);
- bradykinin B2 receptor antagonist icatibant (Firazyr®)
are suitable for AT of HAE.


• Plasma-derived (Berinert®, Cinryze®, Cetor®) efficacy is consistent
at all sites, including laryngeal swellings. Training of patients to
self-administer C1-INH is safe and improves symptom control.
Reports on the use in pregnancy, lactation, very young children and babies
provide unique evidence for the safety and efficacy of this treatment
in these critical subgroups of HAE patients.
Allergic/pseudoallergic systemic reactions in a few patients represent the
only absolute contraindication to C1-INH.


• Plasma-recombinant (Rhucin®/Ruconest®) are unsuitable for patients
with proven rabbit allergy. Skin prick testing or serum-specific IgE
to rabbit epithelium prior to prescribing.
Long-term data on larger populations are required to confirm the safety
of the product.
There are no data in pregnancy or in breastfeeding.

• Kallikrein inhibitor ecallantide (Kalbitor®) should be administered only
by a healthcare professional who has medical support to manage anaphylaxis
and HAE.

1. All patients with HAE owing to C1-INH deficiency, even still if
asymptomatic , should have access to at least one of the specific medicines,
which obtained high grade of evidence for their efficacy in treating acute
attacks ’on demand’.
2. Whenever allowed by drug-specific characteristics, patients should be
trained to self-administer these medicines at home.
3. All attacks are eligible for treatment, ideally before visible or disabling
symptoms develop.
4. Patients should report to the hospital if laryngeal symptoms persist.
1. The goal is to reduce the likelihood of swelling in a patient undergoing a
stressor or a procedure likely to precipitate an attack or to decrease the
number and severity of angioedema attacks (LTP).

WHAT YOU SHOULD HAVE READ BUT….2012

 anaphylaxis
Attilio Boner
University of
Verona, Italy

Classification of anaphylaxis and utility of the EAACI
Taskforce position paper on Anaphylaxis in Children
Vetander Pediat Allergy Immunol 2011;22:369

 371 children with 381 reactions to foods.
 Symptoms/signs of reactions to foods recorded for classification
of anaphylaxis were related to those presented in the EAACI
(Allergy 2007;62:857).
 46 different symptoms/signs of reactions to foods were
retrieved.
 Several severe signs or symptoms from the respiratory tract and
signs indicating reduced brain perfusion were not described in
detail in the EAACI paper, hampering correct classification of
anaphylaxis including grading of severity in our material.

Classification of anaphylaxis and utility of the EAACI
Vetander Pediat Allergy Immunol 2011;22:369
Suggested modification of the EAACI Taskforce position paper on Anaphylaxis in Children table

The symptoms added by us are marked in bold.

Evaluation of National Institute of Allergy and Infectious
Diseases/Food and Anaphylaxis Network criteria for the
diagnosis of anaphylaxis in emergency department
patients Campbell, JACI 2012;129:748

Background: Diagnostic criteria were proposed at the Second
Symposium on the Definition and Management of Anaphylaxis
convened by the National Institute of Allergy and Infectious
Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN).
Validation is needed before these criteria can be widely adapted
into clinical practice.
Objective: Our aim was to retrospectively assess the diagnostic
accuracy of the NIAID/FAAN criteria for the diagnosis of
anaphylaxis in emergency department (ED) patients.

NIAID/FAAD clinical criteria for anaphylaxis

Anaphylaxis is highly likely when any one of the following 3
criteria is fulfilled:
1. Acute onset of an illness (minutes to several hours) with
involvement of the skin, mucosal tissue, or both (eg, generalized
hives, pruritus or flushing, swollen lips-tongueuvula)
AND AT LEAST ONE OF THE FOLLOWING
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm,
stridor, reduced PEF, hypoxemia)
b. Reduced BP or associated symptoms of end-organ dysfunction
(eg, hypotonia [collapse], syncope, incontinence)

Sampson HA, J Allergy Clin Immunol 2006;117:391-7.


1. A

2. Two or more of the following that occur rapidly after exposure
to a likely allergen for that patient (minutes to several hours):
a. Involvement of the skin-mucosal tissue (eg, generalized hives,
itch-flush, swollen lipstongue-uvula)
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm,
stridor, reduced PEF, hypoxemia)
c. Reduced BP or associated symptoms (eg, hypotonia [collapse],
syncope, incontinence)
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain,
vomiting)


1. A
2. A

3. Reduced BP after exposure to known allergen for that patient
(minutes to several hours):
a. Infants and children: low systolic BP (age specific) or greater
than 30% decrease in systolic BP*
b. Adults: systolic BP of less than 90 mm Hg or greater than 30%
decrease from that person’s baseline

PEF, Peak expiratory flow; BP, blood pressure.
*Low systolic blood pressure for children is defined as less than 70 mm Hg from
1 month to 1 year, less than (70 mm Hg + [2 x age]) from 1 to 10 years, and less
than 90 mm Hg from 11 to 17 years.

50 –

b
 A retrospective cohort study of % patients who
ED patients 40 –
40.2%
 214 patients with a diagnosis of 86/214
an allergic reaction or anaphylaxis 30 –
and a subset of patients with 28.5%
20 – 61/214
related diagnosis
 Medical records reviewed to 10 –
determine whether the
NIAID/FAAN criteria were met aaa 0
Met the Had the
 Final diagnosis by allergists NIAID/FAAD allergists’
considered the reference criteria for diagnosis
standard anaphylaxis

50 –

b
 A retrospective cohort study of
59 (96.7%) of whom
% patients who
ED patients 40 –
satisfied the 40.2%
 214 patients with a diagnosis of
NIAID/FAAN criteria 86/214
an allergic reaction or anaphylaxis 30 –
and a subset of patients with 28.5%
20 – 61/214
related diagnosis
 Medical records reviewed to 10 –
determine whether the
NIAID/FAAN criteria were met aaa 0
Met the Had the
 Final diagnosis by allergists NIAID/FAAD allergists’
considered the reference criteria for diagnosis
standard anaphylaxis


The test characteristics of the NIAID/FAAN criteria were as
follows:
 Sensitivity: 96.7%
 Specificity: 82.4%
 Positive predictive value: 68.6%
 Negative predictive value: 98.4%
 Positive likelihood ratio: 5.48
 Negative likelihood ratio: 0.04


The test characteristics of the NIAID/FAAN criteria were as
follows:
 Sensitivity: 96.7% The NIAID/FAAN
criteria are highly
 Specificity: 82.4% sensitive but
 Positive predictive value: 68.6% less specific and
 Negative predictive value: 98.4% are likely to be useful
in the ED for the
 Positive likelihood ratio: 5.48 diagnosis of
 Negative likelihood ratio: 0.04 anaphylaxis

Potter Stewart and the definition of anaphylaxis
Camargo, JACI 2012;129:753
Editorial

• Potter Stewart was an Associate Justice of the US Supreme Court
who might be best known for a snippet from his opinion in the
obscenity case of Jacobellis v Ohio (1964). In that case he
acknowledged that ‘‘hard-core pornography’’ was difficult to define
but then added that ‘‘I know it when I see it.’’
• Even though most allergists/immunologists knew anaphylaxis when
they saw it, clinicians in other fields, such as emergency medicine,
might not.

Editorial

• The original goals of the NIAID/FAAN criteria, which were not
meant to make an actual diagnosis of anaphylaxis but rather to
identify patients who were ‘‘highly likely’’ to have anaphylaxis.
• The intention was not to replace expert opinion but to encourage
consideration of the diagnosis and, on further reflection, the
appropriate use of epinephrine.
• The negative predictive value of 98% sounds impressive, but this
will not be useful to most ED clinicians because overdiagnosis of
anaphylaxis is not a problem. On the contrary, ED studies
consistently suggest underdiagnosis.
FAAD: Food Allergy and Anaphylaxis Network
NIAID: National Institute of Allergy and Infectious Disease

Editorial

• In the context of ED care today, a more valuable combination of
test characteristics would be high sensitivity and very high positive
predictive value.
• The investigators report a sensitivity of 98% but a positive
predictive value of only 69%. In other words, if the NIAID/FAAN
criteria identified 100 patients as being ‘‘highly likely’’ to have
anaphylaxis, only 69 would have anaphylaxis, and 31 would not.
• Although I agree that use of the NIAID/FAAN criteria is likely to
improve ED anaphylaxis care, which remains suboptimal, the
investigators also have demonstrated that clinicians should not follow
the NIAID/FAAN criteria blindly.

Anaphylaxis and reactions to foods in children – a
population-based case study of emergency department
visits. Vetander, Clin Exp Allergy 2012;42:568

Age distribution in relation to
severity of reactions to foods.

 371 children with ED visits
at any of 3 paediatric
hospitals in Stockholm
during 2007.


Eliciting foods in relation to age

population-based case study nuts,
Tree of emergency department
particular cashew, and peanut were the most
common eliciting foods, and in children under 3 yrs,
reactions to these 2 foods allergens were as
Eliciting foods in relation to age
common as reactions to milk and egg.

population-based case study of children
Pollen-allergic emergency department
visits. Vetander, Clin Expdue to food-induced
seemed to be admitted Allergy 2012;42:568
anaphylaxis, more often during the deciduous tree
pollen season compared with the rest of the yr.
(p=0.015).

% of children with symptoms of the
lower airways during the reactions
100 –
90 –
80 –
70 –
60 – 72% p<0.01
50 –
40 –
30 –
49%
20 –
10 –
0
Yes No
Asthma

Provoking allergens and treatment of anaphylaxis in
children and adolescents – data from the anaphylaxis
registry of German-speaking countries
Hompes Pediat Allergy Immunol 2011;22:568

% affected organs during reaction
 Severe systemic
allergic reactions 90 –

with concomitant 80 – 89%
87%
pulmonary and/or 70 –

cardiovascular 60 –

symptoms. 50 –

40 – 47% 43%
 197 reported 30 –

anaphylactic reactions 20 –

from children and 10 –

adolescents. 0
Skin Respiratory Cardiovasc. G-I


Etiology %
 Severe systemic 60 –

allergic reactions 50 – 58%
with concomitant

cardiovascular
30 –
symptoms.
20 – 24%
 197 reported

from children and 0
8%
adolescents. Food Insect Drugs
Allergens venom


The most frequent Etiology %
 Severe systemic
food allergens were
60 –

allergic reactions
peanuts followed by 50 – 58%
with concomitant
tree nuts and animal
related food
cardiovascular
products. 30 –
symptoms.
In 18% aggravating
20 – 24%
 197 reported as
factors such
physical exercise

from childrenby the
were noted and 8%
clinicians.
adolescents.
0
Food Insect Drugs
Allergens venom

% drug used
90 –
 Severe systemic
allergic reactions
80 – 87% 85%
70 –
with concomitant
60 –
pulmonary and/or
cardiovascular 50 –

symptoms. 40 –
30 –
anaphylactic reactions 22%
10 –
from children and 0
adolescents. Antihistamines Corticosteroids Adrenaline

% drug used
90 –
 Severe systemic
26% of the
allergic reactions
80 – 87% 85%
analysed
with concomitant 70 –

patients had

cardiovascular
experienced
50 –

symptoms. 40 –
more than one 30 –

reaction.
22%
from children and 0
adolescents. Antihistamines Corticosteroids Adrenaline

Risk factors for severe pediatric food anaphylaxis in Italy
Calvani Pediat Allergy Immunol 2011;22:813

In children with a clinical
10 –
history of asthma OR for
 163 children with 09 –
08 –
anaphylaxis consecutively
07 –
attending 29 outpatient
6.9
06 –
allergy clinics throughout 05 –
Italy. 04 –
03 –
 Food sensitization was 02 –
evaluated by SPTs. 01 –
00
2.2
Wheezing Respiratory
arrest
During the episode


of chronic gastrointestinal
10 – symptoms OR for

anaphylaxis consecutively 08 – 9.2
07 –
06 –
7.9
Italy. 04 –
03 –
evaluated by SPTs. 01 –
00
2.2
Vomiting Hypotension Bradycardia/
cardiac
arrest


of chronic gastrointestinal
10 – symptoms OR for
Peanut and egg
anaphylaxis consecutively 08 – 9.2
were the most
07 –
06 –
7.9
frequent causes
Italy.
of severe 04 –
03 –
anaphylaxis.
evaluated by skin-prick 01 – 2.2
test. 00
Vomiting Hypotension Bradycardia/
cardiac
arrest

Anaphylaxis to diphtheria, tetanus, and pertussis
vaccines among children with cow’s milk allergy
Kattan JACI 2011;128:215

 The US national Vaccine Adverse Events Reporting System
lists 39 anaphylactic reactions to DTaP, DTP, or Tdap
vaccines for patients aged 0 to 17 years from 2007-2010.

 We noted that these vaccines are labeled as being
processed in medium containing casamino acids (derived
from cow’s milk), raising the concern that residual casein
in the vaccines might have triggered these reactions.

 To investigate this possibility, we tested 8 lots of the
vaccines for residual casein.


Mean casein concentrations in vaccine samples examined


 8 children were obtained by means of chart review.
 These patients were selected based on reports of
anaphylactic reactions to the vaccines and not because
of a history of milk allergy.

 Six of the patients had prior acute allergic reactions
to cow’s milk, including severe reactions in 5 patients
and reactions to trace exposures in 4 patients.

 In conclusion, our novel observation raises a concern
regarding booster vaccination of children with high
levels of milk allergy with Tdap and DTaP.

Anaphylactic reactions caused by oil body fraction
lipoproteins Pineda, Allergy 2011;66:701

1) Allergies to olive fruit and derivative product have seldom
been reported;

2) Few cases of contact dermatitis and contact urticaria caused
by olive oil or olives have been documented, and only three
cases of allergy caused by olive ingestion have been described;

3) Thaumatin-like protein and other proteins with a 10–15 kDa
molecular mass are those described as allergenic in the
patients with olive allergy.


1) A 20-year-old man was admitted to our allergy unit for
investigation into recurrent food-induced anaphylaxis;

2) Skin prick test was positive for Platanus and Parietaria pollen
and only positive for hazelnut, walnut, peach peel, sunflower
seed, and mustard food extracts when testing the panel of
plant food allergens;

3) Further, SPTs were performed using home-made extract of
liposoluble proteins from olives and prick to prick with olive.
A wheal diameter of 13.9 and 10 mm was obtained from olive
and liposoluble proteins from olive fruit respectively.


1) The basophil activation test (BAT)
was performed;

2) The stimuli used were lipoproteins
from olive;

3) The test was positive for olive
fruit (30,5%);

4) The BAT was performed in parallel
with two nonallergic individuals
obtaining a negative result with the Basophil activation test (BAT) to oil
body fraction proteins from hazelnut,
stimuli tested. olive and sesame.

Cow’s milk allergy as a cause of anaphylaxis to systemic
corticosteroids
Savvatianos, Siragakis, Allergy 2011;66:983
milk

 Immediate IgE-mediated allergic reactions to corticosteroids
are rather uncommon, whereas causative agents usually involve
the native steroid molecule or a pharmaceutical excipient, in
most cases as succinate ester bound to methyl-prednisolone or
hydrocortisone;

 We here report two cases of immediate reaction to
methyl-prednisolone, attributed to milk allergen contamination.

corticosteroids
milk

1) A 9 yrs old boy with severe persistent cow’s milk allergy
(CMA) was seen for asthma exacerbation;

2) The boy was administered 40 mg of methyl-prednisolone by
intravenous injection;

3) Paradoxically, wheezing deteriorated;

4) The boy was given another course of the same medication on
assumption of clinical under-responsiveness;

5) Within a few minutes the patient acutely collapsed.

corticosteroids
milk

a) Another patient, a 7-year-old boy with severe CMA was
similarly treated with intravenous administration of 40 mg
methyl-prednisolone;

b) The therapeutic intervention resulted in a full-blown
anaphylactic reaction;

c) Both children were evaluated within the next 6 months for
assumed IgE-mediated reactivity to methyl-prednisolone.

corticosteroids
milk

Skin testing results in both patients with acute
reaction to lactose-containing succinylated
methyl-prednisolone

corticosteroids
milk

Sensitization to theresultssteroid molecule andwith acute
Skin testing native in both patients to the succinate
reaction to lactose-containing succinylated
ester was ruled out by negative skin tests, while both patients exhibited
positive skin response exclusively to lactose-containing preparations.
methyl-prednisolone

corticosteroids
milk
Subsequent drug provocation tests were negative in both patients
Skin a full therapeuticboth patients with acute reaction
for testing results in dose (125 mg) of non-lactose
to lactose-containing succinylated methyl-prednisolone
containing, otherwise identical to the one that elicited the
reaction, succinylated methyl-prednisolone preparation
(Solu-Medrol 125 mg, Pfizer)

Hypersensitivity to total parenteral nutrition
fat-emulsion component in an egg-allergic child
Lunn Pediatrics 2011;128:e1025

 Intravenous fat emulsions (IFEs) are a vital component of total
parental nutrition, because they provide essential fatty acids.

 IFE is a sterile fat emulsion that contains
egg-yolk phospholipids.

 Although egg allergy is listed as a contraindication,
adverse reactions are uncommon.


 2-year-old patient with previously undocumented egg allergy.
 Placed on total parental nutrition and a 20% IFE postoperatively
and developed diffuse pruritus 14 days after initiation of
therapy.


therapy.
 She showed transient improvement with intravenous
antihistamine, but her symptoms did not resolve until the IFE
was stopped.


therapy.
was stopped.
 On the basis of clinical history, including aversion to egg,
we performed skin-prick testing, the results of which were
positive for egg white allergy.


Although ingestion of egg lecithin
in cooked food
therapy.
is generally tolerated by egg-allergic people,
administration of
intravenous egg-containing lipid
was stopped.
 On the basis of clinical may cause significant egg,
emulsions history, including aversion to
adverse reactions.
we performed skin-prick testing, the results of which were
positive for egg white allergy.

Life-threatening anaphylactic reaction after the
administration of airway topical lidocaine
Soong Pediatr Pulmonol 2011;46:505

A 9-year-old boy who developed a life-threatening
anaphylaxis reaction of the airway and subsequent
dyspnea and circulation collapse because of
instilled the topical lidocaine into the airway within 2 min
before performing flexible bronchoscopy (FB).
FB revealed swollen airway mucosa and extensive foamy
secretion that severely compromised the ventilation lumen.
Rapid detection with FB and immediate resuscitation, including
prompt administration of epinephrine, volume expander, and
positive pressure ventilation with pure oxygen via an
endotracheal tube, were successfully save the patient's life.


Summary of patient's clinical course with time and data


An endoscopic view showing Four hours after resuscitation of the
extensive foamy secretion anaphylactic reaction, the chest film
with edematous mucosa in shows edematous infiltrations over
the tracheobronchial lumen. the bilateral lung fields.

Exercise Food Dependent Anaphylaxis

Mast cell activation syndrome: A newly recognized
disorder with systemic clinical manifestations
Hamilton JACI 2011;128:147

 18 patients with MC % patients with
100 –
activation syndrome. 90 –
94%
 Patients enrolled had 80 – 89% 89%
at least. 70 –
72%
 4 of the signs and 60 –
symptoms of abdominal 50 –
pain, diarrhea, flushing, 40 –
dermatographism, 30 –
memory and 20 –
concentration 10 –
difficulties, or 0
headache. Abdominal Dermato- Flushing Constellation
pain graphism of all 3
symptoms


Patients with suspected MCAS were treated by means
of stepwise application of mediator-targeting drugs, as

 Type I and II histamine blockers (ie, diphenhydramine),
cetirizine, loratidine and ranitidine.

 Depending on the response to treatment, additional
medications were sequentially added, including cromolyn
sodium (Gastrocrom) as montelukast.


Signs and symptoms of patients with MCAS

Sign or symptom Total (%), n = 18
Abdominal pain 17 (94)
Dermatographism 16 (89)
Flushing 16 (89)
Headache 15 (83)
Poor concentration and memory 12 (67)
Diarrhea 12 (67)
Naso-ocular 7 (39)
Asthma 7 (39)
Anaphylaxis 3 (17)


•Complete regression
(CR) was resolution of Assessment of treatment response
all symptoms,
•major regression
(MR) was improvement
in symptoms by
greater than 50%,
•partial regression
(PR) was improvement
in symptoms by 10%
to 50%, and
•no regression (NR)
was less than 10%
improvement in
symptoms.

Total serum tryptase levels are higher in young infants
Belhocine Pediat Allergy Immunol 2011;22:600

Serum tryptase levels as a function
of 3-month age groups from birth
to 12 months
 Total serum tryptase
levels (ImmunoCAP;
Phadia).

 372 sera from
infants < 1 yr.

Training of trainers on epinephrine autoinjector use
Arga Pediat Allergy Immunol 2011;22:590

% doctors using correctly
 The majority of physicians
epinephrine autoinjector
do not know how to use
80 –
epinephrine autoinjectors. 74%
70 –

 151 residents, specialists, 60 –

and consultants from 50 –
General Pediatrics 40 –
excluding allergists and 30 –
allergy fellows. 20 –
23%
10 –
 An 8-item questionnaire
0
followed by a practical Before After
session. Training

Training of trainers on epinephrine autoinjector use
Arga Pediat Allergy Immunol 2011;22:590

 The majority of physicians Mean time to administer
do not know how to use on autoinjector (seconds)
epinephrine autoinjectors. 30 –
28 sec.
 151 residents, specialists,
p<0.001
and consultants from 20 –
General Pediatrics
excluding allergists and
10 –
allergy fellows.
5 sec
 An 8-item questionnaire 0
followed by a practical Before After
session. Training

Extremely low prevalence of epinephrine autoinjectors in
high-risk food-allergic adolescents in Dutch high schools
Flokstra-de Blok Pediat Allergy Immunol 2011;22:374
To assess the need for an EAI, we asked
whether the adolescent ever had an life-
threatening anaphylactic reaction to a food
 The aim of the study was to requiring emergency treatment or
estimate the prevalence of hospitalization as a result, whether there was
probable food allergy in coexistent asthma, and whether there had
been clear systemic reactions to traces of
adolescents aged 11–20. food (i.e., itchy palms, food soles and/or
generalized itch, urticaria, swelling of face
 Examine the frequency of and/or body, asthmatic symptoms, dizziness,
epinephrine autoinjector gastrointestinal, or cardiovascular symptoms).
(EAI) ownership among
high-risk individuals.

 Screening questionnaire. 23 adolescents were considered candidates
for an EAI, whereas only 2 of them had
been prescribed this medication.

Extremely low prevalence of epinephrine autoinjectors in
high-risk food-allergic adolescents in Dutch high schools
Flokstra-de Blok Pediat Allergy Immunol 2011;22:374

 A number of studies suggest that the prevalence of food
allergy is increasing.
 The only proven forms of treatment for food allergy are strict
avoidance of the food(s) involved and medication for emergency
treatment.
 When a severe allergic reaction occurs, prompt administration
of epinephrine is essential.
 Therefore, all food-allergic patients at risk for severe allergic
reactions should carry an epinephrine autoinjector (EAI).
 However, there is no definite international consensus on whom
should be prescribed an EAI.
Simons KJ, Curr Opin Allergy Clin Immunol 2010: 10: 354–61.

Prescriptions for self-injectable epinephrine in
emergency department angioedema management
Manivannan Ann Allergy Asthma Immunol 2011;106:489

% patients receiving
90 –

80 – 87.3%
70 –
81.0%
 A retrospective 60 –
cohort study of 50 –
63 ED patients 40 –
with angioedema. 30 –

20 – 27.0%
10 –

.0
Epinephrine Antihistamines Steroids


RR of being treated with epinephrine
5.5 –
5.0 –
5.28
4.5 –
4.0 –

 A retrospective 3.5 –
3.0 –
cohort study of 3.31
2.5 – 3.04
63 ED patients
2.0 –
with angioedema.
1.5 –
1.0 –
0.5 –
0 0
Edema of Tightness/fullness Dyspnea
the tongue of throat wheeze


RR of being treated with epinephrine
5.5 –
5.0 –
5.28
4.5 –
4.0 –
13 patients
 A retrospective 3.5 –
(22.0%) were
cohort study of 3.0 –
3.31
discharged with 2.5 – 3.04
63 ED patients
self-injectable
with angioedema.
2.0 –
epinephrine. 1.5 –
1.0 –
0.5 –
0 0
Edema of Tightness/fullness Dyspnea
the tongue of throat wheeze

The TEN study: time epinephrine needs to reach muscle
Baker Ann Allergy Asthma Immunol 2011;107:235

Relationship between the duration of
injection and amount of epinephrine injected
 An epinephrine autoinjector (circle) and the percentage of epinephrine
(EAI) is designed to deliver absorbed by the marbleized beef (square).
epinephrine into the vastus
lateralis muscle.

 Several studies have
demonstrated both patient
and physician difficulties in
correctly using EAIs,
specifically premature
removal of the device from
the thigh.

The TEN study: time epinephrine needs to reach muscle
Baker Ann Allergy Asthma Immunol 2011;107:235

Relationship between the duration of
injection and amount of epinephrine injected
 An epinephrine autoinjector (circle) and the percentage of epinephrine
(EAI) is designed to deliver absorbed by the marbleized beef (square).

Holding the
epinephrine into the vastus
lateralis muscle.
device in place
 Several studies have is
for 1 second
demonstrated both patient
as effective as
and physician difficulties in
10 seconds.
correctly using EAIs,
specifically premature
removal of the device from
the thigh.

Epinephrine auto-injector use in adolescents at risk
of anaphylaxis: a qualitative study in Scotland, UK
Gallagher Demoly CEA 2011;41:869

1) Most adolescents had not used
the auto-injector in an
anaphylactic emergency.
 26 adolescents 2) Barriers to use, including:
with a history of -failure to recognize anaphylaxis;
anaphylaxis and -uncertainty about auto-injector
28 parents. technique and when to administer
it;
-fear of using the auto-injector.
3) Most adolescents reported
carrying auto-injectors some of
the time, though several found
this inconvenient due to the size.

Anaphylaxis in a New York City pediatric emergency
department: Triggers, treatments, and outcomes
Huang JACI 2012;129:162

Review of pediatric 80 – % reactions due to
emergency
70 –
department (PED)
records for 60 –
71%
anaphylactic 50 –
reactions
over 5 years. 40 –

30 –
213 anaphylactic
reactions in 20 –
192 children 9%
(20 had multiple
10 –
15% 5%
00
reactions). Foods Unknown Drugs Others

Huang JACI 2012;129:162

% reactions treated
Review of pediatric 80 –

79%
emergency
70 –
department (PED)
records for 60 –
anaphylactic 50 –
reactions
over 5 years. 40 –

30 –
213 anaphylactic
reactions in 20 –
192 children 10 –
(20 had multiple
00
reactions).
with epinephrine

Huang JACI 2012;129:162

% reactions treated
Review of27% of
In pediatric 80 –

79%
emergency
reactions 70 –
department (PED)
epinephrine was
records for 60 –
administered
anaphylactic 50 –
reactions arrival
before
over 5 years.PED.
in the 40 –
For 6% of 30 –
213 anaphylactic
the reactions, 20 –
reactions in
2 doses of
192 children 10 –
epinephrine
(20 had multiple
were administered.
reactions). 00
with epinephrine

Huang JACI 2012;129:162

% reactions treated
80 –
Administration of
both epinephrine doses
before arrival
70 –

60 –
79%
to the PED
50 –
was associated with a
lower rate of hospitalization
40 –
compared with 30 –
epinephrine
administration 20 –
in the PED (p<0.05). 10 –

00
with epinephrine

Development and Validation of Educational Materials
for Food allergy. Sicherer, J Pediatr 2012;160:651

Autoinjector competency score.
 Materials developed
through focus groups
and parental and expert
review.
 Submitted to 60 parents
of newly referred
children with a prior
food allergy diagnosis
and an epinephrine
autoinjector.
 The main outcome was
correct demonstration
of an autoinjector.


review. score was
Overall
statistically
significantly increased
of newly referred
from baseline
children with a prior
and mantained
and an12 months.
at epinephrine
autoinjector.
of an autoinjector.


This food allergy
review.
educational curriculum
for parents,
now available online
of newly referred
children withcost
at no a prior
(http://www.cofargroup.org/),
showed high levels
and an epinephrine
of satisfaction
autoinjector.
and efficacy.
of an autoinjector.

Comparing school environments with & without legislation
for the prevention & management of anaphylaxis.
Cicutto, Allergy 2012;67:131

1. Anaphylaxis is a severe, potentially fatal, systemic allergic
reaction that can occur suddenly after contact with
an allergy-causing substance.
2. Prevention is achieved only through allergen avoidance.
3. Allergen exposure is common in school settings with approximately
18% of food allergic reactions occurring at school.
4. Schools in Ontario have a legal obligation to protect the welfare
of students while at school; therefore, they are obliged
to support students at risk for anaphylaxis through allergen
avoidance and management of reactions.
5. However, school personnel often lack the knowledge
and skills necessary to recognize and treat anaphylactic reactions.


Background: School personnel in contact with students with
life-threatening allergies often lack necessary supports, creating
a potentially dangerous situation.
Sabrina’s Law, the first legislation in the world designed to protect
such children, requires all Ontario public schools to have a plan
to protect children at risk.
Although it has captured international attention, the differences a
legislative approach makes have not been identified.
Our study compared the approaches to anaphylaxis prevention and
management in schools with and without legislation.


School board policy consistency with
Canadian guidelines for preventing & managing
 Legislated (Ontario) anaphylaxis at schools.
and nonlegislated
(Alberta, British Columbia,
Newfoundland&Labrador,
and Quebec) environments.
 School board
anaphylaxis policies
were assessed
for consistency with
Canadian anaphylaxis
guidelines.


Parental reports of student food allergy.

Parental reports of their children’s school environments
regarding prevention and management of anaphylaxis.

The use of adrenaline autoinjectors by children and
teenagers. Noimark, Clin Exp Allergy 2012;42:284

% of patients using
adrenaline autoinjector
40 –
 14 paediatric allergy clinics
throughout UK. 30 –
 Questionnaire of allergic
20 –
reactions in the previous yr.
 969 patients. 10 – 16.7%
00
of patients experiencing
anaphylaxis


% of patients prescribed
adrenaline and receiving >1 dose
 14 paediatric allergy clinics
 Questionnaire of allergic
30 – 31.7%
reactions in the previous yr.
 969 patients. 20 –

10 –

00


Commonest reasons for using >1 dose
40 –
 14 paediatric allergy clinics 40%

 Questionnaire of allergic 20 –
reactions in the previous yr. 20%
10 – 13.3%
 969 patients.
00
Severe Lack of Miss-firing
breathing improvment with
difficulties 1stdose

Papaverina chloride as a topical vasodilator in accidental
injection of adrenaline into digital finger
Baris, Allergy 2011;66:1495

1) Restoration of blood flow by immersion in
warm water was attempted unsuccessfully;

2) Papaverine chloride (Papaverin HCl 20 mg/ml) was
diluted (20 mg in 10 ml of saline) and embedded into a
sponge;

3) The sponge was placed around the right thumb, and it
was wrapped with bandage for 3 h;

4) The finger turned to normal appearance and was warm
and pain-free with normal capillary refill time.

Right thumb after injection of
adrenaline auto-injection
 An increasing trend in
accidental injection cases
into digits has been
observed with the
frequent use of adrenaline
auto-injectors;

 This is an annoying situation
with pain and possesses a
potential risk of tissue
necrosis in the victims.

Right thumb after injection of
adrenaline auto-injection
 An increasing trend in
accidental injection cases
intoHer finger
digits has been
was cold and
observed with the
frequent use of adrenaline
auto-injectors; she
pale, and
suffered situation
 This is an annoying
from pain.
with pain and possesses a
potential risk of tissue
necrosis in the victims.


• Immersion into warm water, digital massage, and application of
topical nitroglycerin are announced to be conservative
applications with a wide acceptance;

• Because adrenaline induces a vasoconstriction through
an α-adrenergic effect, the use of topical phentolamine,
which is a nonselective α-adrenergic antagonist, is very
effective in patients unresponsive to the conservative
treatment mentioned earlier.

• Local injection of phentolamine to the area can reverse
ischemia quickly and efficiently.


•However, because of limited space in the
accidental injection area, additional volumes of
phentolamine may cause a possible compartment
syndrome, which may worsen ischemia by extra
induced pressure.
•Papaverine is an opiate, act as smooth muscle
relaxant, which inhibits phosphodiesterase
enzyme, and it is widely used during or after
vascular surgeries to reverse vasospasm.

Comparison of cetirizine and diphenhydramine in the
treatment of acute food-induced allergic reactions
Park, JACI 2011;128:1127

• Diphenhydramine has been commonly used as the antihistamine
of choice for acute food-induced allergic reactions given its
prompt onset of action (15-60 minutes) and ready availability,
although epinephrine is still the first-line therapy for anaphylaxis.
• However, sedation is a common side effect of diphenhydramine,
which can complicate the assessment of a patient being treated
for an acute food-induced allergic reaction.
• Cetirizine is a second-generation antihistamine with a
similar onset (15-30 minutes) but longer duration of action
(≥ 24 hours) compared with diphenhydramine.
• Furthermore, central nervous system effects are less commonly
reported.

Park, JACI 2011;128:1127

 70 allergic reactions % patients experienced
during oral food sedation
challenge
30 –
involving 64 patients
aged 3-19 yrs. ns 28.6%
20 –
 35 reactions included
in each treatment arm.
17.1%
10 –
 Either liquid
diphenhydramine
(1mg/kg) or liquid 0
CETIRIZINE DIPHENHYDRAMINE
cetirizine (0.25 mg/kg)

Park, JACI 2011;128:1127

Mean time of resolution of Mean time of resolution of
urticaria (minutes) pruritus (minutes)
50 – 50 –

40 – 40 –
40.8 42.3
30 – min min 30 –
31.3
min
28.6
20 – 20 –
min
10 – 10 –

00 00
CETIRIZINE DIPHENHYDRAMINE CETIRIZINE DIPHENHYDRAMINE

Park, JACI 2011;128:1127

9 patients in each group required administration of
Mean time of resolution of
steroid or epinephrine for symptomsresolution of
Mean time of of
50 – abdominal pain, nausea,50 –
cough, wheezing, and
angioedema.
40 – 40 –
40.8 42.3
30 – min min 30 –
31.3
min
28.6
20 – 20 –
min
10 – 10 –

00 00

Park, JACI 2011;128:1127

Cetirizine has similar efficacy and onset of action
compared with diphenhydramine in treating
urticaria (minutes)
acute food-induced allergic reactions but(minutes)
pruritus has also
50 – 50 –
longer duration of action compared with
diphenhydramine…
40 – 40 –
40.8 42.3
30 – min min 30 –
31.3
min
28.6
20 – 20 –
min
10 – 10 –

00 00

Park, JACI 2011;128:1127

… Cetirizine is a good treatment option
50 – for acute food induced allergic reactions.
50 –

40 – 40 –
40.8 42.3
30 – min min 30 –
31.3
min
28.6
20 – 20 –
min
10 – 10 –

00 00

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