Dhm12 programm v7

ABSTRACTS
Programme
& Abstract Book

www.eaaci-dhm2012.com Programme & Abstract Book DHM5 2012 | 3
CONTENT
Welcome................................................................................................................................................................4
Organising Committee......................................................................................................................................6
History of DHM....................................................................................................................................................7
EAACI Executive Committee...........................................................................................................................8
General Information A-Z...................................................................................................................................9
Sponsors............................................................................................................................................................14
Map of the Venue „Klinikum rechts der Isar“..........................................................................................15
Programme Overview.....................................................................................................................................18
Scientific Programme.....................................................................................................................................20
Poster Exhibition.............................................................................................................................................28
Abstracts............................................................................................................................................................30
Welcome Reception “Little Oktoberfest”..............................................................................................152
Exhibition Plan...............................................................................................................................................153
List of Exhibitors...........................................................................................................................................154
Imprint.............................................................................................................................................................155

www.eaaci-dhm2012.comProgramme & Abstract Book DHM5 20124 |
Dear Friends and Colleagues,
I warmly welcome you to the 5th edition of the Drug Hypersensitivity Meeting (DHM5), which is
taking place for the first time in Munich, Germany.
Our Academy is aware of the growing interest on Drug Hypersensitivity, and is therefore proud
of supporting the development of active tools for the scientific and research community working
in this field. EAACI has a Drug Allergy Interest Group and diverse Task Forces related to this topic,
which reflects the high profile of this field for our members and our speciality.
The EAACI Drug Allergy Interest Group involves many different groups from all over Europe. The
core group of this Interest Group is called ENDA (European Network of Drug Allergy), and com-
prises active participants with a common area of research e.g. in the epidemiological, clinical, or
fundamental aspects of drug hypersensitivity.
Allergic drug reactions are a continuing challenge for healthcare professionals. There is a lot to
learn and discuss. More and more different types of reactions and mixed types are expected to
occur due to new biologicals that are going to be used in our area. This meeting will give you the
opportunity to learn about new techniques and discuss with other experts about the different
aspects of diagnosis and management of your patients.
With six plenary sessions and twelve parallel symposia, DHM5 2012 will give you up to date
information about basic, translational and clinical aspects of mechanisms and management of
drug hypersensitivity. These scientific sessions will be complemented with practical seminars
and case reports.
The Local Organisers worked tirelessly to make your time in Munich a wonderful scientific experience.
I wish you a very fruitful DHM5 2012 Meeting.
Best regards,
Prof. Cezmi Akdis
EAACI President
WELCOME FROM EAACI

Dear Friends and Colleagues,
As Congress Chairs, we are delighted to welcome you to the Drug Hypersensitivity Meeting 5
(DHM5 2012) and to the beautiful city of Munich.
The success of the previous DHM Meetings as well as the rapidly growing interest in drug
hypersensitivity encouraged EAACI to promote DHM as one of its thematic “Focused Meetings”.In
the light of the increasing knowledge in the field, DHM 2012 will provide you with an excellent
opportunity to learn about and to share major developments, novel ideas and unprecedented
progress in this area. We can all look forward to four intense days of talks, seminars and case
reports and more than 200 posters, but we hope there will also be plenty of time to meet old and
new friends, engage in discussions of science, and experience the amenities of the town. Thank
you for joining us. We are sure that this will be a most enjoyable experience.
The capital of Bavaria is located at the Isar River, north of the Bavarian Alps. Munich is a modern
and cultural city with a rich historic background. We welcome you in the recently renovated
lecture hall buildings of the Faculty of Medicine/Klinikum rechts der Isar, the clinical campus of
the Technische Universität München (TUM) – near to the city center offering rich socio-cultural,
historic and modern-life aspects of Munich hospitality. Don’t miss the welcome reception on
Wednesday, 11 April in the evening, where a “Little Oktoberfest” will be given right on the campus,
hopefully outside (weather permitting).
We would like to thank our corporate sponsors for supporting the meeting and the continued
growth of our specialty. We encourage you to visit them at the exhibition area, located on the
Hörsaal A Foyer.
On behalf of the organising committee and the local and EAACI organisers we cordially welcome
you to Munich wishing you an interesting and stimulating meeting and a chance to meet old and
make new friends!

Knut Brockow Dean Naisbitt
DHM5 2012 Chair DHM5 2012 Vice-Chair
WELCOME TO MUNICH

ORGANISING COMMITTEE
• K. Brockow (DHM5 Chair), Germany
• D. Naisbitt (DHM5 Co-Chair), United Kingdom
• W. Pichler (Past DHM Chair), Switzerland
• B.K. Park (Past DHM Chair), United Kingdom
• J.C. Roujeau (Past DHM Chair), France
• P. Demoly (Past DHM Chair), France
• A. Romano (Past DHM Chair), Italy
• A. Bircher, Switzerland
• M. Blanca, Spain
• M. Castells, USA
• Y.T. Chen, Taiwan
• H.J. Hoffmann, Denmark
• M. Kammüller, Switzerland
• T. Kawabata, USA
• S.H. Kim, South Korea
• S. Mallal, Australia
• S.F. Martin, Germany
• H. Merk, Germany
• M. Mockenhaupt, Germany
• J.F. Nicolas, France
• R. Pieters, The Netherlands
• M. Pirmohamed, United Kingdom
• J. Ring, Germany
• N. Shear, Canada
• T. Shiohara, Japan
• A. Trautmann, Germany
• J. Uetrecht, Canada
• C. Yu , USA
Are you an EAACI Member?
Here are just a few of the benefits Members receive:
Discount on registration fees to EAACI annual
congresses.
Subscription to ALLERGY Journal and the Pediatric
Allergy and Immunology Journal including supplements.
Online access to the oﬃcial EAACI journals.
The EAACI Newsletter.
For more information contact: info@eaaci.org | www.eaaci.net
Ad EAACI Membership_180x100.indd 1 21.04.2011 14:49:21

HISTORY OF DHM
In comparison to other hypersensitivity reactions in allergology and immunology, diagnosis
and therapy of drug hypersensitivity is more complicated, as multiple drugs are able to elicit a
heterogeneous array of symptoms ranging from mild to severe and from exanthematous skin
eruptions to anaphylaxis. Thus, drug hypersensitivity still has to be regarded as a developing
area. In order to combine existing knowledge and share new experiences in drug hypersensitivity,
the Drug Hypersensitivity Meeting (DHM) was created by W. J. Pichler, Bern, which became an
unofficial world congress on drug hypersensitivity.
The 1st
Drug Hypersensitivity Meeting was hosted in Bern, Switzerland, 5 – 8 May 2004.
The programme encompassed all aspects of drug hypersensitivity, and was aimed at scientists
in the fields of Pharmacology, Toxicology, Chemistry, Allergy and Immunology. It should foster
the exchange of knowledge between representatives from academia, industry and the regulatory
agencies interested in drug hypersensitivity and aimed to create a better understanding and
management of adverse drug reactions. The first meeting developed to be a success with more
than 250 delegates and it was decided to continue the meeting every second year.
The 2nd
Drug Hypersensitivity Meeting was organised by Dean J. Naisbitt, Munir Pirmohamed,
and B. Kevin Park in Liverpool, United Kingdom, from 18 – 21 April 2006. It was attended by
about 200 delegates and provided an excellent environment to discuss recent advances in the
understanding of the chemical, cellular, molecular and genetic basis of drug hypersensitivity.
The3rd
DrugHypersensitivityMeetingwashostedbyJean-ClaudeRoujeauandPascalDemolyin
Paris, 11 – 13 April 2008, and successfully continued the interaction between basic scientists
and clinicial researchers. Like the previous Drug Hypersensitivity Meetings, it brought together
international experts with the aim of fostering the exchanges of knowledge in drug hypersensitivity
and improving the management of a constantly evolving problem.
From 22 – 25 April 2010, Antonino Romano organised the 4th
Drug Hypersensitivity Meeting,
now with increasing recognition and support of the European Academy of Allergy and Clinical
Immunology (EAACI). In addition to basic research, it intensified practical clinical approaches in
part by presenting updates on pathogenic mechanisms, diagnosis and prevention provided by
the European Network for Drug Allergy (ENDA), the EAACI Interest Group on Drug Hypersensitivity.
The 5th
Drug Hypersensitivity Meeting, which will be held in Munich 11 – 14 April 2012, will be
the first DHM organised and promoted by the EAACI. The EAACI provides logistic and financial
support and the intense participation by Asian, Australian and American colleagues underline
that it will continue as an international meeting. As in previous meetings, experimental scientists
as well as clinicians will find a platform to discuss their results and hopefully exchange their
approach to drug hypersensitivity research. To enhance the attractiveness of DHM for clinicians,
clinical case reports and practically oriented breakfast seminars will be provided. Let’s hope
that the 5th
DHM will become as successful as the previous ones – the high number of already
registered participants and poster presenters seems to be a big promise for a successful meeting.
Werner Pichler Dean Naisbitt Knut Brockow

EAACI EXECUTIVE COMMITTEE
EAACI Executive Committee
C. Akdis, President
N. Papadopoulos, Secretary General
A. Muraro, Treasurer
J. Lötvall, Past President
P. Demoly, Vice-President Education & Specialty
C. Virchow, Vice-President Congresses
V. Cardona, Vice-President Communications & Membership
Section Chairs
A. Custovic, Asthma Section Chairperson
C. Grattan, Dermatology Section Chairperson
P. W. Hellings, ENT Section Chairperson
E. Knol, Immunology Section Chairperson
G. Roberts, Pediatric Section Chairperson
E. Heffler, JMA Chairperson
Interest Group Representatives
B. Bilo, IG Representative
T. Werfel, IG Representative
Members at Large
I. Agache
M. Jutel
M. Triggiani
P. Eigenmann
R. van Ree
S. Bavbek
Adjunct Members
F. Braido, CME Committee Chair
J. De Monchy, Specialty Committee Chair
J. Gayraud, Ethics Committee
P. Schmid-Grendelmeier, Exam Committee Chair
L. K. Poulsen, SPC Chairperson
C. Skevaki, EAACI Web Editor
M. Walker, Executive Director

GENERAL INFORMATION A-Z
Bank, Cash machine
Cash machines can be found at various bank institutions around the Max-Weber-Platz.
Certificate of Attendance
Participating delegates will receive a Certificate of Attendance at the registration desk on-site.
Climate and Dress Code
In April the average temperature in Munich is approx. 12,6 °C. For weather forecasts please visit
www.weathercity.com/de/munich/
The dress code will be informal throughout the Meeting.
Cloakroom
There will be a supervised cloakroom located on the right side of the entrance to the plenary
hall, Hörsaal A.
CME Credits
We are pleased to inform you that EAACI will offer Continuing Medical Education (CME) Credits
for the Drug Hypersensitivity Meeting 5. The aim of the CME system is to assure a high level
of theoretical and clinical competences through medical specialists’ working life. The EAACI
CME Accreditation Committee guarantees that CME programmes are of a high scientific and
educational standard in agreement with the European and American CME systems. The EAACI
CME Committee has applied to the European Accreditation Council for CME (EACCME) for
European credits recognition.
EACCME Credits will be available to US Doctors attending DHM5, due to a reciprocal agreement
signed by the American Medical Association (AMA) and the European Union of Medical Specialists
(UEMS).
Each medical specialist should claim the recognition of the EAACI/EACCME Credits to his/her
own CME National Authority.
The DHM5 Meeting is certified with 21 CME credit points.
The number of the credits per day will be :
Wednesday: 6
Thursday: 6
Friday: 6
Saturady: 3
Currency
The unit of currency is the Euro (€).
The national currency in Germany is Euro (€).
Disclaimer
The Organisers cannot accept liability for injuries or losses of whatever nature incurred by
participants, nor for loss of or damage to their luggage and/or personal belongings.

EAACI Booth
We invite you to visit the EAACI Booth in the exhibition area just outside the Main Auditorium. If
you have any questions regarding EAACI membership or if you want to settle your membership
fee, the staff from the EAACI Headquarters will be happy to help you.
Samples of EAACI publications will be displayed for your perusal as well as information about
future EAACI events.
We hope to see you at the EAACI Booth. Remember that after the DHM5 2012 you can always
visit the website www.eaaci.net and read the latest news about EAACI activities and publications.
Opening Hours of the EAACI Booth:
Wednesday, 11 April 2012 12:00 – 18:00
Thursday, 12 April 2012 08:00 – 18:00
Friday, 13 April 2012 08:00 – 18:00
Saturday, 14 April 2012 08:00 – 14:00
EAACI Headquarters
Genferstrasse 21
CH-8002 Zurich
Switzerland
Tel: +41 44 205 55 33
Fax: +41 44 205 55 39
E-mail: info@eaaci.org
Website: www.eaaci.net
EAACI Membership
EAACI membership gives its members priority status at EAACI Congresses and Focused Meetings.
Members over 36 years of age receive a discount of EUR 100 on the Registration fee of this
Meeting and Junior members are entitled to register to the Meeting at the low “Student” fee.
EAACI offers free Junior membership to individuals up to 36 years of age (with online access
to the Journals ALLERGY and Pediatric Allergy Immunology). In addition, EAACI also offers a
50 % reduction on membership fees to members from countries with a GNP of less than USD
10’000, with full membership benefits. As an EAACI member you will be kept informed on the
latest research and developments through our official journals ALLERGY and Pediatric Allergy
Immunology (available in printed or electronic version) and Clinical and Translational Allergy
(e-journal). These journals contain editorials, review articles, original articles, educational
series and more. Experience and be part of the advancement of the knowledge and practice of
allergy, asthma and immunology for optimal patient care! For more information and to apply for
membership visit our website: www.eaaci.net
Electricity
220 volts, 50Hz. European-style two-pin plugs are standard.

Exhibition
The Drug Hypersensitivity Meeting 5 includes an exhibition that starts 11 April 2012 and will
be open during the Meeting hours. Opening hours:
Wednesday, 11 April 2012 12:00 – 18:00
Thursday, 12 April 2012 08:00 – 18:00
Friday, 13 April 2012 08:00 – 18:00
Saturday, 14 April 2012 08:00 – 14:00
General Information – Munich
The city of dreams in Southern Germany is situated in the midst of a beautiful pre-alpine
countryside and offers a spectacular variety of culinary, artistic and cultural highlights.
Munich combines the splendour of an old royal seat with the vitality of a modern high-tech
location.
The city owes its generous architecture to the reign of the Bavarian King Ludwig I (1786-1868).
The townscape is marked by broad avenues and the contrast between Classicist restraint and
Baroque profusion. Daring creativity and innovation have placed new architectural accents all
over the city.
The downtown area presents a clear, delightful and charming image marked by the distinctive
feature of the Frauenkirche cathedral whose two towers rise above the roofs of the city.
Munich is the largest city in the south of Germany and is about an hour and a half drive from the
Alps. It is located very close to Austria, Switzerland and after a short hop through Austria, also
Italy.
Information for Speakers / Oral Presentation
Please bring your oral presentation on a memory stick and hand it in, in good time before
your session starts. Only PowerPoint projections will be available in the session halls and only
computers provided on-site can be used. Only PowerPoint version 2007 or previous running
on PC’s will be available. The maximum resolution for the computers and projectors will be set at
1024x768. We recommend that you only use standard fonts and symbols to avoid formatting
issues for your presentation. We also recommend you to include your fonts when you save your
presentation. The standard set-up does not allow audio in your presentation. If you use clips or
attachments, make sure to create a presentation folder where these are included. Only standard
codecs are supported.
Internet
WLAN is available for free for all participants at their own risk in most areas of the lecture hall
building. The name of the SIID-network is “con”, password is not needed.

Language
The official language of the meeting is English.
Simultaneous translation will not be provided.
Media / Press
Press registration is available at the registration desk.
Name Badges
Every participant will receive a name badge at the registration desk. For security reasons all
participants are requested to wear their badges during the DHM5 Meeting. Entrance will not be
permitted to those delegates not wearing their badge.
Badge colours:
Transparent Delegates
Red Faculty
Green Exhibitors
White Press
Blue Staff
Programme Changes
The Organisers cannot assume liability for any changes in the programme due to external
unforeseen circumstances.
Public Transport
Munich has an extensive public transport system consisting of S-Bahn (a mainly above ground
urban railway system), U-Bahn (mainly underground rail system), buses and trams.
All of these can be accessed with the same ticket available from counters or ticket machines
at the S- and U-Bahn stations or on the bus or tram. Different kinds of day passes and group
tickets are also available. The main airport and all train stations are easily accessible by public
transport. More information at: www.mvv-muenchen.de
Registration Desk
The registration desk at the Klinikum rechts der Isar, which can be found opposite to the main
entrance of the lecture hall building, will be open as follows:
Wednesday, 11 April 2012 08:00 – 18:30
Thursday, 12 April 2012 06:30 – 18:30
Friday, 13 April 2012 06:30 – 18:30
Saturday, 14 April 2012 07:00 – 14:00
Phone: +49 (0) 172 58 01 346

Safety
The area around the Lecture Hall Building of Klinikum rechts der Isar is known to be a very safe
zone of Munich. However, please be aware of thieves and pick-pockets like in any major European
city and take respective precautions.
Smoking Policy
In accordance with the policy of EAACI, this is a non-smoking event.
Welcome Reception
You can purchase tickets for the Welcome Reception at the registration desk.
Telephone
The international access code for Germany is + 49. The outgoing code is 00 followed by the
relevant country code (e. g. 0044 for the United Kingdom). Note that telephone numbers in
Germany can range from four to nine digits.
Local emergency telephone numbers are 112 (fire and ambulance) and 110 (police).
Tourist Information
The staff at the registration desk and at the reception of your hotel will be glad to answer any
questions.
Travel Grants
Costs will be refunded after the Meeting, upon presentation of your original tickets and travel
receipts. You will get the reimbursement form at the registration desk.
Venue
The Drug Hypersensitivity Meeting 5 is held at:
Klinikum rechts der Isar
Technische Universität München (TUM)
Faculty of Medicine
Lecture Hall Building
Ismaninger Straße 22
81675 Munich, Germany
Website
www.eaaci-dhm2012.com

SPONSORS
Platinum Sponsor
Research Laboratories
Maruho Co., Ltd.
Silver Sponsor
Diater Laboratorios S.A.
Bronze Sponsor
Deutsche Gesellschaft für Allergologie und
klinische Immunologie e.V. (DGAKI)
Other Contributors
Phadia GmbH
Novartis

KLINIKUM RECHTS DER ISAR
How to get there?
From the Main Central Station
• Take the underground train “U4” in direction to “Arabellapark” or “U5” in direction to
“Neuperlach Süd”
• The stop is “Max-Weber Platz”
• Take the exit “Einsteinstraße” (approx. 4 minutes walk to Klinikum rechts der Isar)
• Take the tram (street train) “18” in direction to “Effnerplatz”
• The stop is “Max-Weber Platz” (approx. 2 minutes walk to Klinikum rechts der Isar)
From Marienplatz
• Take the underground train “U6” in direction to “Garching Forschungszentrum” or “U3” in
direction to “Olympiaeinkaufszentrum OEZ”
• Change at “Odeonsplatz” (1 stop after Marienplatz)
• Take the underground train “U4” in direction to “Arabellapark” or “U5” in direction to
“Neuperlach Süd”
• The stop is “Max-Weber Platz”
• Take the exit “Einsteinstraße” and follow the signs “DHM5” (approx. 4 minutes walk to
Klinikum rechts der Isar)
Klinikum
rechts der Isar
Hörsäle
Lecture Halls

ABSTRACTS
For more information please contact: allergyschools@eaaci.org
www.eaaci.net
Allergy Schools
2012
Asthma Exacerbations
Risk Factors and Management
2 – 5 August 2012
Tallinn, Estonia
Food Allergy Training Course
23 – 25 August 2012
Vienna, Austria
Speciﬁc Allergy and Immunotherapy
15 – 17 November 2012
El Escorial, Spain

ABSTRACTSABSTRACTSHEADLINE
www.eaaci-dhm2012.com Final Programme & Abstract Book DHM 2012 | 17
SERIN 2013
21 – 23 March 2013
Leuven, Belgium
Symposium on Experimental Rhinology and Immunology of the Nose
SAVE THE DATE!
21 – 23 March 2013

PROGRAMME OVERVIEW
Wednesday, 11 April 2012
08:15 - 11:30 Pavillon Pre-congress clinical course and workshop:
Basophil activation test
12:45 - 13:15 Welcome
13:15 - 14:00 Introductory lecture Drug hypersensitivity research:
past, present and future?
14:15 - 16:00 Plenary Drug anaphylaxis
16:00 - 16:30 Coffee break
16:30 - 18:00 Parallel symposia – Approach to drug exanthems
– Drug hypersensitivity and viral disease:
a dynamic interaction?
18:00 Welcome Reception “Little Oktoberfest”
Thursday, 12 April 2012
07:30 - 08:15 Practical seminars – How to manage NSAID hypersensitivity
– Drug desensitization
08:15 - 08:45 Teaching case reports Case report presentations
09:00 - 10:45 Plenary Fundamental immunological principles
relevant to drug hypersensitivity
11:15 - 12:45 Parallel symposia – Diagnostic tools: options and controversies
of in vivo tests
– Relevant models to understand new and
emerging drug hypersensitivity issues
12:45 - 13:15 Snack lunch
13:15 - 14:00 Poster viewing
14:15 - 16:00 Plenary Side effects of biologicals: clinical issues
16:30 - 18:00 Parallel symposia – In vitro diagnostic tools: research instruments
or fit for practice?
– Risk assessment of side effects to biologicals

PROGRAMME OVERVIEW
Friday, 13 April 2012
07:30 - 08:15 Practical seminars – How to manage adverse reactions to
chemotherapy and biologicals
– Drug provocation test
09:00 - 10:45 Plenary Drug-induced liver injury
11:15 - 12:45 Parallel symposia – Clinical hypersensitivity reactions to
important drugs
– What have we learned from genetic studies
on drug hypersensitivity?
14:15 - 16:00 Plenary Severe adverse drug reactions
16:30 - 18:00 Parallel symposia – Contact hypersensitivity meets drug
hypersensitivity
– Progression of allergen recognition to
delayed hypersensitivity
Saturday, 14 April 2012
07:30 - 08:15 Practical seminars – How to manage radiocontrast media
hypersensitivity
– How to manage betalactam hypersensitivity
09:00 - 10:45 Plenary Understanding the structural basis of HLA
associations for drug hypersensitivity
11:15 - 12:45 Parallel symposia – Update on ENDA activities
– Pathomechanisms of SJS/TEN
12:45 - 13:15 Highlights of the meeting: experimental
Highlights of the meeting: clinical

SCIENTIFIC PROGRAMME
Wednesday, 11 April 2012
Pavillon
08:15 – 09:15
09:30 – 11:00
11:00 – 11:30
12:45 - 13:15 Welcome
13:15 - 14:00 Lecture Hall A Chair: K. Brockow, D. Naisbitt
13:15 – 14:00 W. Pichler
14:15 -16:00 Plenary
Lecture Hall A
Chair: J. Ring, P. Demoly
14:15 – 14:45 R. Pumphrey
14:45 – 15:15 P. M. Mertes
15:15 – 15:45 L. Heise Garvey
15:45 – 16:00 F. Gomez
16:30 - 18:00 Parallel symposia
Lecture Hall A
Lecture Hall B
Chair: A. Romano, P. Whitacker
16:30 – 16:52 F. Rueff
16:52 – 17:14 N. Shear
17:14 – 17:36 A. Trautmann
17:36 – 18:00 A. Bircher
Chair: J. C. Roujeau, P. Musette
16:30 – 16:55 T. Shiohara
16:55 – 17:20 H. Hashizume
17:20 – 17:45 P. Musette
17:45 – 18:00 Y.-C. Chen
18:00 Welcome Reception “Little Oktoberfest” at the Mensa / Rechts der Isar

Pre-congress clinical course and workshop: Basophil activation test in drug hypersensitivity
Research tool or diagnostic test?
Drug allergens with BAT
Clinical case reports
Hands-on BAT (provided by Bühlmann Laboratories)
Discussion of case reports with BAT results
Introductory lecture
Drug hypersensitivity research: past, present and future
Drug anaphylaxis
Lessons from fatal anaphylaxis to drugs
Blood derivative-induced anaphylaxis
Hidden allergens in perioperative anaphylaxis
PV 30 Diagnosing immediate hypersensitivity reactions to radio contrast media
Approach to drug exanthems
Morphology and dermatological differential diagnoses
Use of chronology and literature to conclude to the culprit drug
Management: Treating through, cessation or desensitisation?
Non-immediate urticaria and angioedema – does it exist?
Drug hypersensitivity and viral disease: a dynamic interaction?
Characterisation of viral responses in patients with severe drug eruptions
Drug- and virus-specific T-cells as mediators of DRESS
EBV-specific T-cells in DRESS
PV 124: Reactivation of human herpes viruses in various forms of cutaneous adverse drug
reactions: a comparative study in Taiwan

Thursday, 12 April 2012
07:30 - 08:15 Practical seminars Lecture Hall A A. Bircher
Lecture Hall B M. Castells
08:15 - 08:45 Teaching case reports
09:00 - 10:45 Plenary
Lecture Hall A
Chair: T. Shiohara, H. Merk
09:00 – 09:26 O. Rötzschke
09:26 – 09:52 W. Schamel
09:52 – 10:18 S. Martin
10:18 – 10:45 K. Eyerich
Lecture Hall A
Lecture Hall B
Chair: A. Bircher, M. Blanca
11:15 – 11:40 A. Romano
11:40 – 12:05 A. Barbaud
12:05 – 12:30 P. Demoly
12:30 – 12:45 J. Hjortlund
Chair: K. Park, S. Martin
11:15 – 11:37 L. Kwast
11:37 – 11:59 R. Abe
11:59 – 12:21 L. Faulkner
12:21 – 12:45 Y. Yerly
14:15 - 16:00 Plenary
Lecture Hall A
Chair: W. Pichler, M. Castells
14:15 – 14:45 A. Wollenberg
14:45 – 15:15 A. Vultaggio
15:15 – 15:45 L. Macchia
15:45 – 16:00 A. Barbaud
Lecture Hall B
Lecture Hall A
Chair: C. Mayorga, J. Nicolas
16:30 – 16:55 A. Rozieres
16:55 – 17:20 J. Leysen
17:20 – 17:45 J.-L. Guéant
17:45 – 18:00 T. Hanafusa
Chair: A. Vultaggio, Guest: M. Kammueller
16:30 - 16:34 M. Kammüller
16:34 - 16:55 T. Manigold
16:55 - 17:16 S. Spindeldreher
17:16 - 17:37 T. Ishida
17:37 – 18:00 O. Hausmann

How to manage NSAID hypersensitivity
Drug desensitisation
Case report presentations (immediate drug hypersensitivity)
Fundamental immunological principles relevant to drug hypersensitivity
The role of HLA in presentation of peptide and chemical antigens
T-cell activation and signaling
Immune regulation: stimulation of innate immunity by drugs/chemicals
Immune regulation: Th17 cells and Tregs
Diagnostic tools: options and controversies of in vivo tests
What do we know about cross-reactivity in betalactams?
Approach to standardised skin test techniques
Value and limitations of the drug provocation test
PV 74 Prospective study on the diagnosis of penicillin allergy (PEDAL 2)
Relevant models to understand new and emerging drug hypersensitivity issues
Animal models for screening drug hypersensitivity issues
Production of SJS/TEN model mice using patients’ samples
Risk assessment for drugs using genotyped drug naïve volunteers: Liverpool experience
Risk assessment for drugs using genotyped drug naïve volunteers: Bern experience
Side effects of biologicals: clinical approaches
Unusual cutaneous side effects of biologicals
Adverse effects due to antibody formation and test possibilities
PV 58 Rapid desensitisation to rituximab
PV 56 Evaluation of a practice og managing drug eruptions due to pegylated Interferon and
effectiviness of tolerance induction
In vitro diagnostic tools: research instruments or fit for practice?
LTT and ELIspot
Flow cytometry based assays including histoflow
How to develop new specific IgE assays to drugs?
PV 189 Evaluation of drug-specific T-cell population by flow cytometric drug-induced
lymphocyte stimulation test
Risk assessment of side effects to biologicals
Introductory Lecture
Cytokine release syndromes: in vitro risk assessment
Investigating assessment of the immunogenicity risk for biotherapeutics – Available methods
and their predictive value
Cytokine imbalance after biological treatment is responsible for paradoxical deterioration
Acute infusion reactions including anaphylaxis

Friday, 13 April 2012
07:30 - 08:15 Practical seminars Lecture Hall A A. Barbaud
Lecture Hall B P. Demoly
08:15 - 08:45 Teaching case reports Lecture Hall A
09:00 - 10:45 Plenary
Lecture Hall A
Chair: E. Phillips, M. Pirmohamed
09:00 – 09:30 A. K. Daly
09:30 – 10:00 C. Ju
10:00 – 10:30 D. Naisbitt
10:30 – 10:45 N. Wuillemin
Lecture Hall B
Lecture Hall A
Chair: A. Trautmann, H. Merk
11:15 – 11:40 C. Mayorga
11:40 – 12:05 M. Castells
12:05 – 12:30 K. Scherer
12:30 – 12:45 B. Y. Thong
Chair: A. Daly, S. Hung
11:15 – 11:37 M. Mockenhaupt
11:37 – 11:59 Y.-T. Chen
11:59 – 12:21 T. Mushiroda
12:21 – 12:45 M. Pirmohamed
14:15 - 16:00 Plenary
Lecture Hall A
Chair: M. Mockenhaupt, H. Hashizume
14:15 – 14:45 Y. Kano
14:45 – 15:15 J.-F. Nicolas
15:15 – 15:45 J.-C. Roujeau
15:45 – 16:00 E. Genin
Lecture Hall B
Lecture Hall A
Chair: I. Kimber, A. Barbaud
16:30 – 16:55 A. Schnuch
16:55 – 17:20 W. Aberer
17:20 – 17:45 T. Rustemeyer
17:45 – 18:00 P. R. Esser
Chair: A. Rozières, C. Ju
16:30 – 16:52 I. Kimber
16:52 – 17:14 E. Maggi
17:14 – 17:36 S. Lloyd Watkins
17:36 – 18:00 E. Perez-Inestrosa

How to manage adverse reactions to chemotherapy and biologicals
Drug provocation test
Case report presentations (immediate drug hypersensitivity)
Drug induced liver injury
Genome studies and HLA associations in drug-induced liver injury (DILI)
Immunological mechanism of DILI: Lessons from animal models
Immunological mechanism of DILI: Lessons from patients and human volunteers expressing HLA risk alleles
PV 163 Mechanisms of T cell stimulation by flucloxacillin in HLA-B*5701
+ flucloxacillin-naïve individuals
Clinical hypersensitivity reactions to important drugs
Quinolones
Targeted and traditional chemotherapy
Anticoagulants
PV 60 A Retrospective Study on Sequential Desensitisation-Rechallenge for Anti-Tuberculous Drug Allergy
What have we learned from genetic studies on drug hypersensitivity?
Lessons to be learned from epidemiology
Carbamacepine-induced hypersensitivity: HLA, T-cell receptors and pharmacogenetics
HLA-A*3101 allele is a risk factor for different carbamazepine-induced cutaneous adverse drug reactions
Pharmacogenetic screening for drug hypersensitivity: lessons from the ITCH project
Severe cutaneous adverse reactions
Complications and sequelae of severe drug reactions
Are SCADRs allergic? Value of immunobiological tests
Treatment recommendations
PV 130 HLA-A*3101 is more strongly associated with carbamazepine-induced drug reac-
tion with eosinophilia and systemic symptoms than with carbamazepine-induced Stevens-
Johnson syndrome/toxic epidermal necrolysis
Contact hypersensitivity meets drug hypersensitivity
Contact allergy to drugs
Hematogeneous contact allergy
Contact allergy and drug exanthema to drugs: differences and similarities
PV 109 Innate immune responses to contact sensitisers are mediated via ROS production
and HA degradation
Progression of allergen recognition to delayed hypersensitivity
From antigen recognition to dendritic cell migration
From dendritic cell migration to a polarised immune response
T-cell receptor interactions with drugs
Nanostructures mimicking hapten protein

Saturday, 14 April 2012
07:30 - 08:15 Practical seminars Lecture Hall A M. Grosber
Lecture Hall B M. J. Torres
08:15 - 08:45 Teaching case reports
09:00 - 10:45 Plenary
Lecture Hall A
Chair: Y.-T. Chen, D. Yerly
09:00 – 09:26 E. Phillips
09:26 – 09:52 J. Adam
09:52 – 10:18 C. Bell
10:18 – 10:45 S.-I. Hung
Lecture Hall B
Lecture Hall A
Chair: W. Aberer, P. Bonadonna
11:15 – 11:40 I. Terreehorst
11:40 – 12:05 M. Blanca
12:05 – 12:30 P. Whitaker
12:30 – 12:45 E. Gomez
Chair: Y. Kano, N. Shear
11:15 – 11:37 K. Kabashima
11:37 – 11:59 T. Bellón
11:59 – 12:21 K. Nagao
12:21 – 12:45 Y. Aoyama
12:45 - 13:15 K. Park
K. Brockow
13:15 - 14:00 Snack Lunch
www.infoallergy.com
An Allergy Website for Patients
w.infoallergy.com
Untitled-1 1 14.07.2011 15:13:46

How to manage radiocontrast media hypersensitivity
How to manage betalactam hypersensitivity
Case report presentations (miscellaneous)
Understanding the structural basis of HLA associations for drug hypersensitivity
Abacavir and Nevirapine as two distinct models for HLA-binding
T-cell receptor affinity determines reactivity
Chemical restriction of abacavir-responsive T-cells
T-cell receptor use is critical for carbamazepine-induced SJS
Update on ENDA activities
Do we need separate protocols for children with drug hypersensitivity?
Practical workup of patients with NSAID hypersensitivity
Desensitisation in proven non-immediate reactions
PV 169 Accelerated allergic reactions to amoxicillin
Pathomechanisms of Stevens-Johnson-Syndrome / Toxic epidermal necrolysis
Live imaging of T-cells attacking keratinocytes expressing non-self antigens in SJS/TEN
CD94/NKG2C is a killer effector molecule in patients with SJS/TEN
A novel model of interface dermatitis caused by autoreactive CD4+ T-cells
SJS/TEN as the drug-induced variant of paraneoplastic autoimmune multiorgan syndrome
(PAMS)
Highlights of the meeting: experimental
Highlights of the meeting: clinical
BECOME AN EAACI
FACEBOOK FAN!
www.facebook.com/EAACI
EAACI Facebook Ad Final 180x60.indd 1 07.10.2010 14:51:39

POSTER EXHIBITION
The poster exhibition will take place in the Pavillon as well as in the left foyer of the lecture hall
building of Klinikum rechts der Isar.
Hang-up and take down time for posters:
Hang-up: from Wednesday, 11 April 2012, 15:00

Take down: until Saturday, 14 April 2012, 10:00 (after guided walk on Friday)
Poster viewing
Experts will review and discuss selected posters in their field and will select the best
presentations to receive poster prices (2 for clinical and experimental each). Thus, representers
are required to attend to and discuss their posters on Thursday, 12 April 2012, 13:15 – 14:00,
Poster P1 – P110
Poster viewing
Friday, 13 April 2012, 13:15 – 14:00
P 111 – P 231
In addition, poster discussions are encouraged from 18:00 - 19:00 on Thursday and Friday by
some pretzels, water and beer. At 19:00 the meeting location closes.
The poster prizes will be awarded during the closing session on
Saturday, 14 April 2012, 12:45 - 13:15, Lecture Hall A

ABSTRACTS
Posters with Oral Presentations
Drug anaphylaxis
PV30
Diagnosing immediate hypersensitivity reactions to radio contrast media
Gómez F.1
, Torres M.J.1
, Doña I.1
, Gracía Nuñez I.1
, Aranda A.2
, Cañamero D.1
, García Campos J.1
, Mayorga C.2
, Blanca M.1
1
HRU Carlos Haya, Málaga, Spain, 2
IMABIS Foundation-Carlos Haya Hospital, Málaga, Spain
Introduction: The incidence of immediate hypersensitivity reactions to radio contrast media (RCM) is low,
ranging from 0.7-1,3%. Although usually mild, severe reactions and sometimes fatal, have been reported. This
type of reactions has been classically considered as non-allergic in nature and therefore skin tests not useful for
diagnosis. Actually, there is not a consensus on the diagnostic approach in patients with immediate hypersensiti-
vity reactions to RCM.
Objectives: The aim of the study was to analyse in detail the clinical symptoms as well as the diagnosis value
of skin test, drug provocation test (DPT) and basophil activation test (BAT), in a group of patients with symptom
compatible with immediate hypersensitivity reactions to RCM.
Methods: We studied patients referred over 5 years period (2006-2011) with suspicion of immediate hypersen-
sitivity to RCM. Prick and intradermal skin tests with a panel of RCM were done. In mild reactions with skin test
negative pre-medication was recommended and in moderate-severe reactions DPT was done for searching an
alternative. BAT was done in those confirmed as allergic by positive skin tests or DPT.
Results: We studied 146 patients (108 females), with a mean age of 52,6 years. Six (4,11%) patients were
confirmed as allergic, 3 by positive skin tests and 3 by positive DPT. Regarding skin testing: one were prick test
positive (Iodixanol) and two intradermal test positive (Iodixanol, Iohexol and Meglumine Ioxaglate). DPT was positive
to Iodixanol in 2 cases and to Iomeprol, Iohexol and Iobitridol in one case. BAT was positive to Iodixanol, Iomeprol,
Meglumnine Ioxaglate and Iohexol, being in all controls cases (N=10). Patients confirmed as allergic were those
developing anaphilaxis or urticaria while cases with skin test negative had mild symptoms. In this last group the
recommendation was to use premedication.
Conclusions: Only 4,11% of the patients evaluated were confirmed as allergic to RCM, by skin testing or DPT.
These patients were those with moderate or severe reactions. BAT was useful for confirming the diagnosis. Most
patients had mild symptoms, being all skin test negative and having good tolerance to subsequent exposures
when administered with premedication. These results reinforce the need of evaluating patients with immediate
hypersensitivity reactions to RCM, specially dose with more severe reactions.

Drug hypersensitivity and viral disease: a dynamic interaction?
PV124
Reactivation of human herpes viruses in various forms of cutaneous adverse drug reactions - a compara-
tive study in Taiwan
Chen Y.-C.1
, Chang C.-Y.2
, Cho Y.-T.2
, Chiu H.-C.2,3
, Chu C.-Y.2,3
1
Cathay General Hospital, Department of Dermatology, Taipei, Taiwan, Republic of China, 2
National Taiwan
University Hospital, Department of Dermatology, Taipei, Taiwan, Republic of China, 3
National Taiwan University
College of Medicine, Department of Dermatology, Taipei, Taiwan, Republic of China
Purpose: The association of human herpesvirus (HHV) reactivations with DRESS has been reported, but their roles
in the pathogenesis are debating. Viral reactivation might be a secondary event after drug-induced immunological
reactions or the consequence of therapy. The purpose of this study is to investigate the reactivation rates of HHV
in various forms of cutaneous adverse drug reactions (cADRs) by using uniform laboratory methods in a single
medical center in Taiwan.
Materials and methods: From September 2010 to August 2011, we prospectively enrolled patients who were
hospitalized due to drug eruptions. After informed consent, venous blood samples of each patient were obtained
within three days of admission and then every week till they were discharged or resolution of all symptoms.
DNA from serum and peripheral blood mononuclear cells (PBMC) of each sample was extracted and tested by
quantitative polymerase chain reaction (q-PCR) for Epstein-Barr virus (EBV), HHV-6 and cytomegalovirus (CMV)
reactivations. Serological tests were performed to detect changes in antibody titers for the three viruses.

ABSTRACTS
EBV reactivation was defined as a fourfold elevation of IgG antibody titer against EBV early antigen (EA) or viral
capsid antigen (VCA) but without IgM antibodies against VCA, viral DNA loads in sera more than 50 copies/ ml,
or viral loads in PBMC over 103
copies/µg DNA. Reactivation of HHV-6 was defined as a fourfold increase of
anti-HHV-6 IgG antibody titer or positive q-PCR results from serum samples. CMV infection/reactivation was
defined as detection of viral DNA in serum samples or PBMC by q-PCR.
Results: There are 24 cases enrolled in this study: 9 SJS/TEN, 9 DRESS, 1 GBFDE and 5 with generalized
maculopapular eruption (MPE). EBV reactivation was detected in 11 patients, including 6 DRESS (66.7%), 2 SJS/
TEN (22.2%), 2 MPE (40%) and 1 GBFDE patient. Reactivations of HHV-6 and CMV were observed in 4 (44.4%)
and 2 (22.2%) DRESS patients respectively. Those two patients with CMV reactivation also had HHV-6 and EBV
reactivations. Both of them had HHV-6 reactivation first, and then followed by sequential or simultaneous CMV and
EBV reactivations, as well as fluctuating clinical courses.
Conclusions: EBV reactivation, which was detected in various forms of cADRs, is not specific to DRESS, while
HHV-6 and CMV reactivations seem to be more specific to DRESS

Diagnostic Tools: options and controversies of in vivo tests
PV74
Prospective study on the diagnosis of penicillin allergy (PEDAL 2)
Hjortlund J.1
, Mortz C.G.1
, Skov P.S.1
, Bindslev-Jensen C.1
1
Odense University Hospital, Department of Dermatology and Allergy Centre, Odense C, Denmark
Background: The purpose of PEDAL is to improve diagnostic tools in penicillin allergy.
Methods: A total of 334 patients suspected of having penicillin allergy were prospectively investigated at the
Allergy Centre, Odense University Hospital, Denmark in the period Sep. 2010 to Sep. 2011 according to ENDA
guidelines.We used the ENDA questionnaire, specific IgE from Termo Fisher, skin testing in dublicate with penicillin
G and V, amoxicillin, ampicillin, dicloxacillin, mecillinam, PPL and MDM and patch testing with all mentioned except
PPL and MDM. Challenge were performed in consecutive steps: first an intravenous (i.v) titrated challenge with
benzylpenicillin and if negative, an oral challenge (single dose) with phenoxymethylpenicillin, followed by (when
negative) a prolonged oral treatment (p.o.7) for 7 days.
Results: Nineteen of the 334 patients were IgE sensitized to penicillin. None reacted in prick test (SPT). Intra-
cutaneous testing (ICT) was subsequently performed in all patients; including the patients with positive IgE. 22
patients were positive in ICT, 15 cases with late reading positive reactions and 7 with immediate reactions. Only
3 patients had positive ICT to PPL and/or MDM. All was also positive to penicillin G in ICT. Only 4 patients with
positive IgE also showed a positive immediate reaction in ICT. Patch testing was positive in 9 patients; all of
them also had a positive late reaction in ICT. The remaining patients (n=297) were challenged with penicillin.Four
patients were positive in the i.v challenge; the remaining 293 received oral provocation (single dose), where
5 had positive reactions. The remaining 288 patients received p.o.7 and here 23 patients responded with positive
outcome; 15 with urticaria +/- angioedema, 5 with maculopapulous exanthema and 3 with other signs.
Patients with a case history of anaphylaxis, urticaria or angioedema were statistically more likely to be positive
in the tests (IgE, SPT/ICT, patch test or penicillin challenge) than patients reporting unspecific cutaneous rash or
those not remembering the nature of their initial reaction.
Conclusion: We have demonstrated that approximately 25% of all the patients with positive outcome in the peni-
cillin investigation are found by adding a prolonged oral (one week) treatment with penicillin. Skin testing seems
of little value in our region.

Side effects of biologicals: clincal approaches
PV56
Evaluation of a practice of managing drug eruptions due to pegylated interferon and effectivness of tolerance
induction
Poreaux C.1
, Studer M.1
, Waton J.1
, Schmutz J.-L.1
, Bronowicki J.-P.2
, Barbaud A.1
1
CHU, Dermatology, Nancy, France, 2
CHU, Hepatology, Nancy, France
Introduction: Interferons (IFN) are glycoproteins belonging to three major classes (α,b,g) sometimes responsible for
skin manifestations. The main objective is to provide a standardized course of action in the treatment of cutaneous

ABSTRACTS
adverse drug reactions to IFN. Secondary objectives are to assess the effectiveness of treatment when the local and
general pursuit of IFN is essential and the efficiency of a protocol to induce tolerance to IFN when there is no other
alternative therapy.
Patients and methods: This is a cross-sectional clinical study, prospectively conducted from 2009 to 2011. All
patients with drug eruption due to IFN were examined in thrust, and were followed by allergy testing. In absence
of alternative, a tolerance induction has been proposed.
Results: 12 patients (6W, 6M), average aged 54.2 years with a debilitating drug eruption to IFN may have had
allergy testing. The IDT were positive in 9/12 cases with an average time of 48 hours. A cross-reactivity between
PegIFNα2a and PegIFNα2b was observed in 5/10 cases. In 8/12 cases, treatment with IFN was stopped. In 4/12
cases, treatment could be continued. The DC and anti-H1 were sufficient in 2/4 cases. In two other cases, topical
tacrolimus was highly effective. In 8 cases when treatment was stopped, 2 patients had an indication for early
resumption of the anti-viral by pegIFNα. These two patients had positive tests for pegIFNα2a and pegIFNα2b
and received the protocol for inducing tolerance pegIFNα2b successfully. In these two cases, tolerance induction
performed weekly dose has gradually increased the recovery of an anti-viral C.
Discussion: Our study demonstrates the benefit of allergy testing in generalize drug reactions to IFN, the exist-
ence of cross reactions in the same class of IFN and the importance of delayed IDT reading . In case of failure of
DC and anti-H1, we report for the first time in eczema rashes to IFN, UV TL01 or topical tacrolimus may be effective.
On the pegIFNα in patients with active hepatitis C, the tests can, in addition to diagnostic confirmation, guide
the choice of therapeutic alternative or suggest an induction of tolerance to a pegIFN for patients in therapeutic
failure. From this unique series of patients treated with IFN for drug reaction we offer support and if that fails an
allergy tests (IDT) to the choice of alternative IFN. It might be interesting to evaluate the role of induction of tolerance
which we report the effectiveness in 2 patients.
PV58
Rapid desensitization to Rituximab
Macchia L.1
, Lotti A.1
, Kourtis G.1
, Rossi M.P.1
, Giliberti L.A.1
, Loconte F.1
, Perrone T.2
, Gaudio F.2
, Guarini A.3
,
Iacobazzi A.3
, Caiaffa M.F.4
, Ferrara L.5
, Pavone V.5
1
University of Bari - Aldo Moro, Allergology and Clinical Immunology, Bari, Italy, 2
University of Bari - Aldo Moro,
Hematology, Bari, Italy, 3
IRCCS Istituto Tumori ‘Giovanni Paolo II’, Hematology, Bari, Italy, 4
University of Foggia,
Allergology and Clinical Immunology, Foggia, Italy, 5
Hospital ‘Cardinal Panico’, Hematology, Tricase, Italy
Rituximab (Mabthera™) is a chimeric human-mouse anti-CD20 monoclonal antibody with human constant
regions and mouse variable regions, which is currently used in the treatment of B cell malignancies, particularly
non-Hodgkin lymphomas, and other B cell-associated conditions. However, severe adverse reactions preclude
rituximab administration in a number of patients, who would otherwise benefit from this therapy.Thirty-one
patients, with non-Hodgkin B cell lymphoma, who had previously experienced severe side effects following
rituximab infusion, were subjected to a protocol of rapid desensitization, allowing resumption of the infusion therapy
with rituximab in the great majority of cases.The series included 11 male and 20 female patients (mean age 64
years, s.d. 12). All were also receiving standard chemoterapy (various regimens).Sensitization to rituximab was
investigated in vivo by intradermal tests with rituximab at concentrations from 10 µg/ml to 40 mg/ml, respectively.
The procedure proved positive in 25 of the 31 patients.Carefully designed experiments aimed at detecting
rituximab-specific IgE in serum, by using an anti-IgE Mab-based ELISA and biotinylated rituximab, have been
so far unsuccessful.The desensitization protocol consisted of 11 sessions, over 3 weeks. Rituximab was given
subcutaneously every second day, staring with 40 µg at day 1. The desensitizing dose was rapidly raised and,
at session 8, 100 mg were administered (2,500-fold increase). The latter dosage was then repeated 3 times. In
26 out of the 31 patients, the desensitization course allowed full resumption of the infusion therapy. In 3 other
patients the intravenous therapy was resumed but non tolerated. Nevertheless, these patients could be treated by
compact courses of subcutaneous 100 mg rituximab administrations (which were tolerated). In the other 2 cases,
desensitization could not be finalized, due to circumstantial reasons. Approx. 2050 desensitizing injections have
been so far administered. Immediate systemic reactions were never observed. Local reactions were frequent
but mild. Rituximab should be already regarded as a crucial therapeutic option in a number of B cell-associated
conditions and its employment will probably increase in the future. Accordingly, severe adverse reactions are
likely to become more frequent. In these cases, the rapid desensitization procedure we developed can help make
the rituximab approach feasible.

ABSTRACTS
In vitro diagnostic tools: research instruments or fit for practice?
PV189
Evaluation of drug-specific T-cell population by flow cytometric drug-induced lymphocyte stimulation test
Hanafusa T.1
, Azukizawa H.1
, Matsumura S.1
, Katayama I.1
1
Osaka University Graduate School of Medicine, Department of Dermatology, Osaka, Japan
Background: Delayed hypersensitivity is responsible for severe cutaneous adverse drug reactions (cADRs),
especially in Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis, and drug-induced hypersensitivity
syndrome (DIHS) (also known as drug rash with eosinophilia and systemic symptoms [DRESS] syndrome). The
drug-induced lymphocyte stimulation test (DLST), or lymphocyte transformation test (LTT), is used to identify the
culprit drug in severe cADR cases.
Purpose: The aim of this study was to examine the immune reactions in cADR patients through the identification
of the drug-specific proliferating cells by flow cytometric DLST (FCM-DLST).
Materials and methods: The peripheral blood mononuclear cells (PBMCs) of 16 anticonvulsant-induced cADR
patients were investigated by conventional DLST and a FCM-DLST protocol in which CFSE dilution and BrdU
incorporation were combined. FCM-DLST allowed for the identification of the drug-specific proliferating cells in six
cases. Three of these cases were DIHS cases, whereas there was one case of SJS, one case of maculopapular
rash (MP), and one case of erythema multiforme (EM) among the six cases.
Results: In FCM-DLST, drug-specific proliferating T cells were detected as CFSElow
BrdUhigh
cells. The drug-
specific lymphocytes divided approximately five or six times in the 7 days in DLST-culture medium. The average
ratio of drug-specific T cells to PBMCs was estimated to be 0.024 %. These cells corresponded to the cells
incorporating 3
H-thymidine in conventional DLST. Although CD4+
T-cell proliferation dominated the observed
proliferation in most of the cases (in the recovery stage of the three DIHS cases, the MP case, and the EM case),
drug-specific CD8+
cytotoxic T lymphocytes (CTLs) were detected, especially in the acute stages of the SJS case
and one of the DIHS cases. There was a dramatic switch in the predominant drug-specific proliferating T-cell po-
pulation in the course of one of the cases of DIHS in which CD8+
CTLs were predominant initially, whereas CD4+
T cells were predominant later. Moreover, drug-specific CD4+
CD25+
Foxp3+
regulatory T cells (Tregs) proliferated
during the recovery stage in one DIHS case.
Conclusions: FCM-DLST revealed that the cell proliferation detected by conventional DLST is a heterogeneous
proliferation of both CD8+
CTLs and CD4+
T cells that likely includes Tregs. However, the number of cADR cases
in this study was limited, which limits the conclusions that can be drawn from it.

Drug-induced liver injury
PV163
Mechanisms of T cell stimulation by flucloxacillin in HLA-B*5701+
flucloxacillin-naïve individuals
Wuillemin N.1
, Adam J.1
, Fontana S.2
, Krähenbühl S.3
, Pichler W.J.1
, Yerly D.1
1
University Hospital of Bern, Clinic for Rheumatology and Clinical Immunology/Allergology, Bern, Switzerland,
2
Regional Blood Transfusion Service of the Swiss Red Cross, Bern, Switzerland, 3
University Hospital of Basel,
Division of Clinical Pharmacology and Toxicology, Basel, Switzerland
Purpose: Drug induced liver injury (DILI) is a main cause of drug withdrawal. A particularly interesting example
is flucloxacillin (FLUX)-DILI, which is associated with the HLA-B*5701 allele. Despite the strong association with
HLA-B*5701, only 1 in every 500 to 1000 individuals with this genotype will develop a FLUX-DILI. To better under-
stand this side effect, we established an in vitro model for FLUX induced T cell activation.
Materials and methods: Peripheral blood mononuclear cells from FLUX-naïve, HLA-B*5701+
healthy donors
were cultured by iterative in vitro restimulations with FLUX. FLUX-specific T cells (FLUX-Tc) were enriched by
positive selection of CD107a expressing cells and characterized by flow cytometry (IFNγ and CD107a) and
cytotoxicity assay.
Results: FLUX-specific T cells could be generated in 7/7 healthy HLA-B*5701+
donors and are mainly CD8+
. They
react by IFNγ secretion and CD107a upregulation upon drug stimulation and are cytotoxic against autologous
antigen presenting cells (APC). In most T cell lines (TCL), FLUX-pulsed APC were not able to activate FLUX-Tc if
FLUX was not additionally added. The direct addition of FLUX to FLUX-Tc was actually sufficient to fully activate
FLUX-Tc even in the absence of autologous APC. Moreover, proteasome inhibition by lactacystin and bortezomib
did not affect the Tc reactivity. Calcium influx measurement in T cell clones revealed an immediate activation after

ABSTRACTS
the addition of FLUX in solution, reaching a maximum signal after 5 minutes.
In a few FLUX-TCL, the reactivity upon FLUX stimulation was decreased if APC were not pulsed with FLUX in
advance or if APC were not present at all.
Conclusions: The non-involvement of the proteasome and the APC independent T cell reactivity do not support
the classical hapten theory. In contrast FLUX-Tc reactivity is best explained by a direct interaction of FLUX with
the restricting HLA-B*5701 molecule.

Clinical hypersensitivity reactions to important drugs
PV60
A retrospective study on sequential desensitization-rechallenge for anti-tuberculous drug allergy
Thong B.Y.1
, Chia F.L.1
, Tan S.C.1
, Tan T.C.1
, Leong K.P.1
, Tan J.W.1
, Tang C.Y.1
, Hou J.F.1
, Chan G.Y.1
, Chng
H.H.1
1
Tan Tock Seng Hospital, Rheumatology, Allergy and Immunology, Singapore, Singapore
Purpose: To describe the results of sequential desensitization-rechallenge (D-R) for anti-tuberculous (TB) drug
allergy.
Materials and methods: Consecutive patients who had undergone D-R to anti-TB drugs between 1 Sep 1997
and 31 Jan 2012 were recruited for study. Following resolution of the acute reaction, anti-TB drug was restarted
at 1:100 to 1:3 of the final daily dose (FDD), with gradual dose escalation daily to the FDD. Subsequent drugs
were sequentially added ≥ 3 days later when the preceding drug was tolerated. Full blood count and liver function
tests were monitored prior to addition of each new drug.
Results: There were 11 patients of whom 10 were male, predominantly Chinese (8). Six patients received
treatment for pulmonary, 2 extrapulmonary, and 3 for both pulmonary and extrapulmonary TB. The most common
regimen causing TB drug allergy comprised rifampicin (RIF), ethambutol (EMB), isoniazid (INH) and pyrazina-
mide (PZA) (REHZ) in 5 patients. REH was used in 4, RHZ in 1, and REHS containing streptomycin (S) in 1. All
patients had non-immediate reactions. All had cutaneous eruptions, where maculopapular exanthema (MPE) was
most common (8). Drug induced hypersensitivity syndrome (DIHS) occurred in 54.5% (6 patients) of whom all
had fever, 83.3% hepatitis, and 83.3% eosinophilia. Two patients had Stevens Johnson syndrome (SJS). D-R to
INH was successful in 7/9 (77.8%) patients starting at 100 mg/d and achieving 300 mg/d within a mean of 4.3 ±
2.3 days; RIF in 7/7 (100%) starting at 3.6-150 mg/d and achieving 450-600 mg/d in 4.4 ± 1.7 days; EMB in 3/3
(100%) patients starting at 100-200 mg/d and achieving 800-1200 mg/d in 5.0 ± 1.0 days; PZA in 2/2 (100%) pati-
ents starting at 5-100 mg/d and achieving 1000-1250 mg/d in 7 days; S in 1/1 (100%) patient starting at 100 mg/d
and achieving 700 mg/d in 5 days. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3,
the other MPE on day 8. D-R with INH and RIF respectively in the 2 SJS patients was successful in both. Among
DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among
the 11 patients. All patients completed TB treatment of ≥ 5 months’ duration with no cases of drug-resistant TB.
Conclusions: Sequential TB drug D-R is successful with careful dose escalation and close monitoring, even in
DIHS and SJS.

Severe cutaneous adverse reactions
PV130
HLA-A*3101 is more strongly associated with carbamazepine-induced drug reaction with eosinophilia
and systemic symptoms than with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal
necrolysis
Genin E.1
, Chen D.-P.2
, Hung S.-I.3
, Sekula P.4
, Schumacher M.4
, Chang P.-Y.2
, Tsai S.-H.2
, Wu T.-L.2
, Bellon-
Heredia T.5
, Tamouza R.6
, Fortier C.6
, Toubert A.6
, Charron D.6
, Hovnanian A.7
, Wolkenstein P.8
, Chung W.-H.9
,
Mockenhaupt M.10
, Roujeau J.-C.8
1
Inserm, UMR-S946, Paris, France, 2
Chang-Gung Memorial Hospital, Chang Gung University, Department of
Laboratory Medicine; Department of Medical Biotechnology and Laboratory Science, Taoyuan, Taiwan, Republic
of China, 3
Institute of Pharmacology; School of Medicine; National Yang-Ming University, Taipei, Taiwan, Republic
of China, 4
Institute of Medical Biometry and Medical Informatics, University Medical Center, Freiburg, Germany,
5
Hospital Universitario La Paz, IdiPAZ, Madrid, Spain, 6
Institut Universitaire d’Hématologie; Saint-Louis Hospital;
University Paris Diderot, Inserm UMR-S940, Paris, France, 7
Inserm UMR-S 781; Institute of Genetic Diseases

ABSTRACTS
Imagine; University Paris Descartes; Centre Hospitalier Universitaire Necker-Enfants Malades, Department of
Genetics and Dermatology, Paris, France, 8
Hôpital Henri Mondor; Université Paris-Est; Inserm UMR-S 448;
Service de Dermatologie, Créteil, France, 9
Chang Gung Memorial Hospital; Chang Gung University College of
Medicine; Linko, Department of Dermatology, Keelung, Taiwan, Republic of China, 10
Dokumentationszentrum
schwerer Hautreaktionen (dZh), Department of Dermatology, Freiburg, Germany
Purpose: Recently, HLA-A*3101 was reported to be strongly associated with different phenotypes of carbamazepine
(CBZ)- induced hypersensitivity reactions, including mild maculopapular eruption (MPE), drug reaction with
eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis
(TEN) in Europeans. We aim to verify the HLA-A*3101 association with two clinically different CBZ-induced
severe phenotypes, DRESS and SJS/TEN, by conducting an international collaborative study with a standardized
phenotype definition.
Method: 162 cases of CBZ-induced DRESS or SJS/TEN (132 Han Chinese from Taiwan and 30 Europeans from
RegiSCAR) and 144 controls were enrolled in this study. HLA-A genotyping was performed for all cases and
controls.
Result: HLA-A*3101 was strongly associated with CBZ-induced DRESS in Chinese (PFisher
=9x10-7
, OR:16.15
(95%CI 4.04-64.65)) as well as in Europeans (PFisher
=3.98x10-10
, OR:100.54 (95%CI 25.81-391.62)). However,
HLA-A*3101 was not associated with CBZ-SJS/TEN in Chinese (PFisher
=0.69) and was only weakly associated
with this condition in Europeans (PFisher
=0.01, OR:7.6 (95%CI 1.76-27.72)). This latter OR was significantly smaller
than the one associated with DRESS in Europeans (test of homogeneity of OR: P=0.003).
Conclusion: HLA-A*3101 is strongly associated with CBZ-induced DRESS in Chinese and European patients,
but the association is much weaker with CBZ-induced SJS/TEN.

Contact hypersensitivity meets drug hypersensitivity
PV109
Innate immune responses to contact sensitizers are mediated via ROS production and HA degradation
Esser P.R.1
, Wölfle U.2
, Dürr C.3
, von Loewenich F.D.4
, Schempp C.M.2
, Freudenberg M.A.5
, Jakob T.1
, Martin
S.F.1
1
University Freiburg Medical Center, Dermatology, Allergy Research Group, Freiburg im Breisgau, Germany,
2
University Freiburg Medical Center, Dermatology, Skintegral, Freiburg im Breisgau, Germany, 3
University Frei-
burg Medical Center, Haematology and Oncology, Freiburg im Breisgau, Germany, 4
University Freiburg Medical
Center, Medical Microbiology and Hygiene, Freiburg im Breisgau, Germany, 5
Max Planck Institute, Immunobiolo-
gy and Epigenetics, Freiburg im Breisgau, Germany
Allergic contact dermatitis (ACD) represents a severe health problem with increasing prevalence. Contact sensiti-
zers induce a proinflammatory micro-milieu within the skin that results in the activation of DCs and, subsequently,
the priming and activation of T cells. Recent evidence indicates for a crucial role of endogenous activators of
pattern recognition receptors like the Ttoll like receptors (TLR). One candidate is the extracellular matrix (ECM)
component hyaluronic acid (HA), acting as TLR2/4 agonist when degraded to low MW HA fragments.
Aim: We focus in our study on the initial events resulting in the activation of innate immune responses triggered
by contact sensitizers. Therefore, we aimed at unraveling the role of sensitizer induced production of reactive
oxygen species (ROS), the activation of hyaluronidase activity and their contribution to the degradation of HA.
Method: To this end, we detected ROS production by oxidation of fluorescent dyes in vivo and in vitro after
sensitizer treatment. In vivo HA degradation was visualized by staining with a HA binding protein and by gel elec-
trophoresis. The potential role of p38 MAPK activation in the enhancement of sensitizer induced hyaluronidase
activity was adressed by analysis of the effects of a p38 MAPK inhibitor in the contact hypersensitivity (CHS)
model in vivo. In addition, we investigated the influence of antioxidants or a hyaluronidase inhibitor blocking HA
degradation on the CHS response.
Results: We observed that contact sensitizers readily induce ROS production both in vitro and vivo and enhance
the activity of hyaluronidase in vivo. ROS and hyaluronidase both degrade high MW HA into low MW HA frag-
ments as observed both in human and murine skin. Blocking p38MAPK activity, ROS production or hyaluronidase
activity abrogates CHS responses. These effects are reverted by addition of exogenous active hyaluronidase.
Time kinetics indicate the necessity of HA degradation for CHS responses both in the sensitization and elicitation
phase. In summary, we provide a novel mechanism for the early innate immune response triggered by contact
sensitizers resulting in the generation of pro-inflammatory endogenous PRR ligands by ECM breakdown induced
by contact sensitizers.

ABSTRACTS
Conclusions: These findings have implications for the development of in vitro based assays for the identification
of contact sensitizers and for the development of a causative treatment for ACD.

Update on ENDA activities
PV169
Accelerated allergic reactions to amoxicillin
Gomez E.1
, Torres M.J.1
, Chaves P.1
, Doña I.1
, Rodriguez-Bada J.L.1
, Gomez A.I.1
, Blanca M.1
, Mayorga C.1
1
Carlos Haya Hospital, Malaga, Spain
Purpose: Hypersensitivity reactions to betalactams are the most frequent cause of reactions mediated by specific
immunological mechanisms. Levine classified the reactions in three types: immediate, accelerated and delayed,
according to the time between the drug intake and the symptoms appearance. With different immunological me-
chanism involved being IgE-mediated in immediate reactions and T cell mediated in delayed reactions; however
the mechanism involved in accelerated reactions are not sufficiently addressed. Thus we wanted to study the
underlying immunological mechanism in patients with accelerated reaction to amoxicillin (AX).
Materials and methods: Three patients with urticarial/exanthematic reactions appearing between 1-6 hours after
AX or AX-clavulanic acid (AX-CLV) administration were included. The allergological study consisted on skin te-
sting and drug provocation test (DPT) at increases doses. Specific IgE and tryptase determinations were carried
out by immunoCAP system.
The immunological study included cellular markers of lymphocyte subsets, skin homing and chemokines, as well
as their chemokine receptors in peripheral blood (acute phase (T1) and basal) by flow cytometry, and in skin
biopsy (T1) by immunohistochemistry.
Results: Prick and intradermal skin tests with major and minor betalactam determinants including AX and CLV
were negatives in both immediate and delayed lecture. After DPT with AX patients presented generalised erithema
accompanied with angioedema beginning at least 2h after the administration and increasing during the next 10h.
The monitorization of the phenotypical analysis at T1 and basal show an increase in the percentage of CD8
and NK cells (CD56+) producing perforin and granzyme B, indicating an effector response. Moreover, NK cells
showed also a production of IFN-g and TNF-a with no changes in IL4 production
Regarding to skin homing and chemokine we observed an increase in CLA and CCR4 expression in both CD4
and CD8 T cells. The Th1 chemokine receptor CXCR3 was also increase in the two T cell subsets. These results
were confirmed in the immunohistochemical studies. We could not find either specific IgE (< 0.35 kU/ml) nor
tryptase (< 10 µg/ml) in any patients.
Conclusions: The data provided support that accelerated reactions to AX are T-cell mediated with skin homing
and a Th1 pattern with cytotoxic characteristics. Further studies are in progress to characterise in more detail
these allergic responses.

ABSTRACTS
Poster Presentation – Walk of Experts
P1
Clinical analysis of cutaneous adverse drug reactions in Yokohama City University Hospital
Watanabe Y.1
, Sano S.1
, Okada R.1
, Murata N.1
, Nagashima M.1
, Hakuta A.1
, Yamane Y.1
, Ikezawa Z.1
, Aihara M.1
1
Yokohama City University School of Medicine, Department of Dermatology, Yokohama, Japan
Purpose: To evaluate the trends of drug eruptions in university hospitals.
Materials and methods: A retrospective study was performed at Yokohama City University Hospital using
medical records of patients with cutaneous adverse drug reactions (CADR) from April 2003 to March 2009.
Totally, 341 patients were analyzed for clinical features and causative drugs.
Result: The two major causative drugs were antibiotics (29%) and anti-cancer drugs (18%). Among causative
antibiotics, glycopeptide and carbapenem were increased to 13% and 10% with the increase of resistant
bacterias to penicillin and cephem. Among causative anti-cancer drugs, we recorded a greater number of
molecular target drugs compared with previous studies. Although macropapular rash was the most common
reaction, as reported previously, patterns of clinical manifestation were different to those previously recorded.
Notably, in patients treated with anti-cancer drugs, localized macropapular rash, hand-foot syndrome, and severe
acneciform eruption were seen. Regarding the severe types of CADR, Stevens-Johnson syndrome (SJS)/
toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS) accounted for 6% and
2%, respectively, of CADR types. The eosinophilia was observed in 17% of patients, and it showed the highest-
frequency in the patients with erythrodermia. Positive reactions with causative drugs were observed in 34%,
68%, and 60% of patients as determined by patch, intradermal, and drug-induced lymphocyte stimulation tests,
respectively. The positive rate of patch test was over 50% in SJS / TEN and eczema type, which were damaged
mainly epidermis. Patients with macropapular and erythema multifome showed high positive rate of intradermal
tests account for over 60% compared with others. Almost 80% of patients were cured after discontinuing the
causative drugs without any general treatments, including steroids, or could continue the drugs with just topical
therapies.
Conclusion: Clinical manifestations of CADR are changing with changing drug therapies. It is therefore important
to continue clinical analysis of CADR.

P2
The perspective and management of penicillin allergy among Thai physicians
Klaewsongkram J.1
, Suetrong N.1
1
Chulalongkorn University, Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of
Medicine, Bangkok, Thailand
Purpose: This study was to assess the perspective and management of patients with a history of acute
immediate reactions to penicillin in Thailand
Materials and methods: The online questionnaire was emailed to Thai physicians about several aspects of
penicillin allergy management.
Results: The answers from 205 Thai physicians (males: females=89: 116, mean age= 31.2±7.4 years old,) were
analyzed. Most physicians asked for penicillin allergy history before penicillin administration but only 41.8% of
them explored whether they were immediate or non-immediate reactions. Although 44.0% of Thai physicians
know that intradermal test after negative skin prick test is the standard penicillin testing procedure to diagnose
an immediate reaction; only 10.7% of them interpret the result properly. 68.0% of them predicted that ≤ 40%
of patients with a history of penicillin allergy would develop allergic reactions if penicillin is readministered and
62.2% of them believed that ≤ 40% of suspected patients would have positive penicillin skin test. Only 22.7% of
Thai physicians have ever requested or performed penicillin skin test in suspected patients. The lack of penicillin
skin test reagents was the main reason (56.4%) for not performing the test whereas 31.1% of them were not
convinced with skin test diagnostic accuracy.
Aminopenicillins, first-generation cephalosporins, third-generation cephalosporins, and carbapenems were also
avoided by 67.6%, 22.2%, 12.0%, and 9.8% of Thai physicians in patients with a history of penicillin allergy with
unknown penicillin skin test result. 44.9% of Thai physicians agreed that patients with a history of penicillin allergy
should undergo skin testing while 35.6% of them suggested avoiding the use of penicillin in these patients without
skin testing. The main reasons of this suggestion were the availability of alternative drugs (38.7%) and medico-

ABSTRACTS
legal issues (24.4%). Cephalosporins were completedly avoided in patients with penicillin-induced urticarial/
angioedema, maculopapular exanthems, anaphylaxis, and Stevens-Johnson syndrome by 8.9%, 25.3%, 75.1%,
and 86.2% of Thai physicians, respectively.
Conclusions: Thai physicians have certain awareness on the problem of penicillin allergy. However, the lack of
skin test reagents, the availability of alternative drugs, and the medico-legal issues, were the main reasons for not
performing penicillin skin testing in suspected patients and leading to the avoidance of several beta-lactams.

P3
Drug hypersensitivity reactions in children: Comparison of causality assessment results obtained with 2
different methods
Amaral R.1
, Herdeiro T.1,2
, Faria E.3
, Rebelo Gomes E.4
1
Faculty of Medicine - University of Porto, CINTESIS, Porto, Portugal, 2
Faculty of Medicine - University of Porto,
Northern Pharmacovigilance Centre, Porto, Portugal, 3
Hospital Universitario Coimbra, Allergy, Coimbra, Portugal,
4
Hospital Pediatrico Maria Pia, Drug Hypersensitivity Clinic-Allergy, Porto, Portugal
Purpose: To compare causality assessment after clinical workup of drug hypersensitivity (DH) with the results
obtained from the World Health Organization (WHO) global introspection (GI) method.
Materials and methods: Retrospective analysis of a case series of suspected pediatric DH reactions (n=84),
reported to the database of the Northern Portuguese Pharmacovigilance Unit. Patients underwent a standardized
allergy diagnostic workup (including anamnesis, in vitro and in vivo tests), at the Oporto children’s hospital by
an allergist unaware of the pharmacovigilance causality assessment score. This score was based on the WHO
scale of imputability (“Definitive”, “Probable”, “Possible”, “Unlikely”, “Conditional” and “Unclassifiable”) and
were established by a pharmacovigilance expert, unaware of drug testing results, using the GI method. The
gold-standard was considered to be the clinical diagnosis of DH. Multi-level likelihood ratio (LR) and post-test
probability were calculated to assess the diagnostic impact of the GI method on the DH reactions. Post-test
probabilities were calculated using a Fagan monogram.
Results: From the initial 84 reports/patients 53 were excluded (31 because their reports were not accessible
in the database, 17 refused diagnostic investigation, 4 did not have the results by the time of this study and 1
provocation was contra-indicated). 31 reports/patients were finally left for analysis (20 male-64.5%; median age,
8 years). Most of the reactions were non-immediate (>1 hour) (77.4%), cutaneous reactions (88.7%) and were
caused by betalactam antibiotics (40%), followed by non-steroid-anti-inflammatory drugs. After a complete clinical
evaluation, DHs was confirmed in only 5/31 patients (16.1%). DH reactions were classified into “Definitive” in 1/5
of the positive patients and in 1/26 of the negative patients (LR 5.0; post-test probability 0.5); 4/5 of the positive
patients were classified as “Probable” as 23/26 of the negative ones (LR 0.9; post-test probability 0.15) and 2/26
of the negative patients were classified as “Possible”.
Conclusions: Only the causality score “Definitive” had a moderate impact on the likelihood of DH reactions.
Therefore, although being a good hypothesis generator, GI method is not accurate to do definitive decisions in
DH reactions. This method, by itself, cannot replace the standard diagnostic allergy tests.

P4
Drug-induced acute pancreatitis following positive drug rechallenge: A review
Fathallah N.1
, Slim R.1
, Ben Salem C.1
, Bouraoui K.1
1
Faculty of Medicine of Sousse, Department of Clinical Pharmacology, Sousse, Tunisia
Drug-induced pancreatitis is rare with an estimated incidence of 0.1-2%. Over 500 medications have been
associated with this disease. Recrudescence of the pancreatotoxicity upon re-exposure to the suspicious drug
is considered the more reliable evidence of drug-induced pancreatitis. A retrospective review of MEDLINE was
conducted to assess clinical outcomes of positive drug rechallenge following possible drug-induced pancreatitis.
A total number of 250 cases of drug-induced pancreatitis with positive rechallenge were identified, among which,
183 met inclusion criteria for analysis in our review. A broad spectrum of suspect drugs was identified. Analgesics
and anti-inflammatory drugs were incriminated in 28.4% of all cases, antimicrobials in 19.4 %, cardiovascular
agents in 11.4% of cases, immunomodulator drugs in 10.28 % of cases and gastro-intestinal drugs in 4.9 %
of cases. Improved identification and communication of possible drug-induced pancreatitis is needed to avoid
potentially serious and/or fatal drug rechallenges.

ABSTRACTS
P5
Avoidance of NSAIDs despite a negative oral provocation test: what does really happen?
Bommarito L.1
, Zisa G.1
, Riccobono F.1
, D’Antonio C.1
, Calamari M.2
, Poppa M.2
, Moschella A.2
, Di Pietrantonj C.3
,
Galimberti M.1
1
Novara Hospital - Experimental Program Piemonte Allergy Network, Allergology and Immunology Unit, Novara,
Italy, 2
Domodossola Hospital, Allergology and Immunology Unit, Domodossola, Italy, 3
Servizio Regionale di
Epidemiologia SeREMI ASL AL, Alessandria, Italy
Background: Drug provocation tests (DPTs) are the gold standard in diagnosis of nonsteroidal anti-inflammatory
drug (NSAID) hypersensitivity and they have to be performed in hospital setting. Aim of this study was to assess
patient behaviour towards NSAID re-assumption at home and to evaluate the subsequent NSAID tolerability after
negative allergological work-up.
Materials and methods: This is a follow-up study including patients evaluated in the allergy centers of Novara
and Domodossola Hospitals between July 2004 and June 2010 for cutaneous reactions (urticaria and/or
angioedema) following NSAID intake. All the patients who tested negative to the suspected NSAID DPT were
asked by a phone interview (performed not less than 11 months after DPTs) about home NSAID assumption,
tolerance and reasons for avoidance. The negative predictive value (NPV) of DPT was calculated.
Results: 111/142 patients were contacted, 46/111 (41.44%) took the same NSAID as the one tested with 2
reactions reported (4.3%); 65/111 (58.56%) did not take the same NSAID but 34 of them took another as strong
COX-1 inhibitor with 1 reaction. The three reactions reported consisted in mild urticaria, but none of the patients
accepted allergological re-evaluation. NPV overall was 96.25%. 12/65 patients (18.46%) did not take any NSAID,
2 only using non pharmacological therapies as homeopathy or acupuncture. Reasons for avoidance were no
need (29.2%) and fear of reactions (70.8%). A statistical association between re-assumption and type of the drug
tested, being lower for strong COX-1 inhibitors (28/85) than for weak COX-1 inhibitors (28/46), was observed (OR
0.31 CI 95% 0.14-0.66).
Conclusions: Even after ruling out NSAID hypersensitivity diagnosis the majority of patients with a history of
urticaria and/or angioedema continued to avoid NSAID intake at home for fear of new reactions, particularly when
strong COX-1 inhibitor NSAIDs are involved. Nevertheless NSAID DPT showed a good NPV.
P6
ACE induce angioedema according the data of Vilnius university hospital Santariškiu Klinikos
Kozlovska A.1
, Aleksoniene R.1,2
, Kvedariene V.1,2
1
Vilnius University, Faculty of Medicine, Vilnius, Lithuania, 2
Vilnius University Hospital Santariskiu Klinikos, Center
of Pulmonology and Allergology, Vilnius, Lithuania
Angioedema (AE) frequently is rapid and life-threatening reaction. To find the cause is difficult even in the case
when patient takes many drugs at the same time. Diagnostic of ACE and ARB induce angioedema haven’t good
investigated time delay between last drug intake and manifestation of clinical reaction.
Aim of study was to explore frequency of AE induced by ACE and evaluate the role of time delay between last
drug intake and clinical reaction.
Methods: 566 patients with adverse drug reactions were hospitalized in Pulmonology and Allergology center
between 2008 and 2011. ENDA questionnaires were completed for all of them. We chose 46 (8.12%) patients,
who at the moment of AE or urticaria take of ACE or ARB. Solely AE induced by this type of drugs had 36(6.4%)
patients.
Results: Median age of patients was 59[50.3 - 75.5] with min. 34 and max. 87years, it were 19(52.8%) men and
17(47.2%) women. ACE related AE for 31(86.1%) reactions and ARB only in 2(5.6%). In our study ramipril and
enalapril were the most frequently implicated drugs and induce AE in 7(19.4%) of cases for each drug; losartan,
valsartan and traolapril - rarely. Median time delay between last drug intake and clinical reaction was 12[0.8 -
42.0] month. The latest reaction was induced by losartan and appeared after 96months; the earliest AE was
induced by captopril after one week of treatment. All reactions were of non- immediate type.
Conclusion: ACE and ARB induced AE was rare among our patients. Ramipril and enalapril were often
implicated. Only captopril was induced clinical reaction in one week, all other drugs - after one year or late after
start the treatment

ABSTRACTS
P7
Allergic reactions to drugs in Slovenian children
Vesel T.1
, Accetto M.1
, Berce V.2
, Bizjak R.3
, Homšak M.2
, Ihan A.4
, Koren-Jeverica A.1
, Korošec P.5
, Košnik M.5
,
Lužnik Z.6
, Nahtigal M.6
, Obermayer-Temlin A.7
, Posega-Devetak S.8
, Šilar M.5
, Tomšič-Matic M.9
, Toplak N.1
,
Zupančič M.10
, Avčin T.1
1
University Children’s Hospital, University Medical Center, Department of Allergology, Rheumatology and Clinical
Immunology, Ljubljana, Slovenia, 2
University Clinic Maribor, Department of Pediatrics, Maribor, Slovenia, 3
General
Hospital in Šempeter, Nova Gorica, Slovenia, 4
Institute of Microbiology and Immunology, Faculty of Medicine,
Ljubljana, Slovenia, 5
University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia, 6
General Hospital
in Slovenj Gradec, Slovenj Gradec, Slovenia, 7
General Hospital in Celje, Celje, Slovenia, 8
General Hospital in
Izola, Izola, Slovenia, 9
General Hospital in Trbovlje, Trbovlje, Slovenia, 10
University Children’s Hospital, University
Medical Center, Ljubljana, Slovenia
Purpose: Few national epidemiological studies have been performed in children with suspected allergy to
drugs. The incidence of drug allergies and the quantity/quality of their diagnosing procedures have not been
systematically evaluated in pediatric population in Slovenia.
Materials and methods: We analyzed the allergological work-up of children who were referred for investigation
of suspected drug allergy to the allergy clinic at the University Children’s Hospital Ljubljana and to 6 pediatric
departments in the regional hospitals in Slovenia from January 2011 to December 2011.
Results: In 2011, 639 children were referred for investigation of suspected drug allergy. β- lactams (89%) and
non-steroidal anti-inflammatory drugs (NSAIDs) (5,5 %) were most frequently incriminated.
Diagnosis of β-lactam allergy was confirmed in 36 children, 5 children were allergic to corticosteroids, two to
opiods, two to neuromuscular blocking agents (NMBAs), two to benzodiazepines and in one child allergy to
NSAID, gentamicin and growth hormone was confirmed, respectively. Cross-sensitization within the same
group of drug showed 19 children allergic to β-lactams, 2 children allergic to NMBAs, 4 children allergic to
corticosteroids, 2 children allergic to opiods and one child allergic to benzodiazepines. Drug allergy was
confirmed with skin testing in 29 children, more than one diagnosing method in 12 children, reaction during
challenge test in 5 children and basophil activation testing or specific IgE antibodies only in 2 children,
respectively.
Three hundred seventy one children completed allergological work-up with drug challenge. Five out of 7 children
who reacted during drug challenge had negative previous testing result including skin testing and two children
went directly to provocation testing with suspected drug. Positive outcome on penicillin challenge was found after
prolongation of provocation test to three days in one child. The median time between suspected drug reaction
and provocation test was 2.3 years.
Conclusions: The results of the allergological work-up were often negative and positive outcomes in challenge
testing were less than 2 %. The most frequently involved drugs were β- lactams followed by corticosteroids. A
continuing education program for pediatricians and nurses is needed in order to improve the ability of diagnosing
drug allergies in childhood population in Slovenia.

P8
The peculiarities of side effects during cancer patients treatment in oncological dispensary
Kazangapova A.1
, Rozenson R.2
1
Astana Medical University JSC, Children disease #1, Astana, Kazakhstan, 2
Astana Medical University JSC,
Astana, Kazakhstan
There is a gap in knowledge of incidence of the side effects of cancer drug treatment, which may be important
both for study of treatment outcomes and for allergic reactions preparedness in Oncological Dispensary (special
hospital in former Soviet Union for cancer treatment).
Materials and methods: We provided a cohort retrospective study of archival patients in Astana city Oncology
Municipal Dispensary. In total, 463 patients aged 21-67 years in 2011 were studied. Side effects of drug therapy
during treatment in Oncological Dispensary were registered in 96 patients, and after treatment - in 67 patients.
Results and discussion: An average incidence of drug treatment side effects was 20%, from them 38% were
men, and 62% were women. The spectrum of cancer was: 44% - breast cancer, 12% - ovary cancer, 6% - lung
cancer, 6% - gastric cancer, 6% - thyroid cancer, 5% - colon and rectum cancers, 5% - cervical cancer, 5% - non-
Hodgkin’s lymphoma, 4% - myoma, 3% - cancer of pancreas, 2% - lymphosarcoma, 2% - melanoma.
The following medicines were reasons of drug side effects: antibiotics - 36%, analgesic - 13%, salt solutions -

ABSTRACTS
10%, vitamins - 9%, iodine - 6%, gemodez - 3%, antihistamines - 3%, cytostatics - 3%, anti-inflammatory - 3%,
antianemic - 2%, glucose - 1% , other drugs reactions - 10%.
After discharge from oncological dispensary every 2 months we provided the telephone inquiry about possible
side effects of drug therapy in outpatient’s step of treatment. In this step side effects were evident in 67 from 367
patients (18,3%). Among them 48% were patients with urticaria, 27% with atopic dermatitis exacerbations, 11%
with contact dermatitis, and 7% with rhinoconjunctivitis.
The results of retrospective cohort studies showed that side effects were most common among patients with
breast cancer (44%). Mortality rate among breast cancer patients with side effects was significantly higher (p<
0,05), than among breast cancer patients without side effects of treatment.
We concluded that the presence of side effects of treatment was higher among cancer patients with unfavorable
prognosis.

P9
Breakthrough of kids drug allergy reactions in Bosnia
Bajraktarevic A.1
, Miokovic M.1
, Kumasin L.1
, Selimic E.1
, Niksic H.2
, Selimovic A.3
, Mujicic Selimovic E.3
,
Musabegovic J.4
, Sporisevic L.5
1
Public Health Institution of Sarajevo Canton, Pediatrics Department, Sarajevo, Bosnia and Herzegovina, 2
Clinical
Medical Center Sarajevo, Department for Clinical Pharmacology, Sarajevo, Bosnia and Herzegovina, 3
Pediatrics
Clinic Sarajevo, Department for Allergology and Pulmonology, Sarajevo, Bosnia and Herzegovina, 4
Pharmacy
Faculty Sarajevo, Department for Clinical Pharmacology, Sarajevo, Bosnia and Herzegovina, 5
First Medical Aid,
Pediatrics Departrment, Sarajevo, Bosnia and Herzegovina
Background: A drug allergy is an allergic reaction to a medication. Adverse drug reactions as an unpredictable
reaction is related to immunological response and hypersensitivity reactions or nonimmunological response
opposite a predictable drug reaction is related to the pharmacological actions of the drug. Common symptoms
such as rash, hives, and itching can often be controlled with antihistamines and occasionally corticosteroids.
Methods: A retrospective cohort study of pediatric patients who experienced an allergic drug reaction between
January 1, 2009, and December 31, 2010, was conducted at a pediatric primary, secondary and tertiary care,
children´s offices and hospitals in Sarajevo. The first phase included a cross-sectional survey that assessed
the life occurrence of adverse drug reactions and self-reported drug allergy in the outpatient clinic of a pediatric
hospital. The second phase involved a diagnostic workup in children with parent-reported drug allergy, including
detailed clinical history and in vitro and in vivo investigations.
Results: For many, medication allergies go undetected until they take a drug and have an allergic reaction. Some
adverse reactions to drugs are side effects. Among the most common side effects are upset stomach, diarrhea,
vomiting, fever and a skin reaction to sunlight called photosensitivity. Dermatologic signs and symptoms were the
most common 66% (462).
Conclusions: The symptoms of drug allergy may happen immediately or after taking the drug for a week or
more. Disappear on cessation of therapy and reappear after readministration of a small dose. Symptoms of non-
allergic drug reactions vary depending on the type of medication.

P10
Adverse drug reactions notified by an Immunoallergology Department and causality assessment systems
agreement
Costa M.J.1
, Herdeiro M.T.2,3
, Botelho C.4
, Castro E.4
, Cernadas J.R.4
1
Faculty of Medicine, University of Oporto, Department of Biostatistics & Medical Informatics, Oporto, Portugal,
2
Faculty of Medicine, University of Oporto, Northern Pharmacovigilance Centre, Oporto, Portugal, 3
University of
Oporto, Centre for Research in Health Technologies and Information Systems (CINTESIS), Oporto, Portugal, 4
H.
S. João, EPE, Immunoallergology Department, Oporto, Portugal
Background: Adverse drugs reactions (ADRs) are an important public health problem, a major cause of
morbidity and mortality.
Purpose: The main objective was the characterization of ADRs notified from January 2006 to December 2010,
by the Drug Allergy Unit of Immunoallergology Department (ID) of Hospital São João (Oporto), to the North
Pharmacovigilance Unit (NPU) of the Medical Oporto School. The secondary objective was to compare the
results obtained by two causality assessment systems (CAS), the one applied by the NPU and the other applied
by the ID.

ABSTRACTS
Material and methods: An observational retrospective descriptive study was conducted. Participants were all
the patients from the ID, with notified suspected ADRs. The exclusion criteria were the insufficient information
in the notification reports. The ADRs and patient characterization was made. The two CAS, the World Health
Organization (WHO) CAS applied by the NPU and the ID diagnostic work up based in the European Network for
Drug Allergy (ENDA) guidelines, were compared with coefficient kappa weighted determination.
Results: The studied population presented a median age of 41 years (range 8 months to 78 years), with a higher
proportion of the female gender (73.2%). Allergic rhinitis and asthma were the most frequent co morbidities.
All the studied ADRs were type B, for their allergic nature; 89.6% serious; 86.4% not referred in the summary
of the drug characteristics and 97.4% associated with drugs that presented more than two years in the market.
The most represented drug classes were non steroidal anti-inflammatory (56.8%) and antibiotics (27.2%). Skin
complaints represented 61.2% of the total notified signs. The ADRs occurring in less than one hour after intake
represented 52.9%. Following ADRs the most frequent treatment orientation was drug withdraw (80%), followed
by the prescription of anti-histamines (42.2%). The comparison of the two CAS obtained a coefficient kappa
weighted of 0.08 (95% confidence interval: 0-0.21).
Conclusions: From 2006 to 2010, the ADRs notified by the ID to the NPU were predominantly serious and
unexpected. The most frequent drugs were the non steroidal anti-inflammatory and antibiotics, with more than
two years of commercialization.
The two main limitations of this study were the incomplete information, and for the agreement of the CAS, the two
systems were different.

P11
Drug anaphylaxis in Portugal: National Survey 2007-2010
Faria E.1
, Cernadas J.2
, Gaspar A.3
, Botelho C.2
, Castro E.2
, Lopes A.4
, Gomes E.5
, Malheiro D.6
, Cadinha S.6
,
Campina-Costa S.7
, Neto M.8
, Sousa N.1
, Rodrigues-Alves R.9
, Romeira A.10
, Caiado J.4
, Morais-Almeida M.3
,
Interest Group on Drug Allergy of Portuguese Society of Allergology and Clinical Immunology (SPAIC)
1
Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, 2
Centro Hospitalar São João, EPE, Porto,
Portugal, 3
Hospital CUF Descobertas, Lisboa, Portugal, 4
Hospital Santa Maria, Lisboa, Portugal, 5
Hospital Maria
Pia, Porto, Portugal, 6
Centro Hospitalar Vila Nova Gaia/Espinho, Vila Nova Gaia, Portugal, 7
Hospital Egas Moniz,
Lisboa, Portugal, 8
Hospital Pulido Valente, Lisboa, Portugal, 9
Hospital Divino Espirito Santo, Ponta Delgada,
Açores, Portugal, 10
Hospital Dona Estefânia, Lisboa, Portugal
Purpose: To contribute to a better understanding of the epidemiology of drug-induced anaphylaxis in
immunoallergology outpatient consultations in Portugal.
Materials and methods: A national notification system for anaphylaxis was implemented, focused on voluntary
reporting by physicians with allergy differentiation since 2007. From January 2007 to December 2010 data from
313 patients with drug-induced anaphylaxis have been received and analyzed.
Results: The mean age was 43.8 ± 17.4 years, 8% having less than 18 years old. The ratio female / male
was 2:1. The mean age at first episode was 39 ± 18.2 years. Nine patients had more than one cause of drug
anaphylaxis, corresponding to a total of 322 reports. The main culprit drugs were non-steroidal anti-inflammatory
drugs (NSAIDs), antibiotics and anesthetic agents in 48%, 36% and 6% respectively. Other drugs involved were:
cytostatics, corticosteroids, proton pump inhibitors, iodinated contrast media.
There was a predominance of mucocutaneous symptoms (92%), followed by respiratory (81%) and
cardiovascular (49%) symptoms. Patients with NSAIDs anaphylaxis to showed a higher propensity to have co-
respiratory and mucocutaneous manifestations.
Reactions occurred in 53% of cases within 15 minutes after drug administration, in 45% were in hospitalized
patients and in 35% hospitalization were needed. The recurrence of anaphylaxis occurred in 26% of cases and
the risk was significantly higher when NSAIDs were involved.
Only 48% of patients were treated with adrenaline and in 9% of cases a self-injectable adrenaline kit was
prescribed.
Conclusions: In this study the most frequent culprit drugs were NSAIDs and they were associated with a higher
rate of anaphylaxis recurrence. We stress the under-treatment with adrenaline and the need to achieve a better
therapeutic management and prevention of recurrence of anaphylaxis to drugs in Portugal.

Dhm12 programm v7

Recommended

Recommended

More Related Content

Viewers also liked

Viewers also liked (18)

Similar to Dhm12 programm v7

Similar to Dhm12 programm v7 (20)

More from Georgi Daskalov

More from Georgi Daskalov (20)

Recently uploaded

Recently uploaded (20)

Dhm12 programm v7