- Multidisciplinary specialized care and research in children and adults with complex atopic disorders, work-related allergies, mastocytosis, treatment resistant urticaria/angioedema, drug allergy and severe allergic patients receiving immunotherapy.
- A platform for high quality care, and innovative epidemiological, translational and clinical research.
- A network for education of students, training of residents and fellows in the participating disciplines and postgraduate education for other parties.
The ACE Allergic Diseases focus on the following research areas.
* Collaboration between parties within the ACE Allergic Diseases; ** Collaboration with other ACEs
THE ATOPIC CHILD: The ACE aims to optimize the diagnosis and treatment of allergic diseases in children.
1) *Evaluation and validation of IgE profiles to allergen components in food allergy using biochip technology.
2) *The use of efficient and potential cost-effective diagnostic algorithms (for children and adults) , together with the Maasstad ziekenhuis
3) *The measurement of skin barrier dysfunction in children with atopic dermatitis using the Raman technology may lead to personalized treatment.
4) *Optimizing treatment of allergic rhinitis (the Hatsjoe follow-up study),
5) *Optimizing treatment of asthma (Asthma trial)
6) *Optimizing treatment of atopic dermatitis (Eczema trial)
7) Pharmacogenetics in asthmatic children (PUFFIN trial),
8) Prevention of peanut allergy by early introduction : collaboration between the Erasmus MC and the Reinier de Graaf Groep.
9) Use of the NMF biomarker as predictive diagnostic for effective use of cyclosporine in the treatment of eczema. (ZONMw; GGG Personalized medicine).
IMMUNOMODULATION and immunotherapy: Immunomodulation and immunotherapy is an important area for translational research focused on better and novel treatment .
1) *The iAGE study (NWO-STW) has the objective to accelerate the resolution of Cow’s Milk Allergy (CMA) by developing and testing a prototype product containing extensively heated glycated CM protein in a multicentre (N=10) RCT.
2) *As a spin –off, the iAGE Microbiome study focus on identifying and altering specific bacterial species and strains in the pathology of CMA, which may lead to new prevention methods and therapeutic approaches of CMA and related atopic diseases.
3) *The ACE participates in a consortium (LUMC-EMC-AMC) funded by the Lung Foundation, trying to identify molecules from micro-organisms such as Schistosoma, that may modulate the allergic immune response .
4) Epicutaneous immunotherapy with peanut, collaboration with Mount Sinai Hospital NY USA
5) Oral immunotherapy with peanut, to be started.
6) Treatment with recombinant B-cell epitope based grass pollen vaccine, collaboration with University of Vienna.
7) *Optimizing care for patients requiring conventional subcutaneous or sublingual immunotherapy is a topic addressed in a BeterKeten project (Poker Study), a collaboration with several hospitals and general practitioners in the Rijnmond area.
MASTOCYTOSIS is a rare disease covered by the NFU recognized Expertise Center of Mastocytosis. Research , done together with the ACE Immunological rare diseases implies
1) **Research to the characteristics of the disease and the clinical implications for patients.
2) **The detection of a JAK1/JAK2-inhibitor that may inhibit mast cell degranulation and cytokines release may the first step to a new treatment.
URTICARIA. The ACE comprises a national urticaria expertise center being in the process of accreditation in the international network UCARE. Current research focus on treatment with the biological omalizumab and the cost-effectiveness of personalized treatment.
DRUG HYPERSENSITIVITY: Different types of drug hypersensitivity form an emerging challenge for physicians and patients in all medical areas. Current study topics are;
1) *Development and validation of new laboratory technics to diagnose drug hypersensitivity.
2) *Mastocytosis as a risk factor for hypersensitivity reactions to NSAIDS
3) **Safe strategies to introduce antibiotics in patients with a possible penicillin allergy, in collaboration with the ACE ARTE.
4) *Develop, validate and implement a drug allergy questionnaire and an algorithm, to be used in a clinical pathway to confirm or discard beta-lactam allergy, in cooperation with sections of infectious disease, clinical pharmacists and CHIPSOFT.
This ACE is actively involved in the education of bachelor students (BSc) in medicine (especially 2e and 3e year) and in the education of master students (MSc) specifically in infection and immunity.
Furthermore, the ACE is involved in a minor for 3rd year medical students. The minor aims to deepen the understanding of immunological processes - and clinical reasoning in allergic diseases.
Development of novel educational programs (e.g. E-learning modules, interactive sessions, flipping the classroom) and participation in The institute of Medical Education Research Rotterdam (iMERR). Project leadership in a new Educational program: Didactics in medicine. The project aims to improve teaching skills at a medical- student level. "Teach medical students how to teach".
Coordinator of theme 2B3 (infection and immunity). Educational evaluation is performed by yearly PDCA cycles and by SET-Q evaluation. One of the UHDs has been nominated many times as teacher of the year and has won this title in 2014 and in 2018.
At the department pediatrics, residents in ENT, pulmonology, internal medicine and dermatology both from Erasmus MC and from other university centers are trained to handle patients with allergic disease. At the moment there are 6 fellows (allergology and clinical Immunology) and 1 fellow pediatric allergology in training.
The ACE currently comprise 10 PhD students. Students in medicine are invited to actively participate in novel research. Furthermore the ACE yearly organizes both national and internal conferences to broaden the knowledge on allergic and mast cell related diseases.
Internationally, the ACE works together in Task Forces (within EAACI), developing Competencies for Allied health Care Professionals, promoting and achieving excellence in the delivery of integrated Allergy care. Consequently, organizing whole day courses and workshops for "nurse specialists in Allergy".
Finally, the ACE has a leading role in the development of European training requirements for the specialty and subspecialty of Allergology across Europe.
Societal Relevance to Research, Education and Patient Care
The ACE aims to broaden the knowledge on allergic and mast cell related diseases both among workers in the field of medicine as well as among the general public. This is done by publishing articles in peer reviewed magazines and in the lay press .
Furthermore information days/ evenings are organized to inform patients about new and exciting research and developments concerning their disease. Moreover, patient leaflets have been produced and are nationally used through the Netherlands Society of Allergology. The ACE is involved in the development of national and international guidelines in food allergy and anaphylaxis (national: Acute Boekje; richtlijn Anaphylaxis bij kinderen, richtlijn voedselprovocaties), international position papers and guidelines in occupational allergy and allergen immunotherapy. Moreover, the ACE is involved in the establishment of the highly cited ARIA (Allergic Rhinitis and the impact on Asthma) guidelines. Finally, a series of international guidelines on allergen immunotherapy for allergic rhinoconjunctivitis, asthma, insect allergy, food allergy and prevention of allergy have been recently finalised. The ACE was involved in all those guidelines. The international guideline on allergen immunotherapy for allergic rhinoconjunctivitis will be adapted and implemented as a national guideline.
Additionally, the mastocytosis team develops guidelines for diagnostic and therapeutic approach for both children and adults with mast cell related disease . The ACE participates in international trials and develops investigator initiated studies (e.g. on food allergy).
This ACE is actively involved in the education of bachelor and master students in medicine (especially 2e and 3e year) and in the education of master students in infection and immunity.
Finally, the ACE is interacting with:
- Patient organisations: Long fonds, Mastocytose patiënten vereniging Nederland, Nederlands Anafylaxis Netwerk, Stichting Voedselallergie.
- National scientific organisations: NVvA, NvKA, NVK/SKA, NIV
- International scientific organisations: GA2LEN Network of Excellence, EAACI, WAO, ARIA/WHO
- International professional organisations: UEMS
- International regulators: European Medicines Agency (EMA), Paul Ehrlich Institute (PEI)
Viability of Research, Education and Patient Care
While at the beginning of the 20th century allergy was seen as a rare disease, in the last few decades we have witnessed a dramatic increase in disease burden. Today, more than 150 million Europeans suffer from chronic allergic diseases and the current prediction is that by 2025 more than 50% of the entire EU population will be affected. Asthma and allergic rhinitis alone are estimated to result in more than 100 million lost workdays and missed school days in Europe every year. If patients will be treated appropriately with available cost-effective treatments, average savings of 142 billion euro per annum can be realized. Therefore, there is an urgent need to support the establishment of European Academic Centers of Excellence in Allergy, in order to prioritize and concert research efforts in the field of allergy, to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.
The ACE consists of upcoming scientists/specialists and senior scientist/specialists in different age categories. Integration of a new and young Pediatric Allergology subunit with the longstanding Pediatric Pulmonology and Adult Allergology sections strengthens viability. Also, integration of the subspecialties of Allergology and Clinical Immunology into one discipline further enforces sustainability.
Upcoming talent is identified by the recruitment process of residents and fellows for relevant (sub)specialties and PhD students for research projects. Monitoring and reviewing is part of the follow-up.
Finally, in the Netherlands research in allergic diseases - although characterised by good quality - is fragmented. Amsterdam focus on molecular Allergology and occupational dermatoses, Utrecht has special attention for food allergy and occupational asthma, Groningen concentrates on insect allergy and mastocytosis. By combining the different areas of and disciplines involved in allergic diseases from childhood to adults, the ACE Allergic Diseases will be an attractive partner in research and educational activities for relevant stakeholders. Moreover, the ACE aims to have an important impact on referral patterns of patients in need of academic care.
Key and relevant publications of the last five years
- Wartna JB, Bohnen AM, Elshout G, Pijnenburg MW, Pols DH, Gerth van Wijk R, Bindels PJ. Symptomatic treatment of pollen-related allergic rhinoconjunctivitis in children: randomized controlled trial. Allergy. 2017; 72:636-644
- Pols DHJ, Nielen MMJ, Bohnen AM, Korevaar JC, Bindels PJE. Atopic children and use of prescribed medication: A comprehensive study in general practice. PLoS One. 2017; 12:e0182664
- Pijnenburg MW, Baraldi E, Brand PLP, Carlsen K-H, Eber E, Frischer T, Hedlin G, Kulkarni N, Lex C, Mäkelä MJ, Mantzouranis E, Moeller A, Pavord I, Piacentini G, Price D, Rottier BL, Saglani S, Sly PD, Szefler SJ, Tonia T, Turner S, Wooler E, Lødrop Carlsen KC. Monitoring asthma in children. Eur Respir J 2015; 45: 906-925
- Heeringa JJ, Rijvers L, Arends NJ, Driessen GJ, Pasmans SG, van Dongen JJM, de Jongste JC, van Zelm MC. IgE-expressing memory B cells and plasmablasts are increased in blood of children with asthma, food allergy and atopic dermatitis. Allergy 2018;73:1331-6
- Sampson HA, Shreffler WG, Yang WH, Sussman GL, Brown-Whitehorn TF, Nadeau KC, Cheema AS, Leonard SA, Pongracic JA, Delebarre CS, Assaád AH, de Blay F, Bird JA, Tiles SA, Boralevi F, Bourrier T, Hebert J, Green TD, Gerth van Wijk R, Knulst AC, Kanny G, Schnieder LC, Kowalski M, Dupont C. Effect of Varying Doses of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Exposure Among Patients With Peanut Sensitivity: A Randomized Clinical Trial. JAMA. 2017;318(18):1798
- van der Valk JP, Gerth van Wijk R, Dubois AE, de Groot H, Reitsma M, Vlieg-Boerstra B, Savelkoul, HF, Wichers HJ, de Jong NW. Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut. PLoS One. 2016;11(3):e0151055
- Kiel MA, Roder E, Gerth van Wijk R, Al MJ, Hop WC, Rutten-van Molken MP. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy. J Allergy Clin Immunol. 2013;132(2):353-60 e2.
- Hermans MAW, Schrijver B, van Holten-Neelen CCPA, Gerth van Wijk R, van Hagen PM, van Daele PLA, Dik WA. The Jka1/Jak2 inhibitor ruxolinib inhibits mast cell degranulation and cytokine release. Clin Exp Allergy 2018 doi 10.1111/cea `13217 (Epub
- Elbert NJ, van Meel ER, den Dekker HT, de Jong NW, Nijsten TEC, Jaddoe VWV, de Jongste JC, Pasmans SGMA, Duijts L. Duration and exclusiveness of breastfeeding and risk of childhood atopic diseases. Allergy 2017;72:1936-43
- van der Kolk T, van Maaren MS, van Doorn MBA. Personalized omalizumab treatment improves clinical benefit in patients with chronic spontanieous urticaria. J Allergy Clin Imm 2018, in press
- van der Valk JP, Gerth van Wijk R, Vergouwe Y, Steyerberg EW, Reitsma M, Wichers HJ, de Jong N sIgE Ana o 1, 2 and 3 accurately distinguish tolerant from allergic children sensitized to cashew nuts. Clin Exp Allergy. 2017;47(1):113-20.
- Emons JA, Flokstra BM. De Jong C, van der Molen T, Brand HK, Arends NJ, Amaral R, Fonseca JA, Gerth van Wijk R. Use of the Control of Allergic rhinitis and Asthma Tests (CARATkids) in children and adolescents: Validation in Dutch. Pediatric Allergy Immunol 2017;28: 185-190
- Elbert NJ, Kiefte-de Jong JC, Voortman T, Nijsten TEC, de Jong NW, Jaddo VWV, de Jongste JC, Gerth van Wijk R, Duijts L, Pasmans SGMA. Allergenic food introduction and risk of childhood atopic diseases. PLos One 2017;12:e)187999.
- Voorend-van Bergen S, Vaessen-Verberne AA, Brackel HJ, Landstra AM, vd Berg NJ, Hop WC, de Jongste JC, Merkus PJ, Pijnenburg MW. Monitoring strategies in children with asthma: a randomised controlled trial. Thorax 2015; 70: 543-550
- Heeringa JJ, Rijvers L, Arends NJ, Driessen GJ, Pasmans SG, van Dongen JJM, de Jongste JC, van Zelm MC. IgE-expressing memory B cells and plasmablasts are increased in blood of children with asthma, food allergy and atopic dermatitis. Allergy. 2018 Jan 30.
- Totté JEE, Pardo LM, Fieten KB, de Wit J, de Boer DV, van Wamel WJ, Pasmans SGMA. The IgG response against Staphylococcus aureus is associated with severe atopic dermatitis in children. Br J Dermatol. 2017
- Nguyen AN, Elbert NJ, Pasmans SGMA, Kiefte-de Jong JC, de Jong NW, Moll HA, Jaddoe VWV, de Jongste JC, Franco OH, Duijts L, Voortman T. Diet Quality throughout Early Life in Relation to Allergic Sensitization and Atopic Diseases in Childhood. Nutrients. 2017 Aug 5;9(8). pii: E841. doi: 10.3390/nu9080841.
PhD theses of the last five years
- Lonneke van der Mark. Children with asthma in General Practice; The Development of the clinical asthma prediction score. Thesis. University of Amsterdam. 9 oktober 2013. Promotors: PJE Bindels, WMC van Aalderen
- David Pols. Atopic Children in General Practice. Thesis Erasmus University Rotterdam. 6 december 2017. Promotor PJE Bindels. Copromotoren AM Bohnen, MMJ Nielen
- R.J.P. van der Valk, 12 april 2013 (Erasmus Universiteit Rotterdam): Exhaled nitric oxide and asthma in childhood. Promotor: J.C. de Jongste
- Maarten Kuethe. Nurse versus physician led care for the management of paediatric asthma. Thesis. University of Amsterdam. 6 maart 2014. Promotores WMC van Aalderen, PJE Bindels.
- A.M. Sonnenschein-van der Voort, 15 januari 2014 (Erasmus Universiteit Rotterdam): Fetal and infant origins of childhood asthma: the Generation R study. Promotor: J.C. de Jongste, co-promotor: L. Duijts.
- E. Hafkamp-de Groen, 21 mei 2014 (Erasmus Universiteit Rotterdam): Asthma symptoms in early childhood: a public health perspective. Promotor: J.C. de Jongste.
- T.A.S. Voorend-van Bergen, 26 november 2014 (Erasmus Universiteit Rotterdam): Monitoring of childhood asthma. Promotor: J.C. de Jongste, co-promotor: M.W.H. Pijnenburg.
- M. Engelkes, 1 juni 2016 (Erasmus Universiteit Rotterdam): Asthma. Epidemiology, treatment and exacerbations. Promotor: J.C. de Jongste, co-promotor: H.M. Janssens.
- J.P. van der Valk , 22 november 2016 (Erasmus Universiteit Rotterdam) Cashew nut allergy in children. Promotor: R. Gerth van Wijk, co-promotor: NW. De Jong
- M. Reitsma. 10 april 2018 The cashew allergens: a molecular and serological characterization. Wageningen University. Promotor H.J. Wichers. Co-Promotor: NW de Jong
- N.J. Elbert, 24 oktober 2017 (Erasmus Universiteit Rotterdam) . Fetal and infant origins of childhood asthma. Promotor: S.G.M.A Pasmans, co-promotor L. Duijts.
- K. Fieten, 22 december 2017 (Universiteit Utrecht): Complex care for complex eczema in children. Promotores. C.M.A. Bruijnzeel-Koomen, S.G.M.A. Pasmans
- J. Totte, 5 juni 2018 (Erasmus Universiteit Rotterdam) The influence of Staph Aureus on the skin. Promotores: Pasmans SGMA, M.Vos Co-promotores: Cortes L
Non-scientific publications related to the ACE
- 2013/3 Allergie en Voeding- Stichting Voedselallergie. “Het is van belang te zorgen dat alle specialisten het met elkaar eens zijn”. M.S. van Maaren.
- 2013/2 Monitor. Onderzoek naar nieuwe test cashewnotenallergie: “Nooit meer provoceren!” N.W. de Jong
- 2015/2 Pulmonaal Formularium. Interventies bij inhalatieallergie. R Gerth van Wijk
- 2016/4 Modern Medicine. Feit en Fictie over Inhalatie allergieën. M.S. van Maaren
- 2016/2 Algemeen dagblad. Verhit eiwit helpt kind met allergie sneller wennen aan koemelk. N.W. de Jong
- 2016/5 Het allergieboek. R Gerth van Wijk
- 2017/5 Mijn Gezondheidsgids. Hereditair angio-oedeem (HAE): zwellingen door een genetische afwijking. P.L.A. van Daele
- 2018/3 Stichting Voedsel allergie. “Wat is voedsel allergie” M.S. van Maaren
- 2018/7 Zuivelengezondheid. Het behandelen van koemelkallergie met koemelk. N.W. de Jong
- 2018/1 Zalfje. Een vrolijk en leerzaam (voor)leesboek voor kinderen met matig tot ernstig constitutioneel eczeem. Elodie mendels