ORIGINAL ARTICLE ANAPHYLAXIS Anaphylaxis to Patent Blue V. II. A unique IgE-mediated reaction S. G. O. Johansson 1,2 , A. Nopp 1 , H. O ¨ man 3 , P. Stahl-Skov 4 , A. S. Hunting 5 & A. B. Guttormsen 6,7 1 Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institute, Stockholm, Sweden; 2 Department of Clinical Immunol- ogy and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden; 3 MIAB, Uppsala, Sweden; 4 Department of Allergy, Uni- versity Hospital of Copenhagen, Copenhagen, Denmark; 5 Division of Anaesthesiology and Intensive Care Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway; 6 Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway; 7 Section of Anaesthesiology and Intensive Care, Department of Surgical Sciences, University of Bergen, Bergen, Norway To cite this article: Johansson SGO, Nopp A, O ¨ man H, Stahl-Skov P, Hunting AS, Guttormsen AB. Anaphylaxis to Patent Blue V. II. A unique IgE-mediated reac- tion. Allergy 2010; 65: 124–129 Anaphylaxis in relation to anaesthesia and operative proce- dures is rather uncommon but often serious. Thus the preva- lence of severe anaphylaxis to neuromuscular blocking agents (NMBAs) has been reported to approximately 1/5000 in France and Norway and 1/80 000 in Sweden (1, 2). Other agents are chlorhexidine (3, 4), latex (5), antibiotics and opi- oids (1). In the case of the opioids the anaphylaxis is proba- bly not allergic since the reaction has not been proven to be mediated by immunological mechanisms, in contrast to the allergic anaphylaxis initiated by NMBAs, chlorhexidine and latex. The prerequisite for an allergic anaphylaxis is that the patient must be sensitized at the time of exposure and reac- tion, and have IgE antibodies or, in special cases, IgG anti- bodies or sensitized lymphocytes. The IgE-sensitization is the result of prior exposure to either the agent causing the ana- phylaxis or a substance sharing the allergenic epitopes with the agent. Thus, pholcodine in cough syrup seems to be the important immunogenic agent sensitizing individuals to the allergenic epitope of NMBA, the quaternary ammonium ion (QAI), although the QAI can be found on a large variety of environmental chemicals (6). Patent Blue V (PBV) is used to identify the primary drain- ing lymph nodes, the so called sentinel nodes. Severe adverse reactions have been reported and recently a compilation of nine patients investigated in Norway was reported (7). Six of seven patients with anaphylaxis had increased serum tryptase in relation to their reaction. All skin prick tested patients, six Keywords basophils; CD-sens; histamine release. Correspondence S. G. O. Johansson, MD, PhD, Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska University Hospital, L2:04, S-171 76 Stockholm, Sweden. Accepted for publication 2 August 2009 DOI:10.1111/j.1398-9995.2009.02191.x Edited by: Marek Kowalski Abstract Background: Patent Blue V (PBV) is injected in order to map sentinel nodes during cancer staging procedures. Anaphylactic reactions, allegedly IgE antibody mediated, have been reported. The aim of the study was to explore the immunological mecha- nism of anaphylaxis to PBV. Methods: PBV allergen threshold basophil sensitivity, CD-sens, was performed on cells from nine patients diagnosed as having had adverse reactions to PBV. The mechanisms of the CD-sens were studied by immunological and immuno-chemical methods. Results: Five of the nine patients had a positive CD-sens to PBV which was com- pletely eliminated by washing the cells in phosphate buffered saline before allergen challenge. However, the positive CD-sens was completely reconstituted by incubat- ing the cells in plasma or serum of that patient or the other PBV-anaphylactic patients for 15 min at room temperature. In some patients the factor mediating CD- sens was completely or partially destroyed by heating at +56°C for 30 min or being exposed to the low pH used for elution from anti-Ig columns. A 1000-fold excess of monoclonal IgE blocked the reconstitution by approximately 50%. Conclusion: Anaphylactic reactions to PBV are mediated by IgE antibodies giving a classical CD-sens reaction. However, the allergenic configuration seems to constitute a structure completely dependent on PBV, as a hapten, linked to a, so far, unknown carrier that seems to be unique for patients having experienced a PBV-induced reac- tion. Further studies are needed to characterize the postulated carrier. Allergy 124 Allergy 65 (2010) 124–129 ª 2009 John Wiley & Sons A/S