Skin Testing in Patients with Hypersensitivity Reactions to Iodinated Contrast Media – a European Multicenter Study
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View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Repositório Institucional dos Hospitais da Universidade de Coimbra Allergy 2009: 64: 234–241 Ó 2009 The Authors Journal compilation Ó 2009 Blackwell Munksgaard DOI: 10.1111/j.1398-9995.2008.01832.x Original article Skin testing in patients with hypersensitivity reactions to iodinated contrast media – a European multicenter study Background: Iodinated contrast media cause both immediate and nonimmediate K. Brockow1, A. Romano2, hypersensitivity reactions. The aim of this prospective study was to determine W. Aberer3, A. J. Bircher4,A. the specificity and sensitivity of skin tests in patients who have experienced such Barbaud5, P. Bonadonna6, E. Faria7, reactions. G. Kanny8, M. Lerch9, W. J. Pichler9, Methods: Skin prick, intradermal and patch tests with a series of contrast J. Ring1, J. Rodrigues Cernadas10, media were conducted in 220 patients with either immediate or nonimmedi- E. Tomaz11, P. Demoly12, ate reaction. Positive skin tests were defined according to internationally C. Christiansen13, for the European accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who Network of Drug Allergy and the had tolerated contrast medium exposure, served as negative controls. EAACI interest group on drug Results: Skin test specificity was 96–100%. For tests conducted within the hypersensitivity time period from 2 to 6 months after the reaction, up to 50% of immediate 1Department of Dermatology und Allergology reactors and up to 47% of nonimmediate reactors were skin test positive. For Biederstein, Division Environmental Dermatology immediate reactors, the intradermal tests were the most sensitive, whereas and Allergology Helmholtz Zentrum Mnchen/TUM, delayed intradermal tests in combination with patch tests were needed for Technical University Munich, Munich, Germany; optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity 2Allergy Unit, C.I. Columbus, Rome and IRCCS Oasi was more common in the nonimmediate than in the immediate group. Inter- Maria S.S., Troina, Italy; 3Department of estingly, 49% of immediate and 52% of nonimmediate symptoms occurred in Dermatology, Medical University of Graz, Graz, Austria; 4Allergy Unit, Department of Dermatology, previously unexposed patients. Many of these patients were skin test positive, University Hospital, Basel, Switzerland; indicating that they were already sensitized at the time of first contrast medium 5Department of Dermatology, University Hospital, exposure. Fournier Hospital, Nancy, France; 6Allergy Unit, Conclusions: These data suggest that at least 50% of hypersensitivity reactions to Verona Hospital, Verona, Italy; 7Immunoallergology contrast media are caused by an immunological mechanism. Skin testing appears Department, Coimbra University Hospital, Coimbra, 8 to be a useful tool for diagnosis of contrast medium allergy and may play an Portugal; Department of Internal Medicine, Clinical important role in selection of a safe product in previous reactors. Immunology and Allergy, University Hospital, Hospital Central, Nancy, France; 9Clinic for Rheumatology and Clinical Immunology/Allergology, Inselspital, Bern, Switzerland; 10Department of Allergy and Clinical Immunology, University Hospital of S. Jo¼o, Porto, Portugal; 11Hospital S. Bernardo, Setfflbal, Portugal; 12Exploration des Allergies, Maladies Respiratoires, INSERM, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France; 13Research and Development, GE Healthcare, Oslo, Norway Key words: contrast media; hypersensitivity; skin tests. Knut Brockow, MD Department of Dermatology and Allergology Biederstein Technische Universität Mnchen Biedersteiner Str. 29 80802 Mnchen Germany Accepted for publication 20 May 2008 Iodinated contrast media (CM) are highly concentrated are regarded as relatively safe, they are known to cause solutions of iodinated benzene derivatives, used to both immediate ( £ 1 h) and nonimmediate (>1 h) enhance X-ray procedures (1). Although these products hypersensitivity reactions in susceptible individuals (2). 234 Skin testing in contrast media hypersensitivity Immediate hypersensitivity reactions to CM are mainly Skin testing anaphylactic reactions that can be severe or even fatal Skin testing was performed with a minimum delay of 1 week and a (3), whereas nonimmediate reactions predominantly median delay of 6 months after the CM-induced hypersensitivity manifest themselves as exanthematous skin eruptions reaction. Skin prick tests (SPTs) with undiluted CM were followed occurring hours to days after CM application [reviewed by intradermal tests (IDTs) with 10-fold diluted CM and patch tests in Ref. (4)]. Even the newer generation CM cause (PTs) with undiluted CM. SPTs were performed on the volar immediate and nonimmediate reactions in about 1–3% forearm, and were read after 20 min and on days 2 and 3. The SPT of applications (2). These reactions are a serious was considered positive if a wheal of ‡ 3 mm in diameter was problem considering that more than 75 million CM- observed after 20 min (immediate reading) or if an erythematous induration occurred at the skin test site on days 2 or 3 (delayed enhanced X-ray procedures are conducted yearly world reading). Intradermal tests were conducted on either the volar wide (5). forearm or the back. The test solution (0.03–0.05 ml) was injected CM-induced hypersensitivity reactions have tradition- into the skin to produce a bleb of 4–5 mm in diameter. Readings ally been classified as nonallergic reactions (6), and skin were conducted after 20 min and on days 1, 2 and 3. The IDT was tests have been regarded as inappropriate tools in regarded as positive if the size of the initial wheal had increased by patients having experienced such reactions. However, at least 3 mm in diameter and was surrounded by erythema after 20 during the last few years several investigators have min (immediate) or if an erythematous induration at the skin test site was present in the delayed readings. Histamine (0.01%) and reported positive skin tests in patients with both saline (0.9%) served as positive and negative controls, respectively. immediate and nonimmediate hypersensitivity reactions Patch tests were conducted with CM soaked on a filter paper in a 12 after CM exposure, which indicates that immunological mm aluminium Finn chamber, fixed with adhesive tape on the back mechanisms may be involved (7–15). The European for 2 days. Readings were conducted 15 min after removal of the Network of Drug Allergy (ENDA; the EAACI interest strips and 24 h later in accordance with the recommendations of the group on drug hypersensitivity) therefore designed a European Society of Contact Dermatitis (18). Patients were instructed to return to the treating physician in case of positive prospective multicenter study to explore the sensitivity reactions at other time points. and specificity of skin tests in patients who reported Patients were skin tested with the culprit CM (if known) and as typical features of CM hypersensitivity reactions. In many of the following 13 CM as could be practically handled in the this paper we report the results from the first 4 years of respective allergy centers: The three ionic monomers sodium ami- study. dotrizoate, ioxithalamate and iodamide; the ionic dimer ioxaglate; the seven nonionic monomers iohexol, iomeprol, iobitridol, iopamidol, ioversol, iopromide and iopentol; and the two nonionic dimers iodixanol and iotrolan. All solutions had a strength of 300– Methods 320 mgI/ml. All the above listed CM were used for skin testing in 31 or more Patients and negative control subjects nonexposed individuals. While iodamide was tested only in 1 CM exposed control, the other 12 CM were tested in 7 or more of the 11 Patients who were referred to the 12 allergy departments of the individuals in this group. SPT, IDT and PT with immediate and late ENDA CM task force members because of a reported previous readings were conducted, as described above. hypersensitivity reaction after CM exposure were included in the A history of a typical drug hypersensitivity reaction after study. Most cases (95%) were prospectively collected over a 4- administration of CM was used as a gold standard, and skin test year period from January 2003 to December 2006. Eight patients sensitivity was calculated as the percentage of skin test positive in the immediate group and two patients in the nonimmediate among these patients. Skin test specificity was calculated as the group were tested prior to 2003. The same standardized proce- percent of negative controls with positive skin test to any of the dures were used in all patients. Clinical data were recorded using tested CM, indicating possible irritative skin test reactions. an adaptation of the ENDA drug allergy questionnaire (16). The hypersensitivity reaction was classified as immediate (onset £ 1h after CM administration) or nonimmediate (onset >1 h after CM Statistical methods administration). For immediate reactions the severity scale of Ring and Messmer (17) was used: grade I: generalized cutaneous Two-sided 95% confidence intervals (CI) for frequencies were and/or mucocutaneous symptoms; grade II: mild systemic reac- based on Kaplan–Meier estimates, using Minitab 12 software. The tions; grade III: life-threatening systemic reactions; grade IV: Fisher exact test was used for statistical comparison between cardiac and/or respiratory arrest. In patients with nonimmediate groups. Differences with