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Supplementary Material 1

Background. Octylisothiazolinone (OIT) is used as an antifungal agent by the leather industry. Objectives. To show sensitization to OIT from leather, and to highlight the potential implications when cross-reactivity between OIT and methylisothiazolinone (MI) is studied. Methods. Two patients with allergic contact dermatitis caused by a leather belt and shoes, respectively, were patch tested with methylchloroisothiazolinone (MCI)/MI, MI, MCI, OIT, and benzisothiazolinone (BIT). High-performance liquid chromatography with ultraviolet detection (HPLC-UV) was used to detect isothiazolinone derivatives in leather goods. Additionally, files of OIT-sensitized patients, observed at the KU Leuven department during the period 1990-2015, were retrospectively analysed. Results. Both patients had been primarily sensitized to OIT, but the diagnosis in one of them could be achieved only when a higher patch test concentration of OIT (1000 ppm pet.) was used. HPLC-UV confirmed the presence of OIT in their leather goods. Non-relevant sensitization to MI was noted in both cases. Four additional cases of OIT sensitization from leather could be retrieved from the KU Leuven database. Conclusions. Non-occupational sensitization to OIT from leather may occur. Patch test concentrations of >250 ppm pet. may be necessary for diagnosis, and to show cross-reactivity with MI. Safer use limits for OIT in the leather industry may be needed.

Introduction Anaesthesia-related allergy is a rare but potentially life-threatening condition with serious consequences of diagnostic error. The authors report their experience of a 10-year survey in a Flemish referral centre. Methods Between January 2001 and December 2011, a total of 344 patients who experienced perioperative anaphylaxis were referred to our allergy centre. Allergy was documented on the basis of clinical history, skin tests, measurement of specific immunoglobulin E (sIgE) antibodies and/or basophil activation tests. Results A total of 344 patients were studied (111 male, 233 female; age ranging from 21 months to 86 years (median 47 years)). Mild reactions, mostly cutaneous, were reported in 110 patients and severe potentially life-threatening reactions in 176 patients. In the remainder 58 patients severity of the reaction was not reported. An IgE-mediated pathomechanism was documented in 246 cases (72%). Importantly, an IgE-mediated mechanism was not restricted to the severe reactions but also observed in 57% of the mild reactions. The most common offenders were neuromuscular blocking agents (NMBA) (40%), latex (25%), β-lactam antibiotics (12%) and chlorhexidine (9%). In 18 patients (7%) with an IgE-mediated allergy more than 1 causative agent was identified. In 7 patients, an indolent mastocytosis was diagnosed. Conclusion In our region, the most frequent causes of anaphylaxis during general anaesthesia are NMBA, particularly rocuronium, latex, antibiotics and chlorhexidine. Given the prevalence of double sensitization it is advocated to test all potential causative agents. Indolent mastocytosis should not be overlooked. Confirmatory testing should not be restricted to patients with severe anaesthesia-related anaphylaxis but also offered to patients with mild (cutaneous) reactions.

The example reported here illustrates the frequent belief that innocent products such as central venous catheters do not produce allergic reactions. However, they might be impregnated with chlorhexidine and elicit serious life-threatening anaphylaxis in patients with allergy to this antiseptic agent.

Adverse drug reactions (ADR) can result from immune-mediated (drug allergy) and nonimmune-mediated mechanisms. In both types of reaction, conclusive diagnosis and appropriate management remain major problems in daily clinical practice. This review summarizes the potentials and shortcomings of the currently available in vitro tests in the diagnosis of immediate (mostly IgE mediated) and nonimmediate (mostly T-cell mediated) drug allergy, particularly quantification of specific IgE, flow-assisted analysis of in vitro activated lymphocytes and basophils and the enzyme-linked immunosorbent spot.

Background: Allergy to rocuronium can be life-threatening. Correct diagnosis is a prerequisite because of serious consequences of diagnostic error. Objective: To assess skin testing, quantification of specific IgE (sIgE) and flowassisted activation of basophils [basophil activation test (BAT)] in the diagnosis of rocuronium allergy. Methods: This study comprises 104 curarized patients with a history of profound hypotension and severe bronchospasm immediately after induction of anaesthesia. All patients had skin tests, quantification of sIgE and BAT to rocuronium, together with investigations for all relevant compounds administered during anaesthesia that could have evoked the reaction. Diagnosis of rocuronium allergy was considered definite when the patient demonstrated a positive outcome for at least two of the three aforementioned tests. Results: The positive predictive value for skin testing, BAT and sIgE was 98% (CI 95%: 9299%), 97% (CI 95%: 88100%) and 83% (CI 95%: 7489%), respectively. The negative predictive value for skin testing, BAT and sIgE was 96% (CI 95%: 8699%), 75% (CI 95%: 6775%) and 72% (CI 95%: 5883%), respectively. Cross-reactivity with vecuronium was documented in 69% of the patients. Conclusion: Skin testing merits the status of primary diagnostic investigation to document rocuronium allergy and cannot be substituted by quantification of sIgE or BAT. SIgE can offer a diagnostic advantage in cases where skin tests yield negative results. However, additional tests (e.g. BAT) are of capital importance in patients with negative skin tests and positive sIgE results to help in interpreting the clinical significance of a positive sIgE result.