An experimental biological test to diagnose hypersensitivity reactions to carboplatin: new horizons for an old problem.

Carboplatin, a second-generation platinum compound, is a chemotherapeutic drug effective in many types of cancers. Its use is limited by the development of systemic allergic reactions in up to 30% of the cancer patients. Therefore, it is very important to make a correct diagnosis of true carboplatin allergy, for the crucial clinical implications. In this regard, no biological test is actually available to detect specific immunoglobulin E in the sera of patients allergic to carboplatin. We evaluated a new experimental biological test in patients with suspected immunoglobulin E-mediated reactions to carboplatin. Three patients with suspected hypersensitivity reactions to carboplatin underwent skin tests with an undiluted aliquot (10 mg/ml) of carboplatin preparation planned for infusion. Total serum immunoglobulin E and specific immunoglobulin E to the two platinum salts carboplatin and cisplatin were determined with the ImmunoCAP system (Phadia AB, Uppsala, Sweden). We detected specific immunoglobulin E to carboplatin in all three patients, whereas specific immunoglobulin E to cisplatin was observed in one patient. The positivity of specific immunoglobulin E against carboplatin in these three patients is a new and encouraging observation for the development of a new important instrument that can help clinicians in their therapeutic decisions, after a hypersensitivity reaction to a platinum salt.

Evaluation of a new routine diagnostic test for immunoglobulin E sensitization to neuromuscular blocking agents.

BACKGROUND: Neuromuscular blocking agents (NMBA) are responsible for most immediate hypersensitivity reactions during anesthesia, as a result of the presence of a quaternary ammonium ion. The aim of this study was to evaluate the diagnostic performance of a commercial immunoglobulin E (IgE) test (quaternary ammonium morphine [QAM]) for diagnosing sensitivity to NMBA. METHODS: We tested 168 patients exposed to NMBAs during anesthesia. Of those patients, 54 had an uneventful procedure and 114 had immediate hypersensitivity reactions, and 57 patients had positive skin tests to the administered NMBA, whereas 57 had negative skin tests. Specific IgE concentrations determined with the QAM method based on a morphine solid phase were compared with those obtained with a recommended experimental method with a choline solid phase. RESULTS: For the QAM test, a 0.35 kUA/l positivity cutoff was chosen from the receiver operating characteristics curve. QAM-specific IgE was found in 84.2% of skin test-positive reactors (80.7% with the recommended method; no significant difference), and binding was inhibited by the culprit NMBA in 80% of cases. The frequency of QAM-specific IgE positivity was significantly higher in skin test-negative reactors (24.6%) than in controls (9.3%), suggesting NMBA sensitivity. CONCLUSION: Sensitivity of the QAM test (84.2%), together with its simplicity and suitability for routine laboratory use, makes it a valuable tool, in conjunction with skin tests, for diagnosing NMBA sensitivity in patients who react after NMBA injection. The QAM test is of particular interest when skin tests are not available or not reliable or give results poorly compatible with mediator release or clinical features.

Carboplatin-, oxaliplatin-, and cisplatin-specific IgE: cross-reactivity and value in the diagnosis of carboplatin and oxaliplatin allergy.

BACKGROUND: The diagnosis of hypersensitivity reactions (HSR) to platins is based on the characterization of the reaction and the results of skin testing. Platins can be irritants when used in skin testing; therefore, in vitro testing may offer an alternative diagnostic tool. OBJECTIVE: To evaluate sensitivity and specificity of platin specific IgE (sIgE) in patients with HSRs and in controls. METHODS: Twenty-four patients with immediate HSR to platins were included (carboplatin, 12; oxaliplatin, 12): 19 women and 5 men (mean age, 61 years). The control group included 17 patients exposed to platin and with no HSR. Skin testing was performed on 22 patients. Carboplatin sIgE and oxaliplatin sIgE were measured in 24 patients and 17 controls; carboplatin sIgE was measured in 21 patients. RESULTS: Skin test results were positive in 22 patients (carboplatin, 12/12; oxaliplatin, 10/12). Seven of 12 patients sensitive to carboplatin (59%) had positive carboplatin sIgE, 2 also had positive cisplatin sIgE, and all had negative oxaliplatin sIgE; 9 of 12 patients sensitive to oxaliplatin (75%) had positive sIgE to oxaliplatin, 8 of 12 (67%) also had positive carboplatin and cisplatin sIgE, to which they had not been exposed. All 5 carboplatin controls had negative sIgE; 3 oxaliplatin controls (25%) had positive carboplatin sIgE, and 2 had positive oxaliplatin sIgE. CONCLUSION: Carboplatin sIgE is very specific but less sensitive. In contrast, oxaliplatin sIgE had higher sensitivity but lower specificity. Analysis of our data suggests that oxaliplatin exposure was more immunogenic. This could be clinically relevant because patients sensitized to carboplatin may be able to tolerate oxaliplatin, but patients sensitized to oxaliplatin may be at risk when exposed to carboplatin and cisplatin.

Immunoglobulin E antibodies to rocuronium: a new diagnostic tool.

BACKGROUND: Diagnosis of allergy from neuromuscular blocking agents is not always straightforward. The objectives of the current study were to investigate the value of quantification of immunoglobulin E (IgE) by ImmunoCAP (Phadia AB, Uppsala, Sweden) in the diagnosis of rocuronium allergy and to study whether IgE inhibition tests can predict clinical cross-reactivity between neuromuscular blocking agents. METHODS: Twenty-five rocuronium-allergic patients and 30 control individuals exposed to rocuronium during uneventful anesthesia were included. Thirty-two sera (total IgE > 1,500 kU/l) were analyzed for potential interference of elevated total IgE titers. Results were compared with quantification of IgE for suxamethonium, morphine, and pholcodine. Cross-reactivity between drugs was assessed by IgE inhibition and skin tests. RESULTS: Sensitivity of IgE for rocuronium, suxamethonium, morphine, and pholcodine was 68, 60, 88, and 86%, respectively. Specificity was 100% for suxamethonium, morphine, and pholcodine IgE and 93% for rocuronium IgE. ROC analysis between patients and control individuals changed the threshold to 0.13 kUa/l for rocuronium, 0.11 kUa/l for suxamethonium, 0.36 kUa/l for morphine, and 0.43 kUa/l for pholcodine. Corresponding sensitivity was 92, 72, 88, and 86%, respectively. Specificity was unaltered. Interference of elevated total IgE with quantification of IgE was demonstrated by the analysis in sera with a total IgE greater than 1,500 kU/l. IgE inhibition did not predict clinical relevant cross-reactivity. CONCLUSIONS: The rocuronium ImmunoCAP constitutes a reliable technique to diagnose rocuronium allergy, provided an assay-specific decision threshold is applied. IgE assays based on compounds bearing ammonium epitopes are confirmed to represent reliable tools to diagnose rocuronium allergy. High total IgE titers were observed to affect specificity of the assays.

IgE-mediated allergy to chlorhexidine.

BACKGROUND: Investigations at the Danish Anesthesia Allergy Centre have included testing for allergy to chlorhexidine since 1999. OBJECTIVE: To investigate whether measurement of IgE and histamine release confirm an IgE-mediated mechanism for chlorhexidine allergy. METHODS: Twenty-two patients with clinical history suggestive of chlorhexidine allergy were included. Skin tests with chlorhexidine and tryptase measurements were performed during initial investigations. Sera were analyzed retrospectively for IgE and histamine release (passive sensitization) to chlorhexidine. RESULTS: Twelve patients were skin test positive and 10 were skin test negative. Of the skin test-positive patients, 11 of 12 had IgE to chlorhexidine and 7 of 11 had a positive histamine release test. None of the skin test-negative patients had specific IgE or positive histamine release to chlorhexidine. Skin test-positive patients had higher median age (64 vs 49 y) and were mainly male (11/12 vs 6/10). In both groups, 8 patients had hypotension, but bronchospasm mainly appeared in skin test-negative patients (1/12 vs 6/10). Reactions occurred more often during urologic surgery in skin test-positive patients (5/12 vs 0/10). Baseline tryptase was higher in skin test-positive patients (median, 11.5 vs 3.7 microg/L), and 6 of 7 patients had elevated IgE to chlorhexidine in serum at the time of reaction. CONCLUSION: This study confirms that chlorhexidine allergy is IgE-mediated and that measurement of specific IgE and histamine release are good adjuncts to skin testing in patients with clinical history suggesting chlorhexidine allergy. CLINICAL IMPLICATIONS: IgE and histamine release can be used to support the diagnosis of allergy to chlorhexidine.

IgE-mediated anaphylactic reaction induced by succinate ester of methylprednisolone.

BACKGROUND: In systemic administration the prevalence of anaphylactic reactions attributable to corticosteroids is approximately 0.3%. Positive prick tests with different corticosteroids have been reported suggesting an immunoglobulin (Ig)E-mediated mechanism. OBJECTIVE: A 42-year-old man with multiple sclerosis developed flush, erythema, and itching a few minutes after the begin of an intravenous infusion of methylprednisolone-21-sodium succinate. DIAGNOSTIC AND RESULTS: Prick tests were found to be positive with methylprednisolone-21-sodium succinate and prednisolone-21-sodium succinate, whereas prick tests with prednisolone without ester and betamethasone-21-dihydrogen phosphate showed negative results. Oral challenge with prednisolone without ester and intravenous challenge with betamethasone-21-dihydrogen phosphate were well tolerated. Specific IgE-antibodies against methylprednisolone-21-sodium succinate were found in the serum of the patient. Because of the positive prick test and specific IgE antibodies against methylprednisolone-21-sodium succinate, the diagnosis of IgE-mediated anaphylactic reaction could be proven. Succinate ester was suspected to be immunogenic, as other corticosteroids without this particular ester or with other substitutions at the C21 remained negative both in the prick and the challenge tests. CONCLUSIONS: This patient showed an adverse reaction caused by methylprednisolone-21-sodium succinate. The uniqueness in this case was the presence of specific IgE antibodies against this esterified corticosteroid in the patient's serum proving that this reaction was based upon a true IgE-mediated mechanism.