Delayed positive skin tests in patients with immediate hypersensitivity reactions to beta-lactams

Introduction: Allergic and nonallergic hypersensitivity reactions to iodinated contrast media (ICM) and gadolinium-based contrast media are classified as immediate or non-immediate hypersensitivity reactions (IHR and NIHR), respectively. Skin tests and provocation tests are recommended for the evaluation of hypersensitivity reactions to contrast agents; however provocations are not common in clinical practice. Methods: A MEDLINE search was conducted to investigate studies comprising both skin tests and provocation tests that evaluated hypersensitivity reactions to ICM. Results: Nineteen studies were identified that reported on skin tests, followed by provocations. In the case of IHR to ICM, 65/69 (94%) patients with a positive skin test for the culprit media tolerated a challenge with a skin-test-negative alternative ICM. In IHR to ICM with a negative skin test for the culprit media, provocations were positive in 3.2%–9.1% patients. In the case of a NIHR to ICM with a positive skin test, provocation with a skin-test-negative agent was tolerated in 75/105 (71%) of cases. In NIHR with a negative skin test for the culprit agent, re-exposure to the culprit or an alternative was positive in 0%–34.6% patients. Provocations with the same ICM in skin test positive patients with IHR or NIHR were positive for a majority of the patients, although such provocation tests were rarely performed. Data on hypersensitivity reactions, skin tests and provocations with gadolinium-based contrast media were limited; however, they exhibited a pattern similar to that observed in ICM. Conclusion: In both ICM and gadolinium-based contrast media, the risk of an immediate repeat reaction is low when skin tests are negative. In contrast, a provocation with a skin-test-positive contrast medium showed a high risk of an immediate repeat hypersensitivity reaction. Therefore, a thorough medical history is necessary, followed by skin tests. A provocation is recommended, for diagnostic work-up, when the diagnosis is uncertain.

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In Vivo Cysteinyl Leukotriene Release in Allergic and Nonallergic Immediate Hypersensitivity Reactions during Anesthesia

Anesthesiology ◽

10.1097/aln.0000000000001600 ◽

2017 ◽

Vol 126 (5) ◽

pp. 834-841 ◽

Cited By ~ 2

Author(s):

Dominique Laroche ◽

Pierre Léturgie ◽

Delphine Mariotte ◽

Yann Ollivier ◽

Jean-Luc Hanouz ◽

...

Keyword(s):

Mast Cell ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Immediate Hypersensitivity ◽

Mast Cell Tryptase ◽

Cysteinyl Leukotriene ◽

Negative Results ◽

Important Mediator ◽

The Difference

Abstract Background Immediate hypersensitivity reactions occurring during anesthesia are classified as allergic when skin tests and mast cell tryptase are positive and as nonallergic when negative results are obtained. Cysteinyl leukotrienes (cysLTs) are potent mediators synthesized by mast cell and eosinophil that induce bronchial constriction. They could play a role in hypersensitivity reactions. Methods cysLT C4, D4, and E4 concentrations were measured by a competition immunoassay in serial plasma samples obtained prospectively from 21 anesthetized controls and retrospectively from 34 patients who reacted at induction of anesthesia (24 with allergic and 10 with nonallergic reactions). Results In controls, the median (interquartile range) cysLT concentration was 0.83 (0.69 to 1.02) μg/l before anesthesia and was unchanged 30 min, 6 h, and 24 h afterward. In the patients with allergic reactions, the values were highly increased 30 to 60 min after the reaction (17.9 [7.8 to 36.0] μg/l), while the patients with nonallergic reactions had less increased values (7.3 [3.0 to 11.5] μg/l). The difference between the three groups was significant (P < 0.0001). Increased values persisted during the 24 h of observation. Concentrations were significantly higher in patients with bronchospasm (P = 0.016). Conclusions cysLTs appear to be an important mediator of allergic and nonallergic immediate hypersensitivity reactions. These findings might open a new field for management of patients with hypersensitivity reactions, especially nonallergic ones.

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Converter Phenotype: A New Profile That Is Not Exclusive to Taxanes

Frontiers in Allergy ◽

10.3389/falgy.2021.785259 ◽

2022 ◽

Vol 2 ◽

Author(s):

Teodorikez Wilfox Jimenez-Rodriguez ◽

Francisco Manuel Marco de la Calle ◽

Inmaculada Lozano-Cubo ◽

Rosa Ana Montoyo-Anton ◽

Victor Soriano-Gomis ◽

...

Keyword(s):

Clinical Characteristics ◽

Drug Exposure ◽

Drug Hypersensitivity ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Test Results ◽

Drug Reactions ◽

Immediate Hypersensitivity ◽

Drug Hypersensitivity Reactions ◽

Median Interval

Introduction: Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; however, precision medicine has made it possible to characterize new phenotypes. A recent communication proposed the existence of a “converter phenotype,” which would affect patients who present non-immediate hypersensitivity reactions and in subsequent exposures develop immediate hypersensitivity reactions. This study aimed to describe the clinical characteristics of converter phenotype reactions and their evolution during desensitization to chemotherapeutic drugs and monoclonal antibodies.Methods: We retrospectively reviewed our database of patients undergoing desensitization to chemotherapy or biological agents and selected those with a converter phenotype. Demographic and clinical characteristics of the patients, the results of skin tests, tryptase and IL-6 levels, and desensitization outcomes were assessed.Results: Of 116 patients evaluated, 12 (10.3%) were identified as having a converter phenotype. The median interval between drug exposure and reaction was 90.6 h (range 8-288 h). After the conversion, phenotype I was the most frequent (58.3%), followed by cytokine release reactions (33.3%). Fifty-one desensitizations were undertaken and all treatments completed, with 10 (19.6%) breakthrough reactions. No new changes in the phenotype were detected.Conclusions: The symptoms of non-immediate drug hypersensitivity reactions may indicate the need for an early allergological evaluation to assess the risk of future immediate drug reactions. Clinical characteristics, skin test results, and biomarkers can help predict responses to rapid drug desensitization, guiding clinicians on how to optimize therapy delivery while maintaining patient safety.

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Evaluation of a New Routine Diagnostic Test for Immunoglobulin E Sensitization to Neuromuscular Blocking Agents

Anesthesiology ◽

10.1097/aln.0b013e31820164d2 ◽

2011 ◽

Vol 114 (1) ◽

pp. 91-97 ◽

Cited By ~ 52

Author(s):

Dominique Laroche ◽

Sylvie Chollet-Martin ◽

Pierre Léturgie ◽

Laure Malzac ◽

Marie-Claude Vergnaud ◽

...

Keyword(s):

Skin Test ◽

Quaternary Ammonium ◽

Immunoglobulin E ◽

Solid Phase ◽

Specific Ige ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agents ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Immediate Hypersensitivity

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.

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Epidemiology and drug allergy results in children investigated in allergy unit of a tertiary-care paediatric hospital setting

Italian Journal of Pediatrics ◽

10.1186/s13052-019-0753-4 ◽

2020 ◽

Vol 46 (1) ◽

Author(s):

A. Piccorossi ◽

G. Liccioli ◽

S. Barni ◽

L. Sarti ◽

M. Giovannini ◽

...

Keyword(s):

Tertiary Care ◽

Hospital Setting ◽

Clinical History ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Drug Reactions ◽

Positive Skin ◽

History Of ◽

Work Up ◽

Immediate Reactions

Abstract Background and objective Drug Hypersensitivity Reactions (DHRs) are considered adverse effects of medications that resemble allergy symptoms. The reported positive clinical history of pediatric drug reactions is about 10%, however, after allergy investigations, only a small percent is confirmed as hypersensitivity. The aim of this study was to analyze the clinical history, allergy work-up results and sensitization profile of children and adolescents referred to our Allergy Unit for suspected DHRs. Methods The study evaluated data related to a group of children with a positive history of drug reactions during a two-year period. The allergy work-up consisted of in vivo and in vitro tests, in accordance with the recommendations of the ENDA/EAACI guidelines. Results Data from a group of 637 patients [348 M (54.6%); 289 F (45.4%)] were retrospectively analyzed. Beta lactams (BLs) were the most common drugs involved in the reported clinical history, followed by non-steroidal anti-inflammatory drugs (NSAIDs). Severe cutaneous adverse reactions (SCARs) were most frequently observed during BL treatment. The confirmation of BL hypersensitivity was higher for immediate reactions (IRs) [9.4%; 5.1% through positive skin tests (STs) and 5.5% through drug provocation test (DPT)] compared to non-immediate reactions (non-IRs) (8.1%; 2.2% through STs and 6.2% through DPT). A higher number of positive results was obtained for BLs and macrolides when the tests were performed within 12 months after the index reaction (p < 0.05). During DPTs with amoxicillin-clavulanic acid, four hypersensitivity reactions (including one anaphylaxis) occurred despite negative STs. Conclusion Our data demonstrated that only 9.1% of patients resulted in being positive to allergy tests which is in line with the data in literature. An allergy work-up is mandatory for excluding suspected hypersensitivity.

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IgE antibodies and skin tests in immediate hypersensitivity reactions to infliximab in inflammatory bowel disease

European Journal of Gastroenterology & Hepatology ◽

10.1097/meg.0000000000000436 ◽

2015 ◽

Vol 27 (10) ◽

pp. 1200-1208 ◽

Cited By ~ 11

Author(s):

Estelle Fréling ◽

Laurent Peyrin-Biroulet ◽

Claire Poreaux ◽

Alain Morali ◽

Julie Waton ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Immediate Hypersensitivity ◽

Ige Antibodies ◽

Inflammatory Bowel

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Skin Testing for Penicillin Allergy: Its Limited Value

PEDIATRICS ◽

10.1542/peds.52.2.309 ◽

1973 ◽

Vol 52 (2) ◽

pp. 309-309

Author(s):

Renee K. Bergner

Keyword(s):

American Academy ◽

Skin Testing ◽

Skin Tests ◽

Penicillin G ◽

Study Group ◽

Immediate Hypersensitivity ◽

Positive Skin ◽

American Academy Of Pediatrics ◽

History Of ◽

Therapeutic Administration

In its statement, "Anaphylaxis," The American Academy of Pediatrics Committee on Drugs states in part: "If there is a possibility of sensitivity to . . . penicillin, skin testing for immediate hypersensitivity to the agent should be performed prior to its therapeutic administration."1 The Penicillin Study Group of the American Academy of Allergy reported in 1971 that only 17 (30.4%) of 56 patients with a history of immediate (including anaphylactic) reactions to penicillin exhibited positive skin tests to penicillin G.2

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Comparative Assessment of Platinum Salts and Taxane Group Hypersensitivity Reactions, The Role of Skin Tests in Diagnosis?

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211050084 ◽

2021 ◽

pp. 107815522110500

Author(s):

Kadriye Terzioğlu ◽

Murat Ayhan

Keyword(s):

Skin Test ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Positive Skin ◽

Suspect Drug ◽

Platinum Salts ◽

Grade 3 ◽

Pain Symptoms ◽

Very High

Purpose We aimed to investigate the role of skin tests (ST) in the diagnosis of hypersensitivity reactions (HSRs) with platinum salts (PS) and taxane (TX) groups drugs and their reliability in patient management. Materials and Method Patients' data who developed immediate HSR with PS and TX were recorded and ST was performed. The gradual challenge was applied to all patients with ST negative and grade 1–2 with the suspect drug. Results In total, the data of 104 patients (74 with PS, 30 with TX) who developed HSR against PS and TX were shared. The gradual challenge was applied to 72 ST negative and grade 1–2 patients (46 PS group, 26 TX group). The gradual challenge was negative in 39 patients in the PS group and 23 patients in the Tx group. The negative predictive value (NPV) for PS was 83% and NPV for TX was 88%. We found significantly higher skin test positivity in patients with PS and TX and grade 3 HSR ( p = 0.007, p = 0.001). A significant correlation was found between skin test positivity and early onset of symptoms ( p = 0.001 for PS, p = 0.015 for TX). In terms of symptoms witnessed in HSR, we observed the itching, urticaria, hypotension, syncope, and abdominal pain symptoms significantly more in the group with a positive skin test ( p < 0.024, p < 0.001, p < 0.001, p < 0.002, and p < 0.025, respectively). Conclusions We found very high NPV values for PS and TX. We found that the gradual challenge applied to patients with negative skin tests is reliable if Grade 3 HSR is not observed and with this approach, unnecessary desensitization processes and/or drug alterations can be avoided.

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Non-immediate-reading skin tests and prolonged challenges in non-immediate hypersensitivity to beta-lactams in children

Pediatric Allergy and Immunology ◽

10.1111/pai.12826 ◽

2017 ◽

Vol 29 (1) ◽

pp. 84-89 ◽

Cited By ~ 20

Author(s):

G. Lezmi ◽

F. Alrowaishdi ◽

A. Bados-Albiero ◽

P. Scheinmann ◽

J. de Blic ◽

...

Keyword(s):

Skin Tests ◽

Beta Lactams ◽

Immediate Hypersensitivity

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Diagnosing and Managing Patients with Reactions to Radiocontrast Media

Current Treatment Options in Allergy ◽

10.1007/s40521-021-00287-x ◽

2021 ◽

Vol 8 (3) ◽

pp. 210-221

Author(s):

Knut Brockow

Keyword(s):

Skin Testing ◽

Drug Hypersensitivity ◽

Skin Tests ◽

Hypersensitivity Reactions ◽

Positive Skin ◽

Provocation Tests ◽

Ring Molecules ◽

Allergic Skin ◽

Drug Hypersensitivity Reactions ◽

Drug Provocation Tests

Abstract Purpose of the review Iodinated radio contrast media (RCM) belong to the most common elicitors of drug hypersensitivity reactions (HR). Urticaria or anaphylaxis may occur ≤ 1(−6) hour(s) (immediate HR) and exanthems (non-immediate HR) develop > 6 h after application of RCM. Evidence for an immunologic mechanism of RCM HR against the different RCM benzene ring molecules and the benefit of allergological testing in patients with previous hypersensitivity reactions is progressively increasing. Recent findings Positive skin tests can confirm allergy in patients with previous reactions to RCM and help to select alternative better tolerated RCMs. Severe hypersensitivity reactions are mainly caused by an allergic mechanism, whereas the majority of non-severe reactions appear to be non-allergic. Skin testing is highly recommended to help identify allergic hypersensitivity reactions and to select alternatives. Using structurally different RCM is more effective than premedication for the prevention of future reactions. Drug provocation tests to RCM have been increasingly used, but are not yet standardized among different centers. Summary In patients with previous severe hypersensitivity reactions to RCM, skin testing is recommended. For future RCM-enhanced examinations in patients with previous reactions, structurally different, skin test-negative preparations should be applied. Drug provocation tests do confirm or exclude RCM hypersensitivity or may demonstrate tolerability of alternative RCMs.

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