The Combined Utility of Ex Vivo IFN-γ Release Enzyme-Linked ImmunoSpot Assay and In Vivo Skin Testing in Patients with Antibiotic-Associated Severe Cutaneous Adverse Reactions

Trubiano, Jason A; Strautins, K.; Redwood, Alec; Pavlos, Rebecca; Konvinse, Katherine C.; Aung, Ar Kar; Slavin, Monica A; Thursky, Karin; Grayson, M. Lindsay; Phillips, Elizabeth

doi:10.1016/j.jaip.2017.09.004

Cited by 58 publications

(53 citation statements)

References 42 publications

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“…Antimicrobials, radiocontrast agents, anesthetic agents, nonsteroidal anti‐inflammatory drugs, and antiepileptics were most likely to be associated with immunologically mediated reactions, implying that further medication allergy assessment in clinics should focus on these classes, by providing in vitro and/or in vivo causality confirmation, where clinically indicated . For certain medications, especially antimicrobials, further allergy testing not only confirms or refutes causality but may also identify alternate antimicrobials, thereby providing future therapeutic options …”

Section: Discussionmentioning

confidence: 99%

“…31 For certain medications, especially antimicrobials, further allergy testing not only confirms or refutes causality but may also identify alternate antimicrobials, thereby providing future therapeutic options. 32,33 Severe cutaneous adverse drug reactions are life threatening, requiring prompt diagnosis, causality assessment, and clear risk communication to prevent continued or repeated exposure to offending agents. If clinicians are unfamiliar with these conditions, diagnostic and management delays may result.…”

Section: Discussionmentioning

confidence: 99%

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Adverse Drug Reactions Reported by Healthcare Professionals: Reaction Characteristics and Time to Reporting

Aung

Tang

Adler

et al. 2018

The Journal of Clinical Pharma

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We describe adverse drug reaction (ADR) reporting characteristics and factors contributing to length of time to report by healthcare professionals. This is a retrospective study of voluntary reports to an Australian healthcare ADR Review Committee over a 2-year period (2015-2016). Descriptive and univariate models were used for outcomes, employing standardized ADR definitions. Hospital pharmacists reported 84.8% of the 555 ADRs: 70.3% were hospital onset reactions, and 71.7% were at least of moderate severity. Immunologically mediated reactions were most commonly reported (409, 73.7%). The median time to submit an ADR report was 3 (interquartile range 1-10) days. Longer median times to reporting were associated with multiple implicated agents and delayed hypersensitivity reactions, especially severe cutaneous adverse reactions. A total of 650 medications were implicated that involved multiple agents in 165/555 (29.7%) reports. Antimicrobials were the most commonly implicated agents. Immunologically mediated reactions were most commonly associated with antimicrobials and radiocontrast agents (P < .0001, odds ratio [OR] 3.6, 95%CI 2.4-5.5, and P = .04, OR 4.2, 95%CI 1.2-18.2, respectively). Opioids and psychoactive medications were more commonly implicated in nonimmunological reported ADRs (P = .0002, OR 3.9, 95%CI 1.9-7.9, and P < .0001, OR 11.4, 95%CI 4.6-27.8, respectively). Due to the predominant reporting of immunologically mediated reactions, a targeted education program is being planned to improve identification and accuracy of ADR reports, with the overall aim of improved management to ensure quality service provision and patient safety.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Adverse Drug Reactions Reported by Healthcare Professionals: Reaction Characteristics and Time to Reporting

Aung

Tang

Adler

et al. 2018

The Journal of Clinical Pharma

Self Cite

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“…To improve these results, new approaches have been focused on the effector response by determining inflammatory mediators, such as IFN‐gamma producing cells determination by enzyme‐linked immunospot assay (ELISpot), which has shown higher sensitivity and good correlation . Moreover, its combination with STs has demonstrated a potential utility in antibiotic‐induced SCARs . Recently, a modified IFN‐gamma ELISpot using preactivated T cells before exposure to the culprit drugs has shown to be more sensitive than the conventional IFN‐gamma ELISpot …”

Section: Diagnosismentioning

confidence: 99%

“…72,[128][129][130][131] Moreover, its combination with STs has demonstrated a potential utility in antibiotic-induced SCARs. 132 Recently, a modified IFNgamma ELISpot using preactivated T cells before exposure to the culprit drugs has shown to be more sensitive than the conventional IFN-gamma ELISpot. 133…”

Section: Nir In Vitro Testsmentioning

confidence: 99%

Recent developments and highlights in drug hypersensitivity

Mayorga

Fernandez

Montañez

et al. 2019

Allergy

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Drug hypersensitivity reactions (DHRs) are nowadays the third cause of allergy after rhinitis and asthma with a significant increase in prevalence in both adults and paediatric population with new drugs included as culprit. For this, DHRs represent not only a health problem but also a significant financial burden for affected individuals and health systems. Mislabelling DHRs is showing to be a relevant problem for both, false label of drug allergic and false label of nonallergic. All this reinforces the need to improve accurate diagnostic approaches that allow an appropriate management.Moreover, there is a need for training both, nonallergist stakeholders and patients to improve the reaction identification and therefore decrease the mislabelling. The use of allergy cards has shown to be relevant to avoid the induction of DHRs due to the prescription of wrong medication.Recent developments over the last 2 years and highlights about risk factors, diagnostic approaches, mechanisms involved as well as prevention actions, and management have been reviewed. In these papers, it has been outlined the need for correct diagnosis and de-labelling of patients previously false-reported as allergic, which will improve the management and treatment of patients with DHRs. K E Y W O R D Sallergy diagnosis, allergy treatment, basic mechanisms, drug allergy, epidemiology | 2369

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“…The utility of ELISPOT in the diagnosis of drug hypersensitivity has been shown by several authors (Rozieres et al, 2009;Zawodniak et al, 2010;El-Ghaiesh et al, 2012;Esser et al, 2012;Fu et al, 2012;Polak et al, 2013;Tanvarasethee et al, 2013;Ben-Said et al, 2015;Kato et al, 2017;Trubiano et al, 2017), as well as in many case reports. Nevertheless, the target patient population, drug used, cytokine studied and protocols differ considerably.…”

Section: Discussionmentioning

confidence: 93%

Evaluation of IFN-γ Enzyme-linked Immunospot Assay (ELISPOT) as a First-line Test in the Diagnosis of Non-Immediate Hypersensitivity to Amoxicillin and Penicillin

et al. 2018

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The current diagnostic algorithm for beta-lactam allergy is based on skin and provocation tests, both of which carry a certain risk of inducing hypersensitivity reactions. Thus, non-invasive in vitro tests reliable enough to replace skin and provocation tests at least in a portion of patients are desirable. We aimed to verify the utility of IFN-γ ELISPOT as a first-line test in patients with suspected non-immediate hypersensitivity reaction to amoxicillin (AMX) and penicillin (PNC). The prospective observational study included 24 patients with recent, suspected non-immediate hypersensitivity reaction to AMX or PNC and 6 recently-exposed healthy subjects. In vitro tests were performed in all patients and healthy subjects: a) IFN-γ ELISPOT with PNC, AMX and amoxicillin plus clavulanic acid (AMX-CL); b) penicillin specific IgE; c) basophil activation test (BAT). Skin and provocation tests followed only in certain patients. IFN-γ ELISPOT results with PNC and AMX stimulation did not differ from the unstimulated condition. The highest IFN-γ responses to AMX-CL were close to previously published criteria in three patients; one of which had true hypersensitivity according to drug provocation tests. Five patients with confirmed hypersensitivity by skin tests showed no response to the culprit antibiotic on IFN-γ ELISPOT assay. Our results did not support the utility of IFN-γ ELISPOT in the diagnosis of mild, non-immediate hypersensitivity to amoxicillin and penicillin.

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The Combined Utility of Ex Vivo IFN-γ Release Enzyme-Linked ImmunoSpot Assay and In Vivo Skin Testing in Patients with Antibiotic-Associated Severe Cutaneous Adverse Reactions

Cited by 58 publications

References 42 publications

Adverse Drug Reactions Reported by Healthcare Professionals: Reaction Characteristics and Time to Reporting

Adverse Drug Reactions Reported by Healthcare Professionals: Reaction Characteristics and Time to Reporting

Recent developments and highlights in drug hypersensitivity

Evaluation of IFN-γ Enzyme-linked Immunospot Assay (ELISPOT) as a First-line Test in the Diagnosis of Non-Immediate Hypersensitivity to Amoxicillin and Penicillin

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