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• W4253361317 abstract "We thank Li et al1Li P.H. Yeung H.H. Lau C.S. Au E.Y. Excipient allergy and importance of complete allergy histories.J Allergy Clin Immunol Pract. 2020; 8: 2122-2123Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar for their comments on our recent publication.2Sompornrattanaphan M. Wongsa C. Kreetapirom P. Taweechue A.J. Theankeaw O. Thongngarm T. Fatal anaphylaxis from a second amoxicillin/clavulanic acid provocation after a prior negative provocation.J Allergy Clin Immunol Pract. 2020; 8: 752-754Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar We agree with the caution that there is a possibility of drug excipient as a culprit cause in our case. Similar to Hong Kong, drug package inserts are not enforced by law to include excipient lists in Thailand. Therefore, Thai allergists confront a similar situation in practice. The 2 formulations in both drug provocation tests were different. We wrote letters to both pharmaceutical companies, and they replied with some data on excipients (Table I). The trade name and companies' names are not disclosed because of their internal disclosure policies. Some excipients in amoxicillin-clavulanic acid were the same in both formulations used in the 2 provocation tests, but some were not. We have identified the excipients that were different between tests in bold font. The 3 different excipients in the second provocation included apricot powder, caramel powder, and mannitol. There is a possibility that these excipients could have caused an immediate hypersensitivity reaction.3Yamanaka M. Kato A. Moriyama T. Okazaki F. Momma K. Narita H. Food-dependent exercise-induced anaphylaxis due to pickled Japanese apricot.Allergol Int. 2019; 68: 524-526Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar,4Calogiuri G.F. Muratore L. Nettis E. Casto A.M. Di Leo E. Vacca A. Immediate-type hypersensitivity reaction to Mannitol as drug excipient (E421): a case report.Eur Ann Allergy Clin Immunol. 2015; 47: 99-102PubMed Google Scholar Caramel coloring may be derived from various sources that are considered as common allergens, such as starch hydrolysates (from wheat), malt syrup (may have been derived from barley), or lactose (from milk). Our patient had no previous history of food or plant food allergy. However, he reported a history of hypersensitivity to other drugs, including clarithromycin and levofloxacin although he was unable to recall the details of these events.Table IExcipients of amoxicillin-clavulanic used in 2 drug provocation testsFirst provocation (negative)Second provocation (positive)FormulationAM-CL suspensionAM-CL syrupAM:CL ratio200 mg:28.5 mg600 mg:42.9 mgManufacturerCompany ACompany BProduct referenceNot availableNot availableExcipient listAspartame, colloidal silica, hydroxypropyl methylcellulose, monosodium citrate, sodium citrate, strawberry flavor, strawberry guarana flavor, xanthan gum, FD&C red “40”Aspartame, apricot powder, caramel powder, colloidal silica, mannitol, xanthan gumAM, Amoxicillin; CL, clavulanic acid; FD&C, Federal Food, Drug, and Cosmetic Act code.Note: The excipients that were different between the 2 provocations are represented with bold font. Open table in a new tab AM, Amoxicillin; CL, clavulanic acid; FD&C, Federal Food, Drug, and Cosmetic Act code. Note: The excipients that were different between the 2 provocations are represented with bold font. We have read your interesting reports on the importance of excipient allergy in patients with immediate hypersensitivity to systemic corticosteroids.5Li P.H. Wagner A. Thomas I. Watts T.J. Rutkowski R. Rutkowski K. Steroid allergy: clinical features and the importance of excipient testing in a diagnostic algorithm.J Allergy Clin Immunol Pract. 2018; 6: 1655-1661Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar We are well aware that complete allergy testing would increase the chance of culprit(s) identification. When dealing with a complicated situation, such as perioperative hypersensitivity, the excipients and related disinfectants have been routinely included in skin test panels since 2017 in our institution.6Sompornrattanaphan M. Kanistanon D. Srinoulprasert Y. Udnaen S. Jongjarearnprasert K. Wongsa C. et al.Basophil activation test-confirmed, ortho-phthalaldehyde-induced anaphylaxis after cystoscopy [published online ahead of print March 18, 2020].https://doi.org/10.18176/jiaci.0505Google Scholar,7Sompornrattanaphan M. Kreetapirom P. Srinoulprasert Y. Kanistanon D. Klinniyom A. Wongsa C. et al.Severe anaphylaxis after pelvic examination: a case report of dual latex and chlorhexidine allergies.Allergy Asthma Clin Immunol. 2019; 15: 19Crossref PubMed Scopus (10) Google Scholar We could not specifically conclude the culprit in our case because we did not repeat skin tests and perform in vitro testing for clavulanic acid and other excipients, which were limited due to the patient's condition and medications. However, based on the likely trace amounts of excipients ingested, it would be unusual for any of them to cause a fatal reaction. Our reported case together with your valuable suggestion is a cautionary tale to allergists dealing with drug hypersensitivity. We do not have enough evidence to recommend a routine test including excipients at the first evaluation of the beta-lactam allergic patients. There is a lack of excipient skin test standardization, unknown cost utility, and the risk of cutaneous sensitization to excipients. In our opinion, we would perform excipient testing for certain drugs (eg, corticosteroids)5Li P.H. Wagner A. Thomas I. Watts T.J. Rutkowski R. Rutkowski K. Steroid allergy: clinical features and the importance of excipient testing in a diagnostic algorithm.J Allergy Clin Immunol Pract. 2018; 6: 1655-1661Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar and cases with clinical resensitization to different manufactured beta-lactams after delabeling. We also advocate legal regulations to include excipient lists in the package inserts as a part of drug registration, which might lead to more complete allergy histories. We very much appreciate the helpful correspondence you have provided, and we thank your team for the data provided to fulfill the knowledge of drug allergy tests to allergists worldwide. Excipient allergy and importance of complete allergy historiesThe Journal of Allergy and Clinical Immunology: In PracticeVol. 8Issue 6PreviewWe read with great interest Sompornrattanaphan et al's1 report on a case of fatal anaphylaxis from an amoxicillin-clavulanic acid (AMX-CL) drug provocation test (DPT) after a prior negative DPT. The authors postulate that the positive DPT with AMX-CL 300-21.45 mg was compatible with CL resensitization, as the patient previously tolerated a prior DPT with AMX-CL 1520-216.6 mg without reaction. We agree that the initial DPT dose was enough to confirm a negative result but question the seemingly rare possibility of resensitization. Full-Text PDF" @default.
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