Supplementary Material for: Safe De-Labeling of Patients at Low Risk of Penicillin Allergy in Denmark

<b><i>Introduction:</i></b> Penicillin allergy is suspected in 10% of hospital inpatients but can be disproved in 90% of cases. Direct oral provocation without preceding tests among low-risk patients has proven to be safe in studies of both children and adults and is gaining use across the world. The aims of this study were to investigate the rate of severe allergic reactions to direct oral drug provocation, without preceding tests, in penicillin allergy patients stratified to be at low risk, as well as to examine if these patients have barriers to penicillin allergy de-labeling and future use of penicillins. <b><i>Methods:</i></b> Adult patients referred to a university hospital allergy clinic with a suspected penicillin allergy were prospectively risk evaluated. Patients stratified to be at low risk were offered a direct oral provocation with a single-dose amoxicillin followed by 4 days of continued treatment. The same risk stratification criteria were applied to a larger retrospective cohort. <b><i>Results:</i></b> In the prospective study population, 202 patients had a direct oral drug provocation and 20 (10%) were positive. There were no cases of anaphylaxis or severe delayed hypersensitivity. Fifteen reactions were benign rashes with onset &gt;1 day after initial dosing, and 13 of these were maculopapular rashes. The same low-risk criteria were applied retrospectively to patients in a drug provocation database, and 1,759 patients fulfilled the criteria; of these, 10% had positive provocations, and there were no cases of anaphylaxis or severe delayed hypersensitivity. De-labeled patients in the prospective study reported not to fear future penicillin intake, after prolonged provocation. <b><i>Conclusion:</i></b> The risk stratification criteria for identifying low-risk patients for the oral drug provocation test without prior skin testing were safe in terms of avoiding anaphylaxis or severe delayed hypersensitivity. Benign delayed skin reactions still occurred, and access to allergy advice and follow-up is necessary.

<b><i>引言：</i></b> 约10%的住院患者疑似存在青霉素过敏（penicillin allergy），但其中90%的病例可被排除过敏诊断。针对低风险患者无需先行检测的直接口服药物激发试验方案，在儿童及成人研究中均已被证实安全，且目前在全球范围内的应用逐渐推广。本研究旨在探究经风险分层的低风险青霉素过敏患者，在未先行检测的情况下接受直接口服药物激发试验时发生严重过敏反应的比例，同时分析此类患者是否存在青霉素过敏去标记（de-labeling）及未来使用青霉素类药物的障碍。<b><i>方法：</i></b> 本研究前瞻性地对转诊至某大学医院过敏专科门诊、疑似青霉素过敏的成年患者开展风险评估。经分层为低风险的患者，将接受单次剂量阿莫西林（amoxicillin）口服激发试验，后续继续给药4天。同时，将同一套风险分层标准应用于一个更大的回顾性队列。<b><i>结果：</i></b> 在前瞻性研究人群中，共计202例患者接受了直接口服药物激发试验，其中20例（10%）试验结果呈阳性。未出现过敏性休克（anaphylaxis）或严重迟发型超敏反应（delayed hypersensitivity）病例。15例反应为良性皮疹，且于首次给药后1天及以上发作，其中13例为斑丘疹（maculopapular rashes）。将上述低风险分层标准应用于某药物激发试验数据库的回顾性队列中，共计1759例患者符合该标准；其中10%的激发试验结果呈阳性，且未出现过敏性休克或严重迟发型超敏反应病例。前瞻性研究中完成青霉素过敏去标记的患者表示，在接受延长的激发试验后，他们不再畏惧未来使用青霉素类药物。<b><i>结论：</i></b> 本研究采用的、用于筛选无需先行皮肤测试的低风险患者的口服药物激发试验风险分层标准，在规避过敏性休克或严重迟发型超敏反应方面表现安全。不过仍有良性迟发型皮肤反应发生，因此获取过敏咨询及随访服务实属必要。