Recognising antibacterial hypersensitivity in children

Adverse reactions to antibacterial agents are not uncommon in children. They are classified as 'immediate' or 'nonimmediate' according to the time interval between drug administration and onset. Immediate reactions occur within 1 hour and are manifested by urticaria and/or angioedema, bronchospasm and anaphylactic shock; immunological reactions are mediated by IgE antibodies. The main nonimmediate reactions (occuring after more than 1 hour) are maculopapular rash, urticaria and serum sickness; T lymphocytes may participate in maculopapular rash. Clinical assessment of such reactions is complex. The patient's history is fundamental; the allergological examination includes in vivo and in vitro tests selected on the basis of the clinical features and the phase of reaction. In the late phase, prick and intradermal tests are sensitive in evaluating beta-lactam allergy. Together with delayed-reading intradermal testing, patch testing seems to be useful in diagnosing maculopapular reactions to systemically administered aminopenicillins. Determination of specific IgE levels is the most common in vitro method for diagnosing immediate reactions. In the acute phase, serum tryptase and urinary N-methylhistamine assays are reliable in diagnosing type I pathogenic mechanisms in immediate reactions. Unfortunately, there are few in vitro tests for evaluating other reactions, and most are not fully validated. In selected cases, provocation tests should be performed.     

Immediate hypersensitivity reactions to penicillins and other betalactams

Immediate hypersensitivity reactions to betalactams are IgE mediated and constitute the most frequent allergic reactions mediated by specific immunological mechanisms. IgE responses to benzyl penicillin (BP), the first antibiotic producing the benzyl penicilloyl structure (BPO), are characterized by a quick release of inflammatory mediators, resulting in anaphylactic shock, urticaria and angioedema. With the progressive appearance of other structures, comprising cephalosporins, carbapenems, monobactams and clavulanic acid, IgE selective responses and cross-reactivity reactions were observed. The diagnosis of betalactam hypersensitivity, classically based on skin testing with major and minor determinants of benzyl penicillin or in vitro IgE antibodies to BP, has been modified by the inclusion of different determinants generated from these compounds, for which amoxicillin (AX) is the most relevant, followed by cephalosporins. Some subjects develop positive responses to several betalactams, mostly within the same family, but others develop a selective response. These are relevant for the appropriate selection of antimicrobial drugs in patients who have immediate hypersensitivity to betalactams.     

Tolerability of aztreonam in patients with IgE-mediated hypersensitivity to beta-lactams

Cross-reactivity between aztreonam and penicillins is poor, but clinical tolerance of aztreonam has been assessed, by means of tolerance challenge tests, only in a few groups of penicillin-allergic patients. The aim of this study is to evaluate the tolerability of aztreonam in a large group of beta-lactam-allergic patients. We studied all patients (greater than 14 years of age), with a clinical history of immediate reactions to any beta-lactam and with positive immediate-type skin tests and/or positive specific IgE to any of the studied beta-lactam; they were studied by means of: skin prick and intradermal tests with penicilloyl polylysine, minor determinant mixture, semisynthetic penicillins, cephalosporins, aztreonam and imipenem; detection of specific IgE to penicillin G, penicillin V, ampicillin, amoxicillin, cefaclor and ceftriaxone. Patients with negative immediate-type skin tests with aztreonam then underwent a graded intramuscular challenge. Forty-five patients (mean age 46.1 +/- 15.2 years), 27 females and 18 males, had positive skin tests and/or specific IgE to at least one of the studied beta-lactams. The most involved drugs were amoxicillin (23 cases), ampicillin (9 cases), penicillin G (8 cases) and other beta-lactams in the remaining cases. The most frequent reactions were anaphylaxis (27 cases) and urticaria (15 cases). All patients had negative intradermal tests with aztreonam and all patients tolerated the intramuscular graded challenge. Our data confirm the lack of cross-reactivity between beta-lactams and aztreonam. Immediate-type skin tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in beta-lactam-allergic patients who urgently need this drug.     

IgE-mediated hypersensitivity to cephalosporins

Like penicillins, cephalosporins may cause IgE-mediated reactions such as urticaria, angioedema, and anaphylactic shock, which occur because of sensitization to determinants shared with penicillins or to unique cephalosporin haptens. In particular, side-chain structures may be responsible for selective sensitization or cross-reactivity. For this reason, individual free cephalosporins are usually employed in skin testing, in addition to the classic penicillin reagents. Cephalosporin skin tests are sensitive in diagnosing immediate hypersensitivity to these betalactams. As far as in vitro tests are concerned, IgE assays for cephalosporins, specifically sepharose-radioimmunoassays, are a potentially useful tool in evaluating immediate reactions and could be used as complementary tests. In selected cases displaying negative results in both skin tests and IgE assays, a graded challenge with the implicated cephalosporin can be performed. Cephalosporin IgE-mediated hypersensitivity may be a transient condition; therefore, allergologic exams should be repeated in patients with negative initial allergologic work-ups, including challenges. Performing allergologic tests with cephalosporins other than the culprit, as well as with penicillin reagents, allows the identification of cross-reactivity with penicillins, selective responses, or cross-reactivity among cephalosporins. In the latter group, cross-reactivity is more frequently related to R1 than to R2 side-chain recognition. In assessing the selectivity of the response, negative results in skin testing with cephalosporins other than the responsible one appear to be a reliable indicator of tolerability.     

Th(1)/Th(2) responses to drugs

T lymphocytes can be characterized by their pattern of cytokine secretion and be divided into type I (Th(l)/Tc(l)) and type 2 (Th(2)/Tc(2)) subsets. The involvement of type-1 or type 2-like responses in sensitization has been studied in the mouse, with reference contact and respiratory contact sensitizers. One interesting feature with certain drugs, such as beta-lactam antibiotics, is the diversity of clinical manifestations associated with immune-mediated hypersensitivity reactions in humans: immediate reactions such as urticaria, Quincke oedema and anaphylactic shock, and delayed hypersensitivity reactions, such as maculopapular rashes, allergic contact dermatitis and skin reactions of other types. In the mouse, Th(1) and Th(2) cytokines have been shown to regulate primary and secondary benzylpenicilloyl- (BPO-) specific antibody responses. Peripheral blood lymphocytes isolated from patients with a clear history of beta-lactam allergy were assessed for type-1 and type-2 phenotypes. Immediate reactions involved mixed Th(1), Tc(1), and Tc(2) responses, whereas allergic contact dermatitis involved Tc(1) and Th(1) cells. Other delayed hypersensitivity reactions to beta-lactams were restricted to Th(1) responses. It has been demonstrated that both CD4(+) and CD8(+)-lidocaine-specific T cell clones isolated from patients with allergic contact dermatitis produced IFN-gamma, even though CD8(+) clones only produce IFN-gamma, while IFN-gamma producing CD4(+) cells concomitantly produced IL-5 and IL-4. Together these data illustrate the heterogeneity of drug-specific T-cell responses.     

Antimicrobial selection in the penicillin-allergic patient

Patients frequently state that they have a penicillin allergy that often presents a therapeutic problem in treating a variety of infectious disorders. Penicillin and beta-lactam allergic reactions should be determined by a careful history. Many patients who say they have a penicillin allergy, in fact do not. If it is determined that the patient has a penicillin allergy, then the clinician should determine whether it is of an anaphylactic or nonanaphylactic variety. Most reactions to beta-lactams are of the nonanaphylactic variety and are usually manifested clinically as a mild maculopapular rash or drug fever. Uncommonly, penicillin allergies are clinically manifested as anaphylactic reactions, e.g., bronchospasm, laryngospasm, hypotension or hives. Patients' hypersensitivity reactions tend to be stereotyped on rechallenge, which make the reactions predictable. Patients who have a questionable penicillin allergy, or have had only fever or rash, may be safely given beta-lactam antibiotics without fear of anaphylaxis. Patients with a documented history of anaphylactic reactions should receive non-beta-lactam antibiotics. Although monobactams and carbapenems are structurally related to beta-lactams, they are unrelated in terms of allergic potential. There is no cross-reactivity between mono-bactams or carbapenems with beta-lactams, and these drugs may be used safely in patients with anaphylactic reactions to beta-lactams. Because so many antibiotics are available that are allergically unrelated to beta-lactams, beta-lactam desensitization procedures are rarely necessary. (c) 2001 Prous Science. All rights reserved.     

围手术期地塞米松过敏的研究进展

围手术期地塞米松常应用于抗过敏治疗,近年来关于地塞米松引起的过敏反应的报道也越来越多。这些反应主要包括IgE介导的过敏反应和药物直接刺激释放组胺引起的类过敏反应。地塞米松引起的过敏反应是一种全身性或系统性反应,症状可从局部至全身。围手术期过敏原检测起着重要的作用,这些检测方法包括皮肤过敏试验,血清中组胺、类胰蛋白酶和IgE抗体浓度检测等。另外过敏反应发生后及时供氧、扩容和肾上腺素的应用是抢救患者的关键。     

青霉素过敏病人血清特异性IgE和IgG抗体

采用放射过敏原吸附试验(RAST)和酶联免疫吸附试验(ELISA)测定52例青霉素过敏病人血清特异性IgE、IgG抗体，进一步探讨青霉素过敏反应机制。结果 52例过敏病人特异性IgE、IgG抗体的阳性率分别为50％和44．2％，若RAST与ELISA联合检测，IgE和IgG抗体总阳性率增至63.5％。荨麻疹组BPO—IgG水平高于过敏性休克组(P＜0.01)，过敏性休克病人BPA—IgG水平明显高于BPO—IgG(P＜0．01)，荨麻疹组内BPO—IgE水平与BPA—IgE无显著差异(P＞0．05)。但均比过敏性休克组高。研究结果提示，荨麻疹与BPO—IgE和BPA—IgE关系密切，过敏性休克与BPO—IgE和BPA—IgG关系密切；同时检测IgE和IgG抗体，可提高诊断阳性率。     

Delayed allergy to aminopenicillins: clinical and immunological findings

Aminopenicillins are the most used beta-lactam antibiotics. Morbilliform or maculopapular rashes are rather frequent during therapy with aminopenicillins. The pathogenesis of these reactions is often due to a cell-mediated allergy. The aim of this work is to characterize patients with cell-mediated allergy to aminopenicillins and to identify alternative beta-lactam drugs that can be safely administered to these patients. We studied 27 subjects affected by cell-mediated allergy to aminopenicillins. The diagnosis was made on the basis of positivity of patch tests with aminopenicillins. These patients then underwent an allergological evaluation (skin and patch tests, oral and/or intramuscular challenge tests) with a wide spectrum of beta-lactam antibiotics. Our work highlights the following main characteristics of cell-mediated allergy to aminopenicillins: time elapsing between drug administration and onset of symptoms of about 2 days; the maculopapular rash and delayed appearance of urticaria/angioedema were the most typical symptoms (82.8 percent of cases); a cross-reactivity with aminocephalosporins is usually absent, or it is limited to cephalexin (in our study, in fact, just 3 out of 20 patients challenged with cephalexin showed a positive oral challenge test); all the beta-lactams, other than aminopenicillins, are well tolerated. Patch tests represent a specific diagnostic tool with a good predictive value of identifying alternative drugs that can be safely administered to patients with beta-lactam allergy. Our patients could tolerate other beta-lactam drugs after a complete allergological evaluation. On the basis of our study, cell-mediated allergy to aminopenicillins should be considered a well-defined nosologic entity.     

Inhibitory effects of Houttuynia cordata water extracts on anaphylactic reaction and mast cell activation

The present study was investigated the effect of Houttuynia cordata THUNB water extract (HCWE) on mast cell-mediated anaphylactic reactions. The mast cell-mediated anaphylactic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. HCWE has been used as a traditional medicine in Korea and is known to have an antioxidant and anti-cancer activities. However, its specific effect of mast cell-mediated anaphylactic reactions is still unknown. We examined whether HCWE could inhibit compound 48/80-induced systemic anaphylaxis, IgE-mediated passive cutaneous anaphylaxis (PCA), and mast cell activation. The oral administration of HCWE inhibited compound 48/80-induced systemic anaphylaxis in mice. HCWE also inhibited the local allergic reaction, PCA, activated by anti-dinitrophenyl (DNP) IgE antibody in rats. HCWE reduced the compound 48/80-induced mast cell degranulation and colchicine-induced deformation of rat peritoneal mast cells (RPMC). Moreover, HCWE dose-dependently inhibited histamine release and calcium uptake of RPMC induced by compound 48/80 or anti-DNP IgE. HCWE increased the level of intracellular cAMP and inhibited significantly the compound 48/80-induced cAMP reduction in RPMC. These results suggest that HCWE may be beneficial in the treatment of mast cell-mediated anaphylactic responses.     

头孢菌素类抗生素致过敏性休克55例分析

目的:探讨头孢菌素类抗生素致过敏性休克的特点和规律,以预防或避免其重复发生,促进临床合理用药.方法:按文献计量学方法,收集国内34种主要药学期刊1996～2001年6月报道的头孢菌素类抗生素致过敏性休克的个案,采用描述性研究方法进行分析.结果:头孢菌素类抗生素致过敏性休克反应严重,病死率高,临床上应引起高度重视和警惕.结论:使用本类药物前应详问家族过敏史、药敏史和是否为过敏体质,并采用拟用药物做过敏性试验,确保安全用药.     

头孢菌素致过敏性休克459例文献分析

目的：了解头孢菌素致过敏性休克的情况,探究其发生规律。方法：检索《万方数据》和《中国知网》中有关头孢菌素引起过敏性休克的文献资料（1998～2011年）,筛选收集过敏性休克的病例报告,按患者年龄、性别、给药途经、原患疾病、发生时间、愈后等进行统计分析。结果：检索获得头孢菌素引起过敏性休克的病例共459例,以第三代头孢菌素及其酶抑制药复合制剂为主（62.31%）;居前3位的品种为头孢曲松（20.48%）、头孢噻肟（12.85%）、头孢哌酮/舒巴坦（12.85%）。给药途径以静脉用药为主（85.40%）;多发于用药后10 min内（61.66%）;1 min～24 h内缓解或痊愈（87.58%）;有48例（10.46%）死亡。结论：临床应重视头孢菌素引起的过敏性休克,鼓励、推广头孢的皮试工作,以确保用药安全。     

Current understanding of contrast media reactions and implications for clinical management.

Iodinated contrast media (CM) are an integral part of modern diagnostic medicine. Although these agents are considered to be relatively safe, adverse effects in the form of allergy-like reactions occur in a significant number of exposed patients. These reactions may be divided into immediate and delayed responses. Immediate (within 1 hour of administration) anaphylactic reactions range from urticaria and angioedema to laryngeal oedema, hypotension and even death. Delayed reactions to CM occur from 1 hour to 1 week after administration and usually have mostly cutaneous manifestations. History of prior CM reactions and atopy predispose patients to CM reactions. Despite intense research into the pathogenesis of the immediate anaphylactoid responses, new evidence shows that true IgE type I hypersensitivity mediation occurs only in rare, severe cases. The aetiology appears to be multifactorial in most individuals. There is strong evidence to conclude that type IV hypersensitivity is responsible for the delayed reactions to CM. Although switching to non-ionic agents significantly reduces the incidence of immediate reactions to CM, there is little consensus regarding corticosteroid prophylaxis in high-risk individuals. Skin testing and provocative challenges also provide little security. Therefore, physicians must be better prepared to treat immediate anaphylactoid responses. Preventing delayed CM reactions is best performed with patch and delayed intradermal testing in those with a history of prior reactions, although false-negative results have been reported. Corticosteroids and antihistamines may be required for treatment. Until newer agents are developed that negate these issues, healthcare providers must strive to better understand the risk factors associated with CM reactions, as well as the available prophylactic and treatment options.     

Allergy to antibacterials: the problem with beta-lactams and sulfonamides

This paper reviews the incidence, clinical manifestations, differential diagnosis, risk factors and pathogenesis of allergic reactions of two important classes of antimicrobials: beta-lactams and sulfonamides. The diagnostic work-up of a patient with a history of an allergic reaction will be discussed as well as the possibility of safe administration of the drug in the face of an allergy using desensitization. Emerging concepts of beta-lactam side-chain allergy, the role of cellular immune mechanisms and the clinical importance of cross-reactivity of allergic reactions to different classes of beta-lactams will be emphasized.     

270例喜炎平注射液不良反应／事件病例报告的分析

目的探讨喜炎平注射液不良反应,事件发生的一般规律及特点。方法采用回顾性研究方法,对我省药品不良反应监测中心于2004年一2011年收集的270例喜炎平注射液不良反应/事件的自发报告进行分析。结果在270例报告中,14岁以下儿童患者225例,占报告总数的83．4％。不良反应／事件以皮肤及其附件损害为主,表现为皮疹、荨麻疹等,严重者可出现过敏性休克、过敏性紫癜等。结论使用喜炎平注射液应严格按照说明书用药,加强用药过程的监护,尽量减少和避免药品不良反应的发生。     

481例中药注射剂致过敏性休克综合分析

目的探讨中药注射剂引起过敏性休克的特点和规律。方法通过中国医院数字图书馆CHKD期刊知识库检索1994—2007年收载的中文医药期刊报道的中药注射剂致过敏性休克个案,对文献资料进行整理、汇总,并进行分析。结果死亡病例21例,占4．4％;以静脉滴注为主,占89．8％;速发型过敏性休克的病例有382例,占79．4％;涉及中药注射剂45种,其中以双黄连注射剂引起过敏性休克的例数为最多,有71例,占14．8％。过敏性休克临床表现主要以循环系统、呼吸系统和神经系统为主。结论用药前询问过敏史,严格掌握中药注射剂用药指征,密切观察用药后反应,确保用药安全。     

Allergic reactions to beta-lactams

Allergy to beta-lactam antibiotics is the most frequent cause of drug-induced immunological reactions, although the prevalence is not exactly known. IgE- and T-cell-dependent responses are the main mechanisms involved, although other immunological mechanisms can also participate, especially in haematological abnormalities, such as immune haemolytic anaemia or thrombocytopoenia. Aside from their frequency, the clinical entities reported nowadays have changed little since penicillin was first used. The variation in beta-lactams consumption through the year has modified the pattern and specificities of allergic reactions for IgE and T cell responses. Benzylpenicillin is no longer the beta-lactams most frequently prescribed and other chemical structures, with new or modified haptens, have progressively replaced it. This is relevant for the diagnostic evaluation and management of beta-lactam hypersensitivity.     

Update on sensitivity to nonsteroidal antiinflammatory drugs

Non steroidal antiinflammatory drugs (NSAIDs) are among the most frequently prescribed medications worldwide. These drugs are effective for the treatment of a wide spectrum of diseases: musculoskeletal disorders, headhache, fever, pain, and others. Their widespread use explains the very high incidence of intolerance; reactions range from asthma, rhinitis, to urticaria/angioedema, various skin eruptions and anaphylactic shock. The pathogenesis of intolerance is still unclear: immune-mediated reactions have been reported following the use of pyrazolone derivatives and, less commonly aspirin, anthranilic-acid derivatives and diclofenac. It has been suggested that NSAIDs may induce pseudoallergic reactions, while in case of bronchial asthma the inhibition of cyclooxigenase by NSAIDs has been proposed as a pathogenetic mechanism. The diagnosis of NSAIDs sensitivity can usually be established by history; in fact skin prick tests with NSAIDs have not been successful and no reliable in vitro tests are available. The only definitive diagnostic test is oral test dosing. To identify an alternative NSAIDs in a sensitive patient a tolerance test is performed. Here we review the current state of knowledge concerning NSAIDs sensitivity, including personal data to increase awareness on this issue.     

头孢噻肟所致药品不良反应文献分析

目的分析头孢噻肟所致药品不良反应(ADR)的特点,促进临床安全用药。方法检索万方数据库1998年至2019年有关文献资料,按患者的年龄、性别、给药途径、原患疾病、发生时间、预后等进行统计与分析。结果头孢噻肟所致ADR在11岁以内的少年儿童中发生较多(20.12%);静脉滴注(91.72%)是主要给药方式;ADR累及系统/器官多为全身性反应(53.85%)、皮肤及其附件损害(11.83%)、中枢及外周神经系统损害(8.28%);过敏性休克(42.60%)为主要表现形式;ADR发生时间多为用药后30 min内(56.21%),过敏性休克多发生于用药10 min内(77.78%)。5例(2.96%,男3例、女2例)死亡,包括过敏性休克4例和急性喉头水肿1例。ADR与头孢噻肟的使用"肯定有关"10例(5.92%),"很可能有关"155例(91.72%),"可能有关"4例(2.37%)。结论临床应重视头孢噻肟导致的ADR,尤其是过敏性休克等严重ADR,鼓励、推广及规范头孢菌素类药物的皮肤过敏试验工作,以确保用药安全。     

哌拉西林及其复方制剂致过敏性休克的病例报道及文献分析

目的:探讨哌拉西林及其复方制剂致过敏性休克的临床特点,为该严重不良反应的防治提供参考。方法:分析北京大学人民医院(以下简称"我院")1例哌拉西林舒巴坦致过敏性休克病例,同时在Medline、中国知网、万方数据库、维普网中,检索建库起至2020年7月报道的哌拉西林单药及其复方制剂致过敏性休克不良反应的相关文献,对纳入患者的性别与年龄分布、既往过敏史、原发疾病及治疗情况、皮试情况、哌拉西林及其复方制剂给药方式及剂量、过敏性休克发生时间及主要表现、治疗措施及转归情况进行分析,并提出防治建议。结果:我院1例患者为肝部分切除术后转入重症监护病房,使用哌拉西林舒巴坦预防术后感染致患者发生过敏性休克。检索数据库共获得哌拉西林单药及其复方制剂致过敏性休克的相关文献28篇(涉及患者28例)。在所有的29例患者中,男性12例、女性17例,年龄以50~59岁居多(6例,20.69%);3例患者有过敏史(食物、乳胶手套等),患者原发疾病多为感染性疾病或围术期使用该药;22例患者(75.86%)在用药前进行了皮试且结果均为阴性。27例通过静脉途径给药的患者的可能致敏药物包括哌拉西林、哌拉西林舒巴坦、哌拉西林他唑巴坦,给药剂量根据原发疾病及严重程度有所差异,其中14例患者(55.56%)在给药0~5 min内出现休克症状;主要表现为系统性过敏反应症状,主要累及循环系统。除2例死亡外,其余患者经治疗后症状均缓解。结论:过敏史及皮试结果对哌拉西林及其复方制剂所致过敏性休克的预示作用有限;在使用该类药物期间需密切监测患者生命体征变化,做好过敏性休克抢救准备,及时采取应对措施。