Desensitization in patients with beta-lactam drug allergy

BackgroundPatients with a history of beta-lactam antibiotic allergy are often admitted to the hospital with severe or life-threatening infections requiring beta-lactam antibiotics. Strict avoidance of beta lactams to such patients may prevent them from getting adequate coverage and can lead to an increase in the use of alternative antibiotics, which can predispose to antibiotic resistance. Past studies revealed a lower incidence of pen allergy then patients’ histories suggest. Fortunately today, there are three options for patients presenting with a history of beta-lactam allergy. Penicillin skin testing, beta-lactam challenge or beta-lactam desensitization.Recently Pre Pen has been FDA re-approved and when combined with Pen G is a valid way to determine if patients are able to tolerate beta-lactam antibiotic. When these agents are not available one must decide about desensitization or challenge. When a patient has a positive penicillin skin test, desensitization or beta-lactam avoidance are the only options.This paper reviews the safety of beta-lactam desensitization.ObjectiveTo perform a chart review on patients desensitised with beta lactam to determine if desensitizations can be performed safely without minimal complications.MethodsA retrospective chart review was performed on allergy and immunology inpatient consultations for beta-lactam desensitization between September 2003 and August 2006 at the Cedars-Sinai Medical Centre in Los Angeles. Patient data and outcomes of desensitization were analysed.ResultsA total of 13 intravenous desensitizations were performed on 12 patients. The patients consisted of eight females and four males with an average age of 65 years. Age range was 36–92 years old. All 13 intravenous desensitizations were completed without complications. No patient required a slower rate of desensitization or discontinuance of the desensitization. Patients were able to tolerate the initial therapeutic dose of their beta-lactam antibiotic and were then able to complete full therapeutic courses of their antibiotic.ConclusionBeta-lactam antibiotic sensitivity continues to present a challenging problem for physicians. Patients with drug resistant infections who are unable to obtain skin testing or who test positive to skin tests may need either a challenge or desensitization. Desensitization, saved for those with a convincing beta-lactam hypersensitivity history is often the choice of last resort given the associated cost and risk of anaphylaxis. However, once desensitization is complete, patients are usually able to tolerate full doses of antibiotics for full treatment length with minimal side effects.     

Drug allergy in tertiary care in Turkey: Results of a national survey. The ADAPT study: Adult drug allergy perception in Turkey

BackgroundNo data are available on the incidence of drug hypersensitivity (DH) reactions in outpatient settings of tertiary allergy/immunology clinics. Our aims were to document the frequency of outpatient hospital admissions due to DH reactions to allergy/immunology clinics in adults and the management of these reactions in real life. We also investigated whether drug allergy affected social and medical behaviours of the patients.MethodsThis multi-centre study was performed for one year with the participation of 11 out of 16 tertiary allergy/clinical immunology clinics in Turkey. The study group consisted of the patients with DH reactions. Results of a questionnaire including drug reactions and management were recorded.ResultsAmong 54,863 patients, 1000 patients with DH were enrolled with a median of 2.1% of all admissions. In real life conditions, the majority of approaches were performed for finding safe alternatives (65.5%; 1102 out of 1683) with 11.7% positivity. Diagnostic procedures were positive in 27% (154/581) of the patients. The majority of the patients had higher VAS scores for anxiety. A total of 250 subjects (25%) reported that they delayed some medical procedures because of DH.ConclusionOur results documented the frequency of admissions due to DH reactions to allergy/clinical immunology clinics for the first time. Although physicians mostly preferred to perform drug tests in order to find safe alternatives, considering the fact that DH was confirmed in 27% of the patients, use of diagnostic tests should be encouraged, if no contraindication exists in order to avoid mislabelling patients as DH.     

Cross sectional questionnaire-based internet study: Self-perception and clinical course of drug allergy in Greece

Background

Data on self perception of drug allergy in the general population are lacking. Epidemiological studies focus either on specific populations or document adverse drug reactions in general. Our objective was to document self-reported drug allergy in Greece, through a simple, informative internet-based questionnaire.

Molecularly defined adult-type hypolactasia in school-aged children with a previous history of cow＇s milk allergy

AIM: To assess the role of lactase non-persistence/persistence in school-aged children and their milk-related symptoms. METHODS: The genotypes for the C/T-13910 variant associated with lactase non-persistence/ persistence were determined using PCR-minisequencing in a group of 172 children with a mean age of 8.6 years (SE = 0.02, 93 boys) participating in a follow-up study for cow's milk allergy. The parents were asked to assess their children's milk consumption and abdominal symptoms. RESULTS: The presence of allergy to cow's milk was not associated with the C/C-13910 genotype related with a decline of lactase enzyme activity during childhood (lactase non-persistence). The frequency of the C/C-13910 genotype (16%) was similar to published figures for the prevalence of adult-type hypolactasia in Finland. The majority of the children (90%) in this series consumed milk but 26% of their families suspected that their children had milk-related symptoms. Forty-eight percent of the children with the C/C-13910 genotype did not drink milk at all or consumed a low lactose containing diet prior to the genotyping (P< 0.004 when compared to the other genotypes). CONCLUSION: Analysis of the C/T-13910 polymorphism is an easy and reliable method for excluding adult-type hypolactasia in children with milk-related symptoms. Genotyping for this variant can be used to advise diets for children with a previous history of cow's milk allergy.     

Tolerance to intravenous heparin in patients with delayed-type hypersensitivity to heparins: a prospective study

Delayed-type hypersensitivity to subcutaneously injected heparin is relatively common. Particularly, extensive cross-reactivity between different heparins and heparinoids often occurs. Delayed-type hypersensitivity to heparin implies the risk of a generalized eczema when heparin is administered intravenously. However, case reports demonstrated a tolerance to intravenous heparin in patients with delayed-type hypersensitivity to subcutaneous heparin, but prospective studies have not been performed. Our study group, of 28 patients with a proven delayed-type hypersensitivity to subcutaneous heparin, was challenged with intravenous heparin, which was well tolerated in all 28 patients. Therefore, in case of therapeutic necessity, the shift from subcutaneous to intravenous heparin administration is justified.     

Approach to patients with symptoms of food allergy

“Allergy” is a term often used by patients to describe symptoms that arise after eating. The term “adverse reaction to food” is preferred unless the event has an immunologic basis. True food allergy, primarily mediated by immunoglobulin (Ig)E antibodies to food proteins, is present in 3% to 4% of US adults. Symptoms range from mild mouth itching (“oral allergy syndrome”) to anaphylaxis. The diagnosis is established by history and appropriately performed skin testing or in vitro assays for specific IgE antibodies to the suspected food. Because food-allergic reactions can be fatal, it is important to identify and avoid the causative food. Food-allergic reactions are treated by prompt use of intramuscular epinephrine. Patients may be referred to an allergy/immunology specialist when the diagnosis is uncertain or if avoidance measures are not successful. Investigational therapies may ultimately be preventative or curative.     

Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B

Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.     

Development of a tool for screening adverse food reactions and food allergy in Portuguese children

Introduction and objectivesA standardised questionnaire may be an excellent tool for epidemiological studies aiming at screening children with suspected food allergies. Thus, the aim of the present study was to develop a screening questionnaire for assessing children with suspected food allergy and to analyse its reproducibility.Materials and methodsA questionnaire of adverse food reactions was developed by literary review of similar questionnaires validated in other countries as well as less well defined, non-validated Portuguese questionnaires. Peer review of the questionnaire by a panel of specialists and subsequent exploratory analysis was carried out by applying the questionnaire in children with confirmed food allergy. Test–retest analysis was performed by giving a face-to-face questionnaire to 159 children with suspected adverse food reactions, aged between three and 11 years. Temporal stability using Spearman Rho correlation test and reproducibility was studied using Cohen's Kappa index.Results115 children confirmed adverse food reactions that occurred with one or more foods. Retest was given about three weeks after the test, to 50 of these children who were randomly selected. The questionnaire showed good temporal stability (Spearman correlation coefficient of 0.834), and good reproducibility (only two of the 27 items had a Kappa index <0.60).ConclusionsThis questionnaire showed good temporal stability and reproducibility. Its validation for screening children with suspected food allergy will allow a standardised approach to diagnosis and comparison of results obtained in different centres.     

尿道宫颈炎支原体检测情况及药敏分析

目的对2641株培养阳性支原体的药敏结果进行统计分析,以便为临床支原体感染者的药物治疗提供有价值的参考信息,并提高临床疗效。方法采用支原体培养、鉴定、药敏一体化试剂盒(14Drugs),对4714例泌尿生殖道感染患者进行支原体培养鉴定,对2641株支原体进行14种抗生素体外药敏试验。结果4803例患者标本中,支原体培养阳性者2641例,阳性率为54.99%。2641例支原体阳性者中,单纯解脲脲原体(Uu)感染1811例,占68.57%;单纯人型支原体(Mh)感染63例,占2.39%;Uu+Mh混合感染767例,占29.04%。男女患者支原体感染阳性率差异有统计学意义(χ2=152.409,P<0.001)。检出的2641株支原体中,44株全耐药株均为Uu+Mh混合感染,且其检出率逐年上升。耐药现象尤以环丙沙星与红霉素最为严重。单纯Uu感染其敏感性最高的为交沙霉素(99.75%),其次为克拉霉素(97.85%);耐药率最高的为环丙沙星(66.81%)。单纯Mh感染其敏感性最高的为强力霉素(96.83%),其次为交沙霉素(93.65%);耐药率最高的为红霉素(88.89%)。Uu和Mh混合感染的患者,敏感性最高的...     

Three ileus cases associated with the use of dipeptidyl peptidase‐4 inhibitors in diabetic patients

Dipeptidyl peptidase (DPP)‐4 inhibitors are a new class of antidiabetic drugs that increase incretin hormone levels to enhance blood sugar level‐dependent insulinotropic effects, suppress glucagon action, and reduce bowel motility. These incretin effects are ideal for blood sugar control. However, the safety profile of DPP‐4 inhibitors is not yet established. Herein, we present three cases of ileus, considered to be closely related to the use of DPP‐4 inhibitors, in diabetic patients. Each of the three patients exhibited some risk of a deficiency in bowel movement; the onset of ileus was within 40 days after strengthened inhibition of DPP‐4. The use of a DPP‐4 inhibitor could be safe, although the cases presented herein enable us to inform the scientific community to some of the potential adverse effects of the use of DPP‐4 inhibitors in select populations.     

Adverse drug reactions to a cephalosporins in hospitalized patients with a history of penicillin allergy.

Estimates on the cross-reactivity between cephalosporin and penicillin range from 1 to 16%. Patients with a history of penicillin allergy usually receive less optimal and more costly alternatives even if cephalosporins are a more viable alternative. One hundred eighty-six patients admitted to Winthrop University Hospital in a 7.5-month period, who reported penicillin allergy and received cephalosporin, were sent surveys. Eighty-three patients completed the survey and their charts were reviewed. Seven of 83 patients (8.4%) from a larger group of 186 penicillin-allergic patients developed a reaction to a cephalosporin. The exact 95% confidence interval is 3.5-16.6%. Six of seven (85.7%) penicillin-allergic patients who reacted to cephalosporin reported a definite history of an immediate reaction to penicillin, including hives. Only 1 of 62 (1.6%) patients who reported that their penicillin reaction was delayed, probable, or unknown had a cephalosporin reaction (p < 0.001). Thirty percent (3 of 10 patients) of penicillin-allergic patients, who received a second-generation cephalosporin, had a reaction, whereas 5.5% (4 of 73 patients) of those patients given only a first-, third-, and fourth-generation cephalosporin reacted (p < 0.04). None of those patients who received a fourth-generation cephalosporin reacted. Four of 15 (26.7%) patients who received a cephalosporin with an amino benzyl ring developed a reaction, as compared with 3 of 68 (4.4%) patients who received a cephalosporin without the ring (p < 0.02). Four patients with severe cephalosporin reactions had a rash, shortness of breath, difficulty swallowing, lightheadedness, and anaphylaxis. Patients who recall a definite history of an immediate type of penicillin allergy are more likely to develop a cephalosporin reaction compared with patients who reported a delayed, a probable, or an unknown penicillin reaction. Penicillin-allergic patients who receive second-generation cephalosporins, especially those with an amino benzyl side chain, are more likely to develop a reaction to cephalosporin. Although the incidence of reactions to cephalosporin in penicillin-allergic patients is low, those patients who reacted had more severe manifestations including anaphylaxis. Thus, continued caution regarding administration of cephalosporin, especially those with amino benzyl side chains, to patients who have a definite history of an immediate reaction to penicillin is advised.     

Safety profile of tacrolimus in patients with rheumatoid arthritis

We assessed the safety of tacrolimus therapy for rheumatoid arthritis. Forty-two patients who started tacrolimus therapy between April 2005 and July 2006 were investigated retrospectively using data from their medical records up to June 2007. The cumulative treatment continuation rate was assessed by the Kaplan–Meier method. Fisher’s exact test was used to compare gastrointestinal symptoms between different tacrolimus doses and between the presence and absence of each concomitant medication. The mean (±SD) observation period was 288 ± 238 days. The cumulative treatment continuation rate was, respectively, 59.5% and 38.1% at 6 months and 1 year after the patients started treatment. Tacrolimus was discontinued in 28 patients, and was discontinued because of adverse reactions in 21 patients. Gastrointestinal symptoms were the most common adverse reactions (45.2% = 19/42 patients), followed by infections and hyperglycemia. Tacrolimus was discontinued in 9/19 patients with gastrointestinal symptoms, and was discontinued within 60 days of starting treatment in seven of them. Nausea and vomiting led to discontinuation in seven patients (within 60 days of starting treatment in six of them). The incidence of gastrointestinal symptoms was higher in patients receiving a daily dose ≥2 mg than in those receiving <2 mg/day. During treatment of rheumatoid arthritis by oral tacrolimus therapy, gastrointestinal symptoms were common, early, and dose-dependent. However, these symptoms were not severe and did not cause any serious safety problems.     

耐多药肺结核患者既往诊治情况调查研究

摘要：目的 了解耐多药患者从确诊为肺结核病到确诊为耐多药肺结核病之间的治疗行为,以及在此期间所获得的管理服务情况。方法 采用结构式访谈问卷调查在天津市、黑龙江省大庆市、河南省濮阳市3个项目市专科医院住过院的43位耐多药肺结核患者。运用SPSS 16.0软件对获取的资料进行统计分析。结果 53.5%（23/43）的患者首次抗结核治疗是在结核病防治机构（简称结防机构）,37.2%（16/43）的患者首次抗结核没有完成治疗疗程。从确诊为肺结核病到确诊为耐多药肺结核病期间,患者平均治疗天数为767 d,平均费用为24 536元,72.1%（31/43）的患者在2家以上的医疗机构治疗过,23.3%（10/43）的患者存在停药行为,46.5%(20/43)的患者有结核病防治人员访视。结论 研究对象的治疗过程复杂、治疗行为不规范,结防机构的管理也不到位。应当加强对患者的引导和管理,提高患者的治疗依从性,防止耐药的产生。     

Characterisation of immune mediator release during the immediate response to segmental mucosal challenge in the jejunum of patients with food allergy

BACKGROUND: Food allergy is a common complaint among patients with a broad spectrum of abdominal and extra-abdominal symptoms that must be distinguished from other more common non-immunological food intolerances. AIMS: To investigate whether human intestinal hypersensitivity reactions are associated with detectable release of inflammatory mediators from activated cells, which may serve as a biological marker of true allergic reactions. PATIENTS/METHODS: In eight patients with food allergy and seven healthy volunteers, a closed-segment perfusion technique was used to investigate the effects of jejunal food challenge on luminal release of tryptase, histamine, prostaglandin D(2), eosinophil cationic protein, peroxidase activity, and water flux. RESULTS: Intraluminal administration of food antigens induced a rapid increase in intestinal release of tryptase, histamine, prostaglandin D(2), and peroxidase activity (p<0.05 v basal period) but not eosinophil cationic protein. The increased release of these mediators was associated with a notable water secretory response. CONCLUSIONS: These results suggest that human intestinal hypersensitivity reactions are characterised by prompt activation of mast cells and other immune cells, with notable and immediate secretion of water and inflammatory mediators into the intestinal lumen. Analysis of the profile of markers released into the jejunum after food provocation may be useful for the objective diagnosis of food allergy.     

Successful transfemoral aortic Edwards® SAPIEN® bioprosthesis implantation without using iodinated contrast media in a woman with severe allergy to contrast agent

Severe anaphylactoid reaction after the use of iodinated contrast media are rare but can contraindicate the use of contrast agent. It was the case of a 53‐year‐old woman suffering from symptomatic severe aortic stenosis, recused for cardiac surgery because of deleterious effects of chest‐wall irradiation, with porcelain aorta. We decided to implant a 23‐mm Edwards^® SAPIEN^® transcatheter aortic valve via a femoral route without using any contrast media. The implantation was successful after surgical approach of the femoral artery, transesophageal echocardiography guiding, and localization of native leaflets and coronary trunk with catheters. Immediate and one month post‐interventional follow‐up was favorable and echocardiography showed a good functioning of the aortic bioprosthesis. Although conventional angiography is the best way to visualize the good positioning of the valve before deployment, our case suggests that, in special situations, transfemoral implantation of an Edwards^® SAPIEN^® aortic bioprosthesis is feasible without any contrast injection. © 2012 Wiley Periodicals, Inc.     

A pilot study of penicillin skin testing in patients with a history of penicillin allergy admitted to a medical ICU

BACKGROUND: Penicillin skin testing is an accurate method to determine whether a person with a history of penicillin allergy is at risk of having an immediate reaction to penicillin. A patient with a negative reaction to a skin test may be able to use a penicillin compound safely, which could reduce the use of broad-spectrum antibiotics in this patient population. METHODS: We prospectively studied all patients with histories of penicillin allergy who were admitted to a medical ICU during a 3-month period and who received antibiotics. Skin testing was performed with benzylpenicilloyl polylysine and penicillin G. We determined the incidence of true allergy, the percentage of patients in whom antibiotic coverage was modified, and the safety of the test. RESULTS: Two hundred fifty-seven patients were admitted to the medical ICU of The Cleveland Clinic Foundation during the study period. Twenty-four patients (9%), labeled as penicillin allergic and receiving antibiotics, were enrolled. Three patients (13%, 3 of 21) gave histories of type I reaction to penicillin and were not skin tested. Twenty patients (95%, 20 of 21) had negative skin test reactions to penicillin and positive skin test reactions to histamine control. One patient (4%, 1 of 21) with negative skin test reactions to both penicillin and histamine control had a test dose challenge with piperacillin that was well tolerated. There were no adverse events. Antibiotic coverage was changed in 10 patients (48%) as a result of skin testing. CONCLUSION: Most patients with histories of allergy to penicillin have negative reactions to skin tests and may receive penicillin safely. Penicillin skin testing can be utilized as a safe and effective strategy to reduce the use of broad-spectrum antibiotics.