The negative predictive value of 5-day drug provocation test in nonimmediate beta-lactam allergy in children

BackgroundExtending the drug provocation test (DPT) period is recommended for patients with suspected nonimmediate beta-lactam antibiotic (BLA) allergy and negative DPT. No consensus has been reached regarding the duration of prolonged provocation.ObjectiveWe aimed to determine the negative predictive value (NPV) of the 5-day extended DPT.MethodsParents of patients with suspected nonimmediate mild cutaneous reactions with BLAs who had been subjected to 5-day DPT with culprit drugs were questioned by telephone interview about reexposure to the tested drug. Patients with reported reaction during reexposure were reevaluated. Skin tests and serum-specific immunoglobulin E (IgE) analysis were not performed before first DPT.ResultsA total of 355 patients had negative results in 5-day DPT. The median age at DPT was 4.2 years, and 52.9% were male. The families of 255 patients (72%) could be contacted. Of these 255 patients, 179 (70%) had used the same drug, and reactions were reported for 6 (3.4%) of those patients, who were subsequently reevaluated. Five of the 6 patients had DPT with amoxicillin-clavulanate and 1 with cefixime. When detailed history was taken, 2 of the 5 patients with amoxicillin-clavulanate reaction were found to have used the drug unintentionally after their reaction to reexposure and did not have any symptoms. One of the patients underwent allergy workup and tested negative, and the other 2 refused the test. The patient with reported cefixime reaction underwent repeated allergy workup and tested negative. Therefore, the NPV of 5-day prolonged DPT was 98.9%.ConclusionThe 5-day prolonged DPT has high NPV and seems appropriate in duration for children with suspected nonimmediate-BLA allergy.     

Emergence of a predominant sequence type ST7363 and the increasing trend of resistance to cefixime and ceftriaxone in Neisseria gonorrhoeae in Southern Taiwan, 2019–2021

Background/purposeMulti-drug resistance and the presence of epidemic lineages of Neisseria gonorrhoeae locally and globally were important clinical and public health issues. We aimed to investigate the molecular epidemiology and the antimicrobial susceptibility profiles of N. gonorrhoeae in Southern Taiwan.MethodsBetween 2019 and 2021, adult patients who had suspected gonorrhea and attended a urology clinic in southern Taiwan were recruited to participate in this study. Clinical data from medical records and a questionnaire, antimicrobial susceptibility testing using a disk diffusion test in accordance with the guidelines by the Clinical and Laboratory Standards Institute, and Multi-locus sequence typing (MLST) were analyzed.ResultsA total of 500 patients participated in the surveillance study. Among them, 232 N. gonorrhoeae isolates were identified, but only 164 isolates were recovered for further research. ST7363 (n = 83, 50.61%) was found to be the predominant sequence type, followed by ST1583 (n = 24, 14.63%), ST1588 (n = 13, 7.93%), and ST7827 (n = 12, 7.32%). 100% resistance to penicillin and 99.4% non-susceptible rate of ciprofloxacin were observed. The azithromycin resistant rate being 15.24% and the cefixime non-susceptible rate being 17.07% were alarming, both with decreasing trends in susceptibilities during 2019–2021. The 25 azithromycin resistant isolates were mainly belonged to ST7363 (n = 12) and ST7827 (n = 3). Seven (4.2%) isolates were ceftriaxone non-susceptible. Among them, four were assigned to be ST 7827 and three belonged to ST7363.ConclusionWe observed the emergence of a predominant sequence type ST7363 in southern Taiwan. Compared with previous Taiwan studies, the increasing trend of resistance to cefixime and ceftriaxone necessitates clinicians’ alertness for clinical treatment response of the extended spectrum cephalosporins and the further surveillance monitor.     

Detection in vitro of cellular hypersensitivity to drugs

The in vitro macrophage migration inhibition technique was used to detect the presence of cellular hypersensitivity in patients with suspected drug allergies. Blood lymphocytes from 11 patients (3 serum sickness, 1 allergic vasculitis, 2 nitrofuradantoin syndrome, 1 erythema nodosum, 2 erythema multiforme, 1 polymyalgia rheumatica, 1 granulomatous hepatitis) and 10 control subjects were assayed for the in vitro production of migration inhibitory factor (MIF) in response to penicillin G, sulfisoxazole, and nitrofuradantoin. Lymphocytes from 6 of 11 patients with clinical manifestations of drug hypersensitivity produced MIF in response to the suspected drug but not in response to other drugs. The serum from one patient with serum sickness secondary to penicillin allergy stimulated autologous lymphocytes as well as those of control subjects to incorporate increased amounts of ³H-thymidine, a finding that could be explained by the presence of immune complexes in the patient's serum. Lymphocytes from the control subjects did not produce MIF in response to any of the drugs, suggesting that this technique may be of use in the detection of drug allergies.     

The lymphocyte transformation test for the diagnosis of drug allergy: sensitivity and specificity

Background The diagnosis of a drag allergy is mainly based upon a very detailed history and the clinical findings. In addition, several in vitro or in vivo tests can be performed to demonstrate a sensitization to a certain drug. One of the in vitro tests is the lymphocyte transformation test (LTT), which can reveal a sensitization of T-cells by an enhanced proliferative response of peripheral blood mononuclear cells to a certain drag. Objective To evaluate the sensitivity and specificity of the LTT, 923 case histories of patients with suspected drag allergy in whom a LTT was performed were retrospectively analysed. Methods Based on the history and provocation tests, the probability (P) of a drag allergy was estimated to be >0.9, 0.5–0.9, 0.1–0.5 or <0.1, and was put in relation to a positive or negative LTT. Results Seventy-eight of 100 patients with a very likely drag allergy (P<0.9) had a positive LTT, which indicates a sensitivity of 78%. If allergies to betalactam-antibiotics were analysed separately, the sensitivity was 74.4%. Fifteen of 102 patients where a classical drag allergy could be excluded (P<0.1), had nevertheless a positive LTT (specificity thus 85%). The majority of these cases were classified as so-called pseudoallergic reaction to NSAIDs. Patients with a clear history and clinical findings for a cotrimoxazole-related allergy, all had a positive LTT (6/6), and in patients who reacted to drags containing proteins, sensitization could be demonstrated as well (i.e. hen's egg lysozyme, 7/7). In 632 of the 923 cases, skin tests were also performed (scratch and/or epicutaneous), for which we found a lower sensitivity than for the LTT (64%), while the specificity was the same (85%). Conclusion Although our data are somewhat biased by the high number of penicillin allergies and cannot be generalized to drag allergies caused by other compounds, we conclude that the LTT is a useful diagnostic test in drag allergies, able to support the diagnosis of a drag allergy and to pinpoint the relevant drag.     

The epidemiology of milk allergy in US children

BackgroundMilk is one of the most common food allergies in US children, yet little is known about its distribution and diagnosis.ObjectiveTo better understand current pediatric milk allergy distribution and diagnosis trends in the United States.MethodsA randomized, cross-sectional survey was administered to parents belonging to a representative sample of US households with children from June 2009 to February 2010. Data from 38,480 parents regarding demographic characteristics, allergic symptoms associated with food ingestion, and methods used to diagnose food allergy were collected and analyzed as weighted proportions. Adjusted models were estimated to examine association of these aspects with odds of milk allergy.ResultsOf the 3,218 children identified with food allergy, 657 (19.9%) were reported to have milk allergy. Asian (odds ratio [OR], 0.5) and black (OR, 0.4) children were half as likely as white children to develop milk allergy. The highest percentage of milk-allergic children (23.8%) were aged 6 to 10 years, and the lowest percentage of milk-allergic children (15.0%) were aged 11 to 15 years. Nearly one-third (31.4%) of children with milk allergy had a history of severe reactions. Compared with children with other food allergies, children with milk allergy had a higher odds of having physician-diagnosed allergy (OR, 1.7) and were twice as likely (OR, 2.1) to outgrow their milk allergy.ConclusionChildhood milk allergy, which accounts for one-fifth of US food allergies, is less prevalent among Asian and black children than white children. Although less than half of children with milk allergy received confirmatory testing, it is the most commonly diagnosed food allergy.     

Female sex as a risk factor for penicillin allergy.

BACKGROUND: Identification of risk factors is an integral part of a physician's evaluation of a patient. OBJECTIVE: To determine whether female sex is an independent risk factor for penicillin allergy. METHODS: Rates of positive penicillin skin test (PST) results, according to sex, were determined in patients with a history of penicillin allergy undergoing penicillin allergy evaluation with major and minor determinants of penicillin between June 1, 2002, and June 30, 2004. Univariate and multivariate logistic regression analyses were used to calculate unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for sex differences in the rates of positive PST results. RESULTS: Of the 1,921 patients, 1,759 underwent PST and 157 did not; 5 medical records were not available for review. The mean patient age was 60 years. Sixty-four patients (4%) had a positive PST reaction; of these, 53 (83%) were females and 11 (17%) were males (OR, 3.6; 95% CI, 1.9-7.2; P < .001). In a multivariate logistic regression analysis adjusted for age, history of multiple drug allergies, and elapsed time from the initial penicillin adverse drug reaction to PST, female sex again had a significant risk of a positive PST reaction (OR, 3.2; 95% CI, 1.6-6.7; P = .001). CONCLUSION: A greater risk of penicillin allergy exists in association with female sex in patients with a history of penicillin allergy.     

Safety and effectiveness of a preoperative allergy clinic in decreasing vancomycin use in patients with a history of penicillin allergy.

BACKGROUND: We developed a clinical pathway to optimize the use of antimicrobials by decreasing vancomycin use in preoperative patients with a history of penicillin allergy. OBJECTIVE: To decrease the use of vancomycin in surgical patients with a self-reported penicillin allergy. METHODS: In June 2002, same-day allergy consultation and penicillin skin testing were made available for preoperative patients with self-reported penicillin allergy at the preoperative evaluation (POE) clinic. We reviewed the penicillin allergy skin test results, recommendations, and beta-lactam antibiotic administration outcomes from July 1, 2002, to September 16, 2003. RESULTS: A total of 1,204 of 11,819 patients were evaluated for beta-lactam allergy at the POE clinic. Of these, 1,120 were approved by the institutional review board for inclusion in the study and 9 were excluded from the study. Of the remaining 1,111 patients, 1,030 (93%) underwent skin testing for penicillin allergy. Forty-three (4%) had a positive skin test result to penicillin. A total of 947 (85%) of the 1,111 patients with a history of beta-lactam allergy were advised to use a beta-lactam antibiotic, and 164 (15%) were advised to avoid beta-lactams. A total of 955 patients (86%) actually received preoperative antibiotics. Of these 955 patients, 716 (75%) received cefazolin, and only 149 (16%) received vancomycin compared with 30% historical controls (P < .01). Among the patients with a negative penicillin skin test result who received a cephalosporin, 5 (0.7%) of 675 experienced an adverse drug reaction to a cephalosporin. CONCLUSIONS: Establishment of a clinical pathway in a preoperative clinic that includes allergy consultation and penicillin skin testing reduced vancomycin use to only 16% in surgical patients with a history of beta-lactam allergy.     

Diagnosis of reaginic allergy with house dust, animal dander and pollen allergens in adult patients. II. A comparison between skin tests and provocation tests.

The results of skin tests (ST) were compared with those of 2,055 provocation tests (PT) in 403 patients with asthma and/or allergic rhinitis. The overall agreement between ST and PT results was 77%. Various correlation figures were found for different allergens. In patients with pronounced allergy in the shock organ the prportion of positive ST was higher than in those with low-grade allergy. It is concluded that only strong ST reactions should be relied upon. In other cases additional diagnostic methods are reccommended. The diagnostic precision of ST is of the same order of sizes as that of the radioallergosorbent test.     

Diagnostic accuracy of the atopy patch test in children with food allergy-related gastrointestinal symptoms

BACKGROUND: Little is known about the diagnostic accuracy of atopy patch tests (APT) in the clinical practice of pediatric gastroenterology. Moreover, APTs containing purified food extracts have recently become available, but their diagnostic accuracy is largely undefined. PATIENTS AND METHODS: We evaluated the diagnostic accuracy of food challenge, skin prick test (SPT), serum specific IgE determination, and APT using fresh food and commercial food extracts in parallel in children referred for suspected food allergy-related gastrointestinal symptoms. RESULTS: Eighty-nine food challenges were performed in 60 patients (38 boys, median age 23 months, range 3-48 months): 31 tested positive for cow's milk (CM), 19 for hen's egg (HE), and two for wheat. Specific immunoglobulin E (IgE) determination, and SPT, respectively, were positive in 7/31 and 14/31 of patients with cow's milk allergy (CMA), and in 7/19 and 7/19 with HE allergy. The results of APT with fresh food vs a commercial assay were (1) CM: sensitivity: 64.5%vs 6.4%, specificity 95.8%vs 95.6%, positive predictive value (PPV) 95.2%vs 66.6% and negative predictive value (NPV) 67.6%vs 43.1%; (2) HE: sensitivity 84.2%vs 5.2%, specificity 100%vs 100%, PPV 100%vs 100% and NPV 75.0%vs 33.3%. CONCLUSIONS: Atopy patch test is a useful tool in the diagnostic work up of children with food-allergy-related gastrointestinal symptoms. The diagnostic accuracy of ATP was higher with fresh food than with commercial food extracts.     

Allergic skin disease: investigation of both immediate- and delayed-type hypersensitivity is essential

BACKGROUND: In our clinic we routinely patch test patients referred from occupational health for the investigation of latex contact urticaria. We also undertake both patch and prick testing (where indicated) in patients referred with persistent dermatitis/eczema. If investigation of allergic skin disease is undertaken by a non-dermatologist, it is unlikely that patch testing will be performed. OBJECTIVE: To carry out a retrospective analysis of patients who had been prick tested to establish whether an incomplete diagnosis would have been reached if patch testing had been omitted. METHODS: Details of patients who had attended for patch testing between July 2004 and December 2005 were analysed. Patients who had had prick tests and patch testing were identified. The outcomes of prick tests and patch testing were documented together with the clinical relevance. RESULTS: Three hundred and thirty out of 1060 patients referred to the clinic were prick tested. 54.2% patients were referred from dermatologists. 26.6% were referred from occupational health, 68 patients had positive reactions on prick testing of whom 36 had positive patch tests (52.9%), which were of current relevance in 27 patients (39.7%). Nine out of 106 health workers referred to exclude latex contact urticaria had positive prick tests to latex. Fifty of these patients demonstrated delayed-type hypersensitivity with nickel, cobalt, rubber and its additives being the most common allergens found. Of the 262 patients who had negative prick tests, 121 had positive patch tests (46.1%) of current relevance to patient history in 92 subjects (35.1%). While none of the six patients referred for investigation of reaction to local anaesthetics had a positive prick test, one was allergic to local anaesthetic on patch testing. CONCLUSION: Omission of patch testing from the investigation of allergic skin disease, even when contact urticaria may be the sole suspected diagnosis, would result in the frequent missed diagnosis of contact allergy. We recommend that patients with suspected allergic skin disease are investigated in an environment where investigation of both immediate- and delayed-type hypersensitivity can be undertaken. In particular, patients with atopic eczema, suspected latex rubber allergy, hand dermatitis (particularly occupational) and drug reactions should be targeted to receive both investigations.     

Beta lactam allergy and resensitization in children with suspected beta lactam allergy

Background In patients who were clinically diagnosed as having beta lactam allergy and had negative skin tests, the rates of reported resensitization to beta lactams after subsequent exposures, vary significantly. Some allergists advocate skin testing before every exposure to beta lactams.
Objective We sought to determine the true rate of beta lactam allergy and of resensitization in children with a positive history for suspected beta lactam allergy.
Methods The study was conducted from July 1998 to May 2004, with follow-up during 2007. Beta lactam allergy tests with the major determinant and freshly prepared minor determinant mixtures were offered to history positive children. Negative skin tests were followed by oral challenge. The tests were performed again 1–5 months later in order to address the possibility of resensitization.
Results Tests were performed on 166 children: 150 for penicillins alone, 14 for penicillin in combination with cephalosporins, and an additional 2 patients solely for cephalosporins. Only 10 children (6%) were positive in the initial evaluation, four by skin test and six by oral challenge. A second set of tests was performed in 98 children with a negative initial evaluation; only two children (2%) were resensitized. On a follow-up survey of 71 of the 96 patients, 59 (83%) had received beta lactams; only one had developed a minor rash after subsequent exposure to amoxicillin.
Conclusions Most children with suspected beta lactam allergy were not allergic to beta lactams. Resensitization to beta lactam antibiotics in children in this study was infrequent. In children with a clinical diagnosis of beta lactam allergy and negative skin tests, repeated skin testing before every exposure is usually unnecessary.     

Diagnostic Decision Points of Specific IgE Concentrations in Korean Children With Egg and Cow's Milk Allergies

Purpose

The purpose of this study was to evaluate the utility of specific IgE (sIgE) concentrations for the diagnosis of immediate-type egg and cow''s milk (CM) allergies in Korean children and to determine the optimal cutoff levels.

Methods

In this prospective study, children ≥12 months of age with suspected egg or CM allergy were enrolled. Food allergy was diagnosed by an open oral food challenge (OFC) or through the presence of a convincing history after ingestion of egg or CM. The cutoff levels of sIgE for egg white (EW) and CM were determined by analyzing the receiver operating characteristic curves.

Results

Out of 273 children, 52 (19.0%) were confirmed to have egg allergy. CM allergy was found in 52 (23.1%) of 225 children. The EW-sIgE concentration indicating a positive predictive value (PPV) of >90% was 28.1 kU/L in children <24 months of age and 22.9 kU/L in those ≥24 months of age. For CM-sIgE, the concentration of 31.4 kU/L in children <24 months of age and 10.1 kU/L in those ≥24 months of age indicated a >90% PPV. EW-sIgE levels of 3.45 kU/L presented a negative predictive value (NPV) of 93.6% in children <24 months of age, while 1.80 kU/L in those ≥24 months of age presented a NPV of 99.2%. The CM-sIgE levels of 0.59 kU/L in children <24 months of age and 0.94 kU/L in those ≥24 months of age showed NPVs of 100% and 96.9%.

Conclusions

Our results indicate that different diagnostic decision points (DDPs) of sIgE levels should be used for the diagnosis of egg or CM allergy in Korean children. The data also suggest that DDPs with high PPV and high NPV are useful for determining whether OFC is required in children with suspected egg or CM allergy.     

Qualitative analysis of perceived impacts on childhood food allergy on caregiver mental health and lifestyle

BackgroundApproximately 8% of children have food allergy. Yet, little is known about how parents cope with the burden of this disease.ObjectiveThis study aimed to describe the perceptions of food allergy–related mental health issues of parents of children with food allergy.MethodsParents of children with pediatric allergist–diagnosed food allergy were recruited through allergy clinics and education centers in a large Canadian city. We used content analysis to identify overarching themes.ResultsWe interviewed 21 parents with children (boys [13/21; 62.9%]) aged younger than 12 months to 16 years. Interviews averaged 47 (range 33-82) minutes. Most children were diagnosed as infants, and few (7/21; 33.3%) were monoallergic. About one-half (7/16; 43.8%) had a history of anaphylaxis. Parents of children with a single food allergy spoke of “accommodation and adaptation.” In contrast, parents of children with multiple food allergies described “anxiety and isolation” and spoke of being “depressed” and “terrified” about leaving their children in the care of others who may not be equipped to handle food allergy. Many parents felt “overwhelmed and alone,” especially if they lacked support from extended family and/or their social circle. “Fear for today, fear for the future” was commonly described by parents, although a tenuous symbiotic coexistence was developed, with parents stating “Food allergy management has become our normal.” Finally, a small group of parents reported that “Bullying happens, but we are alone to cope with it.”ConclusionMultiple food allergies negatively affect the mental health of parents, in a variety of well-being domains.     

Penicillin skin testing in patients with a history of beta-lactam allergy.

BACKGROUND: Vancomycin and fluoroquinolones are commonly used in patients with a history of penicillin allergy. OBJECTIVE: To determine the safety and utility of penicillin skin testing (PST). METHODS: Retrospective study of patients with a history of penicillin allergy between April 1, 1999, and September 30, 2004. Penicillin skin testing was performed by means of standard methods using benzylpenicilloyl-polysine, penicillin G, and histamine and saline controls. RESULTS: Of 596 patients studied, 25.3% were outpatients, 50.3% were inpatients, and 24.3% were intensive care unit patients. The most common antibiotics used during the time of PST were vancomycin and fluoroquinolones. Results of PST were negative in 88.4% of patients, positive in 8.2%, and indeterminate in 3.4%. One patient (0.17%) developed urticaria immediately after PST. Fifty-five percent of patients with negative PST results were changed to a beta-lactam drug, more frequently in the intensive care unit vs the outpatient setting (70.3% vs 8.6%; P < .001) and in adults vs patients younger than 18 years (58.6% vs 8.1%; P < .001). A beta-lactam antibiotic was used in 290 patients with negative PST results. Of the patients given beta-lactam antibiotics, 5 (1.7%) had adverse reactions: 2 had hives after 16 and 20 days of therapy, 1 had a nonspecific rash after 17 days of therapy, 1 had flushing and urticaria 3 hours after a test dose of piperacillin-tazobactam, and 1 had a pruritic rash after 12 hours of therapy. CONCLUSIONS: Patients with a history of penicillin allergy can safely use beta-lactam drugs if negative PST results.     

The economic burden of antibiotic treatment of penicillin-allergic patients in internal medicine wards of a general tertiary care hospital

BACKGROUND: Penicillin allergy poses a major problem in the management of infectious diseases. OBJECTIVE: We estimated the costs and usage of antibiotic treatment of 'penicillin-allergic' patients in comparison to non-allergic patients in a tertiary care hospital. MATERIALS AND METHODS: The study was based on the records of 118 randomly chosen in-hospital patients labelled as being 'allergic to penicillin' and who were treated with antibiotics. The antibiotic selection and cost of the patients with alleged penicillin allergy were compared to 118 matched patients without an antibiotic allergy (controls). RESULTS: During in-hospital treatment, the mean antibiotic cost for penicillin-allergic patients was 63% higher than the cost for the controls. In addition, there was a 38% higher cost of the recommended anti-microbial treatment regimen to be followed upon discharge by the former compared to the latter. CONCLUSIONS: Penicillin-allergic patients were more likely to receive broader spectrum antibiotics compared to the non-allergic ones. Since many of the patients who are labelled as being 'allergic to penicillin' are, in fact, not allergic to it, inaccurate reporting of penicillin allergies may have costly economic and epidemiologic repercussions in addition to more toxic effects which can occur when choosing alternative drugs in case of penicillin allergy.