Non-anaphylactic Reactions Research Articles

Impaired high-density lipoprotein function and endothelial barrier stability in severe anaphylaxis

Growing evidence demonstrates the importance of high- and low-density lipoprotein cholesterol in certain immune and allergy-mediated diseases. This study aimed to evaluate levels of high- and low-density lipoprotein cholesterol and apolipoproteins A1 and B in sera from a cohort of patients presenting with hypersensitivity reactions. We further assessed the function of high-density lipoprotein particles as well as their involvement in the molecular mechanisms of anaphylaxis. Lipid profile determination was performed in paired (acute and baseline) serum samples from 153 patients. Thirty-eight experienced a non-anaphylactic reaction and 115 had an anaphylactic reaction (88 moderate and 27 severe). Lecithin cholesterol acyl transferase activity was assessed in patient sera, and we also evaluated macrophage cholesterol efflux in response to the serum samples. Last, the effect of anaphylactic-derived high-density lipoprotein (HDL) particles on the endothelial barrier was studied. Detailed methods are provided in the Methods section in this article's Online Repository available at www.jacionline.org. Serum samples from severe anaphylactic reactions show statistically significant low levels of HDL cholesterol, low-density lipoprotein cholesterol, and apolipoproteins A1 and B, which points to their possible role as biomarkers. Specifically, HDL particles play a protective role in cardiovascular diseases. Using functional human serum cell assays, we observed impaired capacity of apolipoprotein B-depleted serum to induce macrophage cholesterol efflux in severe anaphylactic reactions. In addition, purified HDL particles from human anaphylactic sera failed to stabilize and maintain the endothelial barrier. These results encourage further research on HDL functions in severe anaphylaxis, which may lead to new diagnostic and therapeutic strategies.

Drug allergy: A 2022 practice parameter update

Drug allergy: A 2022 practice parameter update

Multidisciplinary Institutional Practice Plan to Safely Administer COVID-19 Vaccination to Health Center Employees

In December 2020 Emergency Use Authorization for two COVID-19 vaccines, Pfizer-BioNTech and Moderna, was authorized. Clinical trials reported severe allergic reactions at less than 2%, but shortly after authorization, severe allergic reactions filled the news cycle. In January 2021, it was reported that anaphylaxis to the Pfizer-BioNTech vaccine was approximately 10 times higher in incidence compared to any previous formulated vaccine. Many subjects report non-anaphylactic reactions to the initial dose of vaccine.

Cohort experience of second messenger RNA vaccine dose tolerance after an initial-dose reaction

Cohort experience of second messenger RNA vaccine dose tolerance after an initial-dose reaction

Anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: a systematic review and meta-analysis

BackgroundCurrently there is no systematic review and meta-analysis of the global incidence rates of anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines in the general adult population.ObjectivesTo estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases.DesignA systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] statement was followed.MethodsElectronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination: anaphylaxis, non-anaphylaxis, anaphylactic reaction, nonanaphylactic reaction, anaphylactic/anaphylactoid shock, hypersensitivity, allergy reaction, allergic reaction, immunology reaction, immunologic reaction, angioedema, loss of consciousness, generalized erythema, urticaria, urticarial rash, cyanosis, grunting, stridor, tachypnoea, wheezing, tachycardia, abdominal pain, diarrhea, nausea, vomiting and tryptase. We included studies in adults of all ages in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses.ResultsOf the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421 vaccine recipients [Pfizer-BioNTech (n = 14,505,399) and Moderna (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of anaphylaxis to both vaccines was 5.0 (95% CI 2.9 to 7.2, I2 = 81%, p = < 0.0001), while the overall pooled prevalence estimate of nonanaphylactic reactions to both vaccines was 53.9 (95% CI 0.0 to 116.1, I2 = 99%, p = < 0.0001). Vaccination with Pfizer-BioNTech resulted in higher anaphylactic reactions compared to Moderna (8.0, 95% CI 0.0 to 11.3, I2 = 85% versus 2.8, 95% CI 0.0 to 5.7, I2 = 59%). However, lower incidence of nonanaphylactic reactions was associated with Pfizer-BioNTech compared to Moderna (43.9, 95% CI 0.0 to 131.9, I2 = 99% versus 63.8, 95% CI 0.0 to 151.8, I2 = 98%). The funnel plots for possible publication bias for the pooled effect sizes to determine the incidence of anaphylaxis and nonanaphylactic reactions associated with mRNA COVID-19 immunization based on mRNA vaccine type appeared asymmetrical on visual inspection, and Egger’s tests confirmed asymmetry by producing p values < 0.05. Across the included studies, the most commonly identified risk factors for anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines were female sex and personal history of atopy. The key triggers to anaphylactic and nonanaphylactic reactions identified in these studies included foods, medications, stinging insects or jellyfish, contrast media, cosmetics and detergents, household products, and latex. Previous history of anaphylaxis; and comorbidities such as asthma, allergic rhinitis, atopic and contact eczema/dermatitis and psoriasis and cholinergic urticaria were also found to be important.ConclusionThe prevalence of COVID-19 mRNA vaccine-associated anaphylaxis is very low; and nonanaphylactic reactions occur at higher rate, however, cutaneous reactions are largely self-limited. Both anaphylactic and nonanaphylactic reactions should not discourage vaccination.

Severity grading system for acute allergic reactions: A multidisciplinary Delphi study

There is no widely adopted severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions, thus limiting the ability to optimize and standardize management practices and advance research. The aim of this study was to develop a severity grading system for acute allergic reactions for use in clinical care and research. From May to September 2020, we convened a 21-member multidisciplinary panel of allergy and emergency care experts; 9 members formed a writing group to critically appraise and assess the strengths and limitations of prior severity grading systems and develop the structure and content for an optimal severity grading system. The entire study panel then revised the grading system and sought consensus by utilizing Delphi methodology. The writing group recommended that an optimal grading system encompass the severity of acute allergic reactions on a continuum from mild allergic reactions to anaphylactic shock. Additionally, the severity grading system must be able to discriminate between clinically important differences in reaction severity to be relevant in research while also being intuitive and straightforward to apply in clinical care. Consensus was reached for all elements of the proposed severity grading system. We developed a consensus severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions. Successful international validation, refinement, dissemination, and application of the grading system will improve communication among providers and patients about the severity of allergic reactions and will help advance future research.

PEMCRC anaphylaxis study protocol: a multicentre cohort study to derive and validate clinical decision models for the emergency department management of children with anaphylaxis

IntroductionThere remain significant knowledge gaps about the management and outcomes of children with anaphylaxis. These gaps have led to practice variation regarding decisions to hospitalise children and length of observation...

Persistent, refractory, and biphasic anaphylaxis: A multidisciplinary Delphi study

The use of inconsistent definitions for anaphylaxis outcomes limits our understanding of the natural history and epidemiology of anaphylaxis, hindering clinical practice and research efforts. Our aim was to develop consensus definitions for clinically relevant anaphylaxis outcomes by utilizing a multidisciplinary group of clinical and research experts in anaphylaxis. Using Delphi methodology, we developed agenda topics and drafted questions to review during monthly conference calls. Through online surveys, a 19-member panel consisting of experts in allergy and/or immunology and emergency medicine rated their level of agreement with the appropriateness of statements on a scale of 1 to 9. Amedian value of 1.0 to 3.4 was considered inappropriate, a median value of 3.5 to 6.9 was considered uncertain, and a median value of 7.0 to 9.0 was considered appropriate. Adisagreement index was then calculated, with values less than 1.0 categorized as "consensus reached." If consensus was not reached after the initial survey, subsequent surveys incorporating the aggregate de-identified responses from prior surveys were sent to panel members. This process was repeated until consensus was reached or 4 survey rounds had been completed, after which the question was categorized as "no consensus reached." The panel developed outcome definitions for persistent, refractory, and biphasic anaphylaxis, as well as for persistent and biphasic nonanaphylactic reactions. There was also consensus among panel members regarding the need to develop an anaphylaxis severity grading system. Dissemination and application of these definitions in clinical care and research will help standardize the terminology used to describe anaphylaxis outcomes and serve asthe foundation for future research, including research aimedat development of an anaphylaxis severity grading system.

Oral Immunotherapy for Peanut Allergy (PACE): A Systematic Review and Meta–analysis of Efficacy and Safety

To systematically review the efficacy and safety of peanut oral immunotherapy (OIT) compared with allergen avoidance or placebo OIT for peanut allergy.The population included individuals with peanut allergy (61% male, 39% female), the majority of whom were children (median age: 8.7 years; interquartile range [IQR]: 5.9–11.2 years) participating in peanut OIT trials in North America, Australia, and Western Europe.This systematic review and meta-analysis included a comprehensive search of international health care databases from the United States, Latin America, Europe, and China through December 2018. Authors performed searches for randomized controlled trials comparing peanut OIT to no OIT for the treatment of peanut allergy. The authors screened studies, extracted data, assessed risk of bias, and assessed quality of evidence by the Grading of Recommendations Assessment, Development, and Evaluation approach. The main outcomes included treatment efficacy (ie, proportion of patients passing an oral food challenge), anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life.Twelve randomized controlled trials were included, with 1041 participants in total undergoing peanut OIT for a median follow-up of 1.0 year (IQR: 0.8–1.4), achieving a median target dose of 2000 mg of peanut protein (IQR: 375–4000). Passing a supervised, in-clinic oral food challenge was more likely in the OIT group. Subjects undergoing peanut OIT had increased anaphylaxis risk (risk ratio: 3.12 [95% confidence interval (CI): 1.76–5.55]), anaphylaxis frequency (incidence rate ratio: 2.72 [95% CI: 1.57–4.72]), and epinephrine use (risk ratio: 2.21 [95% CI: 1.27–3.83]). Peanut OIT increased serious adverse events and nonanaphylactic reactions. These findings were irrespective of OIT protocol, proprietary formulation or not, and phase of OIT (build-up versus maintenance). Quality of life was not different between groups.High-quality evidence shows that current peanut OIT regimens effectively achieve a modest level of desensitization but clinically result in a net increase in anaphylaxis and other allergic reactions compared with avoidance or placebo, rather than preventing them, as intended. These data support the need for improved food allergy treatment approaches with an enhanced safety profile.Hesitancy to implement OIT in routine clinical practice centers around concerns for safety, standardization of approach, practicality of long-term therapy maintenance, and identification of patients who will respond best with the fewest side effects. Although most adverse effects from OIT are mild and do not prevent patients from continuing therapy, the potential for life-threatening anaphylaxis exists. Despite the safety concerns outlined in this report, OIT is being offered in some clinical practices and is expected be available on a larger scale in the near future. It is important to remember that OIT may not be the best fit for many food-allergic patients, and as we near the likely acceptance of a US Food and Drug Administration–approved peanut OIT product, patients will seek advice from their pediatrician before talking to an allergist to help them navigate the pros and cons of interventional therapy versus the traditional approach of maintaining strict allergen avoidance. Salient points for the pediatrician to remember include the following. (1) OIT and all other products currently under investigation for treatment of food allergy provide benefit while on therapy but do not appear to induce sustained remission for the majority of allergic patients. (2) There are no surrogate biomarkers to identify which patients will receive the greatest benefit with the fewest side effects. (3) Anaphylaxis while on therapy is a potential side effect, and patients must continue to carry autoinjectable epinephrine at all times. Shared decision-making and an open and honest discussion with families considering therapeutic options are necessary in providing comprehensive care of our patients with food allergy and their families.

Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety

Oral immunotherapy is an emerging experimental treatment for peanut allergy, but its benefits and harms are unclear. We systematically reviewed the efficacy and safety of oral immunotherapy versus allergen avoidance or placebo (no oral immunotherapy) for peanut allergy. In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, we searched MEDLINE, EMBASE, Cochrane Controlled Register of Trials, Latin American & Caribbean Health Sciences Literature, China National Knowledge Infrastructure, WHO's Clinical Trials Registry Platform, US Food and Drug Administration, and European Medicines Agency databases from inception to Dec 6, 2018, for randomised controlled trials comparing oral immunotherapy versus no oral immunotherapy for peanut allergy, without language restrictions. We screened studies, extracted data, and assessed risk of bias independently in duplicate. Main outcomes included anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life, meta-analysed by random effects. We assessed certainty (quality) of evidence by the GRADE approach. This study is registered with PROSPERO, number CRD42019117930. 12 trials (n=1041; median age across trials 8·7 years [IQR 5·9-11·2]) showed that oral immunotherapy versus no oral immunotherapy increased anaphylaxis risk (risk ratio [RR] 3·12 [95% CI 1·76-5·55], I2=0%, risk difference [RD] 15·1%, high-certainty), anaphylaxis frequency (incidence rate ratio [IRR] 2·72 [1·57-4·72], I2=0%, RD 12·2%, high-certainty), and epinephrine use (RR 2·21 [1·27-3·83], I2=0%, RD 4·5%, high-certainty) similarly during build-up and maintenance (pinteraction=0·92). Oral immunotherapy increased serious adverse events (RR 1·92 [1·00-3·66], I2=0%, RD 5·7%, moderate-certainty), and non-anaphylactic reactions (vomiting: RR 1·79 [95%CI 1·35-2·38], I2=0%, high-certainty; angioedema: 2·25 [1·13-4·47], I2=0%, high-certainty; upper tract respiratory reactions: 1·36 [1·02-1·81], I2=0%, moderate-certainty; lower tract respiratory reactions: 1·55 [0·96-2·50], I2=28%, moderate-certainty). Passing a supervised challenge, a surrogate for preventing out-of-clinic reactions, was more likely with oral immunotherapy (RR 12·42 [95% CI 6·82-22·61], I2=0%, RD 36·5%, high-certainty). Quality of life was not different between groups (combined parents and self report RR 1·21 [0·87-1·69], I2=0%, RD 0·03%, low-certainty). Findings were robust to IRR, trial sequential, subgroup, and sensitivity analyses. In patients with peanut allergy, high-certainty evidence shows that available peanut oral immunotherapy regimens considerably increase allergic and anaphylactic reactions over avoidance or placebo, despite effectively inducing desensitisation. Safer peanut allergy treatment approaches and rigorous randomised controlled trials that evaluate patient-important outcomes are needed. None.

Anaphylaxis to foods in a population of adolescents: incidence, characteristics and associated risks.

Information about severe reactions to foods in adolescence is limited. To describe reactions to foods, including anaphylaxis, with regard to incidence, characteristics and associated risks, among 16-year-olds (adolescents) in a large, population-based birth cohort. Parent-reported questionnaire data from ages 2-3months, and 1, 2 and 16years were used (N=3153). Anaphylaxis at age 16years was defined per NIAID/FAAN criteria. Immunoglobulin E (IgE) antibodies to 14 common food and inhalant allergens were analysed at ages 4 (n=2283) and 16years (n=2510). Among adolescents with food-related symptoms (FRS) and for whom blood was available (n=221), 25 additional food allergen extracts or allergen components were analysed. Associations between reactions to foods, and sensitization and allergic multimorbidity were investigated. In the 12months prior to the 16-year assessment, 8.5% of adolescents had FRS. This included 0.8% (n=24) adolescents who were classified as having anaphylaxis, yielding an incidence rate of 761/100000 person-years. One-third of adolescents accessed health care during anaphylaxis. Allergic multimorbidity in infancy, as well as sensitization to foods and airborne allergens at age 4years, was associated with an increased risk for FRS in adolescence. Peanuts and tree nuts were the most common culprit foods for anaphylaxis, and fruits and vegetables for non-anaphylactic reactions. Adolescents with anaphylaxis were significantly more likely to be sensitized to storage proteins (Ara h 2, Cor a 9, Cor a 14) and to be polysensitized to foods (P<0.001 vs. non-anaphylactic reactions). The incidence of food-induced anaphylaxis during adolescence in our population-based birth cohort is higher than previously reported. Adolescents with anaphylaxis differ from adolescents with non-anaphylactic FRS with regard to culprit foods and sensitization. Adolescents with previous anaphylaxis are likely to be polysensitized to foods, particularly tree nut and peanut storage proteins, and which warrants consideration at follow-up.

Penicillin allergy and surgical prophylaxis: Cephalosporin cross-reactivity risk in a pediatric tertiary care center

BackgroundFirst generation cephalosporins are commonly used as antibiotic prophylaxis prior to surgery. Patients labeled as penicillin-allergic are often precluded from receiving cephalosporins because of an allergic cross-reactivity. The aims of this study were to evaluate the clinical practice for surgical prophylaxis at Nationwide Children's Hospital and to determine the incidence of adverse effects and allergic reactions when using cephalosporins in patients labeled as penicillin-allergic. MethodsA retrospective chart review was performed to identify patients who were allergic to penicillin, penicillin antibiotic family, who required surgical treatment for an existing medical condition, and received an antibiotic to prevent surgical site infection. ResultsFive hundred thirteen penicillin-allergic patients were identified, encompassing 624 surgical cases. Cephalosporins were administered in 153 cases (24.5%) with cefazolin used 83% of the time. Only one documented case of nonanaphylactic reaction was reported. Clindamycin was the most common cephalosporin substitute (n=387), and the reported adverse reaction rate was 1.5%. No cases of anaphylaxis were documented. ConclusionsOur data suggest that the administration of cephalosporins for surgical prophylaxis following induction of anesthesia in a patient with a known or reported penicillin-allergy appears appropriate and results in a lower adverse event rate that when clindamycin is administered.

Risky business? Whether a more accurate picture of risk assessment in food allergic children and young people affects behaviours in school nurses and school first aiders

Background The risk of fatal anaphylaxis in a food allergic person is very low, yet the possibility of this catastrophic event is a major focus for both patients and healthcare professionals. It is unclear how healthcare professionals perceive risk of fatal or non-fatal anaphylaxis in the context of food allergy, and whether their perception of risk influences their management of food allergy. We investigated whether school nurses/first aiders could accurately estimate fatal anaphylaxis risk in children/young people with food allergy, and whether their assessment of risk correlated with their knowledge and management of food allergy in children/young people. Methods Interview-based surveys completed in 30 schools over 6 months included assessment of risk perception in relation to childhood food allergy using a novel risk assessment tool, an assessment of their knowledge of when to administer adrenaline and assessment of their practical ability to use an adrenaline autoinjector. Results Risk perception varied widely but all participants overestimated fatal food anaphylaxis risk more than they overestimated all-cause mortality risk in young people [median log-fold overestimate for all-cause mortality 0.51 (IQR 0.00, 1.48); food anaphylaxis death 1.20 (IQR 0.06, 2.10) p=0.018]. We did not find any association between estimation of anaphylaxis/fatal anaphylaxis risk in a food allergic child, and practical ability to use an adrenaline autoinjector in a simulated scenario. We did however find that participants who state that they would (unnecessarily) dial emergency services for a non-anaphylactic reaction, also significantly overestimated risk of anaphylaxis in a food allergic person (median log-fold overestimate 1.76 (IQR 0.92, 2.33) vs. 0.72 (IQR -1.51, 1.59) for those who would not dial emergency services for a non-anaphylactic reaction (p=0.009). Multivariate analyses showed weak evidence that personal or previous medical experience of allergic disease correlates with increased overestimation of fatal food anaphylaxis risk. Conclusion School nurses/first aiders overestimate fatal food anaphylaxis risk more than overestimating other fatality risks in children. The data suggests that this overestimation of risk is not associated with improved ability to recognise/manage anaphylaxis. These data suggest that correcting any risk misperception among healthcare providers, in relation to risk of anaphylaxis in food allergy, is unlikely to be harmful.

Optimising immunisations in early years – a shared partnership

The UK Childhood Immunisation Programme is vital to an effective Preventative Child Health Service for the Early Years. Evidence-based guidelines (eg. ‘Green Book’) exist to equip Immunisation Practitioners on key practices and vaccination policies. A review of referrals to our Paediatric Immunisation Clinic in a District General Hospital was undertaken to assess for trend in Primary Care referral patterns for immunisation queries, analyse the quality of referrals, and identify areas for improvement to local practice. All referrals made between March 2007 - February 2011 were retrospectively reviewed, including replying correspondence and hospital immunisation records. The reasons for referral, role of the referring healthcare professional, advice given by the attending clinician and details of hospital-supervised immunisations given were the main factors analysed. Data was compared in 12- and 24-month blocks to assess for trends in referral and outcome. 143 referrals were received. Main reason was to request for hospital-supervised immunisation in children with egg allergy - these referrals increased in number and proportion over time (7% in 2007-2008; 31% in 2010-2011). Comparatively fewer enquiries were regarding children with uncertain/incomplete immunisation status, timing of vaccination, or interrupted schedules following non-anaphylactic reactions to immunisations. Referrals were mainly from GPs (53%) and Practice nurses (37%). Thirty-five children (24%) received hospital-supervised immunisations - 54% received MMR vaccine. Overall, there was a decreasing trend in hospital-supervised immunisations (31% in 2007-9; 13.5% in 2009-11), particularly regarding referrals for egg or food allergies (71% in 2007-9; 0% in 2009-11), in line with recommended evidence-based guidelines. This review demonstrates the utility for a local Paediatric Immunisation Advisory Service in addressing local childhood immunisation enquiries, but with great effort from the clinicians involved. However, Paediatricians should not undermine their significant advisory, educational and public health promotion role in partnering with Primary Care to deliver a robust Childhood Vaccination programme. The increasing prevalence of food and egg allergies in children may require a reinforced Public Health message to address this knowledge gap in Primary Care, in order to increase parental acceptance and compliance for optimal uptake of immunisations in the community.

Safety of Meropenem in Patients Reporting Penicillin Allergy: Lack of Allergic Cross Reactions

Over the years, meropenem has become the mainstay of empiric therapy for serious systemic infections in critically ill patients.Although we have had extensive clinical experience since 1996 using meropenem safely in treating hundreds of patients with reported allergic reactions to penicillin without any adverse events, we have not published our experience. This study was conducted to document our clinical practice experience. Accordingly, over a 12-month period we prospectively monitored 110 patients treated with meropenem reporting penicillin allergic reactions for that 12-month period. Since early empiric therapy in such patients is essential, there is often no time for penicillin skin testing. Penicillin skin testing was not done in this “real world” clinical study. Patients were divided into two groups, depending on the nature of their penicillin allergic reactions. During a 12- month period, 110 patients with non-anaphylactic (59) and anaphylactic (51) penicillin allergic reactions tolerated prolonged meropenem therapy (1-4 weeks) safely without any allergic reactions. Based on these data and our previous clinical experience, there appears to be little/no potential cross reactivity between meropenem and penicillins even in patients with a definite history of anaphylactic reactions to penicillins.To the best of our knowledge, this is the first prospective clinical study demonstrating that meropenem may be safely given to patients with known/unknown allergic reactions to penicillin, including those with anaphylactic reactions, without penicillin skin testing. We conclude that meropenem may be given safely to patients reporting a history of non-anaphylactic or anaphylactic allergic reactions to penicillins without penicillin skin testing.

Gelatin-induced T-cell activation in children with nonanaphylactic-type reactions to vaccines containing gelatin

Background: Many cases of anaphylactic or nonanaphylactic reactions have been reported to measles-mumps-rubella vaccine or its component vaccines that contain gelatin as a stabilizer. Increased levels of specific IgE antibodies to gelatin have been reported in children with anaphylactic reactions. However, IgE is not increased in cases of nonanaphylactic reaction, and the mechanisms of the reaction are still controversial. Objective: The study was aimed to elucidate the relationship between nonanaphylactic reaction and gelatin. Methods: We investigated in vitro induction of activated memory helper T cells (CD4 + CD25 + CD45RO + cells) in response to gelatin in children with nonanaphylactic reactions to vaccines containing gelatin. Results: In patients with delayed-type sensitivity to gelatin confirmed with a positive skin test response, CD4 + CD25 + CD45RO + cells were significantly more strongly induced in culture containing gelatin than in control cultures. However, there was no significant difference between cultures with gelatin and those with control solvent in patients without reactions after vaccination. Of 76 patients with nonanaphylactic reactions after immunization with vaccine containing gelatin, 61 had an increased lymphocyte stimulation index to gelatin versus control children. Conclusion: These results suggest the possibility that nonanaphylactic reactions to gelatin-containing vaccine in Japan might be mediated by delayed hypersensitivity reactions against gelatin. (J Allergy Clin Immunol 1998;102:1028-32.)

Acute Psychotic Reactions and Stress Response Syndromes Following Intramuscular Aqueous Procaine Penicillin

Acute non-anaphylactic reactions to procaine penicillin include fear of death, sensations of disintegration, perceived changes of body shape, and visual and auditory hallucinations. Fragments of the original reaction experience, or elaborations of it, feature prominently in a chronic syndrome which persists if the initial reaction is not supported emotionally or professionally. The cultural acceptance of the reality of 'mysterious' forces played a role in the syndrome. Compatible diagnostic labels were panic disorder, post-traumatic disorder, mixed phobic disorder, and depressive illness. The observed period prevalence rate is 5.9 per 1,000.

Skin Tests, Penicillin G Procaine, and Pseudoanaphylaxis

ALTHOUGH true hypersensitivity to penicillin G procaine is well recognized, there has been recent emphasis on nonallergic or pseudoanaphylactic to this preparation. 1,2 True hypersensitivity to penicillin is characterized by anaphylactoid-type reactions, while the pseudoanaphylactictype response is thought to be due to the toxic reaction from the procaine or microembolization of penicillin G procaine aggregates. Since there is no symptom complex resembling anaphylaxis and the term pseudoanaphylaxis is ambiguous, reactions will be used in this report. The nonanaphylactic reaction described by Galpin et al 1 resulted from the inadvertent intravenous administration of penicillin G procaine. In that report, readministration of penicillin was not accompanied by any adverse reaction. Skin testing to penicillin was not reported. The following case report describes ventricular irritability temporally related to intramuscular administration of procaine penicillin G. Initially, this was thought to represent some type of nonanaphylactic or toxic reaction to procaine; subsequent skin