Polythylene glycol severe allergy and SARS-CoV-2 vaccines: usefulness of testing with PEG 1500 extract.

Summary: Background. Polyethylene glycol (PEG) is being used for first time as an excipient for mRNA anti-SARS-CoV-2 vaccines containing PEG 2000, highlighting it as a potential cause of anaphylaxis. Methods. We evaluated 126 patients with moderate-high risk of allergy to SARS-CoV-2 vaccines referred to our department from March-December 2021. Skin tests were performed with PEG 1500 extract (Roxall), using a stepwise approach, with readings at 30 minutes: prick tests with 0.1%, 1% and 10% concentrations; if negative, intradermal tests with 0.0001%, 0.001% and 0.01% concentrations. The same protocol was applied to 5 healthy controls Results. Six patients had positive immediate intradermal tests with PEG 1500, all with severe PEG allergy: one with a near-fatal anaphylaxis after glucocorticoid injection containing PEG 3350 and five with systemic allergic reactions after mRNA vaccines containing PEG 2000 (Pfizer-BioNTech or Moderna). One patient developed anaphylaxis during intradermal test. These six patients were negative to polysorbate 80. The remaining 120 patients had negative tests to PEG 1500; seven had positive tests to polysorbate 80. All controls had negative tests. Conclusions. To our knowledge this is the first study describing the allergy work-up testing with PEG 1500 commercial extract in the scope of SARS-CoV-2 vaccination. The algorithm designed for skin tests revealed to be a useful tool. Severe PEG allergy was diagnosed in 5% of patients, contraindicating PEG-containing vaccines. PEG allergy was excluded in one hundred patients that afterwards took SARS-CoV-2 vaccines containing PEG 2000. Investigation should be conducted in specialized drug allergy centers..

Type I Natural Killer T Cells as Key Regulators of the Immune Response to Infectious Diseases.

The immune system must work in an orchestrated way to achieve an optimal response upon detection of antigens. The cells comprising the immune response are traditionally divided into two major subsets, innate and adaptive, with particular characteristics for each type. Type I natural killer T (iNKT) cells are defined as innate-like T cells sharing features with both traditional adaptive and innate cells, such as the expression of an invariant T cell receptor (TCR) and several NK receptors. The invariant TCR in iNKT cells interacts with CD1d, a major histocompatibility complex class I (MHC-I)-like molecule. CD1d can bind and present antigens of lipid nature and induce the activation of iNKT cells, leading to the secretion of various cytokines, such as gamma interferon (IFN-γ) and interleukin 4 (IL-4). These cytokines will aid in the activation of other immune cells following stimulation of iNKT cells. Several molecules with the capacity to bind to CD1d have been discovered, including α-galactosylceramide. Likewise, several molecules have been synthesized that are capable of polarizing iNKT cells into different profiles, either pro- or anti-inflammatory. This versatility allows NKT cells to either aid or impair the clearance of pathogens or to even control or increase the symptoms associated with pathogenic infections. Such diverse contributions of NKT cells to infectious diseases are supported by several publications showing either a beneficial or detrimental role of these cells during diseases. In this article, we discuss current data relative to iNKT cells and their features, with an emphasis on their driving role in diseases produced by pathogenic agents in an organ-oriented fashion.

Safety and Immunogenicity of an Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Subgroup of Healthy Adults in Chile.

BACKGROUND: The development of effective vaccines against coronavirus disease 2019 is a global priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine with promising safety and immunogenicity profiles. This article reports safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 years in a phase 3 clinical trial. METHODS: Volunteers randomly received 2 doses of CoronaVac or placebo, separated by 2 weeks. A total of 434 volunteers were enrolled, 397 aged 18-59 years and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity. RESULTS: The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-receptor binding domain (RBD) immunoglobulin G (IgG) were 82.22% and 84.44% in the 18-59 year age group and 62.69% and 70.37% in the ≥60 year age group, 2 and 4 weeks after the second dose, respectively. A significant increase in circulating neutralizing antibodies was detected 2 and 4 weeks after the second dose. The cellular evaluation was performed on 47 volunteers. We detected a significant induction of T-cell responses characterized by the secretion of interferon-γ (IFN-γ) upon stimulation with Mega Pools of peptides from SARS-CoV-2. CONCLUSIONS: Immunization with CoronaVac in a 0-14 schedule in Chilean adults aged ≥18 years is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T cells, and promotes the secretion of IFN-γ upon stimulation with SARS-CoV-2 antigens.

Anaphylaxis: A Decade of a Nationwide Allergy Society Registry.

BACKGROUND AND OBJECTIVES: Anaphylaxis is an acute, life-threatening, multiorgan hypersensitivity reaction. Objective: The aim of this study was to identify the causes of anaphylaxis in Portugal in order to improve our knowledge of epidemiology and management. METHODS: We implemented a nationwide notification system for anaphylaxis over a 10-year period, with voluntary reporting by allergists. Data on 1783 patients with anaphylaxis were included. Etiopathogenesis, manifestations, and clinical management were characterized in detail for both children and adults. RESULTS: The mean age was 32.7 (20.3) years, and 30% were under 18 years of age; 58% were female. The mean age at the first anaphylaxis episode was 27.5 (20.4) years (ranging from 1 month to 88 years). The main culprits of anaphylaxis were foods (48%), drugs (37%) (main trigger in adults, 48%), and hymenoptera venom (7%). The main culprit foods were shellfish (27%), fresh fruit (17%), cow's milk (16%), tree nuts (15%), fish (8%), egg (7%), and peanut (7%). The main drugs were nonsteroidal anti-inflammatory drugs (43%), antibiotics (39%), and anesthetic agents (6%). Other causes included exercise (3%), latex (2%), cold-induced anaphylaxis (2%), and idiopathic anaphylaxis (2%). Most patients (80%) were admitted to the emergency department; only 43% received adrenaline. Anaphylaxis recurred in 41% of patients (21% with ≥3 anaphylactic episodes); 7% used an adrenaline autoinjector device. CONCLUSION: Food is the leading cause of anaphylaxis in Portugal, while drugs were the main elicitors in adults. We emphasize undertreatment with adrenaline and recurrent episodes, highlighting the need to improve diagnostic and therapeutic approaches to anaphylaxis.

Antibody development for preventing the human respiratory syncytial virus pathology.

Human respiratory syncytial virus (hRSV) is the most important etiological agent causing hospitalizations associated with respiratory diseases in children under 5 years of age as well as the elderly, newborns and premature children are the most affected populations. This viral infection can be associated with various symptoms, such as fever, coughing, wheezing, and even pneumonia and bronchiolitis. Due to its severe symptoms, the need for mechanical ventilation is not uncommon in clinical practice. Additionally, alterations in the central nervous system -such as seizures, encephalopathy and encephalitis- have been associated with cases of hRSV-infections. Furthermore, the absence of effective vaccines or therapies against hRSV leads to elevated expenditures by the public health system and increased mortality rates for the high-risk population. Along these lines, vaccines and therapies can elicit different responses to this virus. While hRSV vaccine candidates seek to promote an active immune response associated with the achievement of immunological memory, other therapies -such as the administration of antibodies- provide a protective environment, although they do not trigger the activation of the immune system and therefore do not promote an immunological memory. An interesting approach to vaccination is the use of virus-neutralizing antibodies, which inhibit the entry of the pathogen into the host cells, therefore impairing the capacity of the virus to replicate. Currently, the most common molecule targeted for antibody design against hRSV is the F protein of this virus. However, other molecular components of the virus -such as the G or the N hRSV proteins- have also been explored as potential targets for the control of this disease. Currently, palivizumab is the only monoclonal antibody approved for human use. However, studies in humans have shown a protective effect only after the administration of at least 3 to 5 doses, due to the stability of this vaccine. Furthermore, other studies suggest that palivizumab only has an effectiveness close to 50% in high-risk infants. In this work, we will review different strategies addressed for the use of antibodies in a prophylactic or therapeutic context and their ability to prevent the symptoms caused by hRSV infection of the airways, as well as in other tissues such as the CNS.

Histological findings after non-ablative Er:YAG laser therapy in women with severe vaginal atrophy.

Objective: The aim of this study was to evaluate the effect of non-ablative erbium vaginal laser treatment on vaginal mucosa tissue affected by severe atrophy.Methods: Ten patients with severe genitourinary syndrome of menopause were treated with two sessions of the non-ablative erbium-doped yttrium aluminium garnet laser (Er:YAG laser) separated by 4 weeks. Vaginal biopsies were performed before and 3 months after the second treatment. The improvement in vaginal atrophy was assessed using multiple measuring tools before and 6 months after the treatment. The degree of patients' satisfaction was also assessed.Results: Microscopic examination showed significant changes in the main structural components of the vaginal wall mucosa after two non-ablative Er:YAG laser sessions. The epithelial thickness increased from 45 µm (10-106 µm) to 153 µm (97-244 µm) measured 3 months after the final laser treatment. Vaginal atrophy improved in all patients by all measured outcomes. The degree of patient satisfaction was very high (3.6 on the Likert four-point scale). No adverse events or complications were observed in any of the sessions. Conclusion: The non-ablative Er:YAG laser seems to be a safe and effective method to increase epithelial thickness of the vaginal mucosa in patients with severe vaginal atrophy.

Safety of vaginal erbium laser: A review of 113,000 patients treated in the past 8 years.

Background: Energy-based devices are becoming a popular option for minimally invasive vaginal procedures. The aim of this study was to obtain information on the frequency of occurrence of adverse effects (AEs) related to vaginal erbium laser (VEL™) treatment.Materials and methods: The global survey was conducted among practitioners using the non-ablative VEL™ (Fotona, Ljubljana, Slovenia). Users were invited to provide the number of patients treated with VEL™ and the number of observed laser-related AEs.Results: The survey was conducted from August 2018 to April 2019. Responses from 535 practitioners were collected, with a total of 113,174 patients treated in the period from 2012 to 2019. Out of 535 respondents, 160 (30%) shared detailed information about the indications they treated in a population of 62,727 patients, whereas 188 (35%) respondents provided information on the frequency of AEs observed in their treated population of 43,095 patients. All observed AEs were mild to moderate, transient and appeared with low frequencies.Conclusions: Minimally invasive thermal-only laser treatment using the non-ablative VEL™ procedures appears to be safe and the incidence of AEs is low.

Tree Nuts Anaphylaxis in Preschool Age Children.

Summary: Introduction. The incidence of food-induced anaphylaxis (FIA) is increasing in young children. Although the commonest culprits are cow's milk and egg, FIA to tree nuts (TNs) have been increasing. Objective. Characterization of children referred to our allergy department due to TNs-induced anaphylaxis (TNs-FIA) during preschool age. Materials and methods. We have retrospectively included 25 children with clinical history of preschool TNs-FIA, proven by allergological work-up. TNs sensitization was assessed by skin prick tests and/or specific IgE. Results. The mean age of the first anaphylactic episode was 3.1±1.2 years. The majority (92%) had an allergic disease (52% asthma). The implicated TNs were cashew (11 children), walnut (8), pine nut (5), hazelnut (2) and almond (1). The reaction occurred after the first known ingestion in 68%. In 92%, symptoms appeared within 30 minutes after exposure. The most frequent clinical symptoms were mucocutaneous (96%), respiratory (80%) and gastrointestinal (52%). Twenty-one children were admitted to the emergency department, although only 48% were treated with epinephrine. An underneath IgE-mediated mechanism was proven in all cases. Immunologic cross-reactivity with other TNs was identified in 84%, and with peanut in 36%. Overall, in our center, TNs-FIA represents 18% of all causes of FIA. Conclusions. In preschool age children with TNs-FIA, cashew and walnut were the commonest implicated nuts. Most reactions occurred briefly after exposure to minimal amounts of TNs, demonstrating the high potency of these allergens. About one-third also had peanut sensitization. Potentially life-threatening TNs allergy can occur early in childhood and adequate management should be undertaken.

Successful oral desensitization in children with cow's milk anaphylaxis: Clinical and laboratory evaluation up to nine-years follow-up.

INTRODUCTION: Cow's milk protein allergy (CMPA) is the most common food allergy in children worldwide. Some children have severe and persistent CMPA, with near-fatal reactions after exposure to trace amounts of cow's milk-proteins (CMP). Strict avoidance diet is difficult, negatively affects quality of life and represents a conservative approach. Therefore, different therapeutic strategies are necessary. OBJECTIVE: We aimed to assess long-term efficacy and safety of oral immunotherapy (OIT) in children with severe and long-lasting IgE-mediated CMPA. MATERIALS AND METHODS: The authors present four case reports of patients with CMPA who underwent CMP-OIT, that have been under long-term follow-up up to nine years. We provide information about the clinical and laboratory evaluation. Skin prick tests (SPT), specific IgE and IgG4 were performed before, during, and after OIT. Immune profile after OIT was assessed by flow cytometry (lymphocyte subsets, regulatory T and B cells). RESULTS: The success rate was 100%, and all patients currently have a free diet with minimal diary ingestion of 200mL CMP or equivalent. Specific IgE levels and SPT to CMP have progressively decreased, and specific IgG4 levels have increased. CD4+CD25+CD127-/dim regulatory T cells were increased after OIT. CONCLUSIONS: OIT ensured a clinical tolerance state after up to nine years, confirmed by both clinical and immune profile, allowing a diet without restrictions, with high satisfaction from patients and caregivers. We emphasize that OIT should be performed only by allergy experts in the hospital setting, and that only motivated families should be enrolled, since it is essential to ensure CMP daily intake at home.

Anaphylaxis to beta-lactam antibiotics at pediatric age: Six-year survey.

INTRODUCTION: Beta-lactams are the most frequently used antibiotics in pediatric age. Anaphylactic reactions may occur and need to be properly studied, but studies in children are scarce. OBJECTIVE: Characterization of case reports of anaphylaxis in children referred to an allergy department with suspected beta-lactams hypersensitivity. MATERIALS AND METHODS: Retrospective analysis of all children referred to our Drug Allergy Center with suspected beta-lactams hypersensitivity between January 2011 and December 2016. Description of the drug allergy work-up performed studied according to standardized diagnostic procedures of ENDA/EAACI, including specific-IgE assay, skin prick and intradermal tests and diagnostic/alternative drug challenge tests. RESULTS: 146 children with suspected beta-lactams hypersensitivity were studied, and in 21 (14.4%) the diagnosis was confirmed. In all of them, except for three children, an alternative beta-lactam was found. In seven children (33.3% of those with confirmed beta-lactams hypersensitivity) anaphylaxis was confirmed, and all of them described reactions with cutaneous and respiratory or gastrointestinal involvement. The culprit drug was amoxicillin in six and flucloxacillin in one. In this sample, we also performed oral challenge with cefuroxime, being negative in all cases. Almost all cases of confirmed anaphylaxis (six from seven cases) were IgE mediated, with positive skin tests despite negative serum specific-IgE. CONCLUSIONS: Allergic reactions to beta-lactams, although rare in children, require a detailed clinical history and a specialized drug allergy work-up to allow a correct diagnosis as well as to avoid the possibility of a potential life-threatening reaction and provide alternative drugs.

The GM2 ganglioside inhibits iNKT cell responses in a CD1d-dependent manner.

Invariant natural killer T (iNKT) cells are a subset of T lymphocytes that recognize lipid antigens presented on CD1d molecules at the surface of antigen-presenting cells. GM2 is a glycosphingolipid abundant in cellular membranes and known to bind CD1d molecules, but the functional consequences of this binding are not completely clarified. Herein, we analyzed the effect of GM2 in iNKT cell activation. We found that culturing antigen-presenting cells or total peripheral blood mononuclear cells with GM2 did not induce activation of human iNKT cells, implying that this lipid is not antigenic for human iNKT cells. To investigate if this lipid could inhibit iNKT cell activation, we simultaneously incubated antigen-presenting cells with GM2 and the iNKT cell antigen α-Galactosylceramide (α-GalCer) and used them to stimulate iNKT cells. We found that GM2 reduced human iNKT cell activation in a dose-dependent manner. An explanation for this effect could be a direct competition of GM2 with antigenic lipids for CD1d binding. This was demonstrated by the use of an antibody (L363) that stains mouse CD1d:α-GalCer complexes, as in the presence of GM2 the amount of CD1d:α-GalCer complexes are reduced. We further explored the consequences of chronic GM2 overload on human iNKT cells by analyzing iNKT cells in patients diagnosed with GM2 gangliosidoses. We found that pediatric patients present a higher frequency of circulating CD4+ iNKT cells and concomitant lower frequency of CD4-CD8- iNKTs. A lower percentage of iNKT cells expressing the NK marker CD161 was also observed in these patients. In contrast, in two adult patients studied, no differences on iNKT cell phenotype were observed. Altogether, this study uncovers a new role for GM2 in the modulation of iNKT cell activation, thus strengthening the central role of lipid metabolism in iNKT cell biology.

Enteric viruses' dissemination in a private reserve of natural heritage.

This study aimed to assess anthropogenic impact of surrounding population in the Private Reserve of Natural Heritage at Pantanal, the world's largest freshwater wetland ecosystem located in the centre of South America. Viral aetiological agents of acute gastroenteritis as rotavirus A (RVA), noroviruses, human adenoviruses, klassevirus and of hepatitis, as hepatitis A virus, were investigated in different aquatic matrices. Annual collection campaigns were carried out from 2009 to 2012, alternating dry and rainy seasons. Viral particles present in the samples were concentrated by the adsorption-elution method, with negatively charged membranes, and detected by qualitative and quantitative PCR. From a total of 43 samples at least one virus was detected in 65% (28) of them. Viruses were detected in all matrices with concentrations ranging from 2 × 102 to 8·3 × 104 genome copies per litre. A significant higher RVA frequency was observed in the dry season. Our data revealing dissemination of human enteric viruses in water matrices both inside and outside the reserve could be useful to trace faecal contamination in the environment and to minimize the risk of infection by exposure of susceptible individuals. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is part of a collaborative project designed to investigate the environmental and health conditions of the Private Reserve of Natural Heritage at Pantanal, the largest seasonally flooded wetland in the world. The project aimed to promote health and quality of human and wildlife extending technical-scientific knowledge about pathogens present in the region. By assessing the occurrence of human enteric viruses in different water matrices we demonstrated the anthropogenic impact of surrounding population and pointed out the potential risk of infection by exposure of susceptible individuals.

Drug-induced anaphylaxis: seven-year single-center survey.

Summary: Background and Objective. Drug-induced anaphylaxis (DIA) is the most common cause of fatal anaphylaxis. We aimed to characterize patients with DIA and their allergological workup. Methods. Systematic review of patients with history of DIA referred to our center over 7 years. Results. Included 125 patients (10% pediatric age), being 36 years the median age of first episode (from 1 to 74 years). The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (43%), antibiotics (42%) and anesthetic agents (6%). In 24% the reactions occurred in hospital setting and 14% perioperative. The etiology was confirmed in 75% through allergological workup. Conclusions. NSAIDs and antibiotics were responsible for most of DIA. The heterogeneity of mechanisms, the severity of the reactions and the lack of standardized in vivo and/or in vitro tests for some drugs do not allow to confirm the diagnosis in all cases. Patients with DIA should be evaluated in specialized centers to perform accurate diagnosis, to prevent recurrence and to find safe alternatives.

Hypersensitivity to beta-lactam antibiotics: a three-year study.

BACKGROUND: Beta-lactams antibiotics (BL) are the most frequent elicitors of allergic drug reactions. The aim of our study was to characterize the patients referred with suspected hypersensitivity (HS) to BL. METHODS: Over a three-year period (2011-2013), a total of 234 adult and paediatric patients (pts) with suspected HS to BL were investigated according to the European Network for Drug Allergy guidelines. RESULTS: HS to BL was confirmed in 43 pts (18%), without differences between adult and paediatric pts; anaphylaxis was reported by 20 pts. Diagnosis was ascertained by: serum-specific IgE antibodies in 5 pts (12%), skin prick tests in 5 (12%), intradermal tests in 25 (58%), 3 with delayed reading, and the remaining 8 (18%) by drug provocation tests. Penicillins / derivatives were the culprit drugs in 39 pts, mainly amoxicillin, and cephalosporins in 4. CONCLUSION: In most of these patients with suspected HS to BL, allergological work-up was negative and HS was excluded. One fourth of confirmed cases had a plausible non-IgE mediated mechanism.

Hysteresis and change of transition temperature in thin films of Fe{[Me2Pyrz]3BH}2, a new sublimable spin-crossover molecule.

Thin films of the spin-crossover (SCO) molecule Fe{[Me2Pyrz]3BH}2 (Fe-pyrz) were sublimed on Si/SiO2 and quartz substrates, and their properties investigated by X-ray absorption and photoemission spectroscopies, optical absorption, atomic force microscopy, and superconducting quantum interference device. Contrary to the previously studied Fe(phen)2(NCS)2, the films are not smooth but granular. The thin films qualitatively retain the typical SCO properties of the powder sample (SCO, thermal hysteresis, soft X-ray induced excited spin-state trapping, and light induced excited spin-state trapping) but present intriguing variations even in micrometer-thick films: the transition temperature decreases when the thickness is decreased, and the hysteresis is affected. We explain this behavior in the light of recent studies focusing on the role of surface energy in the thermodynamics of the spin transition in nano-structures. In the high-spin state at room temperature, the films have a large optical gap (∼5 eV), decreasing at thickness below 50 nm, possibly due to film morphology.

Thermal conditions in freezing chambers and prediction of the thermophysiological responses of workers.

The present work is dedicated to the assessment of the cold thermal strain of human beings working within freezing chambers. To obtain the present results, both field measurements and a numerical procedure based on a modified version of the Stolwijk thermoregulation model were used. Eighteen freezing chambers were considered. A wide range of physical parameters of the cold stores, the workers clothing insulation, and the working and recovering periods were observed. The combination of these environmental and individual parameters lead to different levels of thermal stress, which were grouped under three categories. Some good practices were observed in the field evaluations, namely situations with appropriate level of clothing protection and limited duration of exposure to cold avoiding unacceptable level of hypothermia. However, the clothing ensembles normally used by the workers do not provide the minimum required insulation, which suggests the possibility of the whole body cooling for levels higher than admissible. The numerical predictions corroborate the main conclusions of the field survey. The results obtained with both methodologies clearly show that, for the low temperature of the freezing chambers, the clothing insulation is insufficient, the exposure periods are too long, and the recovering periods are inadequate. Thus, high levels of physiological strain can indeed be reached by human beings under such working environments.

One-year survey of paediatric anaphylaxis in an allergy department.

AIM: To determine the frequency of anaphylaxis in an allergy outpatient department, allowing a better understanding regarding aetiology, clinical manifestations and management, in children and adolescents. METHODS: From among 3646 patients up to 18 years old observed during one-year period, we included those with history of anaphylaxis reported by allergists. RESULTS: Sixty-four children had history of anaphylaxis (prevalence of 1.8%), with mean age 8.1±5.5 years, 61% being male. Median age of the first anaphylactic episode was 3 years (1 month-17 years). The majority of patients had food-induced anaphylaxis (84%): milk 22, egg 7, peanut 6, tree nuts 6, fresh fruits 6, crustaceans 4, fish 4 and wheat 2. Food-associated exercise-induced anaphylaxis was reported in 2 adolescents. Drug-induced anaphylaxis occurred in 8%: 4 non-steroidal anti-inflammatory drugs and 1 amoxicillin. Three children had cold-induced anaphylaxis, one adolescent had anaphylaxis to latex and one child had anaphylaxis to insect sting. The majority (73%) had no previous diagnosis of the etiologic factor. Symptoms reported were mainly mucocutaneous (94%) and respiratory (84%), followed by gastrointestinal (42%) and cardiovascular (25%). Fifty-one patients were admitted to the emergency department, although only 33% were treated with epinephrine. Recurrence of anaphylaxis occurred in 26 patients (3 or more episodes in 14). CONCLUSIONS: In our paediatric population, the main triggering agent of anaphylaxis was IgE-mediated food allergy. Epinephrine is underused, as reported by others. Often, children have several episodes before being assessed by an allergist. We stress the importance of systematic notification and improvement of educational programmes in order to achieve a better preventive and therapeutic management of this life-threatening entity.

Retrospective study of the medium-chain acyl-CoA dehydrogenase deficiency in Portugal.

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the commonest genetic defect of mitochondrial fatty acid ß-oxidation. About 60% of MCADD patients are homozygous for the c.985A>G (p.Lys329Glu) mutation in the ACADM gene (G985 allele). Herein, we present the first report on the molecular and biochemical spectrum of Portuguese MCADD population. From the 109 patients studied, 83 were diagnosed after inclusion of MCADD in the national newborn screening, 8 following the onset of symptoms and 18 through segregation studies. Gypsy ancestry was identified in 85/109 patients. The G985 allele was found in homozygosity in 102/109 patients, in compound heterozygosity in 6/109 and was absent in one patient. Segregation studies in the Gypsy families showed that 93/123 relatives were carriers of the G985 allele, suggesting its high prevalence in this ethnic group. Additionally, three new substitutions-c.218A>G (p.Tyr73Cys), c.503A>T (p.Asp168Val) and c.1205G>T (p.Gly402Val)-were identified. Despite the particularity of the MCADD population investigated, the G985 allele was found in linkage disequilibrium with H1(112) haplotype. Furthermore, two novel haplotypes, H5(212) and H6(122) were revealed.

Drug-induced anaphylaxis survey in Portuguese Allergy Departments.

BACKGROUND AND OBJECTIVE: Drug-induced anaphylaxis is an unpredictable and potentially fatal adverse drug reaction. The aim of this study was to identify the causes of drug-induced anaphylaxis in Portugal. METHODS: During a 4-year period a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 313 patients with drug anaphylaxis were received and reviewed. Statistical analysis included distribution tests and multiple logistic regression analysis to investigate significance, regression coefficients, and marginal effects. RESULTS: The mean (SD) age of the patients was 43.8 (17.4) years, and 8.3% were younger than 18 years. The female to male ratio was 2:1.The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (47.9% of cases), antibiotics (35.5%), and anesthetic agents (6.1%). There was a predominance of mucocutaneous symptoms (92.2%), followed by respiratory symptoms (80.4%) and cardiovascular symptoms (49.0%). Patients with NSAID-induced anaphylaxis showed a tendency towards respiratory and mucocutaneous manifestations. We found no significant associations between age, sex, or atopy and type of drug. Anaphylaxis recurrence was observed in 25.6% of cases, and the risk was higher when NSAIDs were involved. CONCLUSIONS: NSAIDs were the most common cause of anaphylaxis in this study and were also associated with a higher rate of recurrence. We stress the need for better therapeutic management and prevention of recurring episodes of drug-induced anaphylaxis.