Allergy and anaphylaxis

BACKGROUND:
Allergy to Hymenoptera venom has a low prevalence in the general population, but in beekeepers could be as high as 42%. The exposure to bee sting confers an occupational allergic risk to beekeepers, causing them sensitization during the first years, which if continues for a long time may induce immune tolerance.

OBJECTIVE:
To know some risk factors of allergic reactions to honey-bee stings in a sample of beekeepers through a self-applied questionnaire.

METHODS:
A self-applied questionnaire was performed by beekeepers from the whole country, with questions about age, sex, time of beekeeping activities, average number of stings per month and types of post-sting reactions. The relative risk and the odds ratio were calculated for some risk factors.

RESULTS:
A total of 1541 questionnaires were completed. The average age was 37 years. There were 1289 (84%) men and 252 women. The average time of exposure to honey-bee sting was 7.2 years, and the number of stings per month averaged 33. There was atopic family history in 14.5% of the beekeepers, and 20% of them had personal atopy. In 125 (8%) beekeepers there were local allergic reactions and in 32 (2%) there were systemic allergic reactions. The relative risk for allergy to honey-bee venom in whom had atopic family history was 3.9 (CI 1.7-9.2), in those with less than 4 stings per month was 3.2 (CI 1.12-9.33), in those with more than 20 years exposure was 0.97 (CI 0.95-0.98) and for those over 50 years of age was 0.32 (CI 0.1-0.8). Beekeepers with less than 10 years of exposure had OR of 4.33 (CI 0.5-33.9).

CONCLUSIONS:
The risk factors observed for hypersentivity to honey-bee venom in beekeepers were: atopic family history, less than 10 years of exposure and less than 4 stings per month. As probable protective factors we found the exposure for over 20 years and persons older than 50 years of age.

BACKGROUND:
Honeybee stings can cause toxic and allergic reactions that may lead to severe symptoms, and sometimes to death. Mexico is the third worldës honey country exporter and sixth producer. Due to the arrival of Africanized bees into Mexico in 1986, the National Program for Control of Africanized Bee (NPCAB) was created, in order to reduce the socioeconomic and sanitary impact from the new bee species.

OBJECTIVE:
To report deaths related to honey-bee sting in Mexico, from 1988 to 2009.

METHODS:
Reports gathered from offices of the National Program for the Control of Africanized Honey-Bee throughout the country, were used to show the number of deaths related to honey-bee stings which occurred in Mexico from 1988 to 2009.

RESULTS:
People suffering from multiple honey-bee stings were reported in all the states of the country. Between 1988 and 1998 there were 360 honey-bee related accidents, involving over 5000 people. From 1988 to 2009 there were 480 demised persons with an annual average of 21.8. Regarding age, people over 50 years were the most affected ones. The largest number of fatal cases, 340, occurred from 1990 to 1999, with an annual average of 34, and between 2000 and 2009, the number of cases decreased to 118.

CONCLUSIONS:
There was an average of 21 annual death cases related to honey-bee stings from 1988 to 2009. Toxic reactions caused by multiple stings are the most likely cause of death in the majority of cases. Fatal cases occurred mainly in people older than 50 years. There was a decrease in the mortality rate associated to honey-bee stings in the last decade.

People with allergies know how important it is to stay away from allergens to which they are sensitive.  But what if those substances are in your food and you don't know it?  The “natural flavor” loophole in ingredient labeling means that any food which lists “natural flavors” as an ingredient is potentially hazardous to sensitive people, and should be approached with caution.

Ce este șocul anafilactic? Pentru unii oameni cu alergii severe, atunci când sunt expuși la ceva la care sunt alergici, pot experimenta o reacție care poate pune viața în pericol, numită anafilaxie. Drept urmare, sistemul lor imunitar eliberează substanțe chimice care inundă organismul. Acest lucru poate duce la șoc anafilactic. Când corpul tău intră într-un șoc anafilactic, tensiunea arterială scade brusc și căile respiratorii se îngustează, eventual blocând respirația normală. Această condiție este periculoasă. Dacă nu este tratat imediat, poate duce la complicații grave și poate fi chiar fatal. Care sunt simptomele șocului anafilactic? Veți experimenta simptome de anafilaxie înainte de apariția șocului anafilactic. Aceste simptome nu trebuie ignorate. Simptomele anafilaxiei includ: •reacții cutanate, cum ar fi urticarie, piele înroșită sau paloare •dintr-o dată simțindu-mă prea cald •senzația că ai o gât în gât sau dificultăți înghițirii •greață, vărsături sau diaree •durere abdominală •un puls slab și rapid •nasul curgător și strănutul •limba sau buzele umflate •respirație șuierătoare sau dificultăți de respirație •un sentiment că ceva nu este în regulă cu corpul tău •furnicături ale mâinilor, picioarelor, gurii sau scalpului Dacă credeți că întâmpinați o anafilaxie, solicitați imediat asistență medicală. Dacă anafilaxia a progresat până la șoc anafilactic, simptomele includ: •luptând să respire •ameţeală •confuzie •senzație bruscă de slăbiciune •pierderea conștienței Care sunt cauzele și factorii de risc ai anafilaxiei?

L’anaphylaxie est une réaction d’hypersensibilité (ou allergique) systémique, généralisée, sévère, pouvant engager le pronostic vital. Elle survient après un délai de quelques minutes à quelques heures suivant l’exposition à un facteur déclenchant. Elle se caractérise par l’apparition brutale d’une atteinte des voies aériennes, supérieures ou inférieures, ou cardio-vasculaire potentiellement fatale. Elle est généralement, mais pas systématiquement, associée à une atteinte cutanéomuqueuse [3]. Des signes digestifs peuvent également être présents. Les symptômes dépendent des organes impactés et évoluent rapidement.
Les recommandations internationales se sont accordées sur le terme d’anaphylaxie et n’utilisent plus l’expression « choc anaphylactique » qui focalise sur l’atteinte cardiovasculaire et est responsable d’une sous-évaluation des symptômes respiratoires et digestifs, à l’origine d’un défaut de diagnostic. De plus, l’identification parfois difficile d’un facteur déclenchant et la symptomatologie atypique ou rapidement résolutive participent à une utilisation insuffisante de l’adrénaline (moins d’un tiers des anaphylaxies) [2,4,5]. Enfin, à la sortie de la structure des urgences (SU), une prescription de stylo auto-injecteur d’adrénaline (AIA) et une orientation vers une consultation allergologique semblent insuffisamment réalisées. Ces constats mettent en évidence la nécessité de sensibiliser les professionnels de santé. De nouvelles recommandations européennes et internationales ont récemment été rédigées. Ces éléments justifient la rédaction de recommandations en langue française concernant la prise en charge de l’anaphylaxie en SU.

Ces recommandations formalisées d’experts ont été élaborées par la Société française de médecine d’urgence, avec la collaboration de la Société française d’allergologie, le Groupe francophone de réanimation et urgences pédiatriques, et le soutien de la Société pédiatrique de pneumologie et d’allergologie. Leur but est de sensibiliser les urgentistes au diagnostic précoce de cette réaction d’hypersensibilité sévère potentiellement fatale, aux particularités liées à l’âge et à l’identification de ses facteurs de risque. Le diagnostic d’anaphylaxie est clinique et repose sur l’utilisation des critères cliniques de Sampson. Les auteurs proposent des fiches d’aide à la régulation médicale ainsi que des critères de tri pour les infirmières organisatrices de l’accueil. Comme le soulignent les recommandations internationales, le traitement principal repose sur l’administration précoce d’adrénaline par voie intramusculaire. En présence d’un auto-injecteur d’adrénaline (AIA), le médecin régulateur du service d’aide médical urgente (Centre 15) doit favoriser son utilisation sans attendre l’arrivée des secours. Puis en fonction du contexte, le traitement repose sur l’éviction du facteur déclenchant, une position d’attente adaptée, une oxygénothérapie et, en fonction des symptômes, un remplissage intraveineux, des aérosols de bronchodilatateur ou d’adrénaline. La gravité du pronostic et le caractère imprévisible de l’évolution justifient l’engagement d’une unité mobile hospitalière. Une surveillance minimale de six heures est indiquée en structure hospitalière. Le dosage de la cinétique de la tryptase contribue au diagnostic, a posteriori. À la sortie de l’hôpital, le patient doit avoir une prescription de trousse d’urgence (comportant au minimum deux AIA et des β2-mimétiques), des consignes écrites et un compte rendu écrit détaillé. Une orientation vers une consultation allergologique est indispensable.

Background: Challenge tests for food-dependent exercise-induced anaphylaxis (FDEIA) carry some risk and have a high rate of false negatives. Our aim was to explore the usefulness of an in vitro immunodepletion assay and an allergen microarray test in the identification of IgE-mediated cross-reactive food allergens in patients with suspected FDEIA or food-dependent exercise-induced urticaria and panallergen sensitization. Methods: Three patients with a history of food dependent exercise induced urticaria/anaphylaxis and food panaller-gen sensitization in whom a food-exercise challenge was not feasible were selected: a 25-year-old man with choliner-gic urticaria who experienced generalized urticaria and angioedema during a soccer match after drinking a peach-based soft drink; a 19-year-old woman with allergic rhinitis and controlled asthma who experienced anaphylactic shock while playing soccer, having eaten walnuts in the previous 90 min; and a 57-year-old man with baker's asthma who experienced four episodes of anaphylaxis during exercise after ingesting wheat-containing food. All individuals underwent a diagnostic work-up with skin prick tests, specific IgE (sIgE) and ImmunoCAP ISAC test. For the in vitro immunodepletion procedure, patients' serum was pre-incubated with the suspected native allergen (peach, walnut, or wheat) in solid phase (ImmunoCAP). The eluted serum, containing unbound IgE, was collected and samples were re-tested using Immunocap ISAC 112 and compared with baseline results. Results: All individuals were sensitized to lipid transfer proteins. The first patient was sensitized to Pru p 3, Cor a 8, Jug r 3, and Ara h 9; after pre-incubation with peach there was 100% depletion of sIgE to all components. The second patient was sensitized to Pru p 3, Cor a 8, Jug r 3, and Ara h 9; immunodepletion with walnut depleted sIgE to Ara h 9 by 67%, Pru p 3 and Pla a 3 (60%), Art v 3 (75%), Jug r 3 (88%), and Cor a 8 (100%). The third patient was sensitized to Pru p 3, Jug r 3, Ara h 9, and Tri a 14; immunodepletion with wheat depleted Tri a 14 only (100%). Conclusions: In vitro immunodepletion might be a useful diagnostic tool in food dependent exercise induced urticaria/anaphylaxis with panallergen sensitization, particularly for identifying the culprit allergen and guiding dietary elimination recommendations.

These formalized expert guidelines were written by the French Society of Emergency Medicine (SFMU), in partnership with the French Allergology Society (SFA) and the French Speaking Group in Pediatric Intensive Care and Emergency (GFRUP). Their goal is to educate emergency physicians to early diagnosis of this potentially fatal reaction of severe hypersensitivity, the specific features associated with age, and risk factors identification. Anaphylaxis diagnosis is clinical and used Sampson’s clinical criteria. The authors offer helps sheets for emergency medical services dispatch and triage criteria for emergency department nurses. As underlined by the international guidelines, the main treatment is early administration of intramuscular epinephrine. If an epinephrine auto-injector is available, the emergency medical services dispatch center on-call physician (112-call) should encourage its immediate use. The second line of treatment is based on the eviction of the triggering factor, the appropriate waiting position, oxygen therapy, and depending on the symptoms, fluid therapy, bronchodilator and epinephrine nebulization. The severity of the prognosis and the unpredictability of developments justify the deployment of a mobile intensive care unit. A minimum six-hour hospital observation is indicated. Tryptase kinetics evaluation contributes to a posteriori diagnosis. At emergency department discharge, the patient must have a prescription of an emergency kit (containing two epinephrine
auto-injectors and β2-agonists), written instructions and a detailed written hospital report. A specialized consultation with an allergologist is essential after the emergency department discharge.

This article was initially published as a French version in Annales Françaises de Médecine d’Urgence (Gloaguen A, Poussel G, Cesareo E, et al. Ann Fr Med Urg 2016; 6: 342-64; erratum published in Ann Fr Med Urg, Erratum to: Prise en charge de l’anaphylaxie en médecine d’urgence. Recommandations de la Société française de médecine d’urgence (SFMU) en partenariat avec la Société française d’allergologie (SFA) et le Groupe
francophone de réanimation et d’urgences pédiatriques (GFRUP), et le soutien de la Société pédiatrique de pneumologie et d’allergologie (SP2A)

The Food and Drug Administration (FDA) has recently authorized the two messenger RNA (mRNA) vaccines BNT162b2 and mRNA-1273 for emergency use against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the COVID-19 coronavirus disease. BNT162b2 and mRNA-1273 vaccines were developed by Pfizer-BioNTech and Moderna, respectively, in 2020. The United Kingdom, Bahrain, Canada, Mexico, United States, Singapore, Oman, Saudi Arabia, Kuwait, and European Union began their vaccination programs with the BNT162b2 vaccine, while the United States and Canada also started the mRNA-1273 vaccination program in mid December 2020. On 28th December 2020, studies reported severe allergic reactions in people who received the BNT162b2, and few people who received the mRNA-1273 vaccine. Authors of the letter thus attempt to explore possible causes of anaphylaxis following COVID-19 vaccination.

Purpose of review Food-dependent exercise-induced anaphylaxis (FDEIA) is a form of anaphylaxis that occurs associated with exercise, in which symptoms develop by the combination of food ingestion and physical activity. We aimed to review and discuss the main clinical recommendations for management of FDEIA, focusing on individual factors. Recent findings New diagnostic strategies have been developed to optimize the accuracy of provocation challenges, taking in consideration augmenting factors, such as alcohol or non-steroidal anti-inflammatory drugs. However, FDEIA is still insufficiently diagnosed and a high index of clinical suspicion is usually required. Management is complex and based on preventing the reaction and education of the patient, followed by treatment of the acute episode. Several pharmacological strategies for prophylactic treatment have been proposed; however, they are based mainly in low quality of evidence. Summary For management of FDEIA, the culprit food allergen should be avoided at least 4 h before exercise and the individual needs to be educated on how to practice exercise in safe conditions, particularly recognizing the importance of stopping exercise or physical activity at the earliest manifestation of symptoms. This prevention strategy should be developed accordingly to the specific characteristics of the individual and food allergen involved. Due to the difficulty in avoiding and preventing a reaction, pharmacological prophylactic treatment options, namely antihistamines, montelukast, oral cromolyn sodium, misoprostol, and omalizumab, have been proposed. However, they do not replace current recommendations. The risk and quality-of-life impact of FDEIA warrants more accurate diagnostic tools and management strategies. The improvement on the knowledge of the mechanisms mediating FDEIA will help to find new prevention and treatment targets.

Studies with murine models demonstrate 2 pathways of
systemic anaphylaxis: one mediated by IgE, FceRI, mast cells,
histamine, and platelet-activating factor (PAF), and the other
mediated by IgG, FcgRIII, macrophages, and PAF. The former
pathway requires much less antibody and antigen than the
latter. As a result, IgG antibody can block IgE-mediated
anaphylaxis induced by small quantities of antigen without
mediating FcgRIII-dependent anaphylaxis. The IgE pathway is
most likely responsible for most human anaphylaxis, which
generally involves small amounts of antibody and antigen;
similarities in the murine and human immune systems suggest
that the IgG pathway might mediate disease in persons
repeatedly exposed to large quantities of antigen. Mice, like
human subjects, can experience IgE/FceRI/mast cell–mediated
gastrointestinal and systemic anaphylaxis in response to
ingested antigen. Gastrointestinal symptoms depend on
serotonin and PAF; mediator dependence of systemic
symptoms has not been determined. Both local and systemic
anaphylaxis induced by ingested antigens might be blocked by
IgA and IgG antibodies. IL-4 and IL-13 signaling through the
IL-4 receptor a chain, in addition to promoting the
mastocytosis and IgE antibody production that mediate most
human anaphylaxis, exacerbates the effector phase of
anaphylaxis by increasing target cell responsiveness to
vasoactive mediators. As a result, IL-4 receptor a chain
antagonists might be particularly effective suppressors of
anaphylaxis.

Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) belongs to the
mitogen-activated protein kinase (MAPK) family and plays an important role in many
biological contexts. JNK is deeply involved in several serious human disorders,
including inflammation, obesity, diabetes, neuronal disease and cancer. Accordingly,
JNK has been recognized as an appropriate target for the treatment of these diseases,
and much effort has been expended over the past 15 years to isolate JNK inhibitors that
can inactivate this kinase. In 2001, the compound SP600125 was reported as the first
JNK-specific inhibitor. Many researchers have subsequently employed SP600125 in in
vitro and in vivo models to evaluate whether certain disease-associated events are
JNK-dependent. Indeed, more than 1300 studies citing the use of SP600125 as a JNK
inhibitor in cell cultures and animal models have been reported. However, although
SP600125 has been employed successfully to inhibit JNK in several situations, there
have been questions about its specificity for JNK. In this article, we review both the
usefulness of SP60125 as a JNK inhibitor and the limitations to its specificity.

The actual incidence of anaphylaxis is unknown. Periodical study of the anaphylaxis in different countries will raise the awareness to improve further the prevention and care.
To investigate anaphylaxis among inpatients in the previous decade, we conducted a retrospective study of adult patients between 1992 and 2001 at a tertiary care center in Bangkok.
Of 448,211 admissions, 80 events of anaphylaxis in 79 patients (0.017%) were found. The incidence had increased from 2.6 to 46 per 100,000 inpatients. Mean age +/- SD was 36 +/- 16 years-old, with an equal male:female ratio. Drugs, mainly antibiotics and nonsteroidal anti-inflammatory agents, (48%) and food (31%) were the most common causes. Over-the-counter medication and multiple drug use were responsible for up to a half of the unspecified drug causes. There was no fatality. 84% received epinephrine, but in only 7% it was given intramuscularly. Fifteen cases (20%) had a history of prior anaphylaxis, nonetheless only one had received prefilled epinephrine.
The rise in the incidence of anaphylaxis over the two decades of the study period is alarming. Raising the awareness of anaphylaxis management among healthcare providers and the public is warranted.

OBJECTIVES:
Food allergy is an increasing burden worldwide and is a common problem within paediatric populations, affecting 5%-8% of children. Anaphylaxis caused by food proteins is a potentially life-threatening condition and all healthcare practitioners should be aware of its recognition and management. Russia is the largest country in Europe but it is still unknown whether physicians are prepared to diagnose and manage food-induced anaphylaxis effectively. We aimed to examine physicians' knowledge of diagnosis and management of food-induced anaphylaxis.

SETTING, POPULATION AND OUTCOMES:
A survey was designed and published online at VrachiRF.ru website (for registered Russian-speaking practicing physicians). We obtained information on respondents' clinical settings, experience and specialty. Survey questions were based on a characteristic clinical scenario of anaphylaxis due to food ingestion. Outcome measures consisted of correct answers to the anaphylaxis diagnosis and management questions.

RESULTS:
From a total of 707 of physicians accessed in the survey, 315 (45%) responded to the clinical scenario. 16 respondents reported training in allergy-immunology and have been excluded from the analysis, leaving the final sample size of 299. Respondents were paediatricians (68%) and other specialties adult physicians (32%). Overall, 100 (33%) of respondents diagnosed anaphylaxis, but only 29% of those making the correct diagnosis administered adrenalin (1:1000) intramuscular. Respondents working in secondary/tertiary clinics diagnosed anaphylaxis significantly more often (p=0.04) when compared with primary care/private practice physicians. This difference was also apparent as the most important influence on responses in the multivariate analysis.

CONCLUSIONS:
In this national sample of Russian physicians, we found poor knowledge in both anaphylaxis diagnosis and management. Our data show that the chance of being properly diagnosed with anaphylaxis is 33% and being appropriately treated with adrenalin is 10%. These findings highlight lack of anaphylaxis knowledge among Russian physicians, both paediatricians and other specialists and illustrates the urgent need for allergy/anaphylaxis training.

Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of Fc«RI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage, and neutrophil secretion of platelet-activating factor subsequent to FcgR stimulation by IgG/Ag complexes. We have investigated the contribution of Fyn and Lyn tyrosine kinases to FcgRIIb and FcgRIII signaling in the context of IgG-mediated passive systemic anaphylaxis (PSA). We found that mast cell IgG XL induced Fyn, Lyn, Akt, Erk, p38, and JNK phosphorylation. Additionally, IgG XL of mast cells, basophils, and macrophages resulted in Fyn-and Lyn-regulated mediator release in vitro. FcgR-mediated activation was enhanced in Lyn-deficient (knockout [KO]) cells, but decreased in Fyn KO cells, compared with wild-type cells. More importantly, Lyn KO mice displayed significantly exacerbated PSA features whereas no change was observed for Fyn KO mice, compared with wild-type littermates. Intriguingly, we establish that mast cells account for most serum histamine in IgG-induced PSA. Taken together, our findings establish pivotal roles for Fyn and Lyn in the regulation of PSA and highlight their unsuspected functions in IgG-mediated pathologies.

A atividade antimicrobiana da penicilina foi descoberta por Alexander Fleming, em 1928, quando observou que o fungo Penicillium produzia uma substância responsável pelo efeito bactericida em uma cultura de Staphylococcus spp. 1. A substância foi obtida em sua forma purificada por Howard Florey e Ernst Chain, em 1940. Eles comprovaram as suas qualidades antibióticas em ratos infectados, assim como a sua não-toxicidade 2. Em 1941, os mesmos autores demonstraram os efeitos antibacterianos da penicilina em seres humanos 3,4. Em virtude da relevância da descoberta, Fleming, Florey e Chain receberam o Prêmio Nobel de Medicina e Fisiologia em 1945. O advento da penicilina assinalou inúmeras possibilidades para a redução da morbimortalidade de doenças infecciosas em todo o mundo, em meio ao paradigma da epidemiologia da teoria dos germes 5. Na realidade, trata-se do grupo de antimicrobianos com a maior experiência de uso em todo o mundo, tanto em gestantes 6 quanto na população em geral 7-9. As penicilinas passaram a representar uma opção terapêutica útil no tratamento e na prevenção de diferentes processos infecciosos ou de suas complicações, mesmo ainda no século XXI. São antibióticos de elevada eficácia e de baixo custo, sendo uma opção definida nas infecções por Streptococcus pyogenes e Streptococcus pneumoniae que se mantêm sensíveis a estes antibióticos, na sífilis (neurossífilis, sífilis congênita, sífilis na gestação, em associação à infecção pelo vírus da imunodeficiência humana-HIV), nas profilaxias primária e secundária da febre reumática e da glomerulonefrite pós-estreptocócica 10-12. Portanto, a exclusão destes antibióticos das opções de tratamento deve ser criteriosa, analisando-se inclusive a possibilidade de indução de resistência a antibióticos de maior espectro 6. Em algumas situações, substitutos adequados podem estar disponíveis; no entanto, a indicação da penicilina é indispensável, tal como no tratamento de endocardite enterocócica, abscesso cerebral, meningite bacteriana, e especialmente frente a quadros de neurossífilis, sífilis congênita, sífilis durante a gestação e sífilis associada à infecção pelo HIV 11,13-19. Além das indicações citadas, incluem-se: infecções do trato respiratório superior (amigdalites, faringites, otites etc.), infec

Food allergy is an increasing burden worldwide and is a common problem within paediatric populations, affecting 5%-8% of children. Anaphylaxis caused by food proteins is a potentially life-threatening condition and all healthcare practitioners should be aware of its recognition and management. Russia is the largest country in Europe but it is still unknown whether physicians are prepared to diagnose and manage food-induced anaphylaxis effectively. We aimed to examine physicians' knowledge of diagnosis and management of food-induced anaphylaxis. A survey was designed and published online at VrachiRF.ru website (for registered Russian-speaking practicing physicians). We obtained information on respondents' clinical settings, experience and specialty. Survey questions were based on a characteristic clinical scenario of anaphylaxis due to food ingestion. Outcome measures consisted of correct answers to the anaphylaxis diagnosis and management questions. From a total of 707 of ph...

Allergic reactions related to
insect bites usually cause major
medical problems. Although
many different types of insects
in environment are able to
inflict a poisonous bite or sting,
hymenoptera stings comes
to mind first because of the
importance and frequency. The
vast majority of serious medical
problems and deaths result from
anaphylactic reactions due to
hymenoptera stings. Incidence of
hymenoptera related anaphylaxis
ranges between 0.4% and 5% in
general population.
In 2008, two hymenoptera stings
related deaths were evaluated for
which examination and autopsy
were performed by the Directorate
of Forensic Medicine at Erzurum.
They were two males with the
ages of 48 and 50, respectively.
Autopsy findings of the first case
showed that pharynx had been
obstructed by the lower dental
prosthesis. In the second case,
the reason of death had been
aspiration of stomach contents
into the trachea and bronchus.
These case reports suggest that,
while treating anaphylaxis; it
should always be considered that
a mechanical obstruction of the
airways may be present and an
intact airway may play a key role
in the first aid.Allergic reactions related to
insect bites usually cause major
medical problems. Although
many different types of insects
in environment are able to
inflict a poisonous bite or sting,
hymenoptera stings comes
to mind first because of the
importance and frequency. The
vast majority of serious medical
problems and deaths result from
anaphylactic reactions due to
hymenoptera stings. Incidence of
hymenoptera related anaphylaxis
ranges between 0.4% and 5% in
general population.
In 2008, two hymenoptera stings
related deaths were evaluated for
which examination and autopsy
were performed by the Directorate
of Forensic Medicine at Erzurum.
They were two males with the
ages of 48 and 50, respectively.
Autopsy findings of the first case
showed that pharynx had been
obstructed by the lower dental
prosthesis. In the second case,
the reason of death had been
aspiration of stomach contents
into the trachea and bronchus.
These case reports suggest that,
while treating anaphylaxis; it
should always be considered that
a mechanical obstruction of the
airways may be present and an
intact airway may play a key role
in the first aid.

Commensal microbiota play a critical role in maintaining oral tolerance. The effect of food allergy on the gut microbial ecology remains unknown.

OBJECTIVE:
We sought to establish the composition of the gut microbiota in experimental food allergy and its role in disease pathogenesis.

METHODS:
Food allergy-prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) and wild-type (WT) control animals were subjected to oral sensitization with chicken egg ovalbumin (OVA). Enforced tolerance was achieved by using allergen-specific regulatory T (Treg) cells. Community structure analysis of gut microbiota was performed by using a high-density 16S rDNA oligonucleotide microarrays (PhyloChip) and massively parallel pyrosequencing of 16S rDNA amplicons.

RESULTS:
OVA-sensitized Il4raF709 mice exhibited a specific microbiota signature characterized by coordinate changes in the abundance of taxa of several bacterial families, including the Lachnospiraceae, Lactobacillaceae, Rikenellaceae, and Porphyromonadaceae. This signature was not shared by similarly sensitized WT mice, which did not exhibit an OVA-induced allergic response. Treatment of OVA-sensitized Il4raF709 mice with OVA-specific Treg cells led to a distinct tolerance-associated signature coincident with the suppression of the allergic response. The microbiota of allergen-sensitized Il4raF709 mice differentially promoted OVA-specific IgE responses and anaphylaxis when reconstituted in WT germ-free mice.

CONCLUSION:
Mice with food allergy exhibit a specific gut microbiota signature capable of transmitting disease susceptibility and subject to reprogramming by enforced tolerance. Disease-associated microbiota may thus play a pathogenic role in food allergy.

Anaphylaxis is a challenging condition for any austere environment. It is unpredictable, has sudden onset and a high fatality rate, and is responsive only to epinephrine, a prescription medication. The Wilderness Medical Society has formally recommended that non-medical providers working in austere environments be trained to administer epinephrine. Medical providers frequently prescribe autoinjectors for this purpose due to their ease of use by nonmedical providers. However, auto-injectors have limitations in the wilderness environment, particularly due to their single-dose (or at most 2-dose) design. This paper describes an austere environment technique for obtaining multiple additional doses of epinephrine from auto-injectors that have already been used as designed.

Background-Commensal microbiota play a critical role in maintaining oral tolerance. The effect of food allergy on the gut microbial ecology remains unknown. Objective-We sought to establish the composition of the gut microbiota in experimental food allergy and its role in disease pathogenesis. Methods-Food allergy-prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) and wild-type (WT) control animals were subjected to oral sensitization with chicken egg ovalbumin (OVA). Enforced tolerance was achieved by using allergen-specific regulatory T (Treg) cells. Community structure analysis of gut microbiota was performed by using a high-density 16S rDNA oligonucleotide microarrays (PhyloChip) and massively parallel pyrosequencing of 16S rDNA amplicons. Results-OVA-sensitized Il4raF709 mice exhibited a specific microbiota signature characterized by coordinate changes in the abundance of taxa of several bacterial families,

Background-Commensal microbiota play a critical role in maintaining oral tolerance. The effect of food allergy on the gut microbial ecology remains unknown. Objective-We sought to establish the composition of the gut microbiota in experimental food allergy and its role in disease pathogenesis. Methods-Food allergy-prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) and wild-type (WT) control animals were subjected to oral sensitization with chicken egg ovalbumin (OVA). Enforced tolerance was achieved by using allergen-specific regulatory T (Treg) cells. Community structure analysis of gut microbiota was performed by using a high-density 16S rDNA oligonucleotide microarrays (PhyloChip) and massively parallel pyrosequencing of 16S rDNA amplicons. Results-OVA-sensitized Il4raF709 mice exhibited a specific microbiota signature characterized by coordinate changes in the abundance of taxa of several bacterial families,

Thymoglobulin is an anti-thymocyte globulin derived from rabbits immunized with human T lymphocytes. Since its introduction in the U.S. in
1999, it has become the common therapy used for prophylaxis and treatment of acute rejection in renal transplant patients.
Adverse events include fever, chills, leukopenia, headache, abdominal pain, diarrhea, hypertension, nausea, thrombocytopenia, peripheral edema, dyspnea, asthenia, hyperkalemia, tachycardia and infection.
There have been no reports of thymoglobulin-induced anaphylaxis. We report a case of intraoperative anaphylactic thymoglobulin-induced anaphylaxis, whose diagnosis was confounded by a complicated
intra-operative course in a patient undergoing cadaveric renal transplantation.

BACKGROUND: Large-scale studies of drug provocation testing (DPT) or rapid drug desensitization (RDD) for hypersensitivity to antineoplastics and biologicals are scarce and limited to a few institutions.
OBJECTIVE: Our aim was to review our experience with DPT and RDD in a large number of patients with a history of hypersensitivity to antineoplastics and biologicals and summarize the practical implications of that experience.
METHODS: This was a 7-year prospective, observational, longitudinal study with reactive patients referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were selected after following our systematic and validated diagnostic approach (clinical history, skin test, risk assessment, specific IgE, DPT) before RDD. Candidate patients underwent RDD using the RCUH protocol. Cetuximab reactors underwent 1-bag RDDs.
RESULTS: A total of 1027 intravenous RDDs were performed using the RCUH protocol (399 platins, 395 taxanes, 178 biologicals, 55 other drugs), and 1026 were successfully accomplished in the 186 patients (of 515 referred patients) who met inclusion criteria for RDD. No breakthrough reactions occurred in 88% of RDDs. Most breakthrough reactions were mild. A total of 341 DPTs were performed, and 229 results were negative (67%). DPTs helped exclude hypersensitivity in 44%
(229 of 515) of referred patients. In addition, 77 one-bag RDDs were performed in 6 cetuximab-reactive patients.
CONCLUSIONS: This experience allows us to describe general management plans, as well as specific patient phenotypic patterns, predictors for reactions, and risk considerations that need a tailored approach (taking into account the 3 prominent drug categories: platins, taxanes, and biologicals).

We describe an important number of confirmed hypersensitivity reactions to leucovorin during a one-year period. Leucovorin can be included in FOLFOX/FOLFIRI regimes and be a hidden allergen (making doctors falsely think the reaction was caused by oxaliplatin or irinotecan). We show how patients reacting to leucovorin may also react to l-isomer calcium folinate and we explore the issue of cross-reactivity with oral folinate. We believe protocols studying FOLFOX/FOLFIRI hypersensitivity reactions should be undergone by drug allergy experts and include systematic skin testing and drug provocation testing with folinic acid, to avoid infra-diagnosis and its resulting risks. Moreover, we report the first intravenous rapid desensitization to leucovorin in a reactive patient (confirmed by drug provocation testing).

This document is the result of a consensus on the mechanisms of exercise-induced anaphylaxis (EIAn), an unpredictable and potentially fatal syndrome. A multidisciplinary panel of experts including exercise physiologists, allergists, lung physicians , paediatricians and a biostatistician reached the given consensus. Exercise-induced anaphylaxis (EIAn) describes a rare and potentially fatal syndrome in which anaphylaxis occurs in conjunction with exercise. The pathophysiological mechanisms underlying EIAn have not yet been elucidated although a number of hypotheses have been proposed. This review evaluates the validity of each of the popular theories in relation to exercise physiology and immunology. On the basis of this evidence, it is concluded that proposed mechanisms lack validity, and it is recommended that a global research network is developed with a common approach to the diagnosis and treatment of EIAn in order to gain sufficient power for scientific evaluation.

Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of Fc«RI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage, and neutrophil secretion of platelet-activating factor subsequent to FcgR stimulation by IgG/Ag complexes. We have investigated the contribution of Fyn and Lyn tyrosine kinases to FcgRIIb and FcgRIII signaling in the context of IgG-mediated passive systemic anaphylaxis (PSA). We found that mast cell IgG XL induced Fyn, Lyn, Akt, Erk, p38, and JNK phosphorylation. Additionally, IgG XL of mast cells, basophils, and macrophages resulted in Fyn-and Lyn-regulated mediator release in vitro. FcgR-mediated activation was enhanced in Lyn-deficient (knockout [KO]) cells, but decreased in Fyn KO cells, compared with wild-type cells. More importantly, Lyn KO mice displayed significantly exacerbated PSA features whereas no change was observed for Fyn KO mice, compared with wild-type littermates. Intriguingly, we establish that mast cells account for most serum histamine in IgG-induced PSA. Taken together, our findings establish pivotal roles for Fyn and Lyn in the regulation of PSA and highlight their unsuspected functions in IgG-mediated pathologies.