Contraindications to immunotherapy: a global approach

Background Recommendations on contraindications to allergen immunotherapy (AIT) have been independently developed by National and International Societies/Academies. AIT contraindications are mainly based on case reports, case-series, or experts' opinion, while evidence-based information is limited. The aim of the present review was to describe existing guidelines on contraindications to AIT and to highlight differences between them. Main body An extended review of the literature regarding contraindications to AIT for respiratory allergy and venom hypersensitivity was performed. Furthermore, Societies and Academies registered in the World Allergy Organization and EAACI databases, were asked for additional information. Only AIT guidelines published under official auspicies were included. A large heterogeneity among the various recommendations on contraindications was registered. Common contraindications to most of the guidelines were: lack of adherence, pregnancy before the start of AIT, the use of beta-blockers, certain age groups, uncontrolled asthma, autoimmune diseases and malignancies. Conclusion As new data arise, revisions might soon be needed allowing AIT in the cases of patients treated with ACE inhibitors and beta-blockers, in elderly patients and in patients with concomitant autoimmune diseases and neoplasias in remission. The decision to prescribe AIT is always tailor-made, balancing risk vs benefit. Creating globally accepted guidelines would help Allergologists in their decision making

Educational paper: Abusive Head Trauma Part I. Clinical aspects

Abusive Head Trauma (AHT) refers to the combination of findings formerly described as shaken baby syndrome. Although these findings can be caused by shaking, it has become clear that in many cases there may have been impact trauma as well. Therefore a less specific term has been adopted by the American Academy of Pediatrics. AHT is a relatively common cause of childhood neurotrauma with an estimated incidence of 14–40 cases per 100,000 children under the age of 1 year. About 15–23% of these children die within hours or days after the incident. Studies among AHT survivors demonstrate that approximately one-third of the children are severely disabled, one-third of them are moderately disabled and one-third have no or only mild symptoms. Other publications suggest that neurological problems can occur after a symptom-free interval and that half of these children have IQs below the 10th percentile. Clinical findings are depending on the definitions used, but AHT should be considered in all children with neurological signs and symptoms especially if no or only mild trauma is described. Subdural haematomas are the most reported finding. The only feature that has been identified discriminating AHT from accidental injury is apnoea. Conclusion: AHT should be approached with a structured approach, as in any other (potentially lethal) disease. The clinician can only establish this diagnosis if he/she has knowledge of the signs and symptoms of AHT, risk factors, the differential diagnosis and which additional investigations to perform, the more so since parents seldom will describe the true state of affairs spontaneously

1B/(−)IRE DMT1 Expression during Brain Ischemia Contributes to Cell Death Mediated by NF-κB/RelA Acetylation at Lys310

The molecular mechanisms responsible for increasing iron and neurodegeneration in brain ischemia are an interesting area of research which could open new therapeutic approaches. Previous evidence has shown that activation of nuclear factor kappa B (NF-κB) through RelA acetylation on Lys310 is the prerequisite for p50/RelA-mediated apoptosis in cellular and animal models of brain ischemia. We hypothesized that the increase of iron through a NF-κB-regulated 1B isoform of the divalent metal transporter-1 (1B/DMT1) might contribute to post-ischemic neuronal damage. Both in mice subjected to transient middle cerebral artery occlusion (MCAO) and in neuronally differentiated SK-N-SH cells exposed to oxygen-glucose-deprivation (OGD), 1A/DMT1 was only barely expressed while the 1B/DMT1 without iron-response-element (−IRE) protein and mRNA were early up-regulated. Either OGD or over-expression of 1B/(−)IRE DMT1 isoform significantly increased iron uptake, as detected by total reflection X-ray fluorescence, and iron-dependent cell death. Iron chelation by deferoxamine treatment or (−)IRE DMT1 RNA silencing displayed significant neuroprotection against OGD which concomitantly decreased intracellular iron levels. We found evidence that 1B/(−)IRE DMT1 was a target gene for RelA activation and acetylation on Lys310 residue during ischemia. Chromatin immunoprecipitation analysis of the 1B/DMT1 promoter showed there was increased interaction with RelA and acetylation of H3 histone during OGD exposure of cortical neurons. Over-expression of wild-type RelA increased 1B/DMT1 promoter-luciferase activity, the (−)IRE DMT1 protein, as well as neuronal death. Expression of the acetylation-resistant RelA-K310R construct, which carried a mutation from lysine 310 to arginine, but not the acetyl-mimic mutant RelA-K310Q, down-regulated the 1B/DMT1 promoter, consequently offering neuroprotection. Our data showed that 1B/(−)IRE DMT1 expression and intracellular iron influx are early downstream responses to NF-κB/RelA activation and acetylation during brain ischemia and contribute to the pathogenesis of stroke-induced neuronal damage

The roadmap for the Allergology specialty and allergy care in Europe and adjacent countries. An EAACI position paper

The high prevalence of allergic diseases warrants for sufcient health care provisions available to patients with allergic diseases. Allergy care should be delivered by well-trained specialists. However, the current status of allergy care is not well documented. For this reason a survey among European and a few non-European countries was launched by the National Allergy Society Committee from the European Academy of Allergy and Clinical Immunology and the Union Européenne des Médecins Spécialistes section and board of Allergology. The survey shows that in the vast majority of countries allergy care services are available. However, a substantial heterogeneity is reported regarding recognition of the full specialty, the number of practicing specialists or subspecialists, and training aspects. Growth but also decline of specialty and subspecialties is reported. In addition, the survey gives insight in strengths, weaknesses, opportunities and threats in this feld. It appears that the recognition of the full specialty determines strength as well as weakness. Aging of specialists combined with a decline in the number of trainees form a major threat. Opportunities are seen in creating awareness for allergy, focus on attracting young physicians. The conclusion is that harmonization of allergy services across Europe is needed. Investment in young doctors, creating new opportunities and lobbying for the full specialty is require

Diagnosing, managing and preventing anaphylaxis: Systematic review

none26siBackground: This systematic review used the GRADE approach to compile evidence to inform the European Academy of Allergy and Clinical Immunology's (EAACI) anaphylaxis guideline. Methods: We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18 449 participants: 29 randomized controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarized narratively because studies were too heterogeneous to conduct meta-analysis. Results: It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. There was also insufficient evidence about the impact of most anaphylaxis management and prevention strategies. Adrenaline is regularly used for first-line emergency management of anaphylaxis but little robust research has assessed its effectiveness. Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. We searched for but found little or no comparative effectiveness evidence about strategies such as fluid replacement, oxygen, glucocorticosteroids, methylxanthines, bronchodilators, management plans, food labels, drug labels and similar. Conclusions: Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.nonede Silva D.; Singh C.; Muraro A.; Worm M.; Alviani C.; Cardona V.; DunnGlvin A.; Garvey L.H.; Riggioni C.; Angier E.; Arasi S.; Bellou A.; Beyer K.; Bijlhout D.; Bilo M.B.; Brockow K.; Fernandez-Rivas M.; Halken S.; Jensen B.; Khaleva E.; Michaelis L.J.; Oude Elberink H.; Regent L.; Sanchez A.; Vlieg-Boerstra B.; Roberts G.de Silva, D.; Singh, C.; Muraro, A.; Worm, M.; Alviani, C.; Cardona, V.; Dunnglvin, A.; Garvey, L. H.; Riggioni, C.; Angier, E.; Arasi, S.; Bellou, A.; Beyer, K.; Bijlhout, D.; Bilo, M. B.; Brockow, K.; Fernandez-Rivas, M.; Halken, S.; Jensen, B.; Khaleva, E.; Michaelis, L. J.; Oude Elberink, H.; Regent, L.; Sanchez, A.; Vlieg-Boerstra, B.; Roberts, G