A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta‐lactam (BL) hypersensitivity ...demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost‐effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross‐reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible. Furthermore, the update addresses availability and concentrations of skin test (ST) reagents, ST and drug provocation test (DPT) protocols, and diagnostic algorithms and administration of alternative BL in allergic subjects. Specifically, distinct diagnostic algorithms are suggested depending on risk stratification of the patient into high and low risk based on the morphology and chronology of the reaction, immediate (ie, occurring within 1‐6 hours after the last administered dose) or nonimmediate (ie, occurring more than 1 hour after the initial drug administration), and the reaction severity. Regarding the allergy workup, the main novelty of this document is the fact that in some low‐risk nonimmediate reactions ST are not mandatory, especially in children. For DPT, further studies are necessary to provide data supporting the standardization of protocols, especially of those regarding nonimmediate reactions, for which there is currently no consensus.
In the last several years, intravenous therapy with iron products has been more widely used. Although it has been a standard procedure in dialysis-associated anemia since the early 1990s, its use is ...expanding to a host of conditions associated with iron deficiency, especially young women with heavy uterine bleeding and pregnancy. Free iron is associated with unacceptable high toxicity inducing severe, hemodynamically significant symptoms. Subsequently, formulations that contain the iron as an iron carbohydrate nanoparticle have been designed. With newer formulations, including low-molecular-weight iron dextran, iron sucrose, ferric gluconate, ferumoxytol, iron isomaltoside, and ferric carboxymaltose, serious adverse events are rare.
Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental ...iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.
Controversies exist with regard to in vivo approaches to delayed immunologically mediated adverse drug reactions, such as exanthem (maculopapular eruption), drug reaction with eosinophilia and ...systemic symptoms, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruptions. In particular, widespread differences exist between regions and practice on the availability and use of intradermal and patch testing, the standard drug concentrations used, the use of additional drugs in intradermal and patch testing to help determine cross-reactivity, the timing of testing in relation to the occurrence of the adverse drug reaction, the use of testing in specific phenotypes, and the use of oral challenge in conjunction with delayed intradermal and patch testing to ascertain drug tolerance. It was noted that there have been advances in the science of delayed T cell–mediated reactions that have shed light on immunopathogenesis and provided a mechanism of preprescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine Stevens-Johnson syndrome/toxic epidermal necrolysis in Southeast Asian subjects. Future directions should include the collaboration of large international networks to develop and standardize in vivo diagnostic approaches, such as skin testing and patch testing, combined with ex vivo and in vitro laboratory approaches.
Background Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There ...is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. Objective We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings. Method Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects). Results Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis -regulates HLA-DRB4 , was strongly associated with grass sensitization and weakly with AR ( Pgrass = 1.6 × 10−9 ; PAR = 8.0 × 10−3 ). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32) , which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; Pgrass = 9.4 × 10−9 ; PAR = 3.8 × 10−8 ). The third genome-wide significant variant was rs17513503 (Pgrass = 1.2 × 10−8 ; PAR = 7.4 × 10−7 ) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 ( SLC25A46 ). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin ( TSLP ), Toll-like receptor 6 ( TLR6 ) and nucleotide-binding oligomerization domain containing 1 ( NOD1/CARD4 ). We found no evidence for variants that modified the effect of birth order on either phenotype. Conclusions This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses.
Drugs, such as antibiotics or nonsteroidal anti-inflammatory drugs (NSAIDs), can elicit severe anaphylaxis within a few minutes on parenteral administration and can take up to 1 to 2 hours to do so ...after oral intake. Here the proposed terms are "acute" (immediate to several hours), manifesting as, for example, urticaria and anaphylaxis, and "delayed" (>24 hours), manifesting as mainly cutaneous reactions, such as maculopapular and fixed drug eruptions.1 In the clinical situation the overlap between immediate and nonimmediate reactions can encompass several hours, as shown in Fig 1.4 It appears not very logical to use different terms for the chronology of events for the different drug groups.
Background
Hypersensitivity to metals as a cause of implant‐related complications has been a subject of controversy. Projections indicate an increase in the frequency of joint replacements of between ...300% and 600% by the year 2030; therefore, this issue is of considerable interest.
Objective
To evaluate sensitization to implant materials in patients with implant‐related complications, to identify allergens, and to clarify whether hypersensitivity is a relevant cause.
Methods
Patients with implant‐related complications or a positive history of contact allergy and planned total joint replacements referred for allergological investigation between 2004 and 2017 were retrospectively analysed.
Results
In total, 311 patients were included. A positive patch test reaction to a metal was seen in 64.4% of preoperative patients and in 54.6% of patients with implant‐related complications. Common alloy metals such as cobalt, chromium and titanium gave positive reactions in up to 2.9% of patients with implant‐related complications. None of the patients with skin changes had a positive patch test reaction to an implant metal.
Conclusion
Other factors, such as the type of replaced joint and mechanical stress, seem to be more relevant for implant‐related complications. Sensitization to metals or other materials seems to rarely play a role, and is overestimated.
In 1975, the mummified body of a female has been found in the Franciscan church in Basel, Switzerland. Molecular and genealogic analyses unveiled her identity as Anna Catharina Bischoff (ACB), a ...member of the upper class of post-reformed Basel, who died at the age of 68 years, in 1787. The reason behind her death is still a mystery, especially that toxicological analyses revealed high levels of mercury, a common treatment against infections at that time, in different body organs. The computed tomography (CT) and histological analysis showed bone lesions in the femurs, the rib cage, and the skull, which refers to a potential syphilis case.
Although we could not detect any molecular signs of the syphilis-causing pathogen Treponema pallidum subsp. pallidum, we realized high prevalence of a nontuberculous mycobacterium (NTM) species in brain tissue sample. The genome analysis of this NTM displayed richness of virulence genes and toxins, and similarity to other infectious NTM, known to infect immunocompromised patients. In addition, it displayed potential resistance to mercury compounds, which might indicate a selective advantage against the applied treatment. This suggests that ACB might have suffered from an atypical mycobacteriosis during her life, which could explain the mummy's bone lesion and high mercury concentrations.
The study of this mummy exemplifies the importance of employing differential diagnostic approaches in paleopathological analysis, by combining classical anthropological, radiological, histological, and toxicological observations with molecular analysis. It represents a proof-of-concept for the discovery of not-yet-described ancient pathogens in well-preserved specimens, using de novo metagenomic assembly.
Until recently, food allergies to mammalian meats have been considered to be very rare. The observation that patients not previously exposed to the monoclonal chimeric antibody cetuximab suffered ...from severe anaphylaxis upon first exposure, led to the identification of galactosealpha- 1,3-galactose as a new relevant carbohydrate allergen. These patients later often suffered from anaphylactic reactions to red meat. Epidemiological data indicated that bites by the tick
Amblyomma americanum
in the USA, later also by
Ixodes
species in other continents, resulted in sensitisation to alpha-gal. On the other hand, in African patients with parasitic disorders, a high prevalence of anti-alpha-gal IgE, without clinical relevance, has been reported. In our four cases, one patient with a late onset of meat allergy had a history of a tick bite. The other three patients had symptoms from childhood or at a juvenile age. This indicates that in some patients, other ways of sensitisation may also take place. However, in patients without atopy, tick bite-induced IgE to alpha-gal may be more relevant. Diagnosis is based on a history of delayed onset of anaphylaxis. Skin tests with commercially available meat test solutions are often equivocal or negative; skin tests with raw meat and particularly pork kidney are more sensitive. Determination of specific IgE to alpha-gal is commercially available. The highest sensitivity is observed with skin and basophil activation tests with cetuximab which is, however, limited by its high costs.
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