Digital technology for anaphylaxis management impact on patient behaviour: A randomized clinical trial.

BACKGROUND: Epinephrine is the first-line treatment for anaphylaxis. Patients at risk should always carry an epinephrine autoinjector (EAI). Several EAI gaps have been identified. We sought to evaluate satisfaction using a medical device (digital technology comprising an EAI smart case connected to a mobile APP) with functions that overcome most of the EAI limitations and to determine whether patient behaviour and anaphylaxis management improve with its use. METHODS: This was a randomized, open-label, crossover clinical trial in a tertiary hospital involving patients with history of anaphylaxis carrying an EAI. The study was conducted in two three-month periods, one with and one without the medical device. The primary endpoint was satisfaction with the medical device. Usability, adherence, anxiety and anaphylaxis episodes were evaluated as secondary endpoints. RESULTS: A total of 100 patients were included (mean age 38.1 years, 74% female), and 95 completed the trial. The satisfaction visual analogue scale (VAS) after using the medical device was higher than before its use (89.1 [95% CI, 60.2-99.1] vs 56.3 [95% CI, 48.1-81.4]; P < .0001). The adherence VAS improved from 59.7 (95% CI, 54.0-65.3) to 88.6 (95% CI, 84.2-92.9) (P < .0001). Overall, 90% patients found the medical device easy to use. Patients' anxiety decreased from 52.2% to 29.3% (P < .001). Seven episodes of anaphylaxis occurred during the study, all in patients without the medical device (P = .025). Eighty-eight per cent of patients felt more involved in the management of anaphylaxis when using the medical device. CONCLUSION: This is the first clinical trial evaluating digital technology for EAIs, showing a change of behaviour in patients at risk of anaphylaxis, increasing satisfaction, improving adherence, and reducing anxiety, with good usability.

Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions.

BACKGROUND: Anaphylaxis is an acute, potentially lethal, multisystem syndrome resulting from the sudden release of mast cell-derived mediators into the circulation. OBJECTIVES AND METHODS: We report here that a plasma protease cascade, the factor XII-driven contact system, critically contributes to the pathogenesis of anaphylaxis in both murine models and human subjects. RESULTS: Deficiency in or pharmacologic inhibition of factor XII, plasma kallikrein, high-molecular-weight kininogen, or the bradykinin B2 receptor, but not the B1 receptor, largely attenuated allergen/IgE-mediated mast cell hyperresponsiveness in mice. Reconstitutions of factor XII null mice with human factor XII restored susceptibility for allergen/IgE-mediated hypotension. Activated mast cells systemically released heparin, which provided a negatively charged surface for factor XII autoactivation. Activated factor XII generates plasma kallikrein, which proteolyzes kininogen, leading to the liberation of bradykinin. We evaluated the contact system in patients with anaphylaxis. In all 10 plasma samples immunoblotting revealed activation of factor XII, plasma kallikrein, and kininogen during the acute phase of anaphylaxis but not at basal conditions or in healthy control subjects. The severity of anaphylaxis was associated with mast cell degranulation, increased plasma heparin levels, the intensity of contact system activation, and bradykinin formation. CONCLUSIONS: In summary, the data collectively show a role of the contact system in patients with anaphylaxis and support the hypothesis that targeting bradykinin generation and signaling provides a novel and alternative treatment strategy for anaphylactic attacks.

Evaluation of cytokine profile and HLA association in benznidazole related cutaneous reactions in patients with Chagas disease.

BACKGROUND: Benznidazole is the drug of choice for Chagas disease. The major drawback of this drug is the high adverse events rate, being cutaneous reactions the most frequent one, leading to definitive withdrawal of treatment in 15%-30% of patients. METHODS: Prospective observational study where adult Chagas disease patients accepting to receive benznidazole (100 mg/8 hours for 60 days) were included. The objective was to characterize the skin toxicity of benznidazole in patients with Chagas disease, determine the serum cytokine profile, and evaluate the potential association with specific HLA alleles and benznidazole concentration. Serum cytokine levels were measured at day 0, 15, and 60 of treatment. Class I and II HLA alleles were determined. When cutaneous reaction was detected, a skin biopsy was performed. Serum benznidazole concentration was determined at the time of cutaneous reaction, or at day 15 of treatment. RESULTS: Fifty-two patients were included, 20(38.5%) had cutaneous reaction, and median time of appearance was 9 days. Skin biopsies showed histopathological findings consistent with drug eruption. Patients with cutaneous drug-reaction had higher proportion of eosinophilia during treatment, and higher interleukin (IL)-5 and IL-10 serum concentrations at day 15 of treatment than those without cutaneous reaction. Treatment interruption (that included moderate-severe cutaneous reactions) was more frequent in patients carrying HLA-B*3505 allele (45.5% vs 15.4%, P = .033). No differences in benznidazole serum concentration were found. CONCLUSIONS: Benznidazole related cutaneous reaction rate is high, and it was produced by a delayed hypersensitivity reaction with a Th2 response. Carrying HLA-B*3505 allele could be associated with moderate-severe cutaneous reaction.

Systemic inflammation biomarkers during angioedema attacks in hereditary angioedema.

Background: Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks. Methods: Patients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients F12 gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured. Results: Seventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6-88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for D-dimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 vs. baseline) and D-dimer in 71% (p=0.001 vs. baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p<0. 0001), ESR (p<0.0001) and D-dimer (p= 0.004). No significant differences were observed in CRP (p=0.7), ACE (p=0.67) and WCC (p=0.54). These findings remained consistent regardless of HAE type, disease activity or location of angioedema. Conclusion: The systemic increase in APR observed during HAE attacks suggests that inflammation extends beyond the localized edematous area. This finding underscores the potential involvement of inflammatory pathways in HAE and highlights the need for further investigation into their role in the pathophysiology of HAE.

Challenging dogmas: Intravenous versus oral beta-lactam antibiotic provocation tests.

Background: Drug provocation tests (DPT) are considered the gold standard procedure to ascertain the diagnosis of beta-lactam (BL) allergy. Regarding route of administration, current recommendations prioritize oral challenges, considering them safer, and reserving the intravenous route for drugs for which this is the only formulation. Objective: To compare in terms of tolerance and safety two protocols of BL DPT, using an oral protocol (OR-DPT) and an intravenous protocol (IV-DPT). Methods: A descriptive, retrospective study was performed, including adult patients who underwent IV-DPT or OR-DPT for suspected immediate or delayed hypersensitivity to BL antibiotics, over a period of 4 years (between January 2018 and December 2021). Demographical data, index hypersensivity reactions' characteristics and tolerance to DPT were reviewed. Results: A total of 1036 patients underwent DPT, mean age of 56.8 (standard deviation, SD, 17.8) years, 655 were women (63.2%). Immediate drug hypersensitivity reactions (DHR) had occurred in 564 of patients (54.4%). OR-DPT were performed in 439 (42.4%) and IV-DPT in 597 (57.6%). The frequency of reactions during DPT, regardless of the route used, was low (3.6%): only 16 (3.6%) in OR-DPT and 21 (3.5%) in IV-DPT. From IV-DPT, 16 out 21 DHR during DPT were immediate compared with 4 out of 16 in OR-DPT. Adjusted relative risk of developing a hypersensitivity reaction during IV-DPT versus OR-DPT was 1.13 (95% confidence interval (CI)0.57-2.22). Conclusion: The results suggest that OR-DPT and IV-DPT are both safe procedures when adequately performed. However, IV-DPT protocols showed a higher rate of immediate DHR during DPT probably due to the selection of basal high-risk patients to undergo IV-DPT. In conclusion, IV-DPT may be considered as an option for challenges in drug-allergy studies, entailing a precise administration.

Usefulness and limitations of sequential serum tryptase for the diagnosis of anaphylaxis in 102 patients.

BACKGROUND: The diagnosis of anaphylaxis is based on clinical history since no reliable biological marker is currently available to confirm the diagnosis. OBJECTIVE: It was the aim of this study to determine sequential serum tryptase concentrations during anaphylaxis and to evaluate its potential as a diagnostic marker. METHODS: We performed a prospective study including patients with acute anaphylaxis (according to the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network criteria) attending the emergency department. Demographic characteristics, anaphylactic triggers, specific risk factors, clinical characteristics and management of anaphylaxis were recorded. Serum tryptase was measured at 1-2 h (T1), 4-6 h (T2) and 12-24 h (T3) following onset of the episode and at basal conditions (TB). RESULTS: A total of 102 patients were included (63 females, mean age 47.4 ± 19.1 years). Tryptase concentration at T1 (19.3 ± 15.4 µg/l) was significantly higher than at T2, T3 and TB (all <11.4 µg/l; p < 0.0001). Importantly, tryptase was not raised in 36.3% of cases; furthermore, in 60.6% of these patients, no changes were observed in tryptase levels comparing T1 and TB (ΔT1-TB = 0). Tryptase was more frequently elevated in more severe anaphylaxis (p < 0.0001) and positively correlated with the grades of severity (p < 0.001, r = 0.49). Anaphylaxis was more severe and tryptase concentration higher when the causative agent was a drug compared to food, both at T1 (p = 0.045) and at TB (p = 0.019). Age and coronary risk factors were associated with more severe anaphylaxis (p = 0.001). CONCLUSION: Tryptase is a biomarker related to the severity of anaphylaxis. However, since its concentration remains unaltered in a considerable number of patients during acute anaphylaxis, there is a need for more reliable diagnostic biological tests.

Could it be hereditary angioedema?-Perspectives from different medical specialties.

Hereditary angioedema (HAE) is a rare autosomal dominant disease, with patients often suffering with associated symptoms for many years before receiving a correct diagnosis. The symptoms greatly impact a patient's quality of life (QoL) and include excruciating abdominal pain and angioedema of the skin and submucosa. Angioedema of the larynx represents a significant mortality risk in undiagnosed patients, and a large proportion of patients with HAE receive incorrect diagnoses and undergo unnecessary surgery. HAE-specific treatments can control and prevent acute life-threatening episodes, in addition to improving QoL, emphasizing the value of early diagnosis for patients. Diagnostic delay may be due to a lack of HAE awareness by healthcare professionals and the similarity of HAE symptoms with those of more common conditions, complicating differential diagnosis. The multifaceted nature of the condition may result in visits to one of many different medical settings, for example: the Emergency Room, pediatrics, general practice, otolaryngology, gastroenterology, and dermatology. Therefore, it is crucial that physicians in multiple healthcare specialties are aware of the disease to ensure that patients with HAE receive a timely diagnosis. Using patient cases from various medical specialties, this review highlights the necessity for cross-specialty awareness of HAE and outlines the essential information for the various healthcare professionals that may encounter a patient with HAE symptoms, in order to effectively treat and/or diagnose HAE.

Personalized Surgery Service in a Tertiary Hospital: A Method to Increase Effectiveness, Precision, Safety and Quality in Maxillofacial Surgery Using Custom-Made 3D Prostheses and Implants.

Personalized surgery (PS) involves virtual planning (VP) and the use of 3D printing technology to design and manufacture custom-made elements to be used during surgery. The widespread use of PS has fostered a paradigm shift in the surgical process. A recent analysis performed in our hospital-along with several studies published in the literature-showed that the extensive use of PS does not preclude the lack of standardization in the process. This means that despite the widely accepted use of this technology, standard individual roles and responsibilities have not been properly defined, and this could hinder the logistics and cost savings in the PS process. The aim of our study was to describe the method followed and the outcomes obtained for the creation of a PS service for the Oral and Maxillofacial Surgery Unit that resolves the current absence of internal structure, allows for the integration of all professionals involved and improves the efficiency and quality of the PS process. We performed a literature search on the implementation of PS techniques in tertiary hospitals and observed a lack of studies on the creation of PS units or services in such hospitals. Therefore, we believe that our work is innovative and has the potential to contribute to the implementation of PS units in other hospitals.

Angioedema Due to Acquired Deficiency of C1-Inhibitor: A Cohort Study in Spain and a Comparison With Other Series.

BACKGROUND: Data on acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) from 4 European countries (France, Italy, Germany, and Hungary) were recently published. OBJECTIVE: To report data from a group of 50 patients with acquired C1-INH deficiency from Spain, of whom 46 had angioedema, and compare them with other European series. METHODS: We performed a retrospective observational study of 46 patients with C1-INH-AAE and 4 asymptomatic patients. Clinical and biological characteristics and associated diseases were assessed and compared with other European series. RESULTS: Women accounted for 73.9% of cases. The prevalence of C1-INH-AAE related to hereditary forms was 1/10.1. Overall, 8.7% patients were aged <40 years. Diagnostic delay was 1.1 years. Angioedema mainly affected the face (91.3%), followed by the oropharynx (63%), extremities (50%), and abdomen (37%). Only 1 patient underwent orotracheal intubation. Erythema marginatum was present in 1 patient. A hematologic disorder was recorded in 50% of patients. Angioedema preceded all benign conditions, mostly monoclonal gammopathy of undetermined significance, but appeared very close to or after malignant hematologic diseases (median, 2.2 and 0.29 years). Autoimmune diseases were associated in 50% (autoimmune thyroiditis, 21.5%; systemic lupus erythematosus, 10.9%). Half of them coexisted with hematologic disorders. Anti-C1-INH antibodies were found in 67% of tested patients and were not related to the associated disease. Long-term prophylaxis was necessary in 52.2%, most of whom responded to tranexamic acid. CONCLUSIONS: This study emphasizes the possibility of C1-INH-AAE in patients younger than 40 and in autoimmune diseases other than systemic lupus erythematosus such as autoimmune thyroiditis.

Are antihistamines still used during omalizumab treatment for chronic spontaneous urticaria?

Background: The guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend adding omalizumab to the treatment of patients with uncontrolled disease despite four-fold doses of second-generation antihistamines (AH). On the contrary, some studies revealed that omalizumab was effective without concomitant AH and several authors suggest tapering off AH when CSU is controlled with omalizumab. Objectives: The aim of our study was to evaluate the use of AH during treatment with omalizumab in patients with CSU in real clinical practice. Materials & Methods: This was a multicentre cross-sectional and observational study conducted by the Catalan and Balearic Chronic Urticaria Network (XUrCB) based on a cohort of 298 CSU patients treated with omalizumab. Results: In total, 23.5% of our patients decided themselves to stop taking AH during omalizumab treatment. The ratio of patients with CSU without concomitant inducible urticaria and the percentage of patients with a good response to omalizumab (UAS7≤6 and/or UCT ≥12) were higher in those who stopped taking AH. Conclusion: More studies are required to identify the phenotypic characteristics of patients responding to omalizumab as monotherapy in order to avoid overtreating with AH. Our study suggests that patients with CSU without concomitant inducible urticaria and those who achieve a good response to omalizumab tend to be controlled by omalizumab without AH. In order to establish guidelines on how to stop AH, further evidenced-based studies are required.

Anaphylaxis viewed by experts: unmet needs.

PURPOSE OF REVIEW: The purpose of the review is to identify unmet needs in the management of anaphylaxis, covering aspects such as epidemiology, diagnosis, treatment and prevention. RECENT FINDINGS: Redefinition of clinical diagnostic criteria may allow a better identification of anaphylaxis. International diagnostic coding system improvement will be major step for future policies and epidemiological studies. Digital health can aid in managing anaphylaxis. SUMMARY: Anaphylaxis is a medical emergency; current data show that frequently identification of the reaction, acute and long-term management, are not optimal. Therefore, there is a need to implement strategies to improve the situation. This review has identified unmet needs in anaphylaxis regarding aspects such as epidemiology, severity scoring, definition and diagnostic criteria, anaphylaxis in infants and toddlers, cofactors, biomarkers, long-term management, undertreatment and availability of epinephrine autoinjectors. Strategies focused on education, legislation, digital health and research are proposed.

One-Dilution Rapid Desensitization Protocol to Chemotherapeutic and Biological Agents: A Five-Year Experience.

BACKGROUND: Rapid drug desensitization (RDD) becomes a crucial procedure to allow treatment continuation in patients who suffer drug hypersensitivity reactions (DHRs) to chemotherapeutic (CMT) and biological agents (BA). OBJECTIVE: The aim of the study was to compare the efficacy and safety of a one-bag dilution protocol (1DP) with a conventional three-bag dilution protocol (3DP) for desensitization of patients with CMT or BA hypersensitivity. METHODS: Retrospective analysis of patients with immediate DHRs to CMT or BA who underwent at least 1 RDD procedure in our department between 2014 and 2019 was performed. Demographical data, clinical history, skin tests, tryptase levels, and risk assessment were registered. The safety, tolerability, occurrence, and severity of breakthrough reactions (BTR) with 3DP and 1DP were compared. RESULTS: After the allergy workup, 157 patients fulfilled criteria to undergo RDD (137 females, mean age: 60.44 ± 12.6 years). A total of 639 RDDs (543 CMT and 96 BA) were performed using 3DP in 205 (48 patients) and 1DP in 434 (109 patients). Almost all procedures (636) were completed successfully. No BTR occurred in the first RDD in 52% and 51% of the 3DP and 1DP, respectively. Most BTR were mild. Moderate-severe BTR occurred in 17% with 3DP and 9% with 1DP. There were no statistical differences between protocols regarding the rate and severity of BTR. CONCLUSIONS: RDD with 1DP to CMT and BA has equivalent outcomes to a 3DP desensitization in a selected population of patients in terms of efficacy, tolerability, and safety. Moreover, 1DP reduces the time required for RDD and simplifies the logistics.

Hereditary angioedema due to C1 inhibitor deficiency: real-world experience from the Icatibant Outcome Survey in Spain.

BACKGROUND: The Icatibant Outcome Survey (IOS) is an international registry monitoring the use of icatibant, a bradykinin B2 receptor antagonist indicated for the acute treatment of hereditary angioedema (HAE) attacks. Our goal was to assess disease characteristics and icatibant treatment outcomes in patients with HAE due to C1 inhibitor deficiency (HAE type 1 or 2 (HAE-1/2)) from Spain relative to other countries participating in IOS. METHODS: Descriptive retrospective analyses of data are reported from 10 centers in Spain vs 51 centers in 12 other participating countries (July 2009 to January 2019). RESULTS: No meaningful differences were identified between patients in Spain (n = 119) and patients across other countries (n = 907) regarding median age at symptom onset (15.0 vs 12.0 years) or diagnosis (22.3 vs 20.5 years). Overall HAE attack rates (total attacks/total years of follow-up) were 2.66 in Spain and 1.46 across other countries. Patients in Spain reported fewer severe/very severe HAE attacks before treatment (41.0% vs 45.9%; P < 0.0001) and, for icatibant-treated attacks, longer median time to treatment (2.9 vs 1.0 h), time to attack resolution (18.0 vs 5.5 h), and total attack duration (24.6 vs 8.0 h). Use of androgens for long-term prophylaxis was higher in Spain (51.2% vs 26.7%). CONCLUSION: Patients with HAE-1/2 in Spain reported fewer severe/very severe attacks, administered icatibant later, and had longer-lasting attacks than did patients across other countries in IOS. These differences may indicate varying disease management practices (e.g., delayed icatibant treatment) and reporting. Efforts to raise awareness on the benefits of early on-demand treatment may be warranted. TRIAL REGISTRATION: NCT01034969.

A Comparative Study of Sex Distribution, Autoimmunity, Blood, and Inflammatory Parameters in Chronic Spontaneous Urticaria with Angioedema and Chronic Histaminergic Angioedema.

BACKGROUND: Recurrent idiopathic histaminergic angioedema is currently classified as a subtype of angioedema, as well as a subtype of chronic spontaneous urticaria (CSU), based on the fact that both are mast cell-mediated and respond to the same treatments. OBJECTIVE: In the present work, we sought to verify whether chronic histaminergic angioedema (CHA) is an entity distinct from CSU or represents a CSU subtype that lacks hives. METHODS: We performed a prospective study comparing 68 CHA patients, angioedema without hives, with 63 CSU patients, with hives and angioedema, from whom we collected demographic and clinical data, as well as blood and serum markers. RESULTS: We found key pathogenic features that differentiate CHA from CSU: gender distribution, basophil number, and antibodies against the IgE receptor. The male/female ratio in CHA was 0.78, whereas in CSU it was 0.36 (P = .0466). Basopenia was more often seen in CSU (n = 13 [20%]) than in CHA (n = 5 [7%]). Finally, 31.15% of CSU sera induced basophil activation, whereas no CHA sera were able to activate normal basophils. By contrast, nonspecific inflammation or immune markers, for example, erythrocyte sedimentation rate, C-reactive protein, or IgG antithyroid antibodies, were very similar between both groups. IgE anti-IL-24 could not be assessed because a control population did not differ from CSU. CONCLUSIONS: Inclusion of CHA as part of the spectrum of CSU is an assumption not evidence-based, and when studied separately, important differences were observed. Until there is further evidence, CHA and CSU should not necessarily be considered the same disorder, and it is our opinion that review articles and guidelines should reflect that possibility.

[Common variable immunodeficiency. Prognostic factors for lung damage]. / Inmunodeficiencia común variable: factores pronósticos de lesión pulmonar.

BACKGROUND AND OBJECTIVE: Lung damage is considered to be key to Common Variable Immunodeficiency (CVID) prognosis. We describe lung damage in pediatric CVID patients and assess its relationship with memory B cells (MB) phenotype, immunoglobulin G (IgG) levels at the time of diagnosis, and diagnostic delay. We also assessed the prevalence of allergy and autoimmune phenomena. PATIENTS AND METHOD: Cross-sectional study of 17 CVID patients treated at Vall d'Hebron University Hospital. Prevalence ratio and prevalence odds ratio were used to assess the effect of MB cells phenotype, IgG levels and diagnostic delay on lung damage. RESULTS: Five of seventeen patients presented bronchiectasis. Diagnostic delay >5 years was significantly associated with more severe lung damage. MBO phenotype and low IgG levels at the time of diagnosis showed a trend to more severe lung damage without reaching statistical signification. A higher prevalence of allergic or autoimmune phenomena was not observed. CONCLUSIONS: Latter diagnosis is associated with greater lung damage in CVID patients. The study of MB cells should be included in the study of these patients.

Safety and effectiveness of a microcrystalline tyrosine-associated mite extract immunotherapy for allergic rhinitis.

Aim: To assess the safety and effectiveness of an allergen immunotherapy (AIT) with a microcrystalline tyrosine-associated mite allergoid in real-world patients with allergic rhinitis (AR). Materials & methods: Retrospective, multicenter study assessing the safety of AIT in patients aged 5 to 65 years with AR, with or without asthma, sensitized to mites. Secondary objective was effectiveness, measured as unscheduled visits to healthcare centers and emergency rooms, rhinitis and asthma evolution, medication use and patients' and physicians' disease perception 12 months before and after treatment. Results: The 306 patients evaluated, with a mean (standard deviation) age of 29.68 (14.66) years, received different treatment compositions and regimens, and 25 (8.2%) experienced nonserious adverse reactions. Unscheduled visits to the specialist and emergency room admissions significantly decreased after immunotherapy (mean [standard deviation] 2.11 [1.95] and 0.3 [0.93] vs 0.66 [1.09] and 0.02 [0.2], before and after treatment, respectively). Rhinitis and asthma classification ('AR and its impact on asthma' and 'Guía Española para el Manejo del Asma', respectively) significantly changed (p < 0.0001 for all classifications), showing symptom reduction after AIT. Median (interquartile range)-combined rhinitis and combined asthma medication scores significantly decreased (4.0 [1.33, 7.0] vs 0.25 [0, 10.0]; p < 0.0001 and 6.94 [1.5, 6.0] vs 0.67 [0, 4.67]; p < 0.0001) within 12 months before and after starting AIT, respectively. Conclusion: AIT with microcrystalline tyrosine-associated mite allergoid appears to be safe and effective in treating rhinitis caused by mites.

Biologics and anaphylaxis.

PURPOSE OF REVIEW: The use of biologicals as therapeutic agents in oncology and other inflammatory diseases has dramatically increased during the last years. Due to their biological nature and inherent immunological activity, they are able to induce important adverse events, such as cytokine release reactions (rapid release of proinflammatory cytokines), serum sickness disease, and immediate or delayed hypersensitivity reactions, including anaphylaxis. The aim of the current article is to review the state of the art of anaphylaxis because of biological agents. RECENT FINDINGS: Different phenotypes, and potential underlying endotypes, have been described in anaphylactic reactions to biologicals. There seems to be a spectrum from type 1 reactions (IgE or non-IgE-mediated) to cytokine release reactions, with some reactions falling in between both. Management should be directed according to such phenotypes. SUMMARY: There is ongoing research to further define immediate adverse reactions to biologicals and to find relevant biomarkers to aid in their diagnosis. Such information will serve in defining their immediate and long term management.

Phenotypes, endotypes and biomarkers in anaphylaxis: current insights.

PURPOSE OF REVIEW: The aim of the review is to describe the different clinical pictures of anaphylaxis (phenotypes), in relation to the underlying mechanisms and potential biomarkers, to describe anaphylaxis endotypes. This may aid in achieving a better understanding, management and outcomes of such severe reactions. RECENT FINDINGS: Different anaphylaxis phenotypes have been outlined, ranging from the classical type-I-like to those suggestive of cytokine-storm-like or complement-mediated reactions. Underlying mechanisms differ and biomarkers of cells and systems involved are being identified (tryptase, IL-6, bradykinin etc.) SUMMARY: Identifying specific phenotypes/endotypes will allow the application of precision medicine in patients with anaphylaxis, providing insights to the most appropriate approach in each case.