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Importance: The lack of inclusion of diverse population samples in food allergy immunotherapy clinical trials not only leads to decreased applicability to the general population in terms of results and treatments but can also be seen as a broader social injustice contributing to inequity within the health care system. Objectives: To investigate the racial and ethnic distribution of participants included in food allergy immunotherapy clinical trials, and determine whether the racial and ethnic representation in trials accurately reflects the patients who experience food allergy. Evidence Review: Data were collected from articles found on PubMed and ClinicalTrials.gov using key terms of food hypersensitivity, food allergy, and immunotherapy, while also incorporating specific criteria such as clinical trials conducted within the last 5 years with children aged from birth to 18 years old. Articles were selected based on their relevance to the research question. Main outcomes were totals and percentages of trial participants by race and ethnicity, stratified by pediatric trials, site of study, and National Institutes of Health funding. Findings: Thirty-five articles were initially identified, of which 34 were classified as human clinical trials. Of these trials, 26 met criteria of an original randomized clinical trial and included racial and ethnic demographics for analysis in the study. Among trials included, the majority of the 3689 participants identified as White (2640 participants [72.0%]), followed by Black or African American (293 participants [8.0%]), Asian (239 participants [6.0%]), multiple races or other (210 participants [6.0%]), Hispanic or Latino (96 participants [3.0%]), American Indian (3 participants [<1.0%]), and Native American or Pacific Islander (3 participants [<1.0%]). We observed differences in racial and ethnic inclusion by study site (US vs external to US) and funding support (National Institutes of Health vs industry or other non-National Institutes of Health sources). Conclusions and Relevance: In this systematic review of racial and ethnic diversity in food allergy immunotherapy trials, there was a lack of diversity relative to the overall food allergy burden among Black and Hispanic patients, indicating important gaps in the conduct of pediatric clinical trials, especially for treatments that are meant for use in broad populations where significant race- and ethnicity-related disparities exist. Working to correct this disparity will not only increase the usefulness of future clinical trial data but can further assist in alleviating public health inequities.
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Etnicidad , Hipersensibilidad a los Alimentos , Humanos , Hipersensibilidad a los Alimentos/terapia , Hipersensibilidad a los Alimentos/etnología , Niño , Etnicidad/estadística & datos numéricos , Desensibilización Inmunológica/estadística & datos numéricos , Desensibilización Inmunológica/métodos , Adolescente , Preescolar , Ensayos Clínicos como Asunto/estadística & datos numéricos , Grupos Raciales/estadística & datos numéricos , Masculino , Estados Unidos , Femenino , LactanteRESUMEN
Background: Allergen-specific immunotherapy, a unique inducer of tolerance, may result in T cell exhaution. Aims: To investigate how the duration of house dust mite (HDM) subcutaneous immunotherapy (SCIT) affects the expression of major immune checkpoint (ICP) molecules on the surface of CD4+ T-helper and regulatory T (Treg) cells. Study Design: Cross-sectional study. Methods: We enrolled 28 children with HDM-induced allergic rhinitis (AR) and six controls. The study participants were divided into six groups: one group each of patients in their first, second, and third years of HDM-SCIT; one group each comprising those in the first year following HDM-SCIT and those on pharmacotherapy; and the control group. The expression of ICPs on CD4+ T and Treg cells was determined using flow cytometry, and plasma levels of soluble ICPs were estimated by ELISA. Results: Our results revealed a significant increase in the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3) on CD4+ T cells during the second and third years of SCIT, respectively. Additionally, a strong correlation was observed between the expression of CTLA-4 and T cell immunoglobulin and mucin domain containing molecule-3 in CD4+ T cells. Furthermore, we observed a significant correlation between the expressions of programmed cell death protein-1, CTLA-4, T cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif domain, and LAG-3 on both CD4+ T and Treg cells. A robust correlation was observed between the plasma levels of soluble ICPs. Conclusion: HDM-SCIT induces CD4+ T cell exhaution, which may contribute to tolerance induction in children with AR.
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Linfocitos T CD4-Positivos , Pyroglyphidae , Rinitis Alérgica , Linfocitos T Reguladores , Humanos , Niño , Animales , Rinitis Alérgica/terapia , Rinitis Alérgica/inmunología , Rinitis Alérgica/sangre , Masculino , Estudios Transversales , Femenino , Pyroglyphidae/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T CD4-Positivos/inmunología , Antígeno CTLA-4/análisis , Desensibilización Inmunológica/métodos , AdolescenteRESUMEN
Systemic mastocytosis (SM) is a clonal mast cell disorder that can lead to potentially severe anaphylactic reactions. Hymenoptera sting is one of the most frequent triggers of anaphylaxis in these patients, and diagnosis of indolent SM (ISM) without skin involvement (ISMs) is not rare. In this subgroup of patients, venom immunotherapy (VIT) is an effective treatment decreasing subsequent systemic reactions, and lifelong administration is recommended. An individualized diagnosis is necessary to offer the most adequate VIT, and molecular diagnosis (MD) may be useful to discriminate between primary sensitization and cross-reactivity. Nevertheless, other techniques such as ImmunoCAP inhibition assays may be necessary to identify the genuine sensitization to offer the most suitable VIT. We present a male patient with an anaphylactic reaction following several wasp stings. The patient was diagnosed with ISM, and allergy to both Polistes dominula and Vespula sp venom was confirmed. In this scenario, MD did not discriminate between a genuine double sensitization and venom cross-reactivity between both vespids. Thus, CAP-inhibition assay was performed. This case indicated the importance of an accurate diagnosis of hymenoptera venom allergy (HVA). It also highlights the usefulness of CAP-inhibition assays when MD fails to distinguish between genuine double Polistes-Vespula sensitization and cross-reactivity.
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Anafilaxia , Reacciones Cruzadas , Mordeduras y Picaduras de Insectos , Mastocitosis Sistémica , Venenos de Avispas , Avispas , Humanos , Masculino , Venenos de Avispas/inmunología , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/inmunología , Mastocitosis Sistémica/complicaciones , Animales , Anafilaxia/diagnóstico , Anafilaxia/inmunología , Anafilaxia/etiología , Mordeduras y Picaduras de Insectos/inmunología , Mordeduras y Picaduras de Insectos/diagnóstico , Mordeduras y Picaduras de Insectos/complicaciones , Avispas/inmunología , Reacciones Cruzadas/inmunología , Desensibilización Inmunológica/métodos , Alérgenos/inmunología , Alérgenos/administración & dosificación , Triptasas/sangre , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangreRESUMEN
PURPOSE OF REVIEW: This review will identify and summarize the published existing data pertaining specifically to Hymenoptera venom allergy in children and adolescents, highlighting the major studies currently available on venom immunotherapy (VIT) and its prognosis in children. RECENT FINDINGS: The current review covers the incidence and prevalence of Hymenoptera venom allergy (HVA) in children, factors influencing occurrence and severity of reactions (age, sex, comorbidities, etc.), indications to perform diagnostic tests and start VIT in children, different existing VIT protocols and their safety and efficacy. SUMMARY: Hymenoptera venom allergy is the second most common cause of anaphylaxis in children and it considerably affects quality of life. Cutaneous reactions are the most prevalent clinical presentation in children who usually have a more favourable prognosis than adult patients. However, studies on HVA in children and adolescents are still limited. Currently VIT is the only treatment able to modify the natural history of HVA in adults as well as in children, and to protect patients from systemic reactions after subsequent stings.
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Anafilaxia , Venenos de Artrópodos , Desensibilización Inmunológica , Himenópteros , Mordeduras y Picaduras de Insectos , Humanos , Niño , Adolescente , Animales , Himenópteros/inmunología , Desensibilización Inmunológica/métodos , Venenos de Artrópodos/inmunología , Venenos de Artrópodos/efectos adversos , Mordeduras y Picaduras de Insectos/inmunología , Mordeduras y Picaduras de Insectos/terapia , Mordeduras y Picaduras de Insectos/epidemiología , Mordeduras y Picaduras de Insectos/diagnóstico , Anafilaxia/epidemiología , Anafilaxia/inmunología , Anafilaxia/prevención & control , Anafilaxia/diagnóstico , Anafilaxia/etiología , Anafilaxia/terapia , Hipersensibilidad/inmunología , Hipersensibilidad/terapia , Hipersensibilidad/epidemiología , Hipersensibilidad/diagnóstico , Alérgenos/inmunología , Incidencia , Prevalencia , Calidad de VidaRESUMEN
BACKGROUND: COVID-19 is a new infectious disease. To investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the adverse reactions of subcutaneous specific immunotherapy (SCIT) in children. METHODS: This study was conducted by collecting relevant data from children who underwent house dust mite SCIT from April 3, 2021, to March 18, 2023, including information on the time of COVID-19 infection, symptoms, and adverse reactions after each allergen injection. A mixed effects model was used to analyze the changes in adverse reactions before and after the COVID-19 infection. RESULTS: Among the records of adverse reactions from 2658 injections in 123 children who underwent SCIT, the overall adverse reaction rate before COVID-19 infection was 39.8% and 30.0% after COVID-19 infection. Compared with pre-infection with COVID-19, the risks of overall adverse reactions, local adverse reactions, and systemic adverse reactions of immunotherapy after COVID-19 infection were reduced (odds ratio [OR] = 0.24, 0.31, and 0.28, all P < 0.05). Among the local adverse reactions, the incidence of the unvaccinated group was the highest (15.3% vs. 7.1%). The incidence of overall and local adverse reactions to SCIT decreased in 2-vaccinated COVID-19 recipients (OR = 0.29-0.31, P < 0.05). CONCLUSIONS: In children, SARS-CoV-2 infection does not increase the incidence of adverse reactions to SCIT. This finding can provide a basis for the implementation of allergen-specific immunotherapy (AIT) during the COVID-19 pandemic.
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COVID-19 , Desensibilización Inmunológica , SARS-CoV-2 , Humanos , COVID-19/terapia , COVID-19/inmunología , Niño , Estudios Retrospectivos , Masculino , Femenino , Preescolar , SARS-CoV-2/inmunología , Inyecciones Subcutáneas , Desensibilización Inmunológica/efectos adversos , Desensibilización Inmunológica/métodos , Adolescente , Animales , Pyroglyphidae/inmunología , Alérgenos/inmunología , Alérgenos/efectos adversos , Alérgenos/administración & dosificación , LactanteRESUMEN
INTRODUCTION: Sesame allergy, though with low prevalence, can result in severe, potentially life-threatening reactions and poses challenges in allergen avoidance due to hidden sources. In the majority of patients, sesame allergy persists and there is currently no effective long-term treatment available. Therefore, oral immunotherapy (OIT) is a promising alternative approach to managing sesame allergy. In this study protocol, we present a randomised controlled trial evaluating the efficacy and safety of OIT with low-dose sesame protein in paediatric patients. The study's aim is to compare OIT with a 300 mg maintenance dose of sesame protein against controls. METHODS AND ANALYSIS: 39 participants aged 3-17 with IgE-mediated sesame allergy confirmed by oral food challenge will be enrolled into the study. The trial will be conducted at the Paediatric Hospital of the Medical University of Warsaw, Poland. The study comprises two arms-sesame OIT and control. In the sesame OIT group, interventions will be administered once daily for up to 18 months. During the first phase, the dose will be escalated every 2-4 weeks, and in the second phase, the maintenance dose of 300 mg sesame protein will continue for 3 months. Members of the control group will receive standard treatment, which includes an elimination diet and will remain under observation for 1 year. The primary outcome is the proportion of participants tolerating a single dose of 4000 mg of sesame protein during the final oral food challenge in the experimental group versus the control group. Secondary outcomes assess adverse events, changes in immunological parameters and the maximum tolerated doses of sesame protein in each group. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the Medical University of Warsaw (approval number: KB/269/2023). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT06261554.
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Desensibilización Inmunológica , Hipersensibilidad a los Alimentos , Sesamum , Humanos , Niño , Sesamum/efectos adversos , Sesamum/inmunología , Administración Oral , Hipersensibilidad a los Alimentos/terapia , Hipersensibilidad a los Alimentos/inmunología , Adolescente , Preescolar , Desensibilización Inmunológica/métodos , Desensibilización Inmunológica/efectos adversos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Femenino , Alérgenos/administración & dosificación , Alérgenos/inmunología , PoloniaRESUMEN
Introduction: Atopic diseases have been steadily increasing over the past decades and effective disease-modifying treatment options are urgently needed. These studies introduce a novel synthetic Toll-like receptor 4 (TLR4) agonist, INI-2004, with remarkable efficacy as a therapeutic intranasal treatment for seasonal allergic rhinitis. Methods: Using a murine airway allergic sensitization model, the impact of INI-2004 on allergic responses was assessed. Results: One or two intranasal doses of INI-2004 significantly reduced airway resistance, eosinophil influx, and Th2 cytokine production - providing strong evidence of allergic desensitization. Further investigations revealed that a liposomal formulation of INI-2004 exhibited better safety and efficacy profiles compared to aqueous formulations. Importantly, the liposomal formulation demonstrated a 1000-fold increase in the maximum tolerated intravenous dose in pigs. Pre-clinical GLP toxicology studies in rats and pigs confirmed the safety of liposomal INI-2004, supporting its selection for human clinical trials. Discussion: These findings lay the groundwork for the ongoing clinical evaluation of INI-2004 in allergic rhinitis as a stand-alone therapy for individuals poly-sensitized to multiple seasonal allergens. The study underscores the significance of innovative immunotherapy approaches in reshaping the landscape of allergic rhinitis management.
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Administración Intranasal , Modelos Animales de Enfermedad , Receptor Toll-Like 4 , Animales , Receptor Toll-Like 4/agonistas , Ratones , Porcinos , Femenino , Liposomas , Rinitis Alérgica Estacional/inmunología , Rinitis Alérgica Estacional/tratamiento farmacológico , Alérgenos/inmunología , Alérgenos/administración & dosificación , Desensibilización Inmunológica/métodos , Ratas , Citocinas/metabolismo , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: MTBVAC is a live attenuated tuberculosis vaccine, currently undergoing phase III evaluation for tuberculosis prevention. In previous preclinical studies, we found that local pulmonary administration of MTBVAC via the intranasal route had a strong therapeutic effect against asthma. This effect correlated with the abrogation of allergen-specific Th2 response in the lungs. METHODS: Using different mouse models of asthma, we investigated the effect of MTBVAC administered by intravenous (IV) route and its potential as immunotherapeutic agent to induce desensitisation of allergen-specific responses at a systemic level. We explored the effects of this process in the efficacy against airway hyperresponsiveness (AHR) induced by exposure to different allergens. FINDINGS: IV MTBVAC was highly efficient at reducing AHR induced by different allergens. Additionally, IV MTBVAC was found to be well-tolerated, being progressively eliminated from the different organs analysed. From a mechanistic standpoint, we observed that MTBVAC intravenous, but not intranasal, impaired allergen-specific Th2 response in both lungs and spleen. This reduction at a systemic level correlated with long-term therapeutic protection against allergen exposure. Our results also revealed differential immunological mechanisms governing systemic and local pulmonary allergen desensitisation processes. Notably, in a cohort of patients with asthma sensitive to house dust mite (HDM), in vitro incubation of peripheral blood mononuclear cells (PBMCs) with MTBVAC prevented allergen-specific production of Th2 cytokines IL-4 and IL-5. INTERPRETATION: Altogether, our results suggest that intravenous MTBVAC could be a plausible allergen desensitising approach for treatment of asthma, and could provide long-term protection against allergen exposure. FUNDING: MCIN/AEI/10.13039/501100011033 [grants number RTI2018-097625-B-I00 and PID2022-138624OB-I00]; Consorcio Centro de Investigación Biomédica en Red- (Groups CB06/06/0020 and CB06/06/0013), Instituto de Salud Carlos III.
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Administración Intravenosa , Alérgenos , Asma , Desensibilización Inmunológica , Modelos Animales de Enfermedad , Vacunas contra la Tuberculosis , Animales , Asma/inmunología , Asma/prevención & control , Ratones , Alérgenos/inmunología , Alérgenos/administración & dosificación , Humanos , Desensibilización Inmunológica/métodos , Femenino , Vacunas contra la Tuberculosis/inmunología , Vacunas contra la Tuberculosis/administración & dosificación , Pulmón/inmunología , Pulmón/patología , Células Th2/inmunología , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/administración & dosificación , Citocinas/metabolismo , Ratones Endogámicos BALB CRESUMEN
Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.
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Antígenos HLA , Trasplante de Células Madre Hematopoyéticas , Isoanticuerpos , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Antígenos HLA/inmunología , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Donantes de Tejidos , Rechazo de Injerto/inmunología , Intercambio Plasmático/métodos , Adolescente , Trasplante Haploidéntico/métodos , Adulto Joven , Biomarcadores/sangre , Desensibilización Inmunológica/métodosRESUMEN
BACKGROUND: Subcutaneous immunotherapy (SCIT) can induce systemic reactions (SRs) in certain patients, but the underlying mechanisms remain to be fully elucidated. METHODS: AR patients who were undergoing standardized HDM SCIT (Alutard, ALK) between 2018 and 2022 were screened. Those who experienced two consecutive SRs were included in the study group. A control group was established, matched 1:1 by gender, age, and disease duration with the study group, who did not experience SRs during SCIT. Clinical and immunological parameters were recorded and analyzed both before SCIT and after 1 year of treatment. RESULTS: A total of 161 patients were included, with 79 (49.07%) in the study group. The study group had a higher proportion of AR combined asthma (26.8% vs. 51.8%, p < 0.001) and higher levels of sIgE to HDM and HDM components (all p < .001). Serum IL-4 and IL-13 levels in the study group were higher than those in the control group (p < .05). The study group received a lower maintenance dosage of HDM extracts injections than control group due to SRs (50000SQ vs. 100000SQ, p < .05). After 1 year of SCIT, the VAS score, the lung function parameters of asthmatic patients over 14 years old significantly improved in both groups (all p < .05). After a 7-day exposure to 20 µg/mL HDM extracts, the percentages of Th1, Th17, Tfh10, and Th17.1 in PBMCs decreased, while the Tfh13 cells significantly increased in the study group (p < .05). CONCLUSION: The type 2 inflammatory response is augmented in HDM-induced AR patients who experienced SRs during SCIT. Despite this, SCIT remains effective in these patients when administered with low-dosage allergen extracts.
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Desensibilización Inmunológica , Pyroglyphidae , Rinitis Alérgica , Humanos , Masculino , Femenino , Desensibilización Inmunológica/métodos , Niño , Rinitis Alérgica/inmunología , Rinitis Alérgica/terapia , Pyroglyphidae/inmunología , Inyecciones Subcutáneas , Animales , Adolescente , Antígenos Dermatofagoides/inmunología , Antígenos Dermatofagoides/administración & dosificación , Asma/inmunología , Asma/terapia , Inmunoglobulina E/sangre , Alérgenos/inmunología , Alérgenos/administración & dosificación , Células Th2/inmunologíaRESUMEN
Exposure to HLA alloantigens through pregnancy, blood products, and previous transplantations induce powerful immunologic responses that create an immunologic barrier to successful transplantation. This is commonly detected through screening for HLA antibodies using Luminex beads coated with HLA antigens at transplant evaluation. Currently accepted approaches to desensitization include plasmapheresis/low-dose or high-dose intravenous Ig plus anti-CD20. However, these approaches are often unsuccessful because of the inability to remove high titer circulating HLA antibodies and limit rebound responses by long-lived anti-HLA antibody secreting plasma cells (PCs) and memory B cells (B MEM ). This is especially significant for patients with a calculated panel reactive antibody of 99%-100%. Newer desensitization approaches, such as imlifidase (IgG endopeptidase), rapidly inactivate IgG molecules and create an antibody-free zone by cleaving IgG into F(ab'2) and Fc fragments, thus eliminating complement and cell-mediated injury to the graft. This represents an important advancement in desensitization. However, the efficacy of imlifidase is limited by pathogenic antibody rebound, increasing the potential for antibody-mediated rejection. Controlling antibody rebound requires new strategies that address the issues of antibody depletion and inhibition of B MEM and PC responses. This will likely require a combination of agents that effectively and rapidly deplete pathogenic antibodies and prevent immune cell activation pathways responsible for antibody rebound. Here, using anti-IL-6 receptor (tocilizumab) or anti-IL-6 (clazakizumab) could offer long-term control of B MEM and PC donor-specific HLA antibody responses. Agents aimed at eliminating long-lived PCs (anti-CD38 and anti-B-cell maturation antigen×CD3) are likely to benefit highly HLA sensitized patients. Complement inhibitors and novel agents aimed at inhibiting Fc neonatal receptor IgG recycling will be important in desensitization. Administering these agents alone or in combination will advance our ability to effectively desensitize patients and maintain durable suppression post-transplant. After many years of limited options, advanced therapeutics will likely improve efficacy of desensitization and improve access to kidney transplantation for highly HLA sensitized patients.
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Antígenos HLA , Humanos , Antígenos HLA/inmunología , Listas de Espera , Desensibilización Inmunológica/métodos , Isoanticuerpos/inmunología , Trasplante de Riñón , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & controlRESUMEN
PURPOSE OF REVIEW: To review the updated 2023 Allergy Immunology Joint Task Force on Practice Parameters (JTFPP) GRADE and Institute of Medicine (IOM) Based Guidelines for the management of atopic dermatitis. RECENT FINDINGS: Topical corticosteroids and/or calcineurin inhibitors are recommended in individuals with atopic dermatitis refractory to moisturizer alone and may be used to maintain remission after acute flare control is achieved. Calcineurin inhibitors are a class of immunosuppressants used to effectively manage different autoimmune disorders. Bleach baths and allergen immunotherapy may be beneficial for individuals with moderate-to-severe disease, while elimination diets, azathioprine, methotrexate, mycophenolate, and systemic corticosteroids are not recommended. Dupilumab is strongly recommended for refractory atopic dermatitis. Oral Janus kinase (JAK) inhibitors carry significant risks; however, this class of medicines may be considered in cases of severe or refractory atopic dermatitis with intolerance to dupilumab. Patient preferences regarding cost, availability, feasibility, and tolerability should be integrated into all treatment plans using a shared decision-making approach. SUMMARY: The 2023 JTFPP Atopic Dermatitis Guidelines offer up-to-date guidance for the management of atopic dermatitis of varying severity in infants, children, and adults.
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Dermatitis Atópica , Guías de Práctica Clínica como Asunto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/terapia , Dermatitis Atópica/inmunología , Niño , Inmunosupresores/uso terapéutico , Inhibidores de la Calcineurina/uso terapéutico , Comités Consultivos , Alergia e Inmunología/normas , Desensibilización Inmunológica/métodos , Anticuerpos Monoclonales HumanizadosRESUMEN
PURPOSE OF REVIEW: This review aims to identify phenotypes at-risk of Hymenoptera venom-induced anaphylaxis (HVA), focusing on different perspectives (epidemiological, clinical, and therapeutic) in order to adapt future preventive strategies. RECENT FINDINGS: HVA remains one of the leading causes of anaphylaxis, with a broad pattern of symptoms. Although most cases occur outside healthcare settings, data indicate a high emergency admission rate due to insect stings. Mortality is often underestimated because of the lack of witnesses and difficulties in recognizing the signs and the culprit. Targeting risk factors could be a clue to improve these statistics and the prognosis of the disease.Potential risk factors for severe HVA in the European population are basal serum tryptase (BST) above 8âµg, mast cell disorders, the absence of skin symptoms, and cardiovascular conditions requiring the use of beta blockers and ACE inhibitors. Identifying these criteria, mainly based on clinical patterns, helps to develop personalized strategies for management and prevention. SUMMARY: With a personalized medicine approach, phenotypes must be characterized to adapt to the management of patients suffering from Hymenoptera venom anaphylaxis (HVA), including venom immunotherapy (VIT). In this systematic review, all articles mentioned systemic reactions with heterogeneous severity degrees. Half of those reported grade III-IV systemic reactions (Ring and Messmer). HVA clinical patterns could be worsened by one Hymenoptera sting, a patient's history with mast cell disorders, or cardiovascular diseases. VIT failure was attributed to bee venom extract and monotherapy in two-thirds of publications. Findings stress the difficulty of having uniform epidemiological data on HVA and the lack of financial support in some world regions to support appropriate management of these conditions. Although observing a heterogeneity of data, we were able to identify potential risk factors, in particular for the severe cases. We believe our work will support allergists and health professionals to implement improved personalized management of patients suffering from severe HVA.
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Anafilaxia , Venenos de Artrópodos , Himenópteros , Mordeduras y Picaduras de Insectos , Animales , Humanos , Anafilaxia/inmunología , Anafilaxia/mortalidad , Anafilaxia/prevención & control , Anafilaxia/terapia , Venenos de Artrópodos/administración & dosificación , Venenos de Artrópodos/inmunología , Desensibilización Inmunológica/métodos , Medicina Basada en la Evidencia , Himenópteros/inmunología , Mordeduras y Picaduras de Insectos/complicaciones , Mordeduras y Picaduras de Insectos/inmunología , Mordeduras y Picaduras de Insectos/mortalidad , Mordeduras y Picaduras de Insectos/terapia , Factores de Riesgo , Triptasas/sangreRESUMEN
Food allergy is a growing problem with limited treatment options. It is important to understand the mechanisms of food tolerance and allergy to promote the development of directed therapies. Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that prime adaptive immune responses, such as those involved in the development of oral tolerance and food allergies. The DC subsets in the gut and skin are defined by their surface markers and function. The default response to an ingested innocuous antigen is oral tolerance, which requires either gut DCs or a subset of newly identified RORγt+ APCs to induce the development of gut peripheral regulatory T cells. However, DCs in the skin, gut, and lung can also promote allergic sensitization when they are activated under certain inflammatory conditions, such as with alarmin release or gut dysbiosis. DCs also play a role in the responses to the various modalities of food immunotherapy. Langerhans cells in the skin appear to be necessary for the response to epicutaneous immunotherapy. It will be important to determine which real-world stimuli activate the DCs that prime allergic sensitization and discover methods to selectively initiate a tolerogenic program in APCs.
Asunto(s)
Células Dendríticas , Hipersensibilidad a los Alimentos , Tolerancia Inmunológica , Humanos , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/terapia , Células Dendríticas/inmunología , Animales , Desensibilización Inmunológica/métodos , Linfocitos T Reguladores/inmunología , Alérgenos/inmunologíaRESUMEN
Background: Polymerized allergoids conjugated with mannan represent a novel approach of allergen immunotherapy targeting dendritic cells. In this study, we aimed to determine the optimal dose of mannan-allergoid conjugates derived from grass pollen (Phleum pratense and Dactylis glomerata) administered via either the subcutaneous or sublingual route. Methods: A randomized, double-blind, placebo-controlled trial with a double-dummy design was conducted, involving 162 participants across 12 centers in Spain. Subjects were randomly allocated to one of nine different treatment groups, each receiving either placebo or active treatment at doses of 500, 1,000, 3,000, or 5,000 mTU/mL over four months. Each participant received five subcutaneous (SC) doses of 0.5 mL each, every 30 days, and a daily sublingual (SL) dose of 0.2 mL. Participants who received active treatment through SC, received placebo through SL. Participants who received active treatment through SL, received placebo SC. One Group, as control, received bot SC and SL placebo. The primary efficacy outcome was the improvement in titrated nasal provocation tests (NPT) at the end of the study compared to baseline. Secondary outcomes included specific antibody (IgG4, IgE) and cellular (IL-10 producing and regulatory T cell) responses. All adverse events and side reactions were recorded and assessed. Results: Post-treatment, the active groups showed improvements in NPT ranging from 33% to 53%, with the highest doses showing the greatest improvements regardless of the administration route. In comparison, the placebo group showed a 12% improvement. Significant differences over placebo were observed at doses of 3,000 mTU/mL (p=0.049 for SL, p=0.015 for SC) and 5,000 mTU/mL (p=0.011 for SL, p=0.015 for SC). A dose-dependent increase in IgG4 was observed following SC administration, and an increase in IL-10 producing cells for both routes of administration. No serious systemic or local adverse reactions were recorded, and no adrenaline was required. Conclusion: Grass pollen immunotherapy with mannan-allergoid conjugates was found to be safe and efficacious in achieving the primary outcome, whether administered via the subcutaneous or sublingual routes, at doses of 3,000 and 5,000 mTU/mL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search (EudraCT), identifier 2014-005471-88; https://www.clinicaltrials.gov, identifier NCT02654223.
Asunto(s)
Alérgenos , Alergoides , Desensibilización Inmunológica , Mananos , Poaceae , Polen , Inmunoterapia Sublingual , Humanos , Masculino , Femenino , Adulto , Polen/inmunología , Mananos/administración & dosificación , Alérgenos/inmunología , Alérgenos/administración & dosificación , Inmunoterapia Sublingual/métodos , Inmunoterapia Sublingual/efectos adversos , Inyecciones Subcutáneas , Poaceae/inmunología , Persona de Mediana Edad , Desensibilización Inmunológica/métodos , Desensibilización Inmunológica/efectos adversos , Método Doble Ciego , Rinitis Alérgica Estacional/terapia , Rinitis Alérgica Estacional/inmunología , Administración Sublingual , Resultado del Tratamiento , Adulto Joven , Inmunoglobulina E/inmunologíaRESUMEN
Allergies play a pivotal role in the daily practice of ENT specialists. Allergic symptoms induced by inhalant allergens are widespread in the population and can manifest through a wide range of symptoms, including rhinorrhea, sneezing, conjunctival redness, cough and dyspnea. Inconsistent diagnosis and treatment of allergic conditions can lead to reduced quality of life, decreased work performance, and socioeconomically significant secondary diseases. In addition to the medical history, the skin prick test and serological IgE diagnostics are the most important diagnostic procedure for detecting type-I allergies. To clarify clinical relevance, molecular diagnostics and nasal provocation testing may be employed. The key to effective treatment lies in a comprehensive allergological diagnosis coupled with a detailed patient history. General treatment recommendations such as allergen avoidance and nasal irrigation should complement pharmacological therapy. In the treatment of allergic rhinitis topical steroids are first line treatment options. The primary goal of treatment is symptom control, and if control is insufficient, causal therapy through specific allergen immunotherapy is recommended. Challenges in the ENT clinic involve selecting the necessary diagnostics and appropriate, effective treatments. Hence, using diagnostic and treatment algorithms, as well as standardized patient history questionnaires, can serve as invaluable tools in daily patient interactions, especially considering limited time availability.