Errores innatos de la inmunidad: ¿Qué debe saber y cuándo debe sospechar el otorrinolaringólogo? / Inborn errors of immunity: What should the otolaryngologist know, and when to suspect them?

Introducción: Los errores innatos de la inmunidad, previamente conocidos como inmunodeficiencias primarias, son un grupo heterogéneo de patologías cuya presentación clínica incluye infecciones recurrentes, persistentes o refractarias al tratamiento en el campo de la otorrinolaringología. Materiales y métodos: Se realizó una revisión narrativa de la literatura a partir de la búsqueda de documentos en PUBMED y EMBASE. Discusión y conclusiones: Los pacientes con sospecha de error innato de la inmunidad requieren un diagnóstico temprano con el fin de disminuir las complicaciones a largo plazo, por lo que la valoración y el abordaje inicial desempeñan un papel fundamental en el reconocimiento de estas enfermedades.

Introduction: Inborn errors of immunity, previously known as primary immunodeficiencies, are a heterogeneous group of pathologies whose clinical presentation includes recurrent, persistent and/or refractory infections to treatment in otorhinolaryngology. Materials and methods: Narrative review of the literature was carried out from the search for articles in PUBMED and EMBASE. Discussion and conclusions: Patients with suspected inborn error of immunity require an early diagnosis to reduce long-term complications; the initial assessment and approach play a fundamental role in the recognition of these diseases

Tertiary Lymphoid Organs: A Primer for Otolaryngologists.

OBJECTIVES/HYPOTHESIS: Lymphoid neogenesis or the development of organised, de novo lymphoid structures has been described increasingly in chronically inflamed tissues. The presence of tertiary lymphoid organs (TLOs) has already been demonstrated to result in significant consequences for disease pathology, severity, prognosis and patient outcomes. Whilst the wider medical community has embraced TLOs as important markers of disease and potential therapeutic targets, the otolaryngology field has only begun turning to these entities in an academic capacity. This review aims to outline the role of tertiary lymphoid organs in disease and summarise key early findings in the ENT field. We also an overview of TLOs, their developmental process and clinicopathological implications. STUDY DESIGN: Literature review. METHODS: A literature search for all relevant peer-reviewed publications pertaining to TLOs and ENT diseases. Search was conducted using PubMed, Embase and CINAHL databases. RESULTS: A total of 24 studies were identified relevant to the topic. The majority of TLO research in ENT fell into the areas of oral squamous cell carcinoma (SCC) and chronic rhinosinusitis (CRS). CONCLUSIONS: Early research into both oral SCC and CRS suggests that TLOs have significant roles within ear, nose and throat (ENT) diseases. At this point in time, however, TLOs remain somewhat a mystery amongst otolaryngologists. As information in this field increases, we may develop a better understanding of how lymphoid neogenesis can influence disease outcomes amongst our patients and, ultimately, how they can be utilised in an immunotherapeutic manner. Laryngoscope, 131:1697-1703, 2021.

Rituximab prescription patterns and efficacy in the induction treatment of ANCA-Associated Vasculitis in a Belgian multicenter cohort.

Introduction: The RAVE trial has revolutionized induction treatment of anti-neutrophil cytoplasmic antibodies (ANCA)-Associated Vasculitis (AAV)by demonstrating the non-inferiority of rituximab (RTX) compared with cyclophosphamide.Objectives: We studied AAV patients' characteristics, RTX prescription practices and efficacy in AAV induction treatment in four Belgian university hospitals. The patient population, selected according to the Belgian reimbursement criteria, was relatively homogeneous and comparable to the one of RAVE trial.Methods: 57 patients, receiving RTX as AAV induction therapyfrom May 2014 to June 2017 were enrolled in an observational retrospective multicenter trial involving four Belgian university hospitals. We focused on the type of AAV, ANCA specificity, prescriber's specialty, used reimbursement criteria, organ involvements, severity of the flares and finally RTX efficacy in AAV induction treatment by considering the RAVE primary (complete remission without prednisone) and secondary (complete remission with prednisone <10 mg) outcomes at 6, 12, 18 and 24 months.Results: 66.7% of the patients reached complete remission with prednisone <10 mg at 6 months, 55.3% at 12 months, 40% at 18 months and 25% at 24 months. The rates of complete remission without steroids were very low at 6, 12, 18 and 24 months. The rates of relapses were high between 18 and 24 months. Conclusions: Our results confirm those of RAVE regarding complete remission rates with prednisone <10 mg/day, in a 'real-life' cohort of patients selected according to data of RAVE trial. The high prevalence of relapses - especially after 18 months - underlines the need to optimize maintenance treatment after an induction treatment with RTX..

Contemporary analysis of otolaryngic allergy.

OBJECTIVES: Investigate the current trends in otolaryngic allergy (OA). STUDY DESIGN: Cross-sectional survey. METHODS: Survey of active AAOA membership. RESULTS: Response rate was 27.3%. Regional response distribution rates were proportional to the AAOA membership distribution within the United States (R2 = 0.95; P < 0.001), with no significant regional response bias demonstrated (P = 0.428). Self-reported duration to OA competency was 5.8 years. Physicians reporting OA competency were more likely to be board-certified (P < 0.001) and have AAOA fellowship status (P < 0.001). The AAOA was reported to be the most valuable educational resource toward achieving OA competency, with residency training being least valuable (P < 0.001). 91.5% of respondents' practices offered OA services. Subcutaneous injections predominated at twice the utilization of sublingual immunotherapy. Allergy immunotherapy tablets were rarely utilized. Home allergy shots were offered by 45.2% of respondents. In-office immunotherapy vial compounding was preferred (95.8%) to third-party vendors. 94% of AAOA respondents identified patient compliance to be an issue within OA. Non-inhalant allergy service integration included food allergy (63.5%), asthma (44.9%), allergic fungal sinusitis (43.8%), penicillin allergy (18%), stinging insect allergy (12.6%), and aspirin desensitization (3.9%). CONCLUSION: Reported duration to OA competency after residency was surprisingly long. Further investigation of current and future educational/clinical training is warranted given clinical integration reported for OA. Otolaryngology is in the unique position to develop a comprehensive sino-allergy evidence-based strategy integrating the extensive diagnostic and medical treatment arms alongside the surgical expertise of the specialty within a clinical sino-allergy home concept. LEVEL OF EVIDENCE: 5 Laryngoscope, 130:283-289, 2020.

Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts.

OBJECTIVE: IgG4-related disease (IgG4-RD) is a heterogeneous, multiorgan condition of unclear aetiology that can cause organ failure. Difficulty recognising IgG4-RD contributes to diagnostic delays. We sought to identify key IgG4-RD phenotypes. METHODS: We used two cross-sectional studies assembled by an international, multispecialty network of IgG4-RD specialists who submitted 765 cases to derive and replicate phenotypic groups. Phenotype groups of disease manifestations and key covariate distributions across the identified groups were measured using latent class analysis. RESULTS: In the derivation cohort (n=493), we identified four groups with distinct manifestations: Group 1 (31%), Pancreato-Hepato-Biliary disease; Group 2 (24%), Retroperitoneal Fibrosis and/or Aortitis; Group 3 (24%), Head and Neck-Limited disease and Group 4 (22%), classic Mikulicz syndrome with systemic involvement. We replicated the identification of four phenotype groups in the replication cohort. Compared with cases in Groups 1, 2 and 4, respectively, cases in Group 3 were more likely to be female (OR 11.60 (95% CI 5.39 to 24.98), 10.35 (95% CI 4.63 to 23.15) and 9.24 (95% CI 3.53 to 24.20)) and Asian (OR 6.68 (95% CI 2.82 to 15.79), 7.43 (95% CI 2.97 to 18.56) and 6.27 (95% CI 2.27 to 17.29)). Cases in Group 4 had a higher median serum IgG4 concentration (1170 mg/dL) compared with groups 1-3 (316, 178 and 445 mg/dL, respectively, p<0.001). CONCLUSION: We identified four distinctive IgG4-RD phenotypes according to organ involvement. Being Asian or female may predispose individuals to head and neck-limited disease. These phenotypes serve as a framework for identifying IgG4-RD and studying its aetiology and optimal treatment.

The use of immunohistochemical methods in the study of morphofunctional features of the human paranasal sinuses: literature review.

OBJECTIVE: Introduction:Chronic inflammatory diseases of the mucous membrane of the nose, paranasal sinuses, and pharynx are the most widespread pathology of the upper airways. The thorough study of the features of the organization of local immune protection of the mucous membrane of the paranasal sinuses is crucial for the deep understanding of the causes of the onset and development of this and other pathologies of the paranasal sinuses, the choice of methods of diagnostics and treatment. Consequently, immunohistochemical studies are of great potential and have become preferable for great number of researchers. The aim: The paper was aimed at the analysis of the publications on the use of immunohistochemical methods in the study of the structural and functional features of the paranasal sinuses. PATIENTS AND METHODS: Materials and methods: The bibliosemantic method has been used during the study. Findings of the current research works on the use of immunohistochemical methods in the study of the paranasal sinuses have been analyzed. RESULTS: Review:The findings of the analysis shows that the use of immunohistochemical methods in the otorhinolaryngology is becoming more and more popular in the study of both morphofunctional features of the paranasal sinuses and in various experimental studies. CONCLUSION: Conclusion: The use of immunohistochemical methods in the study of the paranasal sinuses in both clinical otorhinolaryngology and theoretical morphology is relevant to date and is considered reasonable and perspective.

Allergy genuflection? It's surmount with special focus on ear, nose and throat

The system that protects body from infectious agents is immune system. On occasions, the system seldom reacts with some foreign particles and causes allergy. Allergies of the ear, nose and throat (ENT) often have serious consequences, including impairment and emotional strain that lowers the quality of life of patients. This is further responsible for the common cold, cough, tonsillitis, dermal infection, chest pain and asthma-like conditions which disturb one's day to day life. The present review enlightens some common ENT allergies which one can suffer more frequently in one's lifetime, and ignorance leads to making the condition chronic. Information regarding pathophysiology and the management of ENT allergy by this review could help clinicians and common people to better understand the circumstances and treatment of ENT allergy (AU)

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[Epithelial dysfunction associated with pyo-inflammatory diseases of the ENT organs]. / Épitelial'naia disfunktsiia pri gnoino-vospalitel'nykh zabolevaniiakh LOR-organov.

The modern concept of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome associated with pyo-inflammatory ENT diseases is presented. It has provided a basis for the analysis of the initial stages of etiopathogenesis of acute and chronic inflammation in the ENT system including the mucous and associated lymphoid tissues as well as the Pirogov-Waldeyer limphopharyngeal ring making up the first protective barrier. The leading role of dysbiosis of synanthropic microflora and endotoxins of the Gram-negative bacteria in the mechanisms of regional responsiveness of the organism to the infection and chronic endotoxic aggression is demonstrated. The regional and synthetic mechanisms underlying the interaction between the external and internal media of the organism are subjected to the analysis with special reference to those operating in epithelium. The possible variants of the outcome of these processes are considered including both the recovery and the development of chronic inflammation. It has been proved that the exhaustion of the internal reserves for the stabilization of the epithelium-associated lymphoid tissue system including the Pirogov-Waldeyer limphopharyngeal ring leads to the formation of epithelial dysfunction as the initial stage of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome. It is concluded that the modern concept of epithelial-endothelial dysfunction and epithelial-endothelial distress-syndrome is a fundamental interdisciplinary phenomenon.

[The use of propolis-based therapy in otorhionolaryngology]. / Propolisoterapiya v otorinolaringologii.

The authors analyze the literature publications and the results of their original investigations concerning the application of the propolis-based pharmacological products for the treatment of acute and chronic diseases of the upper respiratory tract and ears. The desirability of the more extensive application of the propolis-containing medicines in the routine otorhinolaryngological practice is emphasized bearing in mind their numerous biological effects including antibiotic, anti-inflammatory, immunostimulating, anti-oxidative, anesthetic, and cytostatic actions.

Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (ANCA)-Positive and ANCA-Negative Patients With Granulomatosis With Polyangiitis (Wegener's): Distinct Patient Subsets.

OBJECTIVE: To examine the relationship of antineutrophil cytoplasmic antibody (ANCA) type and ANCA-associated vasculitis (AAV) diagnosis with demographic features, disease manifestations, and clinical outcomes. We focused on patients who account for the differences between ANCA type and disease type classifications: anti-myeloperoxidase (MPO)-ANCA-positive and ANCA-negative patients with granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: We performed a pooled analysis of the Wegener's Granulomatosis Etanercept Trial and the Rituximab in ANCA-Associated Vasculitis trial comparing patients with MPO-ANCA-positive GPA and patients with ANCA-negative GPA to patients with proteinase 3 (PR3)-ANCA-positive GPA and patients with MPO-ANCA-positive microscopic polyangiitis (MPA). RESULTS: Of the 365 patients analyzed, 273 (75%) had PR3-ANCA-positive GPA, 33 (9%) had MPO-ANCA-positive GPA, 15 (4%) had ANCA-negative GPA, and 44 (12%) had MPO-ANCA-positive MPA. MPO-ANCA-positive GPA patients were younger at diagnosis compared to MPO-ANCA-positive MPA patients (53 versus 61 years; P = 0.02). Their disease manifestations and rates of relapse were similar to those of PR3-ANCA-positive GPA patients. Relapse was more frequent in MPO-ANCA-positive GPA patients than in patients with MPO-ANCA-positive MPA at trial entry as well as at 12 and 18 months. ANCA-negative patients with GPA had lower Birmingham Vasculitis Activity Score for Wegener's Granulomatosis scores at trial entry than PR3-ANCA-positive patients with GPA (4.5 versus 7.7; P < 0.01), primarily because of a lower prevalence of renal involvement. CONCLUSION: We were unable to demonstrate important clinical differences between MPO-ANCA-positive and PR3-ANCA-positive patients with GPA. The risk of relapse was associated more closely with disease type than with ANCA type in this patient cohort. These findings deserve consideration in the assessment of relapse risk in patients with AAV.

[The place of otorhinolaryngology in modern medicine].

This publication is devoted to the peculiar features of the development of otorhinolaryngology as an integral component of modern medical science and practice and the place it now occupies among other disciplines. Much attention is given to the formation of the scientific views of focal infections with special reference to tonsillitis, the role of immune pathology an allergic reactions in etiology and pathogenesis of ENT diseases. Also considered is the problem of the elaboration of the new surgical methods and their application for the treatment of ENT pathology.

Immunoglobulin G4-related diseases in the head and neck: a systematic review.

BACKGROUND: Immunoglobulin G4 related disease (IgG4-RD) is a poorly understood chronic inflammatory disorder affecting the middle-aged and elderly that can present to the otolaryngologist. We aim to summarize the current literature regarding the manifestations and management of IgG4-RD in the head and neck. METHODS: Pubmed and EMBASE were searched using the term relevant search algorithm utilizing keywords such as: IgG4 related disease, head and neck, orbit, salivary glands, sialadenitis, Kuttner, angiocentric eosinophilic fibrosis, submandibular, lacrimal, thyroid, dacryoadenitis, nasal, sinus, and Mikulicz's. Reference lists were searched for identification of relevant studies. Case reports, original research and review articles published in English from 1964 to 2014 whose major topic was IgG4-RD affecting the head and neck were included. Data regarding patient demographics, presentation, histopathology, management and treatment outcomes of IgG4-RD were extracted. Level of evidence was also assessed and data were pooled where possible. Three independent reviewers screened eligible studies; extracted relevant data and discrepancies were resolved by consensus, where applicable. Descriptive and comparative statistics were performed. RESULTS: Fourty-three articles met our inclusion criteria. IgG4-RD most often presents as a mass lesion in the head and neck region. Common diagnostic features include: (1) elevated serum IgG4 level, (2) marked infiltration of exocrine glands by IgG4-positive plasma cells with fibrosis, and (3) marked improvement with corticosteroid therapy and additional immunosuppressive therapy in corticosteroid refractory cases. Early diagnosis and involvement of rheumatology is important in management. CONCLUSIONS: IgG4-RD is a challenging non-surgical disease that has multiple manifestations in the head and neck. It must be distinguished from various mimics including malignancy, systemic diseases, and infectious. Otolaryngology-Head and Neck surgeons should be aware of this condition and its management.

[Capabilities of pharmacological correction with Reamberin the cerebrovascular disorders with ENT diseases of the elderly patients].

Endointoxication's syndrome and manifestations of immune deficiency observed among elderly patients with acute exacerbations of ENT diseases and concomitant cerebrovascular pathology. Reamberin in pathogenetic therapy arrests manifestations of intoxication and optimizes immunobiological homeostasis.

Manifestations of immunoglobulin G4 related disease in otolaryngology: case reports and review of the literature.

BACKGROUND: Immunoglobulin G4 related disease is an inflammatory condition characterised by the presence of fibrotic lesions infiltrated by immunoglobulin G4 positive plasma cells. It can arise from almost any region of the body and it is being increasingly recognised in the head and neck. Regardless of the site of involvement, the histopathological resemblance is remarkable. Dense lymphoplasmacytic infiltration, overabundance of immunoglobulin G4 bearing plasma cells and presence of storiform fibrosis are typical findings. CASE REPORTS: This paper presents two cases of immunoglobulin G4 related disease in which there was involvement of the orbit, the infraorbital nerve and the infratemporal fossa. Diagnosis was established in both cases by biopsying radiologically abnormal tissue in the infratemporal fossa. CONCLUSION: An awareness of this condition is required to establish the diagnosis and initiate appropriate therapy. Glucocorticoids are the mainstay of initial treatment. The effectiveness of B-lymphocyte depletion with rituximab has also been reported. Correct diagnosis may spare patients from unnecessarily radical surgery.

Expressions and roles of periostin in otolaryngological diseases.

Periostin is a 90-kDa member of the fasciclin-containing family; it functions as part of matricellular proteins, and its production by airway epithelial cells is induced by IL-4 and IL-13. Periostin is secreted by fibroblasts and upregulated in the airway epithelia of patients with bronchial asthma; it is considered to contribute to remodeling under this pathological condition. However, despite many studies in diverse research areas, our overall understanding of this intriguing molecule is still inadequate. Here, we integrate the available evidence on periostin expression and its roles in otolaryngological diseases, including allergic rhinitis, chronic rhinosinusitis with nasal polyps, aspirin-induced asthma, organized hematoma, eosinophilic otitis media, and IgG4-related disease. Periostin might be involved as an important structural mediator in pathological processes such as insult and injury, Th2-driven inflammation, extracellular matrix restructuring, fibrosclerosis, tumor angiogenesis, and tissue remodeling.